Journal of neurotrauma
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Journal of neurotrauma · Jan 2006
Comparative StudyComparison of seven anesthetic agents on outcome after experimental traumatic brain injury in adult, male rats.
Isoflurane is commonly used in experimental traumatic brain injury (TBI), both before and early after injury, yet it is rarely used clinically. Narcotics and benzodiazepines are frequently used after injury in clinical TBI. We compared seven anesthetic/sedative agents applied after injury in the controlled cortical impact model: diazepam, fentanyl, isoflurane, ketamine, morphine, pentobarbital, and propofol. ⋯ Our data support beneficial effects of isoflurane early after experimental TBI. Our data suggest that the early post-TBI use of isoflurane, despite practical logistical issues, could potentially provide clinical benefits in TBI--versus other commonly used sedatives or analgesics. Furthermore, the choice of post-injury sedation and analgesia could have important implications on attempts to translate novel therapies from bench to field or bedside.
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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.
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Journal of neurotrauma · Jan 2006
Locomotor deficits and adaptive mechanisms after thoracic spinal cord contusion in the adult rat.
The rat is widely used for modeling human spinal cord injury (SCI) and paraplegia. However, quadruped animals adapt trunk, forelimb and hindlimb movements to compensate for deficits, improving their behavioral scores and complicating the interpretation of spontaneous and treatment-induced function recovery. The kinematics of locomotion was studied in rats, both normal and after SCI (T9 contusion), and variables indicative of hindlimb function were related to brain-spinal cord connections (BSCC) spared during lesioning. ⋯ Recovery of hindlimb motor function was proportional to the amount of BSCC. On average, injured animals retained 18% of BSSC and recovered 23% of hindlimb function. These findings show that kinematic analysis is a reliable tool for assessing locomotor deficits and compensations and suggest limited spontaneous motor plasticity after SCI.