Journal of neurotrauma
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Journal of neurotrauma · Feb 2004
Alcohol abuse and traumatic brain injury: quantitative magnetic resonance imaging and neuropsychological outcome.
Prior or concurrent alcohol use at the time of traumatic brain injury (TBI) was examined in terms of post-injury atrophic changes measured by quantitative analysis of magnetic resonance imaging (MRI) and neuropsychological outcome. Two groups of TBI subjects were examined: those with a clinically significant blood alcohol level (BAL) present at the time of injury (TBI + BAL) and those without a significant BAL (TBI-only). To explore the potential impact of both acute and chronic alcohol use, subjects in both groups were further clustered into one of four subgroups (NONE, MILD, MODERATE or HEAVY) based upon available information regarding their pre-injury alcohol use. ⋯ Increased general atrophy was observed in patients with (a) a positive BAL and/or (b) a history of moderate to heavy pre-injury alcohol use. In addition, performance on neuropsychological outcome variables (WAIS-R and WMS-R Index scores) was generally worse in the subgroups of patients with positive BAL and a history of preinjury alcohol use, as compared to the other TBI groups though not statistically significant. Implications of alcohol use, at the time of brain injury, are discussed.
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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.
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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.