Journal of neurotrauma
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Journal of neurotrauma · Mar 2000
Comparative StudySequential mRNA expression for immediate early genes, cytokines, and neurotrophins in spinal cord injury.
In this communication, we demonstrate the sequential expression of endogenous molecules, including immediate early genes (IEGs), cytokines, neurotrophins, and neurotrophin receptors in the injured spinal cord. In the acute phase, expression of IEGs and cytokines mRNAs were rapidly upregulated within 1 h in nonneuronal cells in the lesioned sites and the surrounding spinal white and gray matter. Maximal expression was observed at 1 h for c-fos and TNF-alpha mRNAs, at 3 h for c-jun and IL-6 mRNAs, and at 6 h for IL-1 beta mRNA, and these signals were virtually nondetectable after 6-12 h from the onset of the injury. ⋯ In the subacute phase, expression of NGF, BDNF, NT-3, p75LNGFR and Trk B mRNAs began to increase in the nonneuronal cells and neuronal cells from 6 h, and peaked at 24-72 h in the area where expression of mRNAs for IEGs and cytokines overlapped. Signals for IL-6 mRNA were also observed in motoneurons at 24-72 h after the injury, with the suggestion that these molecules may be involved in promoting axonal sprouting in the injured spinal cord. Of further interest was the finding that this upregulation of IL-1 beta, BDNF, and NT-3 mRNAs in injured spinal cord was attenuated by treatment with high dose glucocorticoids, with the suggestion that the downregulation of BDNF and NT-3 might be disadvantageous to survival and axonal sprouting of spinal neurons.
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Journal of neurotrauma · Feb 2000
Comparative StudyTemporal profile of release of neurobiochemical markers of brain damage after traumatic brain injury is associated with intracranial pathology as demonstrated in cranial computerized tomography.
This study aimed at the investigation of release patterns of neuron specific enolase (NSE) and protein S-100B after traumatic brain injury (TBI) and their association with intracranial pathologic changes as demonstrated in computerized tomography (CT). We analyzed NSE and S-100B concentrations in serial venous blood samples taken one to three days after TBI in 66 patients by the use of immunoluminometric assays. These markers are considered to be specific neurobiochemical indicators of damage to glial (S-100B) or neuronal (NSE) brain tissue. ⋯ Release patterns of S-100B and NSE differed in patients with primary cortical contusions, diffuse axonal injury (DAI), and signs of cerebral edema (ICP) without focal mass lesions. All serum concentrations of NSE and S-100B were significantly correlated with the volume of contusions. The data of the present study indicate that the early release patterns of NSE and S-100 may mirror different pathophysiological consequences of traumatic brain injury.
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Traumatic brain injury (TBI) places enormous early energy demand on brain tissue to reinstate normal ionic balance. Clinical studies have demonstrated a decline in extracellular fluid (ECF) glucose and an increase in lactate after TBI. In vitro studies suggest that this increase in lactate is mediated by increased glutamate and may provide a metabolic substrate for neurons, to aid in ionic restoration. ⋯ Furthermore, in the lactate infusion group, the dialysate glucose levels recovered to baseline levels by 4 h after injury, whereas they remained depressed through out the experiment, in the saline infusion group. We conclude that arterial lactate augmentation can increase brain dialysate lactate, and result in more rapid recovery of dialysate glucose after FPI. This may indicate a beneficial role for lactate, that may be potentially useful in the clinical situation, after TBI.
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Journal of neurotrauma · Feb 2000
Real-time monitoring of glutamate following fluid percussion brain injury with hypoxia in the rat.
In the present study, extracellular glutamate (Glu) was monitored in real time using an enzyme electrode biosensor following traumatic brain injury (TBI) either with or without inducing hypoxia in the rat. We also measured the cortical contusion volume at 3 days after insult by staining with 2,3,5-triphenyltetrazolium chloride (TTC). Male Sprague-Dawley rats (300-400 g) were anesthetized and then subjected to lateral fluid percussion (FP) brain injury of moderate severity (3.5-4.0 atm), using the Dragonfly device model (no. ⋯ To evaluate the possible involvement of apoptosis in groups 1 and 2, separate rats were sacrificed under the same procedures after 1, 6, 24, and 72 h after insult (n = 2/group). Immunohistochemical analysis demonstrated an increased number of both the cysteine protease caspase-3-positive cells at 24 h and TUNEL-positive cells at 72 h in group 2. These results suggest that TBI with moderate hypoxia induced the prolonged efflux of Glu, which thus resulted in more cortical damage due to necrosis and apoptosis.
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Journal of neurotrauma · Jan 2000
Extracellular N-acetyl-aspartate as a biochemical marker of the severity of neuronal damage following experimental acute traumatic brain injury.
We evaluated the acute changes in interstitial and whole brain N-acetyl-aspartate (NAA) measured by high-performance liquid chromatography in animal models of isolated traumatic brain injury (TBI) and TBI combined with secondary insult (hypotension-hypoxia [HH]). The Marmarou impact-acceleration model was used. Four groups were studied: (1) sham-operated control, (2) TBI alone (TBI 500 gm, 2 m), (3) TBI plus 30 min of hypoxia (PaO2, approximately 40 mm Hg) and hypotension (mean arterial blood pressure, approximately 40 mm Hg) (THH), and (4) HH alone. ⋯ The whole brain NAA (NAAw) concentration in controls was 8.5+/-0.5 mmol/kg wet weight. There was no significant difference between TBI and controls; however, there was a significant decrease in NAAw in the THH and HH group compared to controls. Thus, in this animal model of TBI and TBI with secondary insult, we found that persistent, marked elevation in NAA is associated with TBI and secondary ischemic/hypoxic insult, but not with isolated TBI alone.