Journal of neurotrauma
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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.
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Journal of neurotrauma · Oct 2001
Traumatic brain injury-induced changes in gene expression and functional activity of mitochondrial cytochrome C oxidase.
Traumatic brain injury (TBI) is documented to have detrimental effects on CNS metabolism, including alterations in glucose utilization and the depression of mitochondrial oxidative phosphorylation. Studies on mitochondrial metabolism have also provided evidence for reduced activity of the cytochrome oxidase complex of the electron transport chain (complex IV) after TBI and an immediate (lhr) reduction in mitochondrial state 3 respiratory rate, which can persist for up to 14 days postinjury. Using differential display methods to screen for differences in gene expression, we have found that cytochrome c oxidase II (COII), a mitochondrial encoded subunit of complex IV, is upregulated following TBI. ⋯ These differences in cytochrome c oxidase activity were supported by in vitro assay of complex IV using cerebral cortical and hippocampal tissues. Our present results support the hypothesis that COII is selectively vulnerable to TBI and that COII differences may indicate the degree of metabolic dysfunction induced by different pathologies. Taken together, such data will better define the role of metabolic function in long-term recovery after TBI.
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Journal of neurotrauma · Oct 2001
Endothelin-Induced cyclooxygenase-dependent superoxide generation contributes to K+ channel functional impairment after brain injury.
This study determined if endothelin (ET-1) generates superoxide anion (O2-) in a cyclooxygenase-dependent manner and if such production contributes to impairment of dilation to activators of ATP-sensitive K+ (KATP) and calcium-sensitive K+ (Kca) channels following fluid percussion brain injury (FPI) in newborn pigs equipped with closed cranial windows. Superoxide dismutase (SOD)-inhibitable nitroblue tetrazolium (NBT) reduction was determined as an index of O2- generation. Under non-brain injury conditions, topical ET-1 (10(-10) M, the concentration present in CSF following FPI) increased SOD-inhibitable NBT reduction from 1 +/- 1 to 17 +/- 3 pmol/mm2. ⋯ These data show that ET-1 increased O2- production in a cyclooxygenase-dependent manner and contributed to this production after FPI. These data also show that ET-1 blunted KATP and Kca channel-mediated cerebrovasodilation in a cyclooxygenase dependent manner. These data suggest that ET-1-induced cyclooxygenase-dependent O2- generation contributes to KATP and Kca channel function impairment after FPI.