Journal of neurotrauma
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Journal of neurotrauma · Apr 2018
Hyperthermia and Mild Traumatic Brain Injury: Effects on Inflammation and the Cerebral Vasculature.
Mild traumatic brain injury (mTBI) or concussion represents the majority of brain trauma in the United States. The pathophysiology of mTBI is complex and may include both focal and diffuse injury patterns. In addition to altered circuit dysfunction and traumatic axonal injury (TAI), chronic neuroinflammation has also been implicated in the pathophysiology of mTBI. ⋯ Together, these results demonstrate significant differences in the cellular and molecular consequences of raised brain temperature at the time of mTBI. The observed polarization toward a M1-phenotype with mild hyperthermia would be expected to augment chronic inflammatory cascades, sustained functional deficits, and increased vulnerability to secondary insults. Mild elevations in brain temperature may contribute to the more severe and longer lasting consequences of mTBI or concussion reported in some patients.
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Journal of neurotrauma · Apr 2018
Minocycline plus N-Acetylcysteine Reduce Behavioral Deficits and Improve Histology with a Clinically Useful Time Window.
There are no drugs to manage traumatic brain injury (TBI) presently. A major problem in developing therapeutics is that drugs to manage TBI lack sufficient potency when dosed within a clinically relevant time window. Previous studies have shown that minocycline (MINO, 45 mg/kg) plus N-acetylcysteine (NAC, 150 mg/kg) synergistically improved cognition and memory, modulated inflammation, and prevented loss of oligodendrocytes that remyelinated damaged white matter when first dosed 1 h after controlled cortical impact (CCI) in rats. ⋯ These data suggest that MINO (22.5 mg/kg) plus NAC (75 mg/kg) remain potent when dosed at clinically useful time windows. Both MINO and NAC are drugs approved by the Food and Drug Administration and have been administered safely to patients in clinical trials at the doses in the new formulation. This suggests that the drug combination of MINO plus NAC may be effective in treating patients with TBI.
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Journal of neurotrauma · Apr 2018
Traumatic Brain Injury Impairs Myogenic Constriction of Cerebral Arteries: Role of Mitochondria-Derived H2O2 and TRPV4-Dependent Activation of BKca Channels.
Traumatic brain injury (TBI) impairs autoregulation of cerebral blood flow, which contributes to the development of secondary brain injury, increasing mortality of patients. Impairment of pressure-induced myogenic constriction of cerebral arteries plays a critical role in autoregulatory dysfunction; however, the underlying cellular and molecular mechanisms are not well understood. To determine the role of mitochondria-derived H2O2 and large-conductance calcium-activated potassium channels (BKCa) in myogenic autoregulatory dysfunction, middle cerebral arteries (MCAs) were isolated from rats with severe weight drop-impact acceleration brain injury. ⋯ In cultured vascular smooth muscle cells H2O2 activated BKCa currents, which were inhibited by blockade of TRPV4 channels. Collectively, our results suggest that after TBI, excessive mitochondria-derived H2O2 activates BKCa channels via a TRPV4-dependent pathway in the vascular smooth muscle cells, which impairs pressure-induced constriction of cerebral arteries. Future studies should elucidate the therapeutic potential of pharmacological targeting of this pathway in TBI, to restore autoregulatory function in order to prevent secondary brain damage and decrease mortality.
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Journal of neurotrauma · Apr 2018
Increased Myo-Inositol in Primary Motor Cortex of Contact Sports Athletes without a History of Concussion.
The objective of the study was to determine whether repetitive hits to the head at a subclinical level are associated with structural and functional brain abnormalities and whether these effects are influenced by high levels of fitness associated with intense physical activity. Seventy-two college students were recruited: 24 nonathletic, 24 athletes practicing a varsity contact sport, and 24 athletes practicing a varsity noncontact sport. They were recruited for a neuropsychological evaluation and a magnetic resonance imaging session that included magnetic resonance spectroscopy of primary motor cortex (M1) and prefrontal cortex and susceptibility-weighted imaging. ⋯ Varsity contact sports are associated with area-specific alterations in mIns concentration in the primary motor cortex. In the prefrontal cortex, high levels of fitness could modulate the effects of head impact exposure on prefrontal metabolite concentration. Indeed, although athletes in contact and noncontact sports show different neurometabolic profiles, they do not differ from sedentary controls.
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Journal of neurotrauma · Apr 2018
Geriatric Traumatic Brain Injury: Epidemiology, Outcomes, Knowledge Gaps, and Future Directions.
This review of the literature on traumatic brain injury (TBI) in older adults focuses on incident TBI sustained in older adulthood ("geriatric TBI") rather than on the separate, but related, topic of older adults with a history of earlier-life TBI. We describe the epidemiology of geriatric TBI, the impact of comorbidities and pre-injury function on TBI risk and outcomes, diagnostic testing, management issues, outcomes, and critical directions for future research. The highest incidence of TBI-related emergency department visits, hospitalizations, and deaths occur in older adults. ⋯ Yet there are few geriatric-specific TBI guidelines to assist with complex management decisions, and TBI prognostic models do not perform optimally in this population. Major barriers in management of geriatric TBI include under-representation of older adults in TBI research, lack of systematic measurement of pre-injury health that may be a better predictor of outcome and response to treatment than age and TBI severity alone, and lack of geriatric-specific TBI common data elements (CDEs). This review highlights the urgent need to develop more age-inclusive TBI research protocols, geriatric TBI CDEs, geriatric TBI prognostic models, and evidence-based geriatric TBI consensus management guidelines aimed at improving short- and long-term outcomes for the large and growing geriatric TBI population.