Journal of neurotrauma
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Journal of neurotrauma · Feb 2004
Randomized Controlled Trial Clinical TrialRelationships between cerebrospinal fluid markers of excitotoxicity, ischemia, and oxidative damage after severe TBI: the impact of gender, age, and hypothermia.
Excitotoxicity and ischemia can result in oxidative stress after TBI. Female sex hormones are hypothesized to be neuroprotective after TBI by affecting multiple mechanisms of secondary injury, including oxidative damage, excitotoxicity and ischemia. Ca2+ mediated oxidative stress increases with age, and hypothermia is known to attenuate secondary injury. ⋯ These results indicate that females have smaller oxidative damage loads than males for a given excitotoxic or ischemic insult and female gonadal hormones may play a role in mediating this neuroprotective effect. These results also suggest that susceptibility to glutamate mediated oxidative damage increases with age and that hypothermia differentially attenuates CSF glutamate versus F2-isoprostane production. Gender and age differences in TBI pathophysiology should be considered when conducting clinical trials in TBI.
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Journal of neurotrauma · Feb 2004
Selective metabolic reduction in gray matter acutely following human traumatic brain injury.
The aim of this study was to determine whether the apparent loss of overall gray-white matter contrast (GM/WM) seen on FDG-PET imaging reflects the differential changes of glucose metabolic rate (CMRglc) in cortical gray mater (GM) and subcortical white mater (WM) following TBI. The clinical significance of the CMRglc GM-to-WM ratio was also evaluated. Nineteen normal volunteers and 14 TBI patients were studied. ⋯ The patients with higher CMRglc GM-to-WM ratios (>1.54) showed good recovery 12 months after TBI. There was a selective CMRglc reduction in cortical GM following TBI. The pathophysiological basis for the reduction in GM-to-WM CMRglc ratio seen on FDG-PET imaging following TBI remains to be determined.
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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 · Feb 2004
The therapeutic efficacy conferred by the 5-HT(1A) receptor agonist 8-Hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) after experimental traumatic brain injury is not mediated by concomitant hypothermia.
We recently reported that the 5-HT1A receptor agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) attenuated traumatic brain injury (TBI)-induced cognitive deficits and histopathology. However, 8-OH-DPAT also produced mild hypothermia (Hypo), which may have contributed to the benefit. To clarify this issue, we conducted an experiment similar to the previous, but included an 8-OH-DPAT group that was maintained at 37 +/- 0.5 degrees C (normothermia; Normo). ⋯ Both the Injury/DPAT + Normo and Injury/DPAT + Hypo groups exhibited enhanced cognitive performance (spatial acquisition and retention) and reduced histopathology (CA3 cell loss and cortical lesion volume) versus the Injury/ Vehicle group (P < 0.05), but did not differ from one another despite a rapid (15 min), mild (34.4-34.9 degrees C), and transient (~1 h) hypothermic effect in the latter. These data confirm that a single systemic administration of 8-OH-DPAT confers neurological protection after TBI, and demonstrate that the beneficial effect is not mediated by concomitant hypothermia. The mechanisms for the protective effects of 8-OH-DPAT after TBI require further inquiry.
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Journal of neurotrauma · Feb 2004
Transplantation of neuronal and glial precursors dramatically improves sensorimotor function but not cognitive function in the traumatically injured brain.
Embryonic stem (ES) cells have been investigated in various animal models of neurodegenerative disease; however, few studies have examined the ability of ES cells to improve functional outcome following traumatic brain injury (TBI). The purpose of the present study was to examine the ability of pre-differentiated murine ES cells (neuronal and glial precursors) to improve functional outcome. Rats were prepared with a unilateral controlled cortical impact injury or sham and then transplanted 7 days later with 100K ES cells (WW6G) (~30% neurons) or media. ⋯ It was found that transplantation of ES cells prevented the occurrence of multiple small necrotic cavities that were seen in the cortex adjacent to the lesion cavity in media transplanted rats. Additionally, ES cells transplants also significantly reduced lesion size. Results of this study suggest that ES cells that have been pre-differentiated into neuronal precursors prior to transplantation have therapeutic potential.