Journal of neurotrauma
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Journal of neurotrauma · Feb 2011
Comparative StudyDifferential effects of injury severity on cognition and cellular pathology after contusive brain trauma in the immature rat.
Although diffuse brain damage has been suggested to be the predominant predictor of neurological morbidity following closed head injury in infants and children, the presence of contusions also predicts long-term neurobehavioral dysfunction. Contusive brain trauma in the 17-day-old rat resulted in neurodegeneration and caspase activation in the cortex at 1 day, and in the thalamus at 3 days post-injury, and to a greater extent following a deeper impact. Cortical tissue loss in the 4-mm impact group was significantly greater than that in the 3-mm impact group (p < 0.05), and exhibited a time-dependent increase over the first 3 weeks post-injury. ⋯ Similarly, neurodegeneration and caspase activation in the hippocampus was restricted to the dentate gyrus and occurred to a similar extent in both injured groups. Only the 4-mm impact group exhibited learning deficits in the first week (p < 0.0001) that was sustained until the third week post-injury (p < 0.0001), while deficits in the 3-mm impact group were seen only at 3 weeks post-injury (p < 0.02). These observations demonstrate that increasing severity of injury in immature animals does not uniformly increase the extent of cellular damage, and that the progression of tissue damage and behavioral deficits varies as a function of injury severity.
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Journal of neurotrauma · Feb 2011
Effects of continuous intravenous infusion of MCI-186 on functional recovery after spinal cord injury in rats.
We investigated the effects of a free radical scavenger, MCI-186 (edaravone), on neuroprotection in the rat post-traumatic spinal cord using various doses and routes of administration. The injury was produced with a weight-drop device. Lipid peroxide formation in the spinal cord was measured using the thiobarbituric acid test for malonyldialdehyde (MDA). ⋯ In the fourth experiment, a 3 mg/kg bolus given once immediately after injury and twice daily for 3 days, a 3 mg/kg bolus + 3.0 mg/kg/h for 1 day, or a 3 mg/kg bolus + 3.0 mg/kg/h for 3 days were administered. The continuous infusion for 1 day showed significant improvement functionally and histologically, but continuous infusion at the same rate for another 2 days did not show any further improvement. To effectively reduce secondary neuronal damage, strong inhibition of free radical chain reactions at the early stage, particularly within the first 24 h post-trauma, is important.
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Journal of neurotrauma · Feb 2011
Comparative StudyEffect of decompressive craniectomy on aquaporin-4 expression after lateral fluid percussion injury in rats.
Decompressive craniectomy is one therapeutic option for severe traumatic brain injury (TBI), and it has long been used for the treatment of patients with malignant post-traumatic brain edema. A lack of definitive evidence, however, prevents physicians from drawing any conclusions about the effects of decompressive craniectomy for the treatment of TBI. Therefore, the aim of the present study was to investigate the influence of decompressive craniectomy on post-traumatic brain edema formation. ⋯ At 48 h after TBI, AQP4 expression of the DC- group was significantly increased compared with the DC+ group (p < 0.01). In addition, the cortical water content of the DC- group was significantly increased compared to the DC+ group at the same time point (p < 0.05). The present results suggest that decompressive craniectomy may affect AQP4 expression and reduce brain edema formation after TBI.
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Journal of neurotrauma · Feb 2011
A substance P antagonist reduces axonal injury and improves neurologic outcome when administered up to 12 hours after traumatic brain injury.
Previous studies have demonstrated that the compound N-acetyl-L-tryptophan (NAT) reduces brain edema and improves functional outcome following traumatic brain injury (TBI). In this study we examined whether this effect was mediated via the neurokinin-1 receptor, and whether there was an effect on axonal injury. We also explored whether the compound was effective, even when administered at delayed time points. ⋯ NAT also improved cognitive outcome as assessed by the Morris water maze and novel object recognition tests, and reduced axonal injury at 5 and 24 h after TBI as assessed by amyloid precursor protein immunohistochemistry. However, efficacy of the membrane-impermeable NAT was limited to administration within 5 h, whereas administration of a form of NAT, L-732,138 (47 mg/kg), in which a trifluoromethyl benzyl ester group has been added, making it highly lipid soluble and able to cross the intact blood-brain barrier, significantly improved motor outcome, even when administration was delayed by as much as 12 h. We conclude that the neuroprotective effects of NAT are receptor-mediated, and that administration of the membrane-permeable form of the compound can be effective even up to 12 h after TBI.
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Journal of neurotrauma · Feb 2011
Fluoxetine increases hippocampal neurogenesis and induces epigenetic factors but does not improve functional recovery after traumatic brain injury.
The selective serotonin reuptake inhibitor fluoxetine induces hippocampal neurogenesis, stimulates maturation and synaptic plasticity of adult hippocampal neurons, and reduces motor/sensory and memory impairments in several CNS disorders. In the setting of traumatic brain injury (TBI), its effects on neuroplasticity and function have yet to be thoroughly investigated. Here we examined the efficacy of fluoxetine after a moderate to severe TBI, produced by a controlled cortical impact. ⋯ To determine if fluoxetine improves neurological outcomes after TBI, gait function and spatial learning and memory were assessed by the CatWalk-assisted gait test and Barnes maze test, respectively. No differences in these parameters were seen between fluoxetine- and vehicle-treated animals. Thus while fluoxetine enhanced neuroplasticity in the hippocampus after TBI, its chronic administration did not restore locomotor function or ameliorate memory deficits.