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
A Description of a New Continuous Physiological Index in Traumatic Brain Injury Using the Correlation between Pulse Amplitude of Intracranial Pressure and Cerebral Perfusion Pressure.
To describe a new continuous index of physiologic measurement in a traumatic brain injury (TBI) population, the moving correlation coefficient between intracranial pressure (ICP) pulse amplitude (AMP) and cerebral perfusion pressure (CPP), which we refer to as RAC. We use patient examples of sustained intracranial hypertension, systemic arterial hypotension, and plateau waves, as well as the retrospective analysis of 358 non-decompressive craniectomy (DC) TBI patients with high-frequency ICP and arterial blood pressure data, to explore the relationships of this new index, RAC, with AMP, ICP, CPP, RAP (correlation coefficient between AMP and ICP), pressure reactivity index (PRx), and pulse amplitude index (PAx). We compared the RAC-CPP relationship to that observed between CPP and both PRx and PAx. ⋯ RAC appears to carry information regarding both cerebrovascular responsiveness and cerebral compensatory reserve. This contributes to RAC's uniqueness and complex interpretation. Further prospective, clinical studies of RAC in CPP optimum estimation and outcome prediction in TBI are required.
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Journal of neurotrauma · Apr 2018
A Scoping Review of Pain in Children after Traumatic Brain Injury: Is There More Than Headache?
Headache is a common source of pain in children after traumatic brain injury (TBI); however, relatively little is known about nonheadache pain in this pediatric population. The present review seeks to map the extant literature to determine the prevalence, characteristics, and impact of nonheadache pain in children post-TBI of all severities. We found that of 109 studies published on pain in children after a TBI, 95 (87%) were focused exclusively on headache pain and only 14 (13%) reported on nonheadache pain or overall pain, with half (n = 7) in the form of case studies. ⋯ Findings of the current review suggest that pain assessment in children post-TBI needs improvement, given that pain is linked to worse recovery, poorer quality of life, and can be long-lasting. More rigorous examination of nonheadache pain and its role in impeding recovery in children post-TBI is imperative and has the potential to improve the care and management of children with TBI. We conclude with recommendations for pain assessment, discuss gaps in the literature, and highlight directions for future research.