METHODS AND SYSTEMS FOR IDENTIFYING THERAPEUTIC AGENTS FOR IMPROVING BRAIN FUNCTION CROSS-REFERENCE TO RELATED APPLICATIONS The application claims the benefit of U.S. Provisional Application No. 63/330,998, filed April 14, 2022, which is hereby incorporated herein by reference in its entirety. BACKGROUND Hundreds of millions of people worldwide are affected by neurological diseases and disorders. It is currently estimated that there are over 600 different neurological diseases and disorders that affect people. Approximately 6.2 million people die because of stroke each year with over 80% of deaths in low- and middle-income countries. More than 50 million people suffer from epilepsy worldwide. It is estimated that there are globally 35.6 million people with dementia with 7.7 million new cases every year. Alzheimer's disease is the most common cause of dementia and may contribute to 60-70% of cases. The financial burden of neurological disorders is significant. In the United States alone, the cost to treat neurological disorders is estimated to be over $800 billion a year. The global cost of treating neurological disorders is estimated to exceed $6 trillion by the year 2030. New therapeutics for the treatment of neurological diseases and disorders are needed to address these public health concerns. SUMMARY Provided herein are methods of identifying a therapeutic agent for improving brain function. Also provided are methods of assaying the efficacy of a therapeutic agent for improving brain function. Also provided are methods of screening an agent of interest to determine whether it is a suitable therapeutic agent for use in improving brain function. The methods described can include: performing an electrophysiology assay to measure synaptic function in a sample of animal model brain tissue; contacting the sample of animal model brain tissue with an agent of interest; performing an electrophysiology assay to measure synaptic function in the sample of animal model brain tissue following exposure to the agent of interest; comparing synaptic function of the sample of animal model brain tissue before and after contact with the agent of interest; and analyze perfusate from the electrophysiology assay for the presence of a biomarker indicating enhanced neural function or the absence of a biomarker indicative of a brain injury; wherein an increase in the synaptic function, the presence of one or more biomarkers indicating enhanced neural function, the absence of a biomarker indicative of a brain injury, or a combination thereof indicates that the agent of interest is a therapeutic agent for improving brain function. Also described are methods of identifying a therapeutic agent for the treatment of a brain injury, the method can include: performing an electrophysiology assay to measure synaptic function in a sample of animal model brain tissue; contacting the sample of animal model brain tissue with an agent of interest; performing an electrophysiology assay to measure synaptic function in the sample of animal model brain tissue following exposure to the agent of interest; comparing synaptic function of the sample of animal model brain tissue before and after contact with the agent of interest; and analyze perfusate from the electrophysiology assay for the presence of a biomarker indicating enhanced neural function or the absence of a biomarker indicative of a brain injury; wherein an increase in the synaptic function, the presence of one or more biomarkers indicating enhanced neural function, the absence of a biomarker indicative of a brain injury, or a combination thereof indicates that the agent of interest is a therapeutic agent for the treatment of an brain injury. Also described are methods of identifying a therapeutic agent for the treatment of a neurodegenerative disease. These methods can include: performing an electrophysiology assay to measure synaptic function in a sample of animal model brain tissue; contacting the sample of animal model brain tissue with an agent of interest; performing an electrophysiology assay to measure synaptic function in the sample of animal model brain tissue following exposure to the agent of interest; comparing synaptic function of the sample of animal model brain tissue before and after contact with the agent of interest; and analyze perfusate from the electrophysiology assay for the presence of a biomarker indicating enhanced neural function or the absence of a biomarker indicative of a brain injury; wherein an increase in the synaptic function, the presence of one or more biomarkers indicating enhanced neural function, the absence of a biomarker indicative of a brain injury, or a combination thereof indicates that the agent of interest is a therapeutic agent for the treatment of a neurodegenerative disease. In some embodiments, the methods can further include evaluating recovery of motor function, cognitive function, or a combination thereof associated with the administration of the drug to an animal model; wherein an increase in the synaptic function, the presence of one or more biomarkers indicating enhanced neural function, recovery of motor function, recovery of cognitive function, or a combination thereof following administration of the agent of interest indicates that the agent of interest is a therapeutic agent for improving brain function. In some embodiments, the animal model can be a healthy or injured. In some embodiments, the method can further include comparing motor and cognitive function of a healthy animal model before and after contact with the agent of interest to motor and cognitive function of an injured animal model before and after contact with the agent of interest. In some embodiments, the method can further include comparing synaptic function of a sample of a healthy animal model brain tissue before and after contact with the agent of interest to synaptic function of a sample of an injured animal model brain tissue before and after contact with the agent of interest. In some embodiments, the method can further include comparing the presence of one or more biomarkers indicating enhanced neural function of a sample of a healthy animal model brain tissue before and after contact with the agent of interest to the presence of one or more biomarkers indicating enhanced neural function of a sample of an injured animal model brain tissue before and after contact with the agent of interest. In some embodiments, the brain function can include brain plasticity, motor function, cognitive function, or a combination thereof. Described herein are also methods of identifying a biomarker correlated with improved neural function following brain injury, the method can include: performing an electrophysiology assay to measure synaptic function in a sample of animal model brain tissue; contacting the sample of animal model brain tissue with an agent of interest; performing an electrophysiology assay to measure synaptic function in the sample of animal model brain tissue following exposure to the agent of interest; comparing synaptic function of the sample of animal model brain tissue before and after contact with the agent of interest; analyze perfusate from the electrophysiology assay for presence of compounds of interest; and correlate the presence of compounds with an increase in synaptic function to identify the biomarker indicating enhanced neural function. The details of one or more embodiments of the disclosure are set forth in the accompanying drawings and the description below. Other features, objects, and advantages of the disclosure will be apparent from the description and drawings, and from the claims. DESCRIPTION OF DRAWINGS FIG. 1 show illustrates a mouse model of ischemic stroke. Stroke model (intraluminal filament), 45-60 minutes middle cerebral artery occlusion (MCAo), 24h-30 day reperfusion, adult (PND 60-90, Aged: 18-20 months), temperature 36°C to 37°C; occlusion confirmed by laser doppler.

FIG. 2 show illustrates controlled cortical impact injury.

FIG. 3 shows an exemplary setup of a method including electrophysiology following brain injury, paired with recirculation methods and mass spectroscopy methods to analyze biomarkers of cell response for drug screening.

FIG. 4 shows an illustration of lont term potentiation in Hippocampus is a cellular model for learning and memory. Long term potentiation is a persistent and long-lasting increase in synaptic efficacy following high-frequency stimulation of a neuronal synapse or network.

FIGs. 5A-5D show altering GABAA α5 receptors rescue synaptic function after MCAO. Hippocampal slices were superfused in aCSF + L655,708 (100 nM) during baseline recordings and 1 h after TBS. (a) Example fEPSPs from sham-operated control mice before (black) and after (red) TBS. (b) Sham mice (black filled circles), Sham + 100 nM L655,708 treated (green open circles) and L.655,708 treated mice in contralateral (blue filled squares) and Ipsilateral (red open squares) seven days after MCAO. Arrow indicates timing of TBS (40 pulses), (c) Quantification of change in fEPSP slope following TBS. (d) Memory' impairment 30 days after MCAO. Adult mice displayed memory dysfunction after contextual fear conditioning. Mice implanted with mini-osmotic pumps delivered either vehicle or L655,708 4 days before behavioral testing. Quantification of freezing behavior 24 h after contextual fear conditioning in a novel environment (n = 5-8/group).

FIGs. 6A-6D show bcute inhibition of TRPM2 preserves FTP. (a) Time course from male juvenile mice 7 days after sham or CA/CPR mice were administered 20 mg/kg tatSCR (blue) or tatM2NX (green) 30 min after CA/CPR. b) Quantification of change in fEPSP slope 60 minutes after TBS stimulation normalized to 20 minutes of baseline recording(. (c) Time course from female juvenile mice 7 days after sham or CA/CPR mice were administered 20 mg/kg tatSCR (blue) or tatM2NX (green) 30 min after CA/CPR. (d) Quantification of change in fEPSP slope 60 minutes after TBS stimulation.

FIGs. 7A-7B show delayed inhibition of TRPM2 restores memory function, (a) Quantification of freezing behavior 24 hours after contextual fear conditioning in a novel environment in mice administered 20 mg/kg tatSCR (black) or 20 mg/kg tatM2NX (red) after sham surgery or mice administered 20 mg/kg tatSCR (blue) or 20 mg/kg tatM2NX (green) 13 days after recovery from CA/CPR and behavior testing initiated on day 14 after CA/CPR. (b) Quantification of distance traveled in the same mice as in (a) in open field testing, indicating no changes in locomotion to account for differences in freezing.

FIGs. 8A-8C show Nogo- 1 receptor antagonist rescues synaptic impairment when applied seven days after juvenile MCAO.

FIGs. 9A-9D show Nogo-1 receptor antagonist does not affect LTP impairment in adult mice.

FIGs. 10A-10C show TrkB receptor agonist rescues synaptic impairment when bath applied seven days after CA/CPR. (a) Experimental design for LTP experiments, (b) Time course of fEPSP slope from mice seven days after CA/CPR (black, n = 6) and paired slices bath applied with 7,8 dihydroxy flavone (7,8 DHF, 250 nM, n ^===: 6, red). Arrow indicates timing of theta burst stimulation (TBS, 40 pulses, 100 Hz), (c) Quantification of change in fEPSP slope after 60 min following TBS normalized to baseline. Sham and seven-day CA/CPR slices were paired with and without 7,8 DHF and paired experiments are indicated by the line between the pairs.

Like reference symbols in the various drawings indicate like elements.

DETAILED DESCRIPTION

A number of embodiments of the disclosure have been described. Nevertheless, it wall be understood that various modifications may be made without departing from the spirit and scope of the invention. Accordingly, other embodiments are within the scope of the following claims.

Definitions

To facilitate understanding of the disclosure set forth herein, a number of terms are defined below. Unless defined otherwise, all technical and scientific terms used herein generally have the same meaning as commonly understood by one of ordinary skill in the art to which this disclosure belongs. Publications cited herein and the materials for which they are cited are specifically incorporated by reference.

General Definitions

As used in this specification and the following claims, the terms “comprise” (as well as forms, derivatives, or variations thereof, such as “comprising” and “comprises”) and “include” (as well as forms, derivatives, or variations thereof, such as “including” and “includes”) are inclusive (i.e., open-ended) and do not exclude additional elements or steps. For example, the terms "comprise" and/or "comprising," when used in this specification, specify the presence of stated features, integers, steps, operations, elements, and/or components, but do not preclude the presence or addition of one or more other features, integers, steps, operations, elements, components, and/or groups thereof. Other than where noted, all numbers expressing quantities of ingredients, reaction conditions, geometries, dimensions, and so forth used in the specification and claims are to be understood at the very least, and not as an attempt to limit the application of the doctrine of equivalents to the scope of the claims, to be construed in light of the number of significant digits and ordinary rounding approaches. Accordingly, these terms are intended to not only cover the recited element(s) or step(s), but may also include other elements or steps not expressly recited. Furthermore, as used herein, the use of the terms “a”, “an”, and “the” when used in conjunction with an element may mean “one,” but it is also consistent with the meaning of “one or more,” “at least one,” and “one or more than one.” Therefore, an element preceded by “a” or “an” does not, without more constraints, preclude the existence of additional identical elements. Ranges can be expressed herein as from “about” one particular value, and/or to “about” another particular value. By “about” is meant within 5% of the value, e.g., within 4, 3, 2, or 1% of the value. When such a range is expressed, another aspect includes from the one particular value and/or to the other particular value. Similarly, when values are expressed as approximations, by use of the antecedent “about,” it will be understood that the particular value forms another aspect. It will be further understood that the endpoints of each of the ranges are significant both in relation to the other endpoint, and independently of the other endpoint. It is also understood that there are a number of values disclosed herein, and that each value is also herein disclosed as “about” that particular value in addition to the value itself. For example, if the value “10” is disclosed, then “about 10” is also disclosed. A range may be construed to include the start and the end of the range. For example, a range of 10% to 20% (i.e., range of 10%-20%) can includes 10% and also includes 20%, and includes percentages in between 10% and 20%, unless explicitly stated otherwise herein. As used herein, the terms "may," "optionally," and "may optionally" are used interchangeably and are meant to include cases in which the condition occurs as well as cases in which the condition does not occur. Thus, for example, the statement that a formulation "may include an excipient" is meant to include cases in which the formulation includes an excipient as well as cases in which the formulation does not include an excipient. It is understood that when combinations, subsets, groups, etc. of elements are disclosed (e.g., combinations of components in a composition, or combinations of steps in a method), that while specific reference of each of the various individual and collective combinations and permutations of these elements may not be explicitly disclosed, each is specifically contemplated and described herein. “Administration" to a subject includes any route of introducing or delivering to a subject an agent. Administration can be carried out by any suitable route, including oral, topical, transcutaneous, transdermal, intra-joint, intra-arteriole, intradermal, intraventricular, intralesional, intranasal, rectal, vaginal, by inhalation, via an implanted reservoir, parenteral (e.g., subcutaneous, intravenous, intramuscular, intra- articular, intra-synovial, intrasternal, intrathecal, intraperitoneal, intrahepatic, intralesional, and intracranial injections or infusion techniques), and the like. "Concurrent administration", "administration in combination", "simultaneous administration" or "administered simultaneously" as used herein, means that the compounds are administered at the same point in time or essentially immediately following one another. In the latter case, the two compounds are administered at times sufficiently close that the results observed are indistinguishable from those achieved when the compounds are administered at the same point in time. "Systemic administration" refers to the introducing or delivering to a subject an agent via a route which introduces or delivers the agent to extensive areas of the subject's body (e.g. greater than 50% of the body), for example through entrance into the circulatory or lymph systems. By contrast, "local administration" refers to the introducing or delivery to a subject an agent via a route which introduces or delivers the agent to the area or area immediately adjacent to the point of administration and does not introduce the agent systemically in a therapeutically significant amount. For example, locally administered agents are easily detectable in the local vicinity of the point of administration but are undetectable or detectable at negligible amounts in distal parts of the subject's body. Administration includes self-administration and the administration by another. As used here, the terms “beneficial agent” and “active agent” are used interchangeably herein to refer to a chemical compound or composition that has a beneficial biological effect. Beneficial biological effects include both therapeutic effects, i.e., treatment of a disorder or other undesirable physiological condition, and prophylactic effects, i.e., prevention of a disorder or other undesirable physiological condition. The terms also encompass pharmaceutically acceptable, pharmacologically active derivatives of beneficial agents specifically mentioned herein, including, but not limited to, salts, esters, amides, prodrugs, active metabolites, isomers, fragments, analogs, and the like. When the terms “beneficial agent” or “active agent” are used, then, or when a particular agent is specifically identified, it is to be understood that the term includes the agent per se as well as pharmaceutically acceptable, pharmacologically active salts, esters, amides, prodrugs, conjugates, active metabolites, isomers, fragments, analogs, etc. A "decrease" can refer to any change that results in a smaller amount of a symptom, disease, composition, condition, or activity. A substance is also understood to decrease the genetic output of a gene when the genetic output of the gene product with the substance is less relative to the output of the gene product without the substance. Also, for example, a decrease can be a change in the symptoms of a disorder such that the symptoms are less than previously observed. A decrease can be any individual, median, or average decrease in a condition, symptom, activity, composition in a statistically significant amount. Thus, the decrease can be a 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, or 100% decrease so long as the decrease is statistically significant. "Inhibit," "inhibiting," and "inhibition" mean to decrease an activity, response, condition, disease, or other biological parameter. This can include but is not limited to the complete ablation of the activity, response, condition, or disease. This may also include, for example, a 10% reduction in the activity, response, condition, or disease as compared to the native or control level. Thus, the reduction can be a 10, 20, 30, 40, 50, 60, 70, 80, 90, 100%, or any amount of reduction in between as compared to native or control levels. “Inactivate”, “inactivating” and “inactivation” means to decrease or eliminate an activity, response, condition, disease, or other biological parameter due to a chemical (covalent bond formation) between the ligand and a its biological target. By “reduce” or other forms of the word, such as “reducing” or “reduction,” is meant lowering of an event or characteristic (e.g., tumor growth). It is understood that this is typically in relation to some standard or expected value, in other words it is relative, but that it is not always necessary for the standard or relative value to be referred to. For example, “reduces tumor growth” means reducing the rate of growth of a tumor relative to a standard or a control. As used herein, the terms “treating” or “treatment” of a subject includes the administration of a drug to a subject with the purpose of preventing, curing, healing, alleviating, relieving, altering, remedying, ameliorating, improving, stabilizing or affecting a disease or disorder, or a symptom of a disease or disorder. The terms “treating” and “treatment” can also refer to reduction in severity and/or frequency of symptoms, elimination of symptoms and/or underlying cause, prevention of the occurrence of symptoms and/or their underlying cause, and improvement or remediation of damage. By “prevent” or other forms of the word, such as “preventing” or “prevention,” is meant to stop a particular event or characteristic, to stabilize or delay the development or progression of a particular event or characteristic, or to minimize the chances that a particular event or characteristic will occur. Prevent does not require comparison to a control as it is typically more absolute than, for example, reduce. As used herein, something could be reduced but not prevented, but something that is reduced could also be prevented. Likewise, something could be prevented but not reduced, but something that is prevented could also be reduced. It is understood that where reduce or prevent are used, unless specifically indicated otherwise, the use of the other word is also expressly disclosed. For example, the terms “prevent” or “suppress” can refer to a treatment that forestalls or slows the onset of a disease or condition or reduced the severity of the disease or condition. Thus, if a treatment can treat a disease in a subject having symptoms of the disease, it can also prevent or suppress that disease in a subject who has yet to suffer some or all of the symptoms. As used herein, the term “preventing” a disorder or unwanted physiological event in a subject refers specifically to the prevention of the occurrence of symptoms and/or their underlying cause, wherein the subject may or may not exhibit heightened susceptibility to the disorder or event. By the term “effective amount” of a therapeutic agent is meant a nontoxic but sufficient amount of a beneficial agent to provide the desired effect. The amount of beneficial agent that is “effective” will vary from subject to subject, depending on the age and general condition of the subject, the particular beneficial agent or agents, and the like. Thus, it is not always possible to specify an exact “effective amount”. However, an appropriate “effective’ amount in any subject case may be determined by one of ordinary skill in the art using routine experimentation. Also, as used herein, and unless specifically stated otherwise, an “effective amount” of a beneficial can also refer to an amount covering both therapeutically effective amounts and prophylactically effective amounts. An “effective amount” of a drug necessary to achieve a therapeutic effect may vary according to factors such as the age, sex, and weight of the subject. Dosage regimens can be adjusted to provide the optimum therapeutic response. For example, several divided doses may be administered daily or the dose may be proportionally reduced as indicated by the exigencies of the therapeutic situation. As used herein, a “therapeutically effective amount” of a therapeutic agent refers to an amount that is effective to achieve a desired therapeutic result, and a “prophylactically effective amount” of a therapeutic agent refers to an amount that is effective to prevent an unwanted physiological condition. Therapeutically effective and prophylactically effective amounts of a given therapeutic agent will typically vary with respect to factors such as the type and severity of the disorder or disease being treated and the age, gender, and weight of the subject. The term “therapeutically effective amount” can also refer to an amount of a therapeutic agent, or a rate of delivery of a therapeutic agent (e.g., amount over time), effective to facilitate a desired therapeutic effect. The precise desired therapeutic effect will vary according to the condition to be treated, the tolerance of the subject, the drug and/or drug formulation to be administered (e.g., the potency of the therapeutic agent (drug), the concentration of drug in the formulation, and the like), and a variety of other factors that are appreciated by those of ordinary skill in the art. As used herein, the term “pharmaceutically acceptable” component can refer to a component that is not biologically or otherwise undesirable, i.e., the component may be incorporated into a pharmaceutical formulation of the invention and administered to a subject as described herein without causing any significant undesirable biological effects or interacting in a deleterious manner with any of the other components of the formulation in which it is contained. When the term “pharmaceutically acceptable” is used to refer to an excipient, it is generally implied that the component has met the required standards of toxicological and manufacturing testing or that it is included on the Inactive Ingredient Guide prepared by the U.S. Food and Drug Administration. "Pharmaceutically acceptable carrier" (sometimes referred to as a "carrier") means a carrier or excipient that is useful in preparing a pharmaceutical or therapeutic composition that is generally safe and non-toxic and includes a carrier that is acceptable for veterinary and/or human pharmaceutical or therapeutic use. The terms "carrier" or "pharmaceutically acceptable carrier" can include, but are not limited to, phosphate buffered saline solution, water, emulsions (such as an oil/water or water/oil emulsion) and/or various types of wetting agents. As used herein, the term "carrier" encompasses, but is not limited to, any excipient, diluent, filler, salt, buffer, stabilizer, solubilizer, lipid, stabilizer, or other material well known in the art for use in pharmaceutical formulations and as described further herein. As used herein, “pharmaceutically acceptable salt” is a derivative of the disclosed compound in which the parent compound is modified by making inorganic and organic, non- toxic, acid or base addition salts thereof. The salts of the present compounds can be synthesized from a parent compound that contains a basic or acidic moiety by conventional chemical methods. Generally, such salts can be prepared by reacting free acid forms of these compounds with a stoichiometric amount of the appropriate base (such as Na, Ca, Mg, or K hydroxide, carbonate, bicarbonate, or the like), or by reacting free base forms of these compounds with a stoichiometric amount of the appropriate acid. Such reactions are typically carried out in water or in an organic solvent, or in a mixture of the two. Generally, non-aqueous media like ether, ethyl acetate, ethanol, isopropanol, or acetonitrile are typical, where practicable. Salts of the present compounds further include solvates of the compounds and of the compound salts. Examples of pharmaceutically acceptable salts include, but are not limited to, mineral or organic acid salts of basic residues such as amines; alkali or organic salts of acidic residues such as carboxylic acids; and the like. The pharmaceutically acceptable salts include the conventional non-toxic salts and the quaternary ammonium salts of the parent compound formed, for example, from non-toxic inorganic or organic acids. For example, conventional non-toxic acid salts include those derived from inorganic acids such as hydrochloric, hydrobromic, sulfuric, sulfamic, phosphoric, nitric and the like; and the salts prepared from organic acids such as acetic, propionic, succinic, glycolic, stearic, lactic, malic, tartaric, citric, ascorbic, pamoic, maleic, hydroxymaleic, phenylacetic, glutamic, benzoic, salicylic, mesylic, esylic, besylic, sulfanilic, 2- acetoxybenzoic, fumaric, toluenesulfonic, methanesulfonic, ethane disulfonic, oxalic, isethionic, HOOC-(CH2)n- COOH where n is 0-4, and the like, or using a different acid that produces the same counterion. Lists of additional suitable salts may be found, e.g., in Remington's Pharmaceutical Sciences, 17th ed., Mack Publishing Company, Easton, Pa., p. 1418 (1985). Also, as used herein, the term “pharmacologically active” (or simply “active”), as in a “pharmacologically active” derivative or analog, can refer to a derivative or analog (e.g., a salt, ester, amide, conjugate, metabolite, isomer, fragment, etc.) having the same type of pharmacological activity as the parent compound and approximately equivalent in degree. A “control” is an alternative subject or sample used in an experiment for comparison purposes. A control can be "positive" or "negative." As used herein, by a “subject” is meant an individual. Thus, the “subject” can include domesticated animals (e.g., cats, dogs, etc.), livestock (e.g., cattle, horses, pigs, sheep, goats, etc.), laboratory animals (e.g., mouse, rabbit, rat, guinea pig, etc.), and birds. “Subject” can also include a mammal, such as a primate or a human. Thus, the subject can be a human or veterinary patient. The term “patient” refers to a subject under the treatment of a clinician, e.g., physician. Administration of the therapeutic agents can be carried out at dosages and for periods of time effective for treatment of a subject. In some embodiments, the subject is a human. Reference will now be made in detail to specific aspects of the disclosed materials, compounds, compositions, articles, and methods, examples of which are illustrated in the accompanying Examples and Figures. Methods Provided herein are methods of identifying a therapeutic agent for improving brain function. Also provided are methods of assaying the efficacy of a therapeutic agent for improving brain function. Also provided are methods of screening an agent of interest to determine whether it is a suitable therapeutic agent for use in improving brain function. The methods described can include: performing an electrophysiology assay to measure synaptic function in a sample of animal model brain tissue; contacting the sample of animal model brain tissue with an agent of interest; performing an electrophysiology assay to measure synaptic function in the sample of animal model brain tissue following exposure to the agent of interest; comparing synaptic function of the sample of animal model brain tissue before and after contact with the agent of interest; and analyze perfusate from the electrophysiology assay for the presence of a biomarker indicating enhanced neural function or the absence of a biomarker indicative of a brain injury; wherein an increase in the synaptic function, the presence of one or more biomarkers indicating enhanced neural function, the absence of a biomarker indicative of a brain injury, or a combination thereof indicates that the agent of interest is a therapeutic agent for improving brain function. Described are also methods of identifying a therapeutic agent for the treatment of a brain injury, the method can include: performing an electrophysiology assay to measure synaptic function in a sample of animal model brain tissue; contacting the sample of animal model brain tissue with an agent of interest; performing an electrophysiology assay to measure synaptic function in the sample of animal model brain tissue following exposure to the agent of interest; comparing synaptic function of the sample of animal model brain tissue before and after contact with the agent of interest; and analyze perfusate from the electrophysiology assay for the presence of a biomarker indicating enhanced neural function or the absence of a biomarker indicative of a brain injury; wherein an increase in the synaptic function, the presence of one or more biomarkers indicating enhanced neural function, the absence of a biomarker indicative of a brain injury, or a combination thereof indicates that the agent of interest is a therapeutic agent for the treatment of an brain injury. The term “brain injury” refers to any and all injury of the brain and can be caused by fracture or penetration of the skull (i.e. a vehicle accident, fall, gunshot wound), a disease process (i.e. neurotoxins, infections, tumors, metabolic abnormalities, etc.) or a closed head injury such as in the case of rapid acceleration or deceleration of the head (i.e. Shaken Baby Syndrome, blast), blunt trauma, concussions, and concussion syndrome. Brain injury can be any injury to the brain and can be caused by fracture or penetration of the skull, a disease process, or a closed head injury such as rapid acceleration or deceleration of the head. Traumatic Brain Injuries (TBI) can result from a closed head injury or a penetrating head injury. A closed injury occurs when the head suddenly and violently hits an object but the object does not break through the skull. A penetrating injury occurs when an object pierces the skull and enters brain tissue. Skull fractures occur when the bone of the skull cracks or breaks. A depressed skull fracture occurs when pieces of the broken skull press into the tissue of the brain. A penetrating skull fracture occurs when something pierces the skull, such as a bullet, leaving a distinct and localized injury to brain tissue. Skull fractures can cause cerebral contusion. Non-traumatic Brain Injury is any injury to the brain that does not result from any cause that does not injure the brain using physical force, but rather occurs via infection, poisoning, tumor, or degenerative disease. Causes include lack of oxygen, glucose, or blood are considered non-traumatic. Infections can cause encephalitis (brain swelling), meningitis (meningeal swelling), or cell toxicity, as can tumors or poisons. These injuries can occur through stroke, heart attack, near-drowning, strangulation or a diabetic coma, poisoning or other chemical causes such as alcohol abuse or drug overdose, infections or tumors and degenerative conditions such as Alzheimer's disease and Parkinson's disease. Non-traumatic injury, damage is usually spread throughout the brain and exceptions include tumors and an infection that may remain localised or spreads evenly from one starting point. Another insult to the brain that can cause injury is anoxia. Anoxia is a condition in which there is an absence of oxygen supply to an organ's tissues, even if there is adequate blood flow to the tissue. Hypoxia refers to a decrease in oxygen supply rather than a complete absence of oxygen, and ischemia is inadequate blood supply, as is seen in cases in which the brain swells. In any of these cases, without adequate oxygen, a biochemical cascade called the ischemic cascade is unleashed, and the cells of the brain can die within several minutes. This type of injury is often seen in near-drowning victims, in heart attack patients, or in people who suffer significant blood loss from other injuries that decrease blood flow to the brain. All of the above result in neurodegeneration which is the progressive loss of neurons in the brain. Multiple physiological events lead to the neurodegeneration of the brain tissues following a traumatic injury. These events include, for example, cerebral edema, destruction of vascular integrity, increases in the immune and inflammatory response, demyelinization, and lipid peroxidation. In some embodiments, the brain injury can include traumatic brain injury, non-traumatic brain injury, ischemic brain injury, anoxic brain injury, hypoxic brain injury, neuronal damage, neural disorders, brain damage, or neural damage due to drug or alcohol addiction. Described are also methods of identifying a therapeutic agent for the treatment of a neurodegenerative disease, the method can include: performing an electrophysiology assay to measure synaptic function in a sample of animal model brain tissue; contacting the sample of animal model brain tissue with an agent of interest; performing an electrophysiology assay to measure synaptic function in the sample of animal model brain tissue following exposure to the agent of interest; comparing synaptic function of the sample of animal model brain tissue before and after contact with the agent of interest; and analyze perfusate from the electrophysiology assay for the presence of a biomarker indicating enhanced neural function; wherein an increase in the synaptic function, the presence of one or more biomarkers indicating enhanced neural function, or a combination thereof indicates that the agent of interest is a therapeutic agent for the treatment of a neurodegenerative disease. The term "neurodegenerative disease" refers to any disease characterized by the dysfunction and/or death of neurons leading to a loss of neurologic function in the brain, spinal cord, central nervous system, and/or peripheral nervous system. Neurodegenerative diseases can be chronic or acute. Examples of neurodegenerative diseases include, but are not limited to, Alzheimer's disease, Parkinson's disease, frontotemporal dementia, frontotemporal dementia with Parkinsonism, frontotemporal lobe dementia, pallidopontonigral degeneration, progressive supranuclear palsy, multiple system tauopathy, multiple system tauopathy with presenile dementia, Wilhelmsen-Lynch disease, Pick's disease, Pick's disease-like dementia, Mild Cognitive Impairment, Diffuse Lewy body disease, Dementia with Lewy bodies type, demyelinating diseases such as multiple sclerosis and acute transverse myelitis, Balo's Concentric Sclerosis, Acute Disseminating Encephalomyelitis, Neuromyelitis Optica, Transverse Myelitis or Leukodystrophies, amyotrophic lateral sclerosis, Huntington's disease, Creutzfeldt- Jakob disease, AIDs dementia complex, extrapyramidal and cerebellar disorders such as lesions of the corticospinal system, disorders of the basal ganglia, corticobasal ganglionic degeneration, \ progressive supranuclear Palsy, structural lesions of the cerebellum, spinocerebellar degenerations, such as spinal ataxia, Friedreich's ataxia, cerebellar cortical degenerations, multiple systems degenerations (Mencel, Dejerine- Thomas, Shi-Drager, and Machado- Joseph), multiple system atrophy, systemic disorders (Refsum's disease, abetalipoprotemia, ataxia, telangiectasia, and mitochondrial multisystem disorder), disorders of the motor unit such as neurogenic muscular atrophies (anterior horn cell degeneration, infantile spinal muscular atrophy, and juvenile spinal muscular atrophy), Progressive Bulbar Palsy, Down's Syndrome in middle age, subacute sclerosing panencephalitis, Hallervorden-Spatz disease, dementia pugilistica, Primary Lateral Sclerosis, Progressive Pseudobulbar Palsy or Post-polio Syndrome; peripheral neuropathy is inherited (HNPP, CMT1A, CMT1B, DSS, CMT1X, CMT4B1), infectious (Leprosy, HIV), immune (GBS), diabetic (Type I, Type II), injury (transient nerve crush, chronic constriction injury, partial nerve ligation, spinal nerve ligation, spared nerve injury), and chemotherapy (i.e. cisplatin)-induced neuropathies; and the like. Some examples of acute neurodegenerative disease are stroke, ischemia, and multiple infarct dementia. Sudden loss of neurons may also characterize the brains of patients with epilepsy and those that suffer hypoglycemic insults and traumatic injury of the brain, peripheral nerves, or spinal cord. In some embodiments, the methods can further include evaluating recovery of motor function, cognitive function, or a combination thereof associated with the administration of the drug to an animal model; wherein an increase in the synaptic function, the presence of one or more biomarkers indicating enhanced neural function, recovery of motor function, recovery of cognitive function, or a combination thereof following administration of the agent of interest indicates that the agent of interest is a therapeutic agent for improving brain function. In some embodiments, the animal model can be a healthy or injured. In some embodiments, the methods can further include: separating animal model into two populations; administering the agent of interest to only one animal model population; evaluating motor and cognitive function in the animal model populations following administration of the agent of interest to one animal model population; and comparing motor and cognitive function between the animal model populations before and after contact of one of the animal model population with the agent of interest; wherein an increase in the synaptic function, the presence of one or more biomarkers indicating enhanced neural function, recovery of motor function, recovery of cognitive function, or a combination thereof following administration of the agent of interest indicates that the agent of interest is a therapeutic agent for improving brain function. In some embodiments, the methods can further include: evaluating motor and cognitive function in an animal model; administering the agent of interest to the animal model; evaluating motor and cognitive function in the animal model following administration of the agent of interest; and comparing motor and cognitive function of the animal model before and after contact with the agent of interest; wherein an increase in the synaptic function, the presence of one or more biomarkers indicating enhanced neural function, recovery of motor function, recovery of cognitive function, or a combination thereof following administration of the agent of interest indicates that the agent of interest is a therapeutic agent for improving brain function. In some embodiments, the animal model can be a healthy or injured. In some embodiments, the method can further include comparing motor and cognitive function of a healthy animal model before and after contact with the agent of interest to motor and cognitive function of an injured animal model before and after contact with the agent of interest. In some embodiments, the method can further include comparing synaptic function of a sample of a healthy animal model brain tissue before and after contact with the agent of interest to synaptic function of a sample of an injured animal model brain tissue before and after contact with the agent of interest. In some embodiments, the method can further include comparing the presence of one or more biomarkers indicating enhanced neural function of a sample of a healthy animal model brain tissue before and after contact with the agent of interest to the presence of one or more biomarkers indicating enhanced neural function of a sample of an injured animal model brain tissue before and after contact with the agent of interest. In some embodiments, the brain function can include brain plasticity, motor function, cognitive function, or a combination thereof. In some embodiments, measuring synaptic function can include measuring synaptic function (long-term potentiation). In some embodiments, the electrophysiology assay can include stimulating the brain tissue. In some embodiments, stimulating can include high frequency stimulation or low frequency stimulation. In some embodiment, high frequency stimulation can include from 1 to 300 pulses and 1 Hz to 100 Hz, (e.g., 5 pulses to 5 Hz, 10 pulses to 5 Hz, 20 pulses to 5 Hz, 30 pulses to 5 Hz, 40 pulses to 5 Hz, 50 pulses to 5 Hz, 60 pulses to 5 Hz, 70 pulses to 5 Hz, 80 pulses to 5 Hz, 90 pulses to 5 Hz, 100 pulses and 5 Hz, 150 pulses to 5 Hz, 200 pulses to 5 Hz, 300 pulses to 5 Hz, 5 pulses to 10 Hz, 10 pulses to 10 Hz, 20 pulses to 10 Hz, 30 pulses to 10 Hz, 40 pulses to 10 Hz, 50 pulses to 10 Hz, 60 pulses to 10 Hz, 70 pulses to 10 Hz, 80 pulses to 10 Hz, 90 pulses to 10 Hz, 100 pulses and 10 Hz, 150 pulses to 10 Hz, 200 pulses to 10 Hz, 300 pulses to 10 Hz, 5 pulses to 25 Hz, 10 pulses to 25 Hz, 20 pulses to 25 Hz, 30 pulses to 25 Hz, 40 pulses to 25 Hz, 50 pulses to 25 Hz, 60 pulses to 25 Hz, 70 pulses to 25 Hz, 80 pulses to 25 Hz, 90 pulses to 25 Hz, 100 pulses and 25 Hz, 150 pulses to 25 Hz, 200 pulses to 25 Hz, 300 pulses to 25 Hz, 5 pulses to 50 Hz, 10 pulses to 50 Hz, 20 pulses to 50 Hz, 30 pulses to 50 Hz, 40 pulses to 50 Hz, 50 pulses to 50 Hz, 60 pulses to 50 Hz, 70 pulses to 50 Hz, 80 pulses to 50 Hz, 90 pulses to 50 Hz, 100 pulses and 50 Hz, 150 pulses to 50 Hz, 200 pulses to 50 Hz, 300 pulses to 50 Hz, 5 pulses to 100 Hz, 10 pulses to 100 Hz, 20 pulses to 100 Hz, 30 pulses to 100 Hz, 40 pulses to 100 Hz, 50 pulses to 100 Hz, 60 pulses to 100 Hz, 70 pulses to 100 Hz, 80 pulses to 100 Hz, 90 pulses to 100 Hz, 100 pulses and 100 Hz, 150 pulses to 100 Hz, 200 pulses to 100 Hz, or 300 pulses to 100 Hz). In some embodiments, high frequency stimulation can include Theta Burst Stimulation (TBS) (e.g., 4 pulses at 100 Hz, repeated at 5 Hz to total 40 pulses). In some embodiments, low frequency stimulation can include from 1 to 900 Pulses and 0.1 Hz to 5 Hz. In some embodiments, contacting the agent of interest with the brain tissue can happen from 0 seconds to 1 day (e.g., from 0 seconds to 12 hours, from 0 seconds to 10 hours, from 0 seconds to 8 hours, from 0 seconds to 6 hours, from 0 seconds to 4 hours, from 0 seconds to 2 hours, from 0 seconds to 1 hour, from 0 seconds to 30 minutes, from 0 seconds to 15 minutes, from 0 seconds to 10 minutes, from 0 seconds to 5 minutes, from 5 minutes to 12 hours, from 5 minutes to 10 hours, from 5 minutes to 8 hours, from 5 minutes to 6 hours, from 5 minutes to 4 hours, from 5 minutes to 2 hours, from 5 minutes to 1 hour, from 5 minutes to 30 minutes, from 5 minutes 15 minutes, from 5 minutes to 10 minutes, from 30 minutes to 12 hours, from 30 minutes to 10 hours, from 30 minutes to 8 hours, from 30 minutes to 6 hours, from 30 minutes to 4 hours, from 30 minutes to 2 hours, from 30 minutes to 1 hour, from 2 hours to 12 hours, from 2 hours to 10 hours, from 2 hours to 8 hours, from 2 hours to 6 hours, or from 2 hours to 4 hours) after stimulation. In some embodiments, measuring synaptic function in a sample of animal model brain tissue can include placing an electrode in contact with the animal model brain tissue to record excitatory post-synaptic potential signals. In some embodiments, the synaptic function in a sample of animal model brain tissue after contacting the sample of animal model brain tissue with a therapeutic agent is at least 1.3 times greater (e.g., 1.5, 2, 3 time greater, 5 times greater, or 10 times greater). In some embodiments, wherein the excitatory post-synaptic potential signal after contacting the sample of animal model brain tissue with a therapeutic agent is at least 1.3 times greater, (e.g., 1.5, 2, 3 time greater, 5 times greater, or 10 times greater). In some embodiments, evaluating recovery of motor function, cognitive function, or a combination thereof can include performing a behavioral test. In some embodiments, the behavioral test can include measuring freezing behavior, distance traveled, contextual fear conditioning (CFC), spatial or contextual memory, short term memory, long term memory, anxiety, cognition, executive function, open field test, or a combination thereof. In some embodiments, the behavioral test can include contextual fear conditioning (CFC). In some embodiments, the behavioral test can include open field test. In some embodiments, the behavioral test can include measuring distance traveled in an open field test. In some embodiments, distance traveled can be measured before using contextual fear conditioning. In some embodiments, administration of the agent of interest to the animal model can happen from 30 minutes to 120 days (e.g, from 1 hours to 7 days, from 1 hour to 6 days, from 1 hour to 5 days, from 1 hour to 4 days, from 12 hours to 3 days) after a brain injury. In some embodiments, administration of the agent of interest to the animal model can happen from 30 minutes to 120 days (e.g, from 1 hour to 5 days, from 1 hour to 4 days, from 12 hours to 3 days, or from 1 day to 4 days, from 1 day to 5 days) prior to a behavioral test. Described herein are also methods of identifying a biomarker correlated with improved neural function following brain injury, the method can include: performing an electrophysiology assay to measure synaptic function in a sample of animal model brain tissue as described herein; contacting the sample of animal model brain tissue with an agent of interest as described herein; performing an electrophysiology assay to measure synaptic function in the sample of animal model brain tissue following exposure to the agent of interest as described herein; comparing synaptic function of the sample of animal model brain tissue before and after contact with the agent of interest as described herein; analyze perfusate from the electrophysiology assay for presence of compounds of interest; and correlate the presence of compounds with an increase in synaptic function to identify the biomarker indicating enhanced neural function. Described herein are also methods of identifying a biomarker correlated with improved neural function following brain injury, the method can include: performing an electrophysiology assay to measure synaptic function in a sample of animal model brain tissue as described herein; contacting the sample of animal model brain tissue with an agent of interest as described herein; performing an electrophysiology assay to measure synaptic function in the sample of animal model brain tissue following exposure to the agent of interest as described herein; comparing synaptic function of the sample of animal model brain tissue before and after contact with the agent of interest as described herein; analyze perfusate from the electrophysiology assay for presence of compounds of interest; and correlate the absence of compounds with an increase in synaptic function to identify the biomarker indicating enhanced neural function. In some embodiments, analyze perfusate can include measuring the levels of compounds of interest related to enhanced neural function using analytical techniques commonly known by skill person in the art. Suitable analytical techniques can include, but are not limited to chromatographic techniques (such as High Performance Liquid Chromatography), spectroscopic techniques (UV spectroscopy, magnetic resonance spectroscopy), spectrometry techniques (mass spectrometry), electrophoresis, or ligand binding assays (such as western blot, or ELISA). In some embodiments, the method can further include comparing synaptic function of a sample of a healthy animal model brain tissue before and after contact with the agent of interest to synaptic function of a sample of an injured animal model brain tissue before and after contact with the agent of interest. In some embodiments, neural function can include neuroplasticity, motor function, cognitive function, or a combination thereof. In some embodiments, the increase in synaptic function can be at least 1.3 times (e.g., 1.5, 2, 3 times, 5 times, or 10 times). In some embodiments, the increase in excitatory post-synaptic potential signal can be at least 1.3 times, (e.g., 1.5, 2, 3 time, 5 times, or 10 times). In some embodiments, biomarkers indicative of a brain injury, include, but are not limited to those described in U.S. Patent No.7,396,654, which is hereby incorporated by reference in its entirety. All of the compositions and methods disclosed and claimed herein can be made and executed without undue experimentation in light of the present disclosure. While the compositions and methods of this disclosure have been described in terms of preferred embodiments, it will be apparent to those of skill in the art that variations may be applied to the compositions and methods and in the steps or in the sequence of steps of the methods described herein without departing from the concept, spirit and scope of the disclosure. More specifically, it will be apparent that certain agents which are both chemically related may be substituted for the agents described herein while the same or similar results would be achieved. All such similar substitutes and modifications apparent to those skilled in the art are deemed to be within the spirit, scope and concept of the disclosure as defined by the appended claims. By way of non-limiting illustration, examples of certain embodiments of the present disclosure are given below. EXAMPLES Example 1: Acquired brain injury following cerebral ischemia (stroke, cardiac arrest, hemorrhage, others) or mechanical injury (traumatic brain injury) results in histological injury within various brain regions as well as long-term functional deficits. Historically, academics and pharmaceutical companies have tested lead compounds in in vitro and in vivo models of ischemia /injury with a focus on cellular protection. The current application provides an innovative new method of drug screening that promises to identify compounds that provide enhanced brain plasticity and functional recovery. Specifically, a new combination of various experimental models to provide a screening platform for drug discovery. The method can include performing in vivo acquired brain injury (stroke, TBI, CA/CPR) on an animal model (mouse, rat, dog, pig, NHP); Animal survived for >7 days, beyond acute recovery phase. Ex vivo brain network plasticity analysis (synaptic plasticity )-Electrophysiology assays. Drug screen performed ex vivo following recovery from in vivo injury. Small volume recirculation and analysis method to assess interaction between experimental drug and released factors.

The current screening method is a new combination. The use of brain slice electrophysiology following brain injury', paired with recirculation methods and mass spectroscopy methods to analyze biomarkers of cell response for drug screening.

Delayed inhibition of tonic inhibition enhances functional recovery foilowing experimental ischemic stroke

Altering GABAA α5 receptors rescue synaptic function after MCAO. Hippocampal slices were superfused in aCSF + L655,708 (100 nM) during baseline recordings and 1 h after TBS. (a) Example fEPSPs from sham-operated control mice before (black) and after (red) TBS. (b) Sham mice (black filled circles), Sham + 100 nM L655,708 treated (green open circles) and L655,708 treated mice in contralateral (blue filled squares) and Ipsilateral (red open squares) seven days after MCAO. Arrow' indicates timing of TBS (40 pulses), (c) Quantification of change in fEPSP slope following TBS. (d) Memory' impairment 30 days after MCAO. Adult, mice displayed memory' dysfunction after contextual fear conditioning. Mice implanted with mini-osmotic pumps delivered either vehicle or L655,708 4 days before behavioral testing. Quantification of freezing behavior 24 h after contextual fear conditioning in a novel environment (n = 5-8/group). This study focused on the ability to improve cognitive function after stroke with interventions administered at delayed/chronic time points. See Figure 5A to Figure 5D. See Orfila JE, et al., Journal of Cerebral Blood Flow and Metabolism. 2019 Jun; 39(6):1005-1014.

Functional Restoration following Global Cerebral Ischemia in Juvenile Mice following Inhibition of Transient Receptor Potential M2 (TRPM2) Ion Channels Acute inhibition of TRPM2 preserves LTP. (a) Time course from male juvenile mice 7 days after sham or CA/CPR mice were administered 20 mg/kg tatSCR (blue) or tatM2NX (green) 30 min after CA/CPR. b) Quantification of change in fEPSP slope 60 minutes after TBS stimulation normalized to 20 minutes of baseline recording(. (c) Time course from female juvenile mice 7 days after sham or CA/CPR mice were administered 20 mg/kg tatSCR (blue) or tatM2NX (green) 30 min after CA/CPR. (d) Quantification of change in fEPSP slope 60 minutes after TBS stimulation.

Delayed inhibition of TRPM2 restores memory function, (a) Quantification of freezing behavior 24 hours after contextual fear conditioning in a novel environment in mice administered 20 mg/kg tatSCR (black) or 20 mg/kg t.atM2NX (red) after sham surgery or mice administered 20 mg/kg tatSCR (blue) or 20 mg/kg tatM2NX (green) 13 days after recovery from CA/CPR and behavior testing initiated on day 14 after CA/CPR. (b) Quantification of distance traveled in the same mice as in (a) in open field testing, indicating no changes in locomotion to account for differences in freezing. See Figure 6Ato Figure 7B. See Dietz RM, et al., Neural Plast. 2021.

Experimental pediatric stroke shows age-specific recovery of cognition and role of hippocampal Nogo-A receptor signaling

Nogo-1 receptor antagonist rescues synaptic impairment when applied seven days after juvenile MCAO. (a) Time plots of fEPSP slope from mice seven days after sham experiments (black, n = 7) and paired slices bath applied with NEP (1—40) (1 pM, n === 7, red). All slices were exposed to NEP(1-40) or vehicle 30 min prior to TBS and throughout the duration of LTP experiment. Nogo-1 receptor antagonist does not affect LTP impairment in adult mice, (a) Time plots of fEPSP slope from mice seven days after MCAO experiments (black, n === 7) and paired slices bath applied with NEP (1—40) (1 μM, n = 7, red). This study investigated whether increase of Nogo-A, a neurite growth inhibitory factor, is contributor to impaired LTP 7 days following focal cerebral ischemia. See Figure 8 A to Figure 9D. See Orfila .IE, et al., J Cereb Blood Flow Metab. 2019.

Juvenile cerebral ischemia reveals age-dependent BDNF-TrkB signaling changes: Novel mechanism of recovery and therapeutic intervention

TrkB receptor agonist rescues synaptic impairment when bath applied seven days after CA/CPR. (a) Experimental design for LTP experiments, (b) Time course of fEPSP slope from mice seven days after CA/CPR (black, n ^:::: 6) and paired slices bath applied with 7,8 dihydroxyflavone (7,8 DHF, 250 nM, n = 6, red). Arrow indicates timing of theta burst stimulation (TBS, 40 pulses, 100 Hz), (c) Quantification of change in ffiPSP slope after 60 min following TBS normalized to baseline. Sham and seven-day CA/CPR slices were paired with and without 7,8 DHF and paired experiments are indicated by the line between the pairs. This study established the mechanistic impact of BDNF signaling on impaired memory and synaptic function after juvenile cardiac arrest. See Figure 10A to Figure 10C. See Orfila JE, et al., Journal of Cerebral Blood Flow and Metabolism. 2018

The compositions and methods of the appended claims are not limited in scope by the specific compositions and methods described herein, which are intended as illustrations of a few aspects of the claims and any compositions and methods that are functionally equivalent are intended to fall within the scope of the claims. Various modifications of the compositions and methods in addition to those shown and described herein are intended to fall within the scope of the appended claims. Further, while only certain representative compositions and method steps disclosed herein are specifically described, other combinations of the compositions and method steps also are intended to fall within the scope of the appended claims, even if not specifically recited. Thus, a combination of steps, elements, components, or constituents may be explicitly mentioned herein; however, other combinations of steps, elements, components, and constituents are included, even though not explicitly stated.