Journal of neurotrauma
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Journal of neurotrauma · Oct 1997
ReviewIs high extracellular glutamate the key to excitotoxicity in traumatic brain injury?
Traumatic brain injury (TBI) increases extracellular levels of the excitatory amino acid glutamate and aspartate, and N-methyl-D aspartate (NMDA)-receptor antagonists protect against experimental TBI. These two findings have led to the prevalent hypothesis that excitatory amino acid efflux is a major contributor to the development of neuronal damage subsequent to traumatic injury. However, as with stroke, the hypothesis that high extracellular glutamate is the key to excitotoxicity in TBI conflicts with important data. ⋯ Finally, we introduce the notion that beneficial effects of glutamate receptor antagonists in experimental models of neurological disorders do not necessarily imply the occurrence of excitotoxic processes. Indeed, glutamate-receptor blockade may be protective by reducing the energy demand required to counterbalance Na+ influx associated with glutamatergic synaptic transmission. In other words, glutamate receptor antagonists (and blockers of voltage-gated Na+-channels) may help nervous tissue to cope with increased permeability of the cellular membrane to ions and reduced efficacy of Na+ extrusion, and thus prevent the decay of transmembrane ionic concentrations gradients.
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Journal of neurotrauma · Oct 1997
GFAP and S100beta expression in the cortex and hippocampus in response to mild cortical contusion.
We studied the acute response of glial fibrillary acidic protein (GFAP) and S100beta gene expression in the cerebral cortex and hippocampus to mild unilateral cortical contusion. Our goal was to evaluate and compare the expression patterns of each gene in the early stages of the astrocytic response to brain injury. RNA was extracted from the cerebral cortex and hippocampus of male rats at 0, 3, 12, 24, or 96 h after lesion or sham-operation, then quantified using an RNase protection assay. ⋯ Furthermore, all S100beta immunoreactive astrocytes in the lesioned ipsilateral cortex were also GFAP immunoreactive, whereas only about 11% of S100beta positive cells were also GFAP labeled in the contralateral lesioned or the ipsilateral sham cortex. In the hippocampus, all S100beta immunoreactive cells were also GFAP immunoreactive under all conditions. These data correlate with the gene expression data at 96 h, and suggest that, at least in the cortex, resident S100beta-expressing astrocytes produce GFAP at levels that are undetectable by immunocytochemistry until they are activated in response to injury.
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Journal of neurotrauma · Oct 1997
Progressive atrophy and neuron death for one year following brain trauma in the rat.
Although atrophic changes have been well described following traumatic brain injury (TBI) in humans, little is known concerning the mechanisms or progression of brain tissue loss. In the present study, we evaluated the temporal profile of histopathological changes following parasagittal fluid-percussion (FP) brain injury in rats over 1 year postinjury. Anesthetized 3-4 month-old Sprague-Dawley Rats (n = 51) were subjected to FP brain injury of high severity (2.5-2.9 atm, n = 51) or sham treatment (n = 27). ⋯ In addition, reactive astrocytosis in regions of atrophy and progressive bilateral death of neurons in the dentate hilus was observed for 1 year following injury. These results suggest that a chronically progressive degenerative process may be initiated by brain trauma. Thus, there is a temporally broad window within which to introduce novel therapeutic strategies designed to ameliorate the short and long-term consequences of brain trauma.