Articles: traumatic-brain-injuries.
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Journal of neurotrauma · Nov 2023
Optogenetic stimulation of CA1 pyramidal neurons at theta enhances recognition memory in brain injured animals.
Abstract The hippocampus plays a prominent role in learning and memory formation. The functional integrity of this structure is often compromised after traumatic brain injury (TBI), resulting in lasting cognitive dysfunction. The activity of hippocampal neurons, particularly place cells, is coordinated by local theta oscillations. ⋯ Our results show that memory impairments in brain injured animals could be reversed by optogenetically stimulating CA1 pyramidal neurons expressing channelrhodopsin (ChR2) during learning. In contrast, injured animals receiving a control virus (lacking ChR2) did not benefit from optostimulation. These results suggest that direct stimulation of CA1 pyramidal neurons at theta may be a viable option for enhancing memory after TBI.
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Journal of neurotrauma · Nov 2023
Neuropathological outcomes of traumatic brain injury and alcohol use in males and females: studies using preclinical rodent and clinical human specimens.
Traumatic brain injury (TBI) and alcohol misuse are inextricably linked and can increase the risk for development of neurodegenerative diseases, particularly in military veterans and contact sport athletes. Proteinopathy (defects in protein degradation) is considered an underlying factor in neurodegenerative diseases. Whether it contributes to TBI/alcohol-mediated neurodegeneration is unexplored, however. ⋯ We have previously demonstrated that ISGylation is increased in the LSCs of veterans with TBI/ALS (amyotrophic lateral sclerosis). Here, we show increased ISGylation of TDP-43 in the LSCs of TBI/ALS-afflicted female veterans compared with male veterans. Knowing that ISGylation induces proteinopathy, we suggest targeting ISGylation may prevent proteinopathy-mediated neurodegeneration post-TBI, particularly in women; however, causal studies are required to confirm this claim.
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Journal of neurotrauma · Nov 2023
Serum Caffeine Concentration at the Time of Traumatic Brain Injury and its Long-term Clinical Outcomes.
Caffeine is one of the most widely consumed psychoactive drugs in the general population. It has a neuroprotective effect in degenerative neurological disorders; however, the association between caffeine and traumatic brain injury (TBI) outcomes is contradictory. The objective of this study was to evaluate the association between serum caffeine concentration at the time of injury and long-term functional outcomes of patients with TBI visiting the emergency department (ED). ⋯ In multi-variable logistic regression analysis, the low- and intermediate-caffeine groups were significantly associated with a higher probability of 6-month favorable functional recovery compared with the no-caffeine group [AORs (95% CI): 2.82 (1.32-6.02) and 2.18 (1.06-4.47], respectively. This study showed a significant association between a serum caffeine concentration of 0.01 to 1.66 μg/mL and good functional recovery at 6 months after injury compared with the no-caffeine group of patients with TBI with intracranial injury. These results suggest the possibility of using serum caffeine level as a potential biomarker for TBI outcome prediction and of using caffeine as a therapeutic agent in the clinical care of patients with TBI.
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Journal of neurotrauma · Nov 2023
Mitochondrial dysfunction following repeated mild blast traumatic brain injury is attenuated by a mild mitochondrial uncoupling prodrug.
Mild traumatic brain injury (mTBI) results in impairment of brain metabolism, which is propagated by mitochondrial dysfunction in the brain. Mitochondrial dysfunction has been identified as a pathobiological therapeutic target to quell cellular dyshomeostasis. Further, therapeutic approaches targeting mitochondrial impairments, such as mild mitochondrial uncoupling, have been shown to alleviate behavioral alterations after TBI. ⋯ MP201 treatment alleviated elevated glia-enriched mitochondrial oxidative damage following rmbTBI. However, there was a lack of injury-associated differences in oxidative damage in synaptic mitochondria. Overall, our report demonstrates that rmbTBI results in mitochondrial impairment diffusely throughout the brain and mild mitochondrial uncoupling can restore mitochondrial bioenergetics and oxidative balance.
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Journal of neurotrauma · Nov 2023
Randomized Controlled TrialIntegrating, Harmonizing, and Curating Studies with High-Frequency and Hourly Physiological Data: Proof of Concept from Seven Traumatic Brain Injury Datasets.
Research in severe traumatic brain injury (TBI) has historically been limited by studies with relatively small sample sizes that result in low power to detect small, yet clinically meaningful outcomes. Data sharing and integration from existing sources hold promise to yield larger more robust sample sizes that improve the potential signal and generalizability of important research questions. However, curation and harmonization of data of different types and of disparate provenance is challenging. ⋯ Our harmonized data set included data on 1536 patients from the Citicoline Brain Injury Treatment Trial (COBRIT), Effect of erythropoietin and transfusion threshold on neurological recovery after traumatic brain injury: a randomized clinical trial (EPO Severe TBI), BEST-TRIP, Progesterone for the Treatment of Traumatic Brain Injury III Clinical Trial (ProTECT III), Transforming Research and Clinical Knowledge in Traumatic brain Injury (TRACK-TBI), Brain Oxygen Optimization in Severe Traumatic Brain Injury Phase-II (BOOST-2), and Ben Taub General Hospital (BTGH) Research Database studies. We conclude with process recommendations for data acquisition for future prospective studies to aid integration of these data with existing studies. These recommendations include using common data elements whenever possible, a standardized recording system for labeling and timing of high-frequency physiological data, and secondary use of studies in systems such as Federal Interagency Traumatic Brain Injury Research Informatics System (FITBIR), to engage investigators who collected the original data.