Journal of neurotrauma
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Journal of neurotrauma · Feb 2004
Nociceptin/orphanin FQ alters prostaglandin cerebrovascular action following brain injury.
Previous studies have observed that fluid percussion brain injury (FPI) elevated the CSF concentration of the opioid nociceptin/orphanin FQ (NOC/oFQ). In separate studies, FPI impaired pial artery dilation to the prostaglandins PGI2 and PGE2. This study was designed to investigate the following: (1) role of NOC/oFQ in impaired dilation to PGI2 and PGE2, (2) the effects of FPI on vasoconstriction to the TXA2 mimic U46619 and PGF2alpha, and (3) the role of NOC/oFQ in such FPI induced effects on U46619 and PGF(2alpha). ⋯ Additionally, these data show that administration of a NOC/oFQ receptor antagonist prevented such FPI associated events. NOC/oFQ administrated in a concentration observed after FPI produced blunted dilator prostaglandin and potentiated vasoconstriction prostaglandin vascular responses under nonbrain injury conditions. Finally, these data suggest that NOC/oFQ alters prostaglandin cerebrovascular action following brain injury.
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Journal of neurotrauma · Jan 2004
Marked gender effect on lipid peroxidation after severe traumatic brain injury in adult patients.
Striking gender differences have been reported in the pathophysiology and outcome of acute neurological injury. Greater neuroprotection in females versus males may be due, in part, to direct and indirect sex hormone-mediated antioxidant mechanisms. Progesterone administration decreases brain levels of F(2)-isoprostane, a marker of lipid peroxidation, after experimental traumatic brain injury (TBI) in male rats, and estrogen is neuroprotective in experimental neurological injury. ⋯ To our knowledge, this is the first study showing gender differences in lipid peroxidation after clinical TBI. Lipid peroxidation occurs early after severe TBI in adults and is more prominent in males vs females. These results established that gender is an important consideration in clinical trial design, particularly in the case of antioxidant strategies.
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Journal of neurotrauma · Jan 2004
Intravenous administration of marrow stromal cells (MSCs) increases the expression of growth factors in rat brain after traumatic brain injury.
This study was designed to investigate the effects of intravenous administration of marrow stromal cells (MSCs) on the expression of growth factors in rat brain after traumatic brain injury (TBI). The fate of transplanted MSCs and expression of growth factors was examined by immunohistochemistry. In addition, the level of growth factors was measured quantitatively using enzyme linked immunosorbent assay (ELISA). ⋯ We found that after transplantation, MSCs preferentially migrated into the injured hemisphere and there was a statistically significant improvement in the functional outcome of MSC-treated rats compared to control rats. NGF, BDNF, and bFGF were expressed in the injured brain of both treated as well as control rats; however, quantitative ELISA studies showed that expression of NGF and BDNF was significantly increased (p < 0.05) in the treated group. This study shows that intravenous administration of MSCs after TBI increases the expression of growth factors (NGF, BDNF), which possibly contributes to the improvement in functional outcome seen in these rats.
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Journal of neurotrauma · Dec 2003
Enhanced vulnerability to NMDA toxicity in sublethal traumatic neuronal injury in vitro.
Traumatic brain injury causes neuronal disruption and triggers secondary events leading to additional neuronal death. To study injuries triggered by secondary events, we exposed cultured cortical neurons to sublethal mechanical stretch, thus eliminating confounding death from primary trauma. Sublethally stretched neurons maintained cell membrane integrity, viability, and electrophysiological function. ⋯ To test whether this specificity requires physical interactions between NMDARs and cytoskeletal elements, we perturbed actin filaments and microtubules, both of which are linked to NMDARs. This had no effect on the stretch-induced vulnerability to NMDA, suggesting that sublethal stretch does not affect cell survival through the cytoskeleton. Our data illustrate that sublethal in vitro stretch injury triggers distinct signaling pathways that lead to secondary injury, rather than causing a generalized increase in vulnerability to secondary insults.
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Journal of neurotrauma · Dec 2003
Moderate controlled cortical contusion in pigs: effects on multi-parametric neuromonitoring and clinical relevance.
Over the last decade, routine neuromonitoring of ICP and CPP has been extended with new on-line techniques such as microdialysis, tissue oxygen (ptiO(2)), acid-base balance (ptiCO(2), pH) and CBF measurements, which so far have not lead to clear-cut therapy approaches in the neurointensive care unit. This is partially due to the complex pathophysiology following a wide-range of brain injuries, and the lack of suitable animal models allowing simultaneous, clinically relevant neuromonitoring under controlled conditions. Therefore, a controlled cortical impact (CCI) model in large animals (pig) has been developed. ⋯ Evaluation of brain water content and histology (12 h post-CCI) showed ipsilateral brain swelling by 5% and massive cell damage underneath the injury site which correlated with changes of ICP, CPP, glutamate, lactate, and ptiO(2) within the first hours post-CCI. Moderate controlled cortical contusion in pigs induced a complex pattern of pathophysiological processes which led to 'early' histological damage. Thus, this new large animal model will enable us to investigate the effect of therapeutic interventions on multi-parametric neuromonitoring and histological outcome, and to translate the data into clinical practice.