Journal of neurotrauma
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Journal of neurotrauma · Jan 2017
Combining the antipsychotic drug haloperidol and environmental enrichment after traumatic brain injury is a double-edged sword.
Environmental enrichment (EE) confers significant benefits after experimental traumatic brain injury (TBI). In contrast, the antipsychotic drug (APD) haloperidol (HAL) exerts deleterious effects on neurobehavioral and cognitive recovery. Neurorehabilitation and management of agitation, however, are integral components of the treatment strategy for patients with TBI. ⋯ What was surprising was that the therapeutic effects of EE were greatly reduced by concomitant administration of HAL. No differences in cortical lesion volumes were observed among the groups (p > 0.05). The potential clinical implications of these findings suggest that administering HAL to patients undergoing neurorehabilitation may be a double-edged sword because agitation must be controlled before rehabilitation can be safely initiated and executed, but its use may compromise therapeutic efficacy.
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Journal of neurotrauma · Jan 2017
Pioglitazone attenuates neuroinflammation and promotes dopaminergic neuronal survival in the nigrostriatal system of rats after diffuse brain injury.
Increasing evidence suggests that traumatic brain injury (TBI) may raise the risk of developing late-onset Parkinson's disease (PD). Recently, the peroxisome proliferation-activated receptor gamma (PPARγ) agonist pioglitazone has been demonstrated to be neuroprotective in animal models of neurodegeneration. The present study investigates the vulnerability of the nigrostriatal system after TBI, and intervention with pioglitazone treatment. ⋯ Loss of neurons was accompanied by increased extracellular dopamine (DA) turnover in the striatum, indicating enhanced dopaminergic activity in functional compensation after nigrostriatal damage. Strikingly, pioglitazone treatment greatly attenuated microglial activation and improved dopaminergic neuronal survival in the nigrostriatal system, which may promote locomotor recovery. These results suggest that interventions that attenuate secondary inflammation could be a feasible therapeutic treatment to improve outcome after TBI.
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Journal of neurotrauma · Jan 2017
TREM2 deficiency alters acute macrophage distribution and improves recovery after TBI.
Traumatic brain injury (TBI) affects 1.7 million persons annually in the United States (Centers for Disease Control and Prevention). There is increasing evidence that persons exposed to TBI have increased risk of the development of multiple neurodegenerative conditions, including Alzheimer disease (AD). TBI triggers a strong neuroinflammatory response characterized by astrogliosis, activation of microglia, and infiltration of peripheral monocytes. ⋯ Further, Trem2-/- mice exposed to TBI exhibited enhanced macrophage activation near the lesion, but significantly less macrophage activation away from the lesion when compared with B6 mice exposed to TBI. In addition, at 120 DPI, Trem2-/- mice exposed to TBI demonstrated reduced hippocampal atrophy and rescue of TBI-induced behavioral changes when compared with B6 mice exposed to TBI. Taken together, this study suggests that TREM2 deficiency influences both acute and chronic responses to TBI, leading to an altered macrophage response at early time points, and improved pathological and functional outcomes at later time points.
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Journal of neurotrauma · Jan 2017
Hemolysed blood elicits - calcium antagonist and high CO2 reversible - constrictions via elevation of Ca2+ in isolated cerebral arteries.
During acute subarachnoid hemorrhage, blood is hemolyzed, which is followed by a significant cerebrovascular spasm resulting in a serious clinical condition. Interestingly, however, the direct vasomotor effect of perivascular hemolyzed blood (HB) has not yet been characterized, preventing the assessment of contribution of vasoconstrictor mechanisms deriving from brain tissue and/or blood and development of possible treatments. We hypothesized that perivascular HB reduces the diameter of the cerebral arteries (i.e., basilar artery [BA]; middle cerebral artery [MCA]) by elevating vascular tissue [Ca2+]i level. ⋯ After washout of HB, nitric oxide-mediated dilations remained significantly reduced compared to control. HB significantly increased the ratiometric Ca signal, which returned to control level after washout. In conclusion, perivascular hemolyzed blood elicits significant-nifedipine and high CO2 reversible-constrictions of isolated BAs and MCAs, primarily by increasing intracellular Ca2+, findings that can contribute to the refinement of local treatment of subarachnoid hemorrhage.
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Journal of neurotrauma · Jan 2017
Comprehensive Profiling of Modulation of Nitric Oxide levels and Mitochondrial Activity in Injured Brain: An Experimental Study based on the Fluid Percussion Injury Model in Rats.
Nitric oxide (NO) has frequently been associated with secondary damage after brain injury. However, average NO levels in different brain regions before and after traumatic brain injury (TBI) and its role in post-TBI mitochondrial dysfunction remain unclear. In this comprehensive profiling study, we demonstrate for the first time that basal NO levels vary significantly in the healthy cortex (0.44 ± 0.04 μM), hippocampus (0.26 ± 0.03 μM), and cerebellum (1.24 ± 0.08 μM). ⋯ NO-mediated impairment of mitochondrial state 3 respiration dependent on complex I substrates was transient and confined to the ipsilateral cortex. Our results demonstrate that NO dynamics and associated effects differ in various regions of the injured brain. A potential association between the observed mitochondrial electron flow through complex I, but not complex II, and the modulation of TBI induced NO levels in different brain regions has to be prospectively analyzed in more detail.