Minimal Traumatic Brain Injury Research Articles

Behavioral consequences of minimal traumatic brain injury in mice.

Victims of minor traumatic brain injury (mTBI), who show no clear morphological brain defects, frequently manifest cognitive, behavioral and emotional difficulties that can be long-lasting. In this paper we present a modified weight drop model used to deliver a closed head minimal traumatic brain injury to mice, which closely mimics real-life injuries and the symptoms observed in mTBI patients. Our choice of impact force does not produce structural damage to the brain and its surrounding tissue (as examined by MRI), any skull fracture, no edema and no evident damage to the blood-brain barrier (BBB). Moreover, our mTBI mice show no abnormal behavior on recovering from the weight drop, or any change in other brain functions such as reflexes, balance, exploration, strength, locomotor activity and swim speed. Since our mTBI model does not produce neurological, motor or sensory damage to the mice, it allows the direct evaluation of mTBI sequelae on the mice behavior and cognitive abilities. Using a variety of cognitive and behavioral tests (Morris water maze, staircase test, passive avoidance test, water T-maze, hot palate, elevated plus maze and forced swimming test) we assessed the short- and long-term sequelae induced by our model. Our results indicate that our closed head mTBI cause profound and long-lasting, irreversible learning and memory impairments, accompanied by a depressive-like behavior in mice that are evident even 90 days post injury. Our results indicate that the closed head mTBI model presented here may be useful in the development of novel therapeutic approaches, such as neuroprotective agents, for mTBI.

The intriguing effects of ecstasy (MDMA) on cognitive function in mice subjected to a minimal traumatic brain injury (mTBI)

The use of ecstasy (MDMA) among young adults has dramatically increased over the years. Since MDMA may impair the users' driving ability, the risk of being involved in a motor vehicle accident (MVA) is notably increased. Minimal traumatic brain injury (mTBI) a common consequence of MVAs-produces short- and long-term physical, cognitive, and emotional impairments. To investigate the effects of an acute dose of MDMA in mice subjected to closed head mTBI. Mice received 10mg/kg MDMA 1h prior to the induction of mTBI. Behavioral tests were conducted 7 and 30days post-injury. In addition to the behavioral tests, phosphorylation of IGF-1R, ERK, and levels of tyrosine hydroxylase (TH) were measured. mTBI mice showed major cognitive impairments in all cognitive tests conducted. No additional impairments were seen if mTBI was preceded by one dose of MDMA. On the contrary, a beneficial effect was seen in these mice. The western blot analysis of TH revealed a significant decrease in the mTBI mice. These decreases were reversed in mice that were subjected to MDMA prior to the trauma. The presence of MDMA at the time of mTBI minimizes the alteration of visual and spatial memory of the injured mice. The IGF-1R pathway was activated due to mTBI and MDMA but was not the main contributor to the cognitive improvements. MDMA administration inverted the TH decreases seen after injury. We believe this may be the major cause of the cognitive improvements seen in these mice.

Returning to play after concussion

Most agree that organized sports provide a vital source of therapeutic satisfaction for our patients. It is our responsibility to encourage these activities, while also fostering safety and reducing the risk of injury. One such risk, concussion, has always been an inherent danger — one that medical professionals, trainers and equipment designers are still striving to understand. Recent reports of a high incidence of early dementia after repeated head traumas in professional ice hockey and American football players have brought a new immediacy to the problem. These represent some of the more powerful and prominent examples of a topic that the medical community must address at every level of sports. Here are some questions that I have been asked: My son had a concussion in last night’s ice hockey game. How long should he stay out? My daughter was knocked unconscious for just a few seconds in this weekend’s basketball game. She had a CT scan and the emergency room doctor said that everything was okay. Should I be concerned? My son plays football. He’s never had a concussion, but I find that he has become very sensitive to light, and after maintaining an A average for several years, his grades have begun to slip. My doctor says that there is nothing to worry about. Has my son sustained head injury? Concussion, also called minimal traumatic brain injury, has become a prominent issue in the last 10 years (1). Conferences and symposia are now dedicated to addressing the risks of head trauma (2), and the US Centers for Disease Control and Prevention has instituted programmes aimed at reducing the incidence of concussion (3,4). These meetings and hundreds of papers are dedicated to prevention, diagnosis and treatment as well to broadening our understanding of the longand short-term impact of concussion (5).

Posttraumatic epilepsy and treatment

Posttraumatic epilepsy (PTE) is a major long-term complication of traumatic brain injury (TBI). PTE usually develops within 5 years of head injury. The risk for developing PTE varies with TBI type. Both Korean and Vietnam war veterans with penetrating TBI had a 53% risk of developing PTE. The risk of developing PTE is between 10% and 25% in combat-associated closed-head trauma with positive brain imaging and about 5% in moderately severe closed-head injury without imaging finding. We do not know the risk of PTE among Operation Iraqi Freedom/Operation Enduring Freedom veterans with minimal TBI because of blast exposure.Partial seizures may manifest with subtle behavioral alterations that can be mistaken for manifestations of posttraumatic stress disorder and improperly treated. Accidents and medical complications commonly occur during seizures. Sudden unexpected death in epilepsy is most frequent among 20- to 40-year-olds. Seizures increase the likelihood of refractory seizures years after TBI. Seizures are also a social stigma that compromise veterans' reintegration into society. People with uncontrolled epilepsy are not allowed to drive and have difficulty obtaining or maintaining employment. Optimal seizure control is essential to the physical and emotional health of veterans with TBI and to their ability to lead productive lives.

Minimal Traumatic Brain Injury Induce Apoptotic Cell Death in Mice

In the United States, 1.4 million people suffer from traumatic brain injury (TBI) each year because of traffic, sports, or war-related injuries. The majority of TBI victims suffer mild to minimal TBI (mTBI), but most are released undiagnosed. Detailed pathologies are poorly understood. We characterized the microscopic changes of neurons of closed-head mTBI mice after increased unilateral trauma using hematoxylin and eosin (H&E) stain, and correlated it with the expression of the apoptotic proteins c-jun, p53, and BCL-2. Minimal damage to the brain increases the number of pyknotic appearing neurons and activates the apoptotic proteins in both hemispheres. Although minimal, increased impact was positively correlated with the increased number of damaged neurons. These results may explain the wide variety of behavioral and cognitive deficits closed-head mTBI causes in mice. Our cumulative results point to the pathological origin of post-concussion syndrome and may aid in the development of future neuroprotective strategies for the disease.

Sports Related Minimal Traumatic Brain Injury (MTBI) With An Atypical Progress

Sports Related Minimal Traumatic Brain Injury (MTBI) With An Atypical Progress

Apoptotic changes in the cortex and hippocampus following minimal brain trauma in mice

Interpretation of the cellular and molecular pathogenic basis of post-minimal traumatic brain injury is a significant clinical and scientific problem, especially due to the high prevalence of motor vehicle—and other accidents. Pathogenetic brain mechanisms following traumatic impact are usually investigated by using models of severe or moderate trauma. Apoptotic neuronal degeneration after notable brain trauma is a well-known phenomenon, but the source of its activation is not clear, especially after mild, subclinical brain trauma. In the present study, we used a closed head weight-drop model to induce minimal brain injury in mice. Pellets of 5, 10, 15, 20, 25 and 30 g were dropped on the right side of mice's head kept under light ether anesthesia. No abnormal behavioral or neurophysiological changes were seen following the head trauma. Morphological assessment was done 72 h after the traumatic impact using TUNEL assay and silver staining. We found gradual increase of TUNEL-positive and silver-impregnated cells number in different cortical and hippocampal regions of both injured and contralateral hemispheres. The threshold of traumatic impact that caused a significant activation was 10–15 g pellets (evident by silver staining), and 15–20 g for apoptosis. The most sensitive zones for trauma were anterior cingulate cortex and CA3 area of hippocampus. No bilateral hemispheric differences were found. Our results demonstrate that even closed head minimal traumatic brain injury can cause diffused neuronal damage and apoptosis. This results correlate well with cognitive and behavioral deficits described for mice suffering similar mTBI and can also explain the wide variety of mental disturbances described for post-concussion syndrome in patients who suffered mild head injury.

Acetazolamide-enhanced neuroSPECT scan reveals functional impairment after minimal traumatic brain injury not otherwise discernible

A patient suffering from aggressive personality changes and cognitive impairment following head trauma, without neurological or anatomical imaging findings, underwent neuroSPECT scans with and without acetazolamide injection, both before treatment and during treatment with valproate. Acetazolamide injection induced increased prefrontal perfusion not evident at baseline. Valproate treatment was associated with increased prefrontal perfusion concomitant with clinical improvement and abolished response to acetazolamide challenge.

Closed-head minimal traumatic brain injury produces long-term cognitive deficits in mice

Victims of minimal traumatic brain injury (mTBI) do not show clear morphological brain defects, but frequently suffer lasting cognitive deficits, emotional difficulties and behavioral disturbances. In the present study we adopted a non-invasive closed-head weight-drop mouse model to produce mTBI. We examined the effects of 20, 25, or 30 g weight drop 7, 30, 60 and 90 days following injury on mice’s ability to perform the Morris water maze. The mice suffered profound long-lasting learning and memory deficits that were force- and time-dependent. Although the injured mice could acquire the task, they could not improve their initial escape latency by more than 50%, while normal mice improved by up to 450% ( P<0.001). In order to directly compare the learning ability of individual mice following our mTBI we have devised a new measure which we term learning rate. We define learning rate as the rate the mouse improved its own performance in consecutive trials in a given experimental day. The learning rate of control mice increased linearly throughout the testing period with a slope of approximately 0.9. Injured mice that sustained 20 and 25 g weight drop could also improve their learning rate linearly but with a slope of only 0.2. Mice who sustained 30 g weight drop could not improve their learning rate linearly and reached a plateau after the third experimental learning day. These results indicate that the severity of injury may correlate with the degree of integration of the learning task. These cognitive deficits occurred without any other clear neurological damage, no evident brain edema, no notable damage to the blood–brain barrier and no early anatomical changes to the brain (observed by magnetic resonance imaging imaging). These results demonstrate that persistent deficits of cognitive learning abilities in mice, similar to those observed in human post-concussive syndrome, can follow mTBI without any anatomical damage to the brain and its surrounding tissue.