Journal of neurotrauma
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Journal of neurotrauma · Mar 2024
Metabotropic glutamate receptor 2 expression is chronically elevated in male rats with post-traumatic stress disorder related behavioral traits following repetitive low-level blast exposure.
Many military veterans who experienced blast-related traumatic brain injuries in the conflicts in Iraq and Afghanistan currently suffer from chronic cognitive and mental health problems that include depression and post-traumatic stress disorder (PTSD). Male rats exposed to repetitive low-level blast develop cognitive and PTSD-related behavioral traits that are present for more than 1 year after exposure. We previously reported that a group II metabotropic receptor (mGluR2/3) antagonist reversed blast-induced behavioral traits. ⋯ Immunohistochemical staining revealed no changes in the principally presynaptic localization of mGluR2 by blast exposure. Administering the mGluR2/3 antagonist LY341495 after behavioral traits had emerged rapidly reversed blast-induced effects on novel object recognition and cued fear responses 10 months following blast exposure. These studies support alterations in mGluR2 receptors as a key pathophysiological event following blast exposure and provide further support for group II metabotropic receptors as therapeutic targets in the neurobehavioral effects that follow blast injury.
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Journal of neurotrauma · Mar 2024
Longitudinal Brain Perfusion and Symptom Presentation Following Pediatric Concussion: A PedCARE+MRI Substudy.
Emerging evidence suggests that advanced neuroimaging modalities such as arterial spin labelling (ASL) might have prognostic utility for pediatric concussion. This study aimed to: 1) examine group differences in global and regional brain perfusion in youth with concussion or orthopedic injury (OI) at 72 h and 4 weeks post-injury; 2) examine patterns of abnormal brain perfusion within both groups and their recovery; 3) investigate the association between perfusion and symptom burden within concussed and OI youths at both time-points; and 4) explore perfusion between symptomatic and asymptomatic concussed and OI youths. Youths ages 10.00-17.99 years presenting to the emergency department with an acute concussion or OI were enrolled. ⋯ At 4 weeks, the symptomatic sub-group (n = 10) showed lower adjusted perfusion within the right cerebellum and lingual gyrus, while the asymptomatic sub-group (n = 59) showed lower adjusted perfusion within the left calcarine, but greater perfusion within the left medial orbitofrontal cortex, right middle frontal gyrus, and bilateral caudate compared with OIs. Yet, no group differences were observed in the number of abnormal perfusion clusters or volumes at any visit. The present study suggests that symptoms may be associated with changes in regional perfusion, but not abnormal perfusion levels.
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Journal of neurotrauma · Mar 2024
Experimental study on intracranial pressure and biomechanical response in rats under the blast wave.
Explosion overpressure propagates extracranially and causes craniocerebral injury after being transmitted into the brain. Studies on the extent of skull to reduce impact overpressure are still lacking. Therefore, it is necessary to study the relationship between intracranial pressure (ICP) and external field pressure and the situation of craniocerebral injury under the blast wave. ⋯ The fitting curve of air overpressure and ICP can be used to predict the changes of ICP under different external blast overpressure. Analysis of cranial injury showed that the area of cranial hemorrhage with extremely severe injury increased by 107.9% compared with mild injury, increased by 53.3% compared with moderate injury, and increased by 21.6% compared with severe injury. This work may provide references for the dynamic response of biological cranial and brain injury mechanism under the effect of blast wave.
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Journal of neurotrauma · Mar 2024
Protective effects of Hinokitiol on neuronal ferroptosis by activating the KEAP1/NRF-2/HO-1 pathway in traumatic brain injury.
In this study, we investigated the effects of hinokitiol, a small-molecule natural compound, against neuronal ferroptosis after traumatic brain injury (TBI). A controlled cortical impact (CCI) mouse model and excess glutamate-treated HT-22 cells were used to study the effects of hinokitiol on TBI. Hinokitiol mitigated TBI brain tissue lesions and significantly improved neurological function. ⋯ Mechanistically, hinokitiol upregulated heme oxygenase-1 (HO-1) expression, promoted nuclear factor-erythroid factor 2-related factor 2 (Nrf2) nuclear translocation, and inhibited the activation of microglia and astrocyte after TBI. These results suggest that hinokitiol has neuroprotective effects on rescuing cells from TBI-induced neuronal ferroptosis. In summary, hinokitiol is a potential therapeutic candidate for TBI by activating the Nrf2/Keap1/HO-1 signaling pathway.
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Journal of neurotrauma · Mar 2024
Delayed administration of an angiotensin II type 2 receptor agonist promotes functional recovery of the brain and heart after traumatic brain injury.
Cardiac injury is a common complication following traumatic brain injury (TBI) that can lead to poor clinical outcomes. Angiotensin II type 2 receptor (AT2R) activation exerts protective roles in the brain and heart, yet its potential impact on TBI or TBI-induced cardiac deficits remains elusive. The goal of this study was to investigate the influence of AT2R activation on recovery after TBI-induced cognitive and cardiac injury using the selective nonpeptide AT2R agonist compound 21 (C21). ⋯ Meanwhile, C21 benefited cardiac function, as identified by increased left ventricular ejection fraction 1 month after TBI. In addition, C21 alleviated TBI-induced cardiac hypertrophy and fibrosis; however, blood pressure was not affected. Our results demonstrate that AT2R activation ameliorates TBI-induced neurological and cardiac deficits.