15 research outputs found
Mild head injury increasing the brain's vulnerability to a second concussive impact
Object. Mild, traumatic repetitive head injury (RHI) leads to neurobehavioral impairment and is associated with the early onset of neurodegenerative disease. The authors developed an animal model to investigate the behavioral and pathological changes associated with RHI.
Methods. Adult male C57BL/6 mice were subjected to a single injury (43 mice), repetitive injury (two injuries 24 hours apart 49 m ice), or no impact (36 mice). Cognitive function was assessed using the Morris water maze test, and neurological motor function was evaluated using a battery of neuroscore, rotarod, and rotating pole tests. The animals were also evaluated for cardiovascular changes, blood-brain barrier (BBB) breakdown, traumatic axonal injury, and neurodegenerative and histopathological changes between 1 day and 56 days after brain trauma. No cognitive dysfunction was detected in any group. The single-impact group showed mild impairment according to the neuroscore test at only 3 days postinjury, whereas RHI caused pronounced deficits at 3 days and 7 days following the second injury. Moreover, RHI led to functional impairment during the rotarod and rotating pole tests that was not observed in any animal after a single impact. Small areas of cortical BBB breakdown and axonal injury, observed after a single brain injury, were profoundly exacerbated after RHI. Immunohistochemical staining for microtubule-associated protein-2 revealed marked regional loss of immunoreactivity only in animals subjected to RHI. No deposits of beta -amyloid or tau were observed in any brain-injured animal.
Conclusions. On the basis of their results, the authors suggest that the brain has an increased vulnerability to a second traumatic insult for at least 24 hours following an initial episode of mild brain trauma
A review and rationale for the use of genetically engineered animals in the study of traumatic brain injury
The mechanisms underlying secondary cell death after traumatic brain injury (TBI) are poorly understood. Animal models of TBI recapitulate many clinical and pathologic aspects of human head injury, and the development of genetically engineered animals has offered the opportunity to investigate the specific molecular and cellular mechanisms associated with cell dysfunction and death after TBI, allowing for the evaluation of specific cause-effect relations and mechanistic hypotheses. This article represents a compendium of the current literature using genetically engineered mice in studies designed to better understand the posttraumatic inflammatory response, the mechanisms underlying DNA damage, repair, and cell death, and the link between TBI and neurodegenerative diseases
Transient Loss of Microtubule-Associated Protein 2 Immunoreactivity after Moderate Brain Injury in Mice
Motor and cognitive function evaluation following experimental traumatic brain injury
Traumatic brain injury (TBI) in humans may cause extensive sensorimotor and cognitive dysfunction. As a result, many TBI researchers are beginning to assess behavioral correlates of histologically determined damage in animal models. Although this is an important step in TBI research, there is a need for standardization between laboratories. The ability to reliably test treatments across laboratories and multiple injury models will close the gap between treatment success in the lab and success in the clinic. The goal of this review is to describe and evaluate the tests employed to assess functional outcome after TBI and to overview aspects of cognitive, sensory, and motor function that may be suitable targets for therapeutic intervention
Wallerian Degeneration in the Optic Nerve Stretch-Injury Model of Traumatic Brain Injury: A Stereological Analysis
Temporal window of vulnerability to repetitive experimental concussive brain injury
OBJECTIVE: Repetitive concussive brain injury (CBI) is associated with cognitive alterations and increased risk of neurodegenerative disease. MOTHODS: To evaluate the temporal window during which the concussed brain remains vulnerable to a second concussion, anesthetized mice were subjected to either sham injury or single or repetitive CBI (either 3, 5, or 7 days apart) using a clinically relevant model of CBI. Cognitive, vestibular, and sensorimotor function (balance and coordination) were evaluated, and postmortem histological analyses were performed to detect neuronal degeneration, cytoskeletal proteolysis, and axonal injury. RESULTS: No cognitive deficits were observed in sham-injured animals or those concussed once. Mice subjected to a second concussion within 3 or 5 days exhibited significantly impaired cognitive function compared with either sham-injured animals (P < 0.05) or mice receiving a single concussion (P < 0.01). No cognitive deficits were observed when the interconcussion interval was extended to 7 days, suggestive of a transient vulnerability of the brain during the first 5 days after an initial concussion. Although all concussed mice showed transient motor deficits, vestibulomotor dysfunction was more pronounced in the group that sustained two concussions 3 days apart (P < 0.01 compared with all other groups). Although scattered degenerating neurons, evidence of cytoskeletal damage, and axonal injury were detected in selective brain regions between 72 hours and 1 week after injury in all animals sustaining a single concussion, the occurrence of a second concussion 3 days later resulted in significantly greater traumatic axonal injury (P < 0.05) than that resulting from a single CBI. CONCLUSION: These data suggest that a single concussion is associated with behavioral dysfunction and subcellular alterations that may contribute to a transiently vulnerable state during which a second concussion within 3 to 5 days can lead to exacerbated and more prolonged axonal damage and greater behavioral dysfunction
Transplanted neural stem cells survive, differentiate, and improve neurological motor function after experimental traumatic brain injury
OBJECTIVE: Using the neural stem cell (NSC) clone C17.2, we evaluated the ability of transplanted murine NSCs to attenuate cognitive and neurological motor deficits after traumatic brain injury.
METHODS: Nonimmunosuppressed C57BL/6 mice (n = 65) were anesthetized and subjected to lateral controlled cortical impact brain injury (n = 52) or surgery without injury (sham operation group, n = 13). At 3 days postinjury, all brain-injured animals were, reanesthetized and, randomized to receive stereotactic injection of NSCs or control Cells (human embryonic kidney cells) into the cortex-hippocampus interface in either the ipsilateral-or the contralateral hemisphere. One group of animals (n = 7) was killed. at either 1 or 3 weeks postinjury to assess NSC survival in the acute posttraumatic period. Motor function was evaluated at weekly intervals for 12 weeks in the remaining animals, and cognitive (i.e., learning) deficits were assessed at 13 and 12 weeks after transplantation.
RESULTS: Brain-injured animals that, received either ipsilateral or contralateral NSC transplants showed significantly improved motor function in selected tests as compared with human embryonic kidney cell-transplanted animals during the 12-week observation period. Cognitive, dysfunction was unaffected by transplantation at either 3 or. 12 weeks postinjury. Histological analyses showed that NSCs survive for as long as 13 weeks after transplantation and were detected in the hippocampus and/or cortical areas adjacent to the, injury cavity. At 13 weeks, the, NSCs transplanted ipsilateral to the impact site expressed neuronal (NeuN) or astrocytic (glial fibrillary acidic protein) markers, but not, markers of oligodendrocytes (2'3'cyclic nucleotide 3'-phoshodiesterase), whereas, the contralaterally transplanted NSCs expressed neuronal but not glial markers (double-labeled immunofluorescence and confocal microscopy).
CONCLUSION: These data suggest that transplanted NSCs can survive in the traumatically injured brain, differentiate into neurons and/or glia, and attenuate motor dysfunction after traumatic brain injury