Journal of neurotrauma
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Journal of neurotrauma · Jan 2017
Acute white matter tract damage following frontal mild traumatic brain injury.
Our understanding of mild traumatic brain injury (mTBI) is still in its infancy and to gain a greater understanding, relevant animal models should replicate many of the features seen in human mTBI. These include changes to diffusion tensor imaging (DTI) parameters, absence of anatomical lesions on conventional neuroimaging, and neurobehavioral deficits. The Maryland closed head TBI model causes anterior-posterior plus sagittal rotational acceleration of the brain, frequently observed with motor vehicle and sports-related TBI injuries. ⋯ A significant decrease was observed in ambulatory distance, average velocity, stereotypic counts, and vertical counts compared with baseline. Histological examination of the mTBI brain sections indicated a significant decrease in the expression of myelin basic protein in the fimbria, splenium, and internal capsule. Our findings demonstrate the vulnerability of the white matter tracts, specifically the fimbria and splenium, and the ability of DTI to identify changes to the integrity of the white matter tracts following mTBI.
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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
Unfolded Maps for Quantitative Analysis of Cortical Lesion Location and Extent after Traumatic Brain Injury.
We aimed to generate two-dimensional (2D) unfolded cortical maps from magnetic resonance (MR) images to delineate the location of traumatic brain injury (TBI)-induced cortical damage in functionally diverse cytoarchitectonic areas of the cerebral cortex, and to predict the severity of functional impairment after TBI based on the lesion location and extent. Lateral fluid-percussion injury was induced in adult rats and T2 maps were acquired with magnetic resonance imaging (MRI) at 3 days post-TBI. Somatomotor deficits were assessed based on the composite neuroscore and beam balance test, and spatial learning was assessed in the Morris water maze. ⋯ Subsequent receiver operating characteristic analysis indicated that severity of the MRI lesion in S1ULp and S2 was a sensitive and specific predictor of poor performance in the beam balance test. Moreover, MRI lesions in the S1ULp, S2, S1BF, and Ect and PRh cortices predicted poor performance in the Morris water maze test. Our findings indicate that 2D-unfolded cortical maps generated from MR images delineate the distribution of cortical lesions in functionally different cytoarchitectonic regions, which can be used to predict the TBI-induced functional impairment.
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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.