Journal of neurotrauma
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The high rates of traumatic brain injury (TBI) and post-traumatic stress disorder (PTSD) diagnoses encountered in recent years by the United States Veterans Affairs Healthcare System have increased public awareness and research investigation into these conditions. In this review, we analyze the neural mechanisms underlying the TBI/PTSD comorbidity. TBI and PTSD present with common neuropsychiatric symptoms including anxiety, irritability, insomnia, personality changes, and memory problems, and this overlap complicates diagnostic differentiation. ⋯ These disturbances produce neuronal death and degeneration, axonal injury, and dendritic spine dysregulation and changes in neuronal morphology. In laboratory studies, various forms of pharmacological or psychological treatments are capable of reversing these detrimental processes and promoting axonal repair, dendritic remodeling, and neurocircuitry reorganization, resulting in behavioral and cognitive functional enhancements. Based on these mechanisms, novel neurorestorative therapeutics using anti-inflammatory, antioxidant, and anticonvulsant agents may promote better outcomes for comorbid TBI and PTSD.
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Journal of neurotrauma · Jan 2018
Effects of mild blast traumatic brain injury on cerebral vascular, histopathological and behavioral outcomes in rats.
To determine the effects of mild blast-induced traumatic brain injury (bTBI), several groups of rats were subjected to blast injury or sham injury in a compressed air-driven shock tube. The effects of bTBI on relative cerebral perfusion (laser Doppler flowmetry [LDF]), and mean arterial blood pressure (MAP) cerebral vascular resistance were measured for 2 h post-bTBI. Dilator responses to reduced intravascular pressure were measured in isolated middle cerebral arterial (MCA) segments, ex vivo, 30 and 60 min post-bTBI. ⋯ Because impact TBI (i.e., non-blast TBI) is often associated with reduced cerebral perfusion and impaired cerebrovascular function in part because of the generation of reactive oxygen and nitrogen species such as peroxynitrite (ONOO-), the effects of the administration of the ONOO- scavenger, penicillamine methyl ester (PenME), on cerebral perfusion and cerebral vascular resistance were measured for 2 h post-bTBI. Mild bTBI resulted in reduced relative cerebral perfusion and MCA dilator responses to reduced intravascular pressure, increases in cerebral vascular resistance and in the numbers of FJC-positive cells in the brain, and significantly impaired working memory. PenME administration resulted in significant reductions in cerebral vascular resistance and a trend toward increased cerebral perfusion, suggesting that ONOO- may contribute to blast-induced cerebral vascular dysfunction.
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Journal of neurotrauma · Jan 2018
Cerebral Blood Flow after Mild Traumatic Brain Injury: Associations between Symptoms and Post-Injury Perfusion.
Arterial spin labeling (ASL) has emerged as a technique for assessing mild traumatic brain injury (mTBI), as it can noninvasively evaluate cerebrovascular physiology. To date, there is substantial variability in methodology and findings of ASL studies of mTBI. While both increased and decreased perfusion are reported after mTBI, more consistency is emerging when perfusion is examined with regard to symptomology. ⋯ Perfusion in the left dorsal ACC was higher in athletes reporting physical symptoms six weeks post-injury compared with asymptomatic athletes and controls. Overall, these findings are inconsistent with reports of reduced rCBF after mTBI but coherent with studies that report increased perfusion in persons with greater or persistent mTBI-related symptomology. Future work should continue to assess how CBF perfusion relates to symptomology and recovery after mTBI.
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Journal of neurotrauma · Jan 2018
Post-injury administration of galantamine reduces traumatic brain injury pathology and improves outcome.
Acetylcholine is an excitatory neurotransmitter in the central nervous system that plays a key role in cognitive function, including learning and memory. Previous studies have shown that experimental traumatic brain injury (TBI) reduces cholinergic neurotransmission, decreases evoked release of acetylcholine, and alters cholinergic receptor levels. Galantamine (U. ⋯ Specifically, significant improvements in the Morris water maze, novel object recognition, and context-specific fear memory tasks were observed in injured animals treated with galantamine. Although messenger RNAs for both M1 (Nos2, TLR4, and IL-12ß) and M2 (Arg1, CCL17, and Mcr1) microglial phenotypes were elevated post-TBI, galantamine treatment did not alter microglial polarization tested 24 h and 6 days post-injury. Taken together, these findings support the further investigation of galantamine as a treatment for TBI.
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Journal of neurotrauma · Jan 2018
Transcranial Doppler Systolic Flow Index and ICP Derived Cerebrovascular Reactivity Indices in TBI.
The purpose of our study was to explore relationships between transcranial Doppler (TCD) indices of cerebrovascular reactivity and those derived from intracranial pressure (ICP). Goals included: A) confirming previously described co-variance patterns of TCD/ICP indices, and B) describing thresholds for systolic flow index (Sx; correlation between systolic flow velocity [FVs] and cerebral perfusion pressure [CPP]) associated with outcome. In a retrospective cohort of traumatic brain injury (TBI) patients: with TCD and ICP monitoring, we calculated various continuous indices of cerebrovascular reactivity: A) ICP (pressure reactivity index [PRx]: correlation between ICP and mean arterial pressure [MAP]; PAx: correlation between pulse amplitude of ICP [AMP] and MAP; RAC: correlation between AMP and CPP) and B) TCD (mean flow index [Mx]: correlation between mean flow velocity [FVm] and CPP; Mx_a: correlation between FVm and MAP; Sx: correlation between FVs and CPP; Sx_a: correlation between FVs and MAP; Dx: correlation between diastolic flow velocity [FVd] and CPP; Dx_a: correlation between FVd and MAP). ⋯ TCD systolic indices are most closely associated with ICP indices. Sx and Sx_a likely provide better approximation of ICP indices, compared with Mx/Mx_a/Dx/Dx_a. Sx provides superior outcome prediction, versus Mx, with defined thresholds.