Journal of neurotrauma
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Journal of neurotrauma · Apr 2007
NMDA receptor antagonist felbamate reduces behavioral deficits and blood-brain barrier permeability changes after experimental subarachnoid hemorrhage in the rat.
Increased levels of glutamate and aspartate have been detected after subarachnoid hemorrhage (SAH) that correlate with neurological status. The NMDA receptor antagonist felbamate (FBM; 2-phenyl-1,3-propanediol dicarbamate) is an anti-epileptic drug that elicits neuroprotective effects in different experimental models of hypoxia-ischemia. The aim of this dose-response study was to evaluate the effect of FBM after experimental SAH in rats on (1) behavioral deficits (employing a battery of assessment tasks days 1-5 post-injury) and (2) blood-brain barrier (BBB) permeability changes (quantifying microvascular alterations according to the extravasation of protein-bound Evans Blue by a spectrophotofluorimetric technique 2 days post-injury). ⋯ FBM also decreased BBB permeability changes in frontal, temporal, parietal, occipital, and cerebellar cortices; subcortical and cerebellar gray matter; and brainstem. This study demonstrates that, in terms of behavioral and microvascular effects, FBM is beneficial in a dose-dependent manner after experimental SAH in rats. These results reinforce the concept that NMDA excitotoxicity is involved in the cerebral dysfunction that follows SAH.
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Journal of neurotrauma · Apr 2007
low-level laser therapy applied transcranially to mice following traumatic brain injury significantly reduces long-term neurological deficits.
Low-level laser therapy (LLLT) has been evaluated in this study as a potential therapy for traumatic brain injury (TBI). LLLT has been found to modulate various biological processes. Following TBI in mice, we assessed the hypothesis that LLLT might have a beneficial effect on their neurobehavioral and histological outcome. ⋯ The lesion volume of the laser treated mice was significantly lower (1.4%) than the non-treated group (12.1%). Our data suggest that a non-invasive transcranial application of LLLT given 4 h following TBI provides a significant long-term functional neurological benefit. Further confirmatory trials are warranted.
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Journal of neurotrauma · Apr 2007
Trauma-associated inflammatory response impairs embryonic stem cell survival and integration after implantation into injured rat brain.
Pluripotent embryonic stem cells were shown to survive and differentiate into mature neuronal cells after implantation in experimental models of Parkinson disease and cerebral ischemia. Embryonic stem cell transplantation has also been proposed as a potential therapy for cerebral trauma, characteristic of massive loss of multiple cell types due to primary insult and secondary sequelae. Green fluorescent protein (GFP)-transfected murine embryonic stem cells were implanted into the ipsi or contralateral cortex of male Sprague-Dawley rats 72 h after fluid-percussion injury. ⋯ Cerebral trauma, induced 3 days prior to implantation, has activated the inflammatory potential of otherwise immunologically privileged tissue. Subsequent cell implantation was accompanied by reactive astrogliosis, activation of microglia, as well as a massive invasion of macrophages into transplantation sites even if the grafts were placed into contralateral healthy hemispheres, remote from the traumatic lesion. Our results demonstrate a significant post-traumatic inflammatory response, which impairs survival and integration of implanted stem cells and has generally not been taken into account in designs of previous transplantation studies.
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Journal of neurotrauma · Mar 2007
Global white matter analysis of diffusion tensor images is predictive of injury severity in traumatic brain injury.
Conventional clinical neuroimaging is insensitive to axonal injury in traumatic brain injury (TBI). Immunocytochemical staining reveals changes to axonal morphology within hours, suggesting potential for diffusion-weighted magnetic resonance (MR) in early diagnosis and management of TBI. Diffusion tensor imaging (DTI) characterizes the three-dimensional (3D) distribution of water diffusion, which is highly anisotropic in white matter fibers owing to axonal length. ⋯ Increased diffusion in the short axis dimension, likely reflecting dysmyelination and swelling of axons, accounted for most of the FA decrease. FA is globally deceased in WM, including mild TBI, possibly reflecting widespread involvement. FA changes appear to be correlated with injury severity suggesting a role in early diagnosis and prognosis of TBI.
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Journal of neurotrauma · Mar 2007
Calpain-mediated collapsin response mediator protein-1, -2, and -4 proteolysis after neurotoxic and traumatic brain injury.
Collapsin response mediator proteins (CRMPs) are important molecules in neurite outgrowth and axonal guidance. Within the CRMP family, CRMP-2 has been implicated in several neurological diseases (Alzheimer's, epilepsy, and ischemia). Here, we investigated the integrity of CRMPs (CRMP-1, -2, -4, -5) after in vitro neurotoxin treatment and in vivo traumatic brain injury (TBI). ⋯ Collectively, this study demonstrated that CRMP-1, -2, and -4 are degraded following both acute traumatic and neurotoxic injury. Furthermore, calpain-2 was identified as the possible proteolytic mediator of CRMP-2 following excitotoxic injury and TBI, which appears to correlate well with neuronal cell injury and neurite damage. It is possible that the calpain-mediated truncation of CRMPs following TBI may be an inhibiting factor for post-injury neurite regeneration.