Articles: traumatic-brain-injuries.
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Journal of neurotrauma · Jul 2022
Randomized Controlled TrialPlasma Neurofilament Light and Glial Fibrillary Acidic Protein Levels over Thirty Days in a Porcine Model of Traumatic Brain Injury.
To establish the clinical relevance of porcine model of traumatic brain injury (TBI) using the plasma biomarkers of injury with diffusion tensor imaging (DTI) over 30 days, we performed a randomized, blinded, pre-clinical trial using Yorkshire pigs weighing 7-10 kg. Twelve pigs were subjected to Sham injury (n = 5) by skin incision or TBI (n = 7) by controlled cortical impact. Blood samples were collected before the injury, then at approximately 5-day intervals until 30 days. ⋯ Porcine model of TBI replicates the acute increase in plasma biomarkers seen in clinical TBI. Further, long term white matter injury is confirmed in the areas such as the splenium and corona radiata. However, future study stratifying severe and mild TBI, as well as comparison with other subtypes of TBI such as diffuse axonal injury, may be warranted.
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In this report, we discuss the controversy of the diverse traumatic brain injury (TBI) categorization and taxonomy and the need to develop a new multidimensional and multidisciplinary categorization system that can be an aid in improved diagnostic and prognostic outcomes. Of interest, the heterogeneity of TBI marks the major obstacle to develop effective therapeutic interventions. Currently, the Glasgow Coma Scale has been utilized to guide in the prognosis and clinical management of TBI; it does not encompass the pathophysiological mechanisms leading to neurological deficits that can impede therapeutic interventions and consequently the failure of clinical trials. An unfortunate gap exists between advances in TBI research and existing U.S. Department of Defense (DoD) definitions, categorization, and management. Part I illustrates a unique posterior-focused TBI case report that does not fit any existing TBI definitions. Part II summarizes new animal-based TBI research that supports the case report as a legitimate TBI category. Part III critiques existing TBI criteria and their controversies. ⋯ This dilemma requires a multidisciplinary, science/medicine-led panel to actively reassess TBI criteria that take into consideration the latest research including non-cerebral hemispheric injuries. We recommend that DoD/Veterans Affairs establish a commission to regularly review the academic-related scientific evidence and incorporate these findings in a timely fashion into their operational definitions. This would guarantee that recognition, diagnosis, and follow-up of all TBIs are properly understood, managed, and documented.
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Little is known about the out-of-hospital blood pressure ranges associated with optimal outcomes in traumatic brain injuries (TBI). Our objective was to evaluate the associations between out-of-hospital systolic blood pressure (SBP) and multiple hospital outcomes without assuming any predefined thresholds for hypotension, normotension, or hypertension. ⋯ Optimal adjusted mortality was associated with a surprisingly high SBP range (130 to 180 mmHg). Below this level, there was no point or range of inflection that would indicate a physiologically meaningful threshold for defining hypotension. Nonmortality outcomes showed very similar patterns. These findings highlight how sensitive the injured brain is to compromised perfusion at SBP levels that, heretofore, have been considered adequate or even normal. While the study design does did not allow us to conclude that the currently recommended treatment threshold (<90 mmHg) should be increased, the findings imply that the definition of hypotension in the setting of TBI is too low. Randomized trials evaluating treatment levels significantly higher than 90 mmHg are needed.
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Journal of neurotrauma · Jul 2022
Glucocorticoid Receptor Overexpression in the Dorsal Hippocampus Attenuates Spatial Learning and Synaptic Plasticity Deficits Following Pediatric Traumatic Brain Injury.
Traumatic brain injury (TBI) in children <4 years of age leads to long-term deficits in cognitive and learning abilities that can persist or even worsen as these children age into adolescence. In this study, the role of glucocorticoid receptor (GR) function in the dorsal hippocampus (DH) in hippocampal-dependent cognitive function and synaptic plasticity were assessed following injury to the 11-day-old rat. Brain injury produced significant impairments in spatial learning and memory in the Morris water maze in male and female rats at 1-month post-injury (adolescence), which was accompanied by impairments in induction and maintenance of long-term potentiation (LTP) in the CA1 region of the DH. ⋯ Lentiviral transfection of the human GR (hGR) in the DH improved spatial learning and memory in the Morris water maze and attenuated LTP deficits following TBI. GR overexpression in the DH was also associated with a significant increase in the mRNA expression levels of sgk1, and the glutamate receptor subunits GluA1 and GluA2 within the hippocampus. Overall, these findings support an important role for dorsal hippocampal GR function in learning and memory deficits following pediatric TBI and suggest that these effects may be related to the regulation of glutamate receptor subunit expression in the DH.