Journal of neurotrauma
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Journal of neurotrauma · Feb 2006
Neuroprotective effects of selective group II mGluR activation in brain trauma and traumatic neuronal injury.
The effects of group II mGluR activation by selective agonist (-)-2-oxa-4-aminobicyclo[3.1. 0]hexane-4,6-dicarboxylate (LY379268) were examined in a mouse model of controlled cortical impact (CCI)-induced brain injury and in primary neuronal/glial and neuronal cultures subjected to mechanical trauma. Systemic administration of LY379268 to mice at 30 min after CCI significantly improved both motor and cognitive recovery as compared with vehicle-treated control animals. ⋯ The neuroprotective effect of LY379268 in vitro was abolished by co-administration of the mGluR2/3 antagonist (s)-alpha-ethylglutamic acid (EGLU); however, co-application of selective mGluR3 antagonist beta-N-acetyl-aspartyl-glutamate (NAAG) had no significant influence in the same system. Together, these findings demonstrate the neuroprotective activity of group II mGluR activation and underscore the role of the mGluR2 subtype for this effect.
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Journal of neurotrauma · Feb 2006
Correlation between target reinnervation and distribution of motor axons in the injured rat sciatic nerve.
Peripheral nerve injuries are rarely followed by complete return of function. Deficits are particularly important for motor function, resulting in paralysis and muscle atrophy. In different groups, the sciatic nerve was either crushed or transected and repaired by direct suture or by tube repair using silicone or collagen tubes. ⋯ The normal fascicular architecture and grouping of ChAT+ fibers were maintained after nerve crush, but lost after section and repair, where motor fibers were scattered within small regenerated fascicles throughout the nerve. The loss of fascicular organization was related to the deficient recovery of locomotor function. Thus, labeling of motor axons by ChAT immunohistochemistry provides useful information for the study of the degree and specificity of nerve regeneration.
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Journal of neurotrauma · Jan 2006
Randomized Controlled TrialCyclosporin A disposition following acute traumatic brain injury.
Although the precise mechanism of action remains to be defined, Cyclosporin A (CsA) has demonstrated potential for neuroprotection in animal models. Predictive dosing strategies for CsA in acute traumatic brain injured (TBI) patients must account for the influence of the acute phase response on drug disposition. To characterize CsA pharmacokinetic parameters early following acute TBI, serial blood samples from patients enrolled into a Phase II dose-escalation trial were analyzed. ⋯ Whole blood clearance, steady state volume of distribution, and beta half-life were independent of dose and higher than published reports from other populations: 0.420 L/h/kg, 5.91 L/kg, and 17.3 h, respectively. These data show patients with acute severe TBI demonstrate a more rapid clearance and a larger distribution volume of CsA. Pharmacokinetic parameters derived from this study will guide dosing strategies for future prospective clinical trials evaluating CsA therapy following acute TBI.
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Journal of neurotrauma · Jan 2006
Early, transient increase in complexin I and complexin II in the cerebral cortex following traumatic brain injury is attenuated by N-acetylcysteine.
Alteration of excitatory neurotransmission is a key feature of traumatic brain injury (TBI) in which extracellular glutamate levels rise. Although increased synaptic release of glutamate occurs at the injury site, the precise mechanism is unclear. Complexin I and complexin II constitute a family of cytosolic proteins involved in the regulation of neurotransmitter release, competing with the chaperone protein alpha-SNAP (soluble N-ethylmaleimide-sensitive factor-attachment protein) for binding to the synaptic vesicle protein synaptobrevin as well as the synaptic membrane proteins SNAP-25 and syntaxin, which together form the SNAP receptor (SNARE) complex. ⋯ Neuronal loss was also reduced in the injured hemisphere with post-TBI NAC treatment. Our findings suggest a dysregulation of both inhibitory and excitatory neurotransmission following traumatic injury that is responsive to antioxidant treatment. These alterations in complexin levels may also play an important role in neuronal cell loss following TBI, and thus contribute to the pathophysiology of cerebral damage following brain injury.
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Journal of neurotrauma · Jan 2006
Behavioral and histological characterization of unilateral cervical spinal cord contusion injury in rats.
Most experimental studies of spinal cord injury (SCI) in rats damage the thoracic cord, with the consequent functional loss being due to interruption of long tracts connecting the caudal spinal cord to the rostral nervous system. Less work has been done evaluating injury to the cervical cord, even though it is the most common level of human SCI. In addition to the long tracts, the cervical spinal cord contains the sensory and motor neurons responsible for upper extremity function. ⋯ Compared to controls, animals receiving SCI exhibited injury severity-specific deficits in forelimb, locomotor, and hindlimb function persisting for 6-weeks post-SCI. Histological analysis revealed ipsilateral containment of the injury, and differentiation between groups on all measures except motor neuron counts. This model has many advantages: (1) minimal animal care requirements post-SCI, (2) within subject controls, (3) functional loss involves primarily the ipsilateral forelimb, and (4) it is a behavioral and histological model for both gray and white matter damage caused by contusive SCI.