Journal of neurotrauma
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Journal of neurotrauma · May 2012
Comparative StudyTBI sex dependently upregulates ET-1 to impair autoregulation, which is aggravated by phenylephrine in males but is abrogated in females.
Traumatic brain injury (TBI) contributes to morbidity in children, and boys are disproportionately represented. Endothelin-1 (ET-1) contributes to impaired autoregulation via oxygen (O₂⁻) after TBI in piglets, but its relative role in males compared with females has not been previously investigated. Increased cerebral perfusion pressure (CPP) via phenylephrine (Phe) sex dependently improves impairment of autoregulation after TBI through modulation of extracellular signal-related kinase (ERK) mitogen-activated protein kinase (MAPK) upregulation, aggravated in males, but blocked in females. ⋯ These data indicate that TBI upregulates ET-1 more in males than in females. Elevation of CPP with Phe sex dependently prevents impairment of cerebral autoregulation after TBI through modulation of ET-1, O₂⁻, and ERK mediated impairment of K channel vasodilation. These observations advocate for the consideration of development of sex-based therapies for the treatment of hemodynamic sequelae of pediatric TBI.
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Journal of neurotrauma · May 2012
Prevention of traumatic brain injury-induced neuron death by intranasal delivery of nicotinamide adenine dinucleotide.
Traumatic brain injury (TBI) is one of the most devastating injuries experienced by military personnel, as well as the general population, and can result in acute and chronic complications such as cognitive impairments. Since there are currently no effective tools for the treatment of TBI, it is of great importance to determine the mechanisms of neuronal death that characterize this insult. Several studies have indicated that TBI-induced neuronal death arises in part due to excessive activation of poly(ADP-ribose) polymerase-1 (PARP-1), which results in nicotinamide adenine dinucleotide (NAD⁺) depletion and subsequent energy failure. ⋯ In addition, delayed microglial activation normally seen after TBI was reduced by NAD⁺ treatment at 7 days after insult. Neuronal superoxide production and PARP-1 accumulation after TBI were not inhibited by NAD⁺ treatment, indicating that reactive oxygen species (ROS) production and PARP-1 activation are events that occur upstream of NAD⁺ depletion. This study suggests that intranasal delivery of NAD⁺ represents a novel, inexpensive, and non-toxic intervention for preventing TBI-induced neuronal death.
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Journal of neurotrauma · May 2012
Comparative StudyEffects of hypothermia on cerebral autoregulatory vascular responses in two rodent models of traumatic brain injury.
Traumatic brain injury (TBI) can trigger disturbances of cerebral pressure autoregulation that can translate into the generation of secondary insults and increased morbidity/mortality. Few therapies have been developed to attenuate the damaging consequences of disturbed autoregulatory control, although some suggest that hypothermia may exert such protection. Here we reexamine this issue of traumatically induced autoregulatory disturbances and their modulation by hypothermic intervention, examining these phenomena in two different models of TBI. ⋯ However, with LFPI, the use of 2 h of hypothermia provided partial vascular protection. These results clearly illustrate that TBI can alter the cerebral autoregulatory vascular response to sequentially induced hypotensive insult, whereas the use of post-traumatic hypothermia provides benefit. Collectively, these studies also demonstrate that different animal models of TBI can evoke different biological responses to injury.
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There has recently been a call for the adoption of comparative effectiveness research (CER) and related research approaches for studying traumatic brain injury (TBI). These methods allow researchers to compare the effectiveness of different therapies in producing patient-oriented outcomes of interest. Heretofore, the only measures by which to compare such therapies have been mortality and rate of poor outcome. ⋯ No consistent effect or age, gender, or years of education was seen. As expected, QOL decreased with functional outcome as described by the GOSE. The results of this study will provide the groundwork for future groups seeking to apply CER methods to clinical studies of TBI.
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Journal of neurotrauma · May 2012
Effect of blast exposure on the brain structure and cognition in Macaca fascicularis.
Blast injury to the brain is one of the major causes of death and can also significantly affect cognition and physical and psychological skills in survivors of blast. The complex mechanisms via which blast injury causes impairment of cognition and other symptoms are poorly understood. In this study, we investigated the effects of varying degrees of primary blast overpressure (BOP; 80 and 200 kPa) on the pathophysiological and magnetic resonance imaging (MRI) changes and neurocognitive performance as assessed by the monkey Cambridge Neuropsychological Test Automated Battery (mCANTAB) in non-human primates (NHP). ⋯ Increased apoptosis appeared to involve astrocytes and oligodendrocytes in the animals following blast exposure. The small sample size could have contributed to the non-significant outcome in cognitive performance post-blast and limited quantitative analyses. Nevertheless, the study has provided initial descriptive changes for establishing a primary BOP threshold for brain injury to serve as a useful platform for future investigations that aim to estimate brain injury potential and set safe limits of exposure.