Journal of neurotrauma
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Journal of neurotrauma · Oct 2001
Talampanel, a novel noncompetitive AMPA antagonist, is neuroprotective after traumatic brain injury in rats.
Talampanel [(R)-7-acetyl-5-(4-aminophenyl)-8,9-dihydro-8-methyl-7H-1,3-dioxolo[4,5-h][2,3] benzodiazepine] is an orally active noncompetitive antagonist of the AMPA subtype of glutamate excitatory amino acid receptors. The purpose of this study was to determine whether treatment with talampanel would protect in a rat model of traumatic brain injury (TBI). Twenty-four hours prior to TBI, a fluid-percussion interface was positioned parasagittally over the right cerebral cortex. ⋯ In addition, treatment with talampanel starting at 30 min significantly attenuated neuronal damage in all three subsectors of the hippocampal CA1 sector compared to vehicle-treated rats (normal-neuron counts, right (ipsilateral) medial CA1: 80.3 +/- 2.0 [talampanel] vs. 66.3 +/- 2.1 [vehicle] (mean +/- SEM); middle CA1: 71.5 +/- 2.0 vs. 60.3 +/- 2.2; lateral CA1: 74.5 +/- 3.0 vs. 63.0 +/- 3.2, respectively). By contrast, when talampanel treatment was begun at 3 h, normal pyramidal-neuron counts were almost identical in both groups. Our findings document that talampanel therapy instituted 30 min after trauma significantly reduces histological damage.
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Journal of neurotrauma · Oct 2001
Effects of binge ethanol administration on the behavioral outcome of rats after lateral fluid percussion brain injury.
This study examined the effects of 4 weeks of binge ethanol administration (BEAn) on the behavioral outcome in rats after lateral fluid percussion (FP) brain injury. Rats were intragastrically given 7.5 mL/kg of either 40% ethanol in 5% glucose solution (3 g ethanol/kg; binge ethanol group), or 5% glucose solution (vehicle group), twice on Thursday and Friday of 3 consecutive weeks. Then rats from both groups were subjected to either lateral FP brain injury of moderate severity (1.8 atm) or to sham operation. ⋯ Histologic analysis of injured animals from both injured ethanol and vehicle groups revealed similar extents of ipsilateral cortical and observable hippocampal damage. These results suggest that 4 weeks of binge ethanol treatment followed by ethanol intoxication at the time of injury worsens some aspects of the spatial learning ability of rats. This worsening is probably caused by subtle, undetectable morphologic damage by binge ethanol administration.
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Journal of neurotrauma · Oct 2001
Skeletal muscle adaptations following spinal cord contusion injury in rat and the relationship to locomotor function: a time course study.
Experimental spinal cord injury (SCI) via contusion of moderate severity results in residual locomotor deficits, including a lack of coordination and trunk stability. Given that muscle contractile properties and fiber composition adapt to reduced neural input and/or weight bearing, contusion-induced locomotor deficits may reflect changes in hindlimb skeletal muscle. Therefore, we examined muscle adaptations during early (1 week), intermediate (3 week), and late (10 week) stages of motor recovery after moderate SCI. ⋯ By 3 weeks, the loss of weight-bearing activity early after SCI induced significant decreases in SOL peak twitch and peak tetanic tension as well as significantly greater IIx MHC expression in the EDL. By 10 weeks post-SCI, after several weeks of weight supported stepping, muscle wet weight, contractile properties and MHC composition returned to baseline levels except for MG/LG atrophy. Thus, muscle plasticity appears to be extremely sensitive to locomotor deficits and their resolution after moderate spinal cord contusion.
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Journal of neurotrauma · Oct 2001
N-Acetylaspartate reduction as a measure of injury severity and mitochondrial dysfunction following diffuse traumatic brain injury.
N-Acetylaspartate (NAA) is considered a neuron-specific metabolite and its reduction a marker of neuronal loss. The objective of this study was to evaluate the time course of NAA changes in varying grades of traumatic brain injury (TBI), in concert with the disturbance of energy metabolites (ATP). Since NAA is synthesized by the mitochondria, it was hypothesized that changes in NAA would follow ATP. ⋯ These data show that, at 48 h post diffuse TBI, reduction of NAA is graded according to the severity of insult. NAA recovers if the degree of injury is moderate and not accompanied by secondary insult. The highly similar time course and correlation between NAA and ATP supports the notion that NAA reduction is related to energetic impairment.
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Journal of neurotrauma · Oct 2001
Autonomic dysreflexia and primary afferent sprouting after clip-compression injury of the rat spinal cord.
Spinal cord injury leads to many forms of autonomic dysfunction including autonomic dysreflexia, a condition involving recurrent episodes of paroxysmal hypertension and associated bradycardia. This hypertension may reach intensities that are life-threatening. We investigated autonomic dysreflexia and the sprouting of central processes of primary afferent neurons (a potential mechanism for autonomic dysreflexia) in a clinically-relevant calibrated clip-compression model of spinal cord injury in the rat. ⋯ These findings suggest that after severe but not mild clip compression injury of the spinal cord, sprouting of the afferent component of the spinal reflex are contributes to the development of autonomic dysreflexia. Neither dysreflexia, nor changes in the afferent arbor size occurred after mild cord injury. This clinically relevant clip compression cord injury model, studied more frequently for locomotor function, is excellent for investigating mechanisms for the development of autonomic dysreflexia and strategies for its prevention.