Journal of neurotrauma
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Journal of neurotrauma · Jan 2012
Alterations of A-type potassium channels in hippocampal neurons after traumatic brain injury.
Traumatic brain injury (TBI) is associated with cognitive deficits, memory impairment, and epilepsy. Previous studies have reported neuronal loss and neuronal hyperexcitability in the post-traumatic hippocampus. A-type K+ currents (I(A)) play a critical role in modulating the intrinsic membrane excitability of hippocampal neurons. ⋯ Furthermore, there was an increased sensitivity to bicuculline-induced seizures in TBI rats. At 8 weeks after TBI, immunohistochemical staining and electrophysiological recording indicated that I(A) returned to control levels. These findings suggest that TBI causes a transient downregulation of I(A) in hippocampal CA1 neurons, which might be associated with the hyperexcitability in the post-traumatic hippocampus, and in turn leads to seizures and epilepsy.
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Journal of neurotrauma · Jan 2012
Repeated mild lateral fluid percussion brain injury in the rat causes cumulative long-term behavioral impairments, neuroinflammation, and cortical loss in an animal model of repeated concussion.
There is growing evidence that repeated brain concussion can result in cumulative and long-term behavioral symptoms, neuropathological changes, and neurodegeneration. Little is known about the factors and mechanisms that contribute to these effects. The current study addresses the need to investigate and better understand the effects of repeated concussion through the development of an animal model. ⋯ Neuropathological analysis revealed short-term neuroinflammation in 3-injury rats, and both short- and long-term neuroinflammation in 5-injury rats. There was also evidence that repeated injuries induced short- and long-term cortical damage. These cumulative and long-term changes are consistent with findings in human patients suffering repeated brain concussion, provide support for the use of repeated mild lateral fluid percussion injuries to study repeated concussion in the rat, and suggest that neuroinflammation may be important for understanding the cumulative and chronic effects of repeated concussion.
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Journal of neurotrauma · Jan 2012
Molecular mechanisms underlying effects of neural stem cells against traumatic axonal injury.
Transplantation of neural stem cells (NSCs) improves functional outcomes following traumatic brain injury (TBI). Previously we demonstrated that human NSCs (hNSCs) via releasing glial cell line-derived neurotrophic factor (GDNF), preserved cognitive function in rats following parasagittal fluid percussion. However, the underlying mechanisms remain elusive. ⋯ In summary, we demonstrate for the first time that hNSC grafts and treatment with GDNF acutely reduce traumatic axonal injury and promote neurite outgrowth. Possible mechanisms underlying GDNF-mediated neurite protection include balancing the activity of calcineurin, whereas GDNF-induced neurite outgrowth may result from the reduction of the abnormal α-SMA expression and actin aggregation via blocking Rho signals. Our study also suggests the necessity of further exploring the roles of α-SMA in the central nervous system (CNS), which may lead to a new avenue to facilitate recovery after TBI and other injuries.
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Journal of neurotrauma · Jan 2012
Histopathological and behavioral effects of immediate and delayed hemorrhagic shock after mild traumatic brain injury in rats.
The purpose of this study was to investigate the increased susceptibility of the brain, after a controlled mild cortical impact injury, to a secondary ischemic insult. The effects of the duration and the timing of the secondary insult after the initial cortical injury were studied. Rats anesthetized with isoflurane underwent a 3 m/sec, 2.5-mm deformation cortical impact injury followed by hypotension to 40 mm Hg induced by withdrawing blood from a femoral vein. ⋯ The perfusion deficit was worst at the impact site, but also significant in the pericontusional brain. With 50 and 60 min of hypotension, CBF did not recover following resuscitation at the impact site, and recovered only transiently in the pericontusional brain. These results demonstrate that mild TBI, like more severe levels of TBI, can impair the brain's ability to maintain CBF during a period of hypotension, and result in a worse outcome.
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Journal of neurotrauma · Jan 2012
Ghrelin prevents disruption of the blood-brain barrier after traumatic brain injury.
Significant effort has been focused on reducing neuronal damage from post-traumatic brain injury (TBI) inflammation and blood-brain barrier (BBB)-mediated edema. The orexigenic hormone ghrelin decreases inflammation in sepsis models, and has recently been shown to be neuroprotective following subarachnoid hemorrhage. We hypothesized that ghrelin modulates cerebral vascular permeability and mediates BBB breakdown following TBI. ⋯ Our data suggest that ghrelin prevents BBB disruption after TBI. This is evident by a decrease in vascular permeability that is linked to a decrease in AQP-4. This decrease in vascular permeability may diminish post-TBI brain tissue damage was evident by decreased S100B.