Journal of neurotrauma
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Journal of neurotrauma · Jan 2012
Mechanisms of dendritic spine remodeling in a rat model of traumatic brain injury.
Traumatic brain injury (TBI), a leading cause of death and disability in the United States, causes potentially preventable damage in part through the dysregulation of neural calcium levels. Calcium dysregulation could affect the activity of the calcium-sensitive phosphatase calcineurin (CaN), with serious implications for neural function. The present study used both an in vitro enzymatic assay and Western blot analyses to characterize the effects of lateral fluid percussion injury on CaN activity and CaN-dependent signaling in the rat forebrain. ⋯ These changes occurred bilaterally in the neocortex and hippocampus, appeared to persist for hours after injury, and coincided with synapse degeneration, as suggested by a loss of the excitatory post-synaptic protein PSD-95. Interestingly, the effect of TBI on cofilin in some brain regions was blocked by a single bolus of the CaN inhibitor FK506, given 1 h post-TBI. Overall, these findings suggest a loss of synapse stability in both hemispheres of the laterally-injured brain, and offer evidence for region-specific, CaN-dependent mechanisms.
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Journal of neurotrauma · Jan 2012
Progesterone increases circulating endothelial progenitor cells and induces neural regeneration after traumatic brain injury in aged rats.
Vascular remodeling plays a key role in neural regeneration in the injured brain. Circulating endothelial progenitor cells (EPCs) are a mediator of the vascular remodeling process. Previous studies have found that progesterone treatment of traumatic brain injury (TBI) decreases cerebral edema and cellular apoptosis and inhibits inflammation, which in concert promote neuroprotective effects in young adult rats. ⋯ Progesterone treatment significantly improved neurological outcome after TBI measured by the modified neurological severity score, Morris Water Maze and the long term potentiation in the hippocampus as well as increased the circulating EPC levels compared to TBI controls (p<0.05). Progesterone treatment also significantly increased CD34 and CD31 positive cell number and vessel density in the injured brain compared to TBI controls (p<0.05). These data indicate that progesterone treatment of TBI improves multiple neurological functional outcomes, increases the circulating EPC level, and facilitates vascular remodeling in the injured brain after TBI in aged rats.
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Journal of neurotrauma · Jan 2012
Failure of delayed intravenous administration of bone marrow stromal cells after traumatic brain injury.
Traumatic brain injury (TBI) is a leading cause of mortality and morbidity worldwide. Currently, there is no effective strategy to treat the functional sequelae associated with TBI. Experimental evidence shows that the intravenous administration of bone marrow stromal cells (BMSC) during the first week after TBI prevents neurological deficits, but no experimental studies have shown evidence of the effect of intravenous BMSC on chronic brain injury sequelae. ⋯ At the end of the study period the animals were sacrificed and their brains were studied to evaluate possible differences between groups. Two months after BMSC administration no significant differences were detected in the motor and sensory evaluation between animals treated with BMSC and controls, and no differences were detected after histological study of the brains. Our present results suggest that intravenous administration of BMSC after TBI, when the neurological deficits are well established, has no beneficial effect in neurological outcomes or on brain tissue.
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Journal of neurotrauma · Jan 2012
ReviewEfficacy and safety of dopamine agonists in traumatic brain injury: a systematic review of randomized controlled trials.
In the intensive care unit, dopamine agonists (DA) have been used in traumatic brain injury (TBI) patients to augment or accelerate cognitive recovery and rehabilitation. However, the efficacy and safety of DA in this population is not well established. We conducted a systematic review of randomized controlled trials (RCTs) examining the clinical efficacy and safety of DA in patients with TBI. ⋯ No trend could be drawn from the analysis of efficacy and safety. Important sources of bias in the studies were of major concern. Considering the absence of consensus regarding clinical outcome, the lack of safety assessment, and the high risk of bias in the included trials, more research is warranted before DA can be recommended in critically ill TBI patients.
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Journal of neurotrauma · Jan 2012
Increased risk of multiple sclerosis after traumatic brain injury: a nationwide population-based study.
The etiology of multiple sclerosis (MS) is still not well known. Previous data show conflicting results regarding the association between MS and prior brain trauma. This study aims to investigate the risk for MS following a traumatic brain injury (TBI) using a large-scale cohort study design. ⋯ Patients with TBI had a higher incidence of MS during the 6-year period than the comparison group (0.055% versus 0.037%). After excluding cases who died from non-MS causes, stratifying for hospitalization of cases as a proxy for severity, and adjusting for monthly income and geographic region of the community in which the patient resided, the hazard ratio (HR) of MS for patients with hospital-treated TBI injuries was 1.97 (95% CI 1.31,2.93, p<0.01) that of patients without TBI during the 6-year follow-up period after index health care use. Our study concludes that patients with TBI are at higher risk for subsequent MS over a 6-year follow-up period.