Journal of neurotrauma
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Journal of neurotrauma · May 2002
Caspase-3-mediated cleavage of amyloid precursor protein and formation of amyloid Beta peptide in traumatic axonal injury.
Immunohistochemical studies demonstrate accumulation of the beta-amyloid precursor protein (APP) within injured axons following traumatic brain injury (TBI). Despite such descriptions, little is known about the ultimate fate of accumulating APP at sites of traumatic axonal injury (TAI). Recently, caspase-3-mediated cleavage of APP and subsequent Abeta deposition was linked to apoptotic neuronal death pathways in hippocampal neurons following ischemic and excitotoxic brain injury. ⋯ Further, CMAP was colocalized with Abeta formation in foci of TAI. The current study demonstrates that caspase-3 cleavage of APP occurs in TAI and is associated with formation of Abeta peptide. These findings are of interest given recent epidemiological studies supporting an association between TBI and later risk for AD development.
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Journal of neurotrauma · Apr 2002
Attenuation of working memory and spatial acquisition deficits after a delayed and chronic bromocriptine treatment regimen in rats subjected to traumatic brain injury by controlled cortical impact.
Cognitive impairments are pervasive and persistent sequelae of human traumatic brain injury (TBI). In vivo models of TBI, such as the controlled cortical impact (CCI) and fluid percussion (FP), are utilized extensively to produce deficits reminiscent of those seen clinically with the hope that empirical study will lead to viable therapeutic interventions. Both CCI and FP produce spatial learning acquisition deficits, but only the latter has been reported to impair working memory in rats tested in the Morris water maze (MWM). ⋯ Additionally, the injured bromocriptine-treated group exhibited significantly more morphologically intact CA3 neurons than the injured vehicle-treated group (55.60 +/- 3.10% vs. 38.34 +/- 7.78% [p = 0.03]). No significant differences were observed among TBI groups in CA1 cell survival (bromocriptine, 40.26 +/- 4.74% vs. vehicle, 29.13 +/- 6.63% [p = 0.14]) or cortical lesion volume (bromocriptine, 17.78 +/- 0.62 mm3 vs. vehicle, 19.01 +/- 1.49 mm3 [p > 0.05]). These data reveal that CCI produces working memory deficits in rats that are similar to those observed following FP, and that the delayed and chronic bromocriptine treatment regimen conferred cognitive and neural protection after TBI.
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Journal of neurotrauma · Apr 2002
Fiberoptic intraparenchymal brain pressure monitoring with the Camino V420 monitor: reflections on our experience in 163 severely head-injured patients.
To assess the safety and accuracy of the Camino intraparenchymal sensor, we prospectively evaluated hemorrhagic complications, zero-drift, infection, and system malfunction in 163 patients monitored after a severe head injury. Mean duration of intracranial pressure (ICP) monitoring was 5 +/- 2.2 days (range: 12 h to 11 days). Of the 141 patients with a control CT scan, four showed a 1-2-cc collection of blood at the catheter's end. ⋯ In conclusion, continuous ICP monitoring using the Camino intraparenchymal sensor has a low complication rate. However, this sensor may underread the real ICP values in a high number of patients. The lack of correlation between duration of ICP monitoring and zero-drift suggests that, contrary to the recommendations of other reports, the intraparenchymatous Camino sensor can provide reliable readings after the fifth day of use.
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Journal of neurotrauma · Apr 2002
Heme oxygenase-1 expression after spinal cord injury: the induction in activated neutrophils.
Tissue damage and neurological dysfunction after spinal cord injury may result, in part, from delayed or secondary mechanisms that appear to involve several endogenous factors. Among them, neutrophils are known to play important roles in the pathomechanisms of the secondary injury, that is, neutrophils are activated by an interaction with the endothelial cells, migrate into the damaged tissue and release several kinds of proteases or oxygen radicals. In the present study, we examined heme oxygenase-1 expression in the damaged spinal cord. ⋯ We found that many neutrophils expressing heme oxygenase-1 mRNA and protein were recruited into the damaged spinal cord with extensive hemorrhages during early stage of spinal cord injury. In an in vitro study, neutrophils incubated with proinflammatory cytokines, such as interleukin-1, 6 or interferon-gamma, expressed heme oxygenase-1 mRNA and protein. Based on these findings we conclude that the activated neutrophils can express heme oxygenase-1 in the injured spinal cord tissue, perhaps expecting modulatory and neuroprotective actions in the inflammatory response to spinal cord injury.
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Journal of neurotrauma · Mar 2002
Acute ethanol intake attenuates inflammatory cytokines after brain injury in rats: a possible role for corticosterone.
It has been reported that acute ethanol intoxication exerts dose-dependent effects, both beneficial and detrimental, on the outcome of traumatic brain injury (TBI), although the mechanism(s) has not been determined. Given that pro-inflammatory cytokines are either neuroprotective or neurotoxic, depending on their tissue levels, ethanol-induced alterations in brain cytokine production may be involved in determining the recovery after TBI. The present study was undertaken to examine the effect of acute ethanol pretreatments (producing blood alcohol concentrations of 100+/-16 mg/dL, and 220+/-10 mg/dL, considered low and intoxicating doses, respectively) on interleukin-1beta (IL-1beta) and tumor necrosis factor-alpha (TNF-alpha) levels in discrete brain regions. ⋯ Ethanol pretreatment lowered cytokine levels in the cortex, hippocampus and hypothalamus in a dose-dependent manner after TBI compared to the untreated injured rats. Serum corticosterone levels were markedly increased in the injured rats, and were further augmented in the ethanol-pretreated injured animals in a dose-dependent manner. Our findings suggest that ethanol-induced decrease in pro-inflammatory cytokine production may be linked to increased circulating corticosterone, both of which may contribute to the outcome of brain injury.