Name: investigations on alterations of hippocampal circuit function following mild traumatic brain injury
Uploaded: 2012-11-19T12:00:00
Description: Watch this Scientific Journal Video about Investigations on Alterations of Hippocampal Circuit Function Following Mild Traumatic Brain Injury at JoVE.com

The authors would like to thank Elliot Bourgeois for his technical assistance. This work was funded by the National Institutes of Health grants R01HD059288 and R01NS069629.

1. Lateral Fluid Percussion Injury
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 <li>Anaesthetize the mouse using a mixture of ketamine and xylazine given intraperitoneally. Then prepare the mouse's head for incision using an iodine scrub.</li>
 <li>Perform a craniectomy over the right parietal area using 3 mm (outside diameter) trephine.</li>
 <li>Secure Luer-loc needle hub (inside diameter 3 mm) over the craniectomy using cyanoarylate and dental acrylic.</li>
 <li>24 hr later, anaesthetize the mouse using isoflurane via inhalation.</li>
 <li>Once normal br...

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	<li>Faul, M., Xu, L., Wald, M. M., Coronado, V. G. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Traumatic+Brain+Injury+in+the+United+States:+Emergency+Department+Visits+Hospitalizations+and+Deaths+2002-2006.">Traumatic Brain Injury in the United States: Emergency Department Visits Hospitalizations and Deaths 2002-2006.</a> Centers for Disease Control and Prevention, National Center for Injury Prevention and Control. , (2010).</li><li>McAllister, T. W. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Neuropsychiatric+sequelae+of+head+injuries.">Neuropsychiatric sequelae of head injuries.</a> Psychiatr. Clin. North Am. 15, 395-413 (1992).</li><li>Pierce, J. E., Smith, D. H., Trojanowski, J. Q., McIntosh, T. K. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Enduring+cognitive,+neurobehavioral+and+histopathological+changes+persist+for+up+to+one+year+following+severe+experimental+brain+injury+in+rats.">Enduring cognitive, neurobehavioral and histopathological changes persist for up to one year following severe experimental brain injury in rats.</a> NSC. 87, 359-369 (1998).</li><li>Dixon, C. E., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=A+fluid+percussion+model+of+experimental+brain+injury+in+the+rat.">A fluid percussion model of experimental brain injury in the rat.</a> J. Neurosurg. 67, 110-119 (1987).</li><li>McIntosh, T. K., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Traumatic+brain+injury+in+the+rat:+characterization+of+a+lateral+fluid-percussion+model.">Traumatic brain injury in the rat: characterization of a lateral fluid-percussion model.</a> Neuroscience. 28, 233-244 (1989).</li><li>Carbonell, W. S., Grady, M. S. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Regional+and+temporal+characterization+of+neuronal,+glial,+and+axonal+response+after+traumatic+brain+injury+in+the+mouse.">Regional and temporal characterization of neuronal, glial, and axonal response after traumatic brain injury in the mouse.</a> Acta Neuropathol. 98, 396-406 (1999).</li><li>Toth, Z., Hollrigel, G. S., Gorcs, T., Soltesz, I. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Instantaneous+perturbation+of+dentate+interneuronal+networks+by+a+pressure+wave-transient+delivered+to+the+neocortex.">Instantaneous perturbation of dentate interneuronal networks by a pressure wave-transient delivered to the neocortex.</a> J. Neurosci. 17, 8106-8117 (1997).</li><li>D'Ambrosio, R., Maris, D. O., Grady, M. S., Winn, H. R., Janigro, D. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Selective+loss+of+hippocampal+long-term+potentiation,+but+not+depression,+following+fluid+percussion+injury.">Selective loss of hippocampal long-term potentiation, but not depression, following fluid percussion injury.</a> Brain Res. 786, 64-79 (1998).</li><li>Witgen, B. M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Regional+hippocampal+alteration+associated+with+cognitive+deficit+following+experimental+brain+injury:+A+systems,+network+and+cellular+evaluation.">Regional hippocampal alteration associated with cognitive deficit following experimental brain injury: A systems, network and cellular evaluation.</a> Neuroscience. 133, 1-15 (2005).</li><li>Schwarzbach, E., Bonislawski, D. P., Xiong, G., Cohen, A. S. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Mechanisms+underlying+the+inability+to+induce+area+CA1+LTP+in+the+mouse+after+traumatic+brain+injury.">Mechanisms underlying the inability to induce area CA1 LTP in the mouse after traumatic brain injury.</a> Hippocampus. 16, 541-550 (2006).</li><li>Cole, J. T. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Dietary+branched+chain+amino+acids+ameliorate+injury-induced+cognitive+impairment.">Dietary branched chain amino acids ameliorate injury-induced cognitive impairment.</a> Proceedings of the National Academy of Sciences. 107, 366-371 (2010).</li></ol>

Each technique outlined above contributes to the greater understanding of the underlying mechanism causing the observed behavioral deficit. By combining the unique information gained from each method we are able to examine the biological mechanisms with more precision.
	Measuring fEPSPs is useful for quantifying the net synaptic efficacy of large, spatially defined regions of neurons. It also can provide information about the potential of a group of cells to undergo synaptic plasticity, a ne...

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 <td>Axopatch 200B amplifier</td>
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 <td>Patch-clamp rig</td>
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 <td>Molecular Devices</td>
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 <td>MULTICLAMP 700B</td>
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 <td>BX51WI microscope </td>
 <td>Olympus</td>
 <td>BX51WI</td>
 <td>Multipurpose (field) rig</td>
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 <td>Axoclamp 900A amplifier</td>
 <td>Molecular Devices</td>
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 <td>Digidata 1322 digitizer</td>
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investigations on alterations of hippocampal circuit function following mild traumatic brain injury

Traumatic Brain Injury (TBI) afflicts more than 1.7 million people in the United States each year and even mild TBI can lead to persistent neurological impairments 1. Two pervasive and disabling symptoms experienced by TBI survivors, memory deficits and a reduction in seizure threshold, are thought to be mediated by TBI-induced hippocampal dysfunction 2,3. In order to demonstrate how altered hippocampal circuit function adversely affects behavior after TBI in mice, we employ lateral fluid percussion injury, a commonly used animal model of TBI that recreates many features of human TBI including neuronal cell loss, gliosis, and ionic perturbation 4-6.
	Here we demonstrate a combinatorial method for investigating TBI-induced hippocampal dysfunction. Our approach incorporates multiple ex vivo physiological techniques together with animal behavior and biochemical analysis, in order to analyze post-TBI changes in the hippocampus. We begin with the experimental injury paradigm along with behavioral analysis to assess cognitive disability following TBI. Next, we feature three distinct ex vivo recording techniques: extracellular field potential recording, visualized whole-cell patch-clamping, and voltage sensitive dye recording. Finally, we demonstrate a method for regionally dissecting subregions of the hippocampus that can be useful for detailed analysis of neurochemical and metabolic alterations post-TBI.
	These methods have been used to examine the alterations in hippocampal circuitry following TBI and to probe the opposing changes in network circuit function that occur in the dentate gyrus and CA1 subregions of the hippocampus (see Figure 1). The ability to analyze the post-TBI changes in each subregion is essential to understanding the underlying mechanisms contributing to TBI-induced behavioral and cognitive deficits. 
	The multi-faceted system outlined here allows investigators to push past characterization of phenomenology induced by a disease state (in this case TBI) and determine the mechanisms responsible for the observed pathology associated with TBI.

Watch this Scientific Journal Video about Investigations on Alterations of Hippocampal Circuit Function Following Mild Traumatic Brain Injury at JoVE.com

Investigations on Alterations of Hippocampal Circuit Function Following Mild Traumatic Brain Injury

A multi-faceted approach to investigating functional changes to hippocampal circuitry is explained. Electrophysiological techniques are described along with the injury protocol, behavioral testing and regional dissection method. The combination of these techniques can be applied in similar fashion for other brain regions and scientific questions.

Traumatic Brain Injury (TBI) afflicts more than 1.7 million people in the United States each year and even mild TBI can lead to persistent neurological ...

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Research

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Neuroscience

Effects of Blast-induced Neurotrauma on Pressurized Rodent Middle Cerebral Arteries

Though there have been studies on the histopathological and behavioral effects of blast exposure, fewer have been dedicated to blast&#39;s cerebral vascular effects. Impact (i.e., non-blast) traumatic brain injury (TBI) is known to decrease pressure autoregulation in the cerebral vasculature in both humans and experimental animals. The hypothesis that blast-induced traumatic brain injury (bTBI), like impact TBI, results in impaired cerebral vascular reactivity was tested by measuring myogenic dilatory responses to reduced intravascular pressure in rodent middle cerebral arterial (MCA) segments from rats subjected to mild bTBI using an Advanced Blast Simulator (ABS) shock tube. Adult, male Sprague-Dawley rats were anesthetized, intubated, ventilated and prepared for Sham bTBI (identical manipulation and anesthesia except for blast injury) or mild bTBI. Rats were randomly assigned to receive Sham bTBI or mild bTBI followed by sacrifice 30 or 60 min post-injury. Immediately after bTBI, righting reflex (RR) suppression times were assessed, euthanasia at the time points post-injury was completed, the brain was harvested and the individual MCA segments were collected, mounted and pressurized. As the intraluminal pressure perfused through the arterial segments was reduced in 20 mmHg increments from 100 to 20 mmHg, MCA diameters were measured and recorded. With decreasing intraluminal pressure, MCA diameters steadily increased significantly above baseline in the Sham bTBI groups while MCA dilator responses were significantly reduced (p &#60; 0.05) in both bTBI groups as evidenced by the impaired, smaller MCA diameters recorded for the bTBI groups. In addition, RR suppression in the bTBI groups was significantly (p &#60; 0.05) higher than in the Sham bTBI groups. MCA&#39;s collected from the Sham bTBI groups exhibited typical vasodilatory properties to decreases in intraluminal pressure while MCA&#39;s collected following bTBI exhibited significantly impaired myogenic vasodilatory responses to reduced pressure that persisted for at least 60 min after bTBI.

Here, we present a protocol to describe methods for ex vivo vascular reactivity determination following a primary blast traumatic brain injury (bTBI) using isolated, pressurized, rodent middle cerebral arterial (MCA) segments. bTBI induction is accomplished using a shock tube, also known as an Advanced Blast Simulator (ABS) device.

Though there have been studies on the histopathological and behavioral effects of blast exposure, fewer have been dedicated to blast&#39;s cerebral ...

Investigating Alterations in Caecum Microbiota After Traumatic Brain Injury in Mice

Increasing evidence shows that the microbiota-gut-brain axis plays an important role in the pathogenesis of brain diseases. Several studies also demonstrate that traumatic brain injuries cause changes to the gut microbiota. However, mechanisms underlying the bidirectional regulation of the brain-gut axis remain unknown. Currently, few models exist for studying the changes in gut microbiota after traumatic brain injury. Therefore, the presented study combines protocols for inducing traumatic brain injury using a lateral fluid percussion device and analysis of caecum samples following injury for investigating alterations in the gut microbiome. Alterations of the gut microbiota composition after traumatic brain injury are determined using 16S-rDNA sequencing. This protocol provides an effective method for studying the relationships between enteric microorganisms and traumatic brain injury.

Presented here is a protocol to induce diffuse traumatic brain injury using a lateral fluid percussion device followed by the collection of the caecum content for gut microbiome analysis.

Increasing evidence shows that the microbiota-gut-brain axis plays an important role in the pathogenesis of brain diseases. Several studies also ...

Advanced Diffusion Imaging in The Hippocampus of Rats with Mild Traumatic Brain Injury

Mild traumatic brain injury (mTBI) is the most common type of acquired brain injury. Since patients with traumatic brain injury show a tremendous variability and heterogeneity (age, gender, type of trauma, other possible pathologies, etc.), animal models play a key role in unraveling factors that are limitations in clinical research. They provide a standardized and controlled setting to investigate the biological mechanisms of injury and repair following TBI. However, not all animal models mimic the diffuse and subtle nature of mTBI effectively. For example, the commonly used controlled cortical impact (CCI) and lateral fluid percussion injury (LFPI) models make use of a craniotomy to expose the brain and induce widespread focal trauma, which are not commonly seen in mTBI. Therefore, these experimental models are not valid to mimic mTBI. Thus, an appropriate model should be used to investigate mTBI. The Marmarou weight drop model for rats induces similar microstructural alterations and cognitive impairments as seen in patients who sustain mild trauma; therefore, this model was selected for this protocol. Conventional computed tomography and magnetic resonance imaging (MRI) scans commonly show no damage following a mild injury, because mTBI induces often only subtle and diffuse injuries. With diffusion weighted MRI, it is possible to investigate microstructural properties of brain tissue, which can provide more insight into the microscopic alterations following mild trauma. Therefore, the goal of this study is to obtain quantitative information of a selected region-of-interest (i.e., hippocampus) to follow up disease progression after obtaining a mild and diffuse brain injury.

The overall goal of this procedure is to obtain quantitative microstructural information of the hippocampus in a rat with mild traumatic brain injury. This is done using an advanced diffusion-weighted magnetic resonance imaging protocol and region-of-interest based analysis of parametric diffusion maps.

Mild traumatic brain injury (mTBI) is the most common type of acquired brain injury. Since patients with traumatic brain injury show a tremendous ...

Low-intensity Blast Wave Model for Preclinical Assessment of Closed-head Mild Traumatic Brain Injury in Rodents

Traumatic brain injury (TBI) is a large-scale public health problem. Mild TBI is the most prevalent form of neurotrauma and accounts for a large number of medical visits in the United States. There are currently no FDA-approved treatments available for TBI. The increased incidence of military-related, blast-induced TBI further accentuates the urgent need for effective TBI treatments. Therefore, new preclinical TBI animal models that recapitulate aspects of human blast-related TBI will greatly advance the research efforts into the neurobiological and pathophysiological processes underlying mild to moderate TBI as well as the development of novel therapeutic strategies for TBI.
Here we present a reliable, reproducible model for the investigation of the molecular, cellular, and behavioral effects of mild to moderate blast-induced TBI. We describe a step-by-step protocol for closed-head, blast-induced mild TBI in rodents using a bench-top setup consisting of a gas-driven shock tube equipped with piezoelectric pressure sensors to ensure consistent test conditions. The benefits of the setup that we have established are its relative low-cost, ease of installation, ease of use and high-throughput capacity. Further advantages of this non-invasive TBI model include the scalability of the blast peak overpressure and the generation of controlled reproducible outcomes. The reproducibility and relevance of this TBI model has been evaluated in a number of downstream applications, including neurobiological, neuropathological, neurophysiological and behavioral analyses, supporting the use of this model for the characterization of processes underlying the etiology of mild to moderate TBI.

We present here a protocol of a blast wave model for rodents to investigate neurobiological and pathophysiological effects of mild to moderate traumatic brain injury. We established a gas-driven, bench-top setup equipped with pressure sensors allowing for reliable and reproducible generation of blast-induced mild to moderate traumatic brain injury.

Traumatic brain injury (TBI) is a large-scale public health problem. Mild TBI is the most prevalent form of neurotrauma and accounts for a large number of ...

A Metric Test for Assessing Spatial Working Memory in Adult Rats Following Traumatic Brain Injury

Impairments to sensory, short-term, and long-term memory are common side effects after traumatic brain injury (TBI). Due to the ethical limitations of human studies, animal models provide suitable alternatives to test treatment methods, and to study the mechanisms and related complications of the condition. Experimental rodent models have historically been the most widely used due to their accessibility, low cost, reproducibility, and validated approaches. A metric test, which tests the ability to recall the placement of two objects at various distances and angles from one another, is a technique to study impairment in spatial working memory (SWM) after TBI. The significant advantages of metric tasks include the possibility of dynamic observation, low cost, reproducibility, relative ease of implementation, and low stress environment. Here, we present a metric test protocol to measure impairment of SWM in adult rats after TBI. This test provides a feasible way to evaluate physiology and pathophysiology of brain function more effectively.

Traumatic brain injury (TBI) is commonly associated with memory impairment. Here, we present a protocol to assess spatial working memory after TBI via a metric task. A metric test is a useful tool to study spatial working memory impairment after TBI.

Impairments to sensory, short-term, and long-term memory are common side effects after traumatic brain injury (TBI). Due to the ethical limitations of ...

Electromagnetic Controlled Closed-Head Model of Mild Traumatic Brain Injury in Mice

Highly reproducible animal models of traumatic brain injury (TBI), with well-defined pathologies, are needed for testing therapeutic interventions and understanding the mechanisms of how a TBI alters brain function. The availability of multiple animal models of TBI is necessary to model the different aspects and severities of TBI seen in people. This manuscript describes the use of a midline closed head injury (CHI) to develop a mouse model of mild TBI. The model is considered mild because it does not produce structural brain lesions based on neuroimaging or gross neuronal loss. However, a single impact creates enough pathology that cognitive impairment is measurable at least 1 month after injury. A step-by-step protocol to induce a CHI in mice using a stereotaxically guided electromagnetic impactor is defined in the paper. The benefits of the mild midline CHI model include the reproducibility of the injury-induced changes with low mortality. The model has been temporally characterized up to 1 year after the injury for neuroimaging, neurochemical, neuropathological, and behavioral changes. The model is complementary to open skull models of controlled cortical impact using the same impactor device. Thus, labs can model both mild diffuse TBI and focal moderate-to-severe TBI with the same impactor.

The protocol describes mild traumatic brain injury in a mouse model. In particular, a step-by-step protocol to induce a mild midline closed head injury and the characterization of the animal model is fully explained.

Highly reproducible animal models of traumatic brain injury (TBI), with well-defined pathologies, are needed for testing therapeutic interventions and ...

Assessing Changes in Synaptic Plasticity Using an Awake Closed-Head Injury Model of Mild Traumatic Brain Injury

Mild traumatic brain injuries (mTBIs) are a prevalent health issue in North America. There is increasing pressure to utilize ecologically valid models of closed-head mTBI in the preclinical setting to increase translatability to the clinical population. The awake closed-headed injury (ACHI) model uses a modified controlled cortical impactor to deliver closed-headed injury, inducing clinically relevant behavioral deficits without the need for a craniotomy or the use of an anesthetic.
This technique does not normally induce fatalities, skull fractures, or brain bleeds, and is more consistent with being a mild injury. Indeed, the mild nature of the ACHI procedure makes it ideal for studies investigating repetitive mTBI (r-mTBI). Growing evidence indicates that r-mTBI can result in a cumulative injury that produces behavioral symptoms, neuropathological changes, and neurodegeneration. r-mTBI is common in youths playing sports, and these injuries occur during a period of robust synaptic reorganization and myelination, making the younger population particularly vulnerable to the long-term influences of r-mTBI.
Further, r-mTBI occurs in cases of intimate partner violence, a condition for which there are few objective screening measures. In these experiments, synaptic function was assessed in the hippocampus in juvenile rats that had experienced r-mTBI using the ACHI model. Following the injuries, a tissue slicer was utilized to make hippocampal slices to evaluate bidirectional synaptic plasticity in the hippocampus at either 1 or 7 days following the r-mTBI. Overall, the ACHI model provides researchers with an ecologically valid model to study changes in synaptic plasticity following mTBI and r-mTBI.

Here, it is demonstrated how an awake closed-head injury model can be used for examining the effects of repeated mild traumatic brain injury (r-mTBI) on synaptic plasticity in the hippocampus. The model replicates important features of r-mTBI in patients and is used in conjunction with in vitro electrophysiology.

Mild traumatic brain injuries (mTBIs) are a prevalent health issue in North America. There is increasing pressure to utilize ecologically valid models of ...

Validating Injury Response and Behavioral Assessments in an mTBI Rat Model

Rat Model of Closed-Head Mild Traumatic Injury and its Validation

Animal models are crucial for advancing our understanding of mild traumatic brain injury (mTBI) and guiding clinical research. To achieve meaningful insights, developing a stable and reproducible animal model is essential. In this study, we report a detailed description of a closed-head mTBI model and a representative validation method using Sprague-Dawley rats to verify the modeling effect. The model involves dropping a 550 g mass weight from a height of 100 cm directly onto the head of a rat on a destructible surface, followed by a 180-degree turn. To assess the injury, rats underwent a series of neurobehavioral assessments 10 min post-injury, including time of loss of consciousness, first seeking-behavior time, escape ability, and beam balance ability test. During the acute and subacute stages following the injury, behavioral tests were conducted to assess motor coordination ability (Beam task), anxiety (Open Field test), and learning and memory abilities (Morris Water Maze test). The closed-head mTBI model produced a consistent injury response with minimal mortality and replicated real-life situations. The validation method effectively verified the model development and ensured the stability and consistency of the model.

Author Spotlight: Advancing Traumatic Brain Injury Research - A Closed-Head Model for Accurate Replication and Rapid Assessment 

Here, we present a closed-head mild traumatic brain injury (mTBI) rat model and its validation exhibiting remarkable similarity to human mTBI concerning behavioral manifestations during the acute and subacute stages.

Animal models are crucial for advancing our understanding of mild traumatic brain injury (mTBI) and guiding clinical research. To achieve meaningful ...

Experimental Set Up to Create a Rat Model of Mild Traumatic Brain Injury (mTBI)

Experimental Set Up to Create a Rat Model of Mild Traumatic Brain Injury (MTBI)  

To begin, place a 12-centimeter thick sponge with a 35D hardness in an acrylic box, lacking a top cover. Then, cut a sheet of tinfoil and adhere it to the acrylic box with adhesive tape to create a fragile surface capable of supporting the weight of a rat. Also, mark a 10-centimeter long line as the designated location for positioning the rat's head.Using an iron stand, firmly secure a polyvinyl chloride or PVC tube in place. Prepare a perforated weight weighing 550 grams with an 18-millimeter diameter. Attach the weight to a fishing line at a height of one meter inside the PVC tube and adjust the position of the guide tube three centimeters above the tin foil.Next, make a helmet from a stainless steel disc. Prepare a wedge-shaped sponge pillow to place under the rat's head. Swiftly position the anesthetized rat on its chest in the tinfoil.Slide the pillow beneath the rat, ensuring its head remains parallel to the foil surface. Align the helmet with the rat's ears, and securely fasten it in place. Confirm that the PVC pipe is directly above the helmet.Then, release the weight and allow it to impact the rat's head resulting in a fall onto the sponge and a 180 degree rotation. Afterwards, position the rat on its back inside a clean cage.

Acute Neurobehavioral Assessments of the Closed-Head Mild Traumatic Brain Injury (mTBI) Rat Model

Acute Neurobehavioral Assessments of the Closed-Head Mild Traumatic Brain Injury (MTBI) Rat Model  

After inducing a mild traumatic brain injury in an anesthetized rat, position it on its back inside a clean cage. Record the duration from when the rat is anesthetized to when it regains the righting reflex. Also record the time it takes for the rat to exhibit its first seeking behavior from the moment of anesthesia.Next place the rat in the center of a circular apparatus with an exit. Measure and record the time it takes for the rat to exit the circle. Then place the rat successively on three beams of varying length each for a duration of one minute.Score the rat on a scale of zero to six, depending on their performance on the beam. mTBI rats exhibited a significantly prolonged recovery from unconsciousness. The seeking behavior increased significantly in the mTBI group during the recovery period.Also, the mTBI rats took longer to exit the circle compared to sham rats. The beam balance test showed a significant injury effect in wide beam tasks indicating balance impairment in mTBI rats 10 minutes post impact. The 2 and 1.5 centimeter wide beams effectively differentiated between sham and mTBI groups in three independent experiments.