Journal of neurotrauma
-
Journal of neurotrauma · Mar 2018
Delayed Hypoxemia Following Traumatic Brain Injury Exacerbates Long-Term Behavioral Deficits.
Hypoxemia during initial stabilization of patients with severe traumatic brain injury (TBI) has been associated with poorer outcomes. However, the effects of delayed hypoxemia occurring during intensive care post-TBI on outcome is unclear. Pre-clinical models of TBI have rarely shown cognitive or behavioral deficits beyond 6 weeks post-injury and commonly have not included modeling of secondary insults. ⋯ CCI + H had larger lesion volumes compared to CCI alone (14.0% vs. 9.9%; p < 0.003). Glial fibrillary acidic protein IHC at 6 months post-injury demonstrated increased astrogliosis in the ipsilateral white matter of CCI + H compared to CCI alone. To summarize, this clinically relevant model of delayed hypoxia post-TBI resulted in long-term behavioral deficits and evidence of exacerbated structural injury.
-
Journal of neurotrauma · Mar 2018
A Novel Method for Quantifying Human In Situ Whole Brain Deformation under Rotational Loading Using Sonomicrometry.
Traumatic brain injuries (TBI) are one of the least understood injuries to the body. Finite element (FE) models of the brain have been crucial for understanding concussion and for developing injury mitigation systems; however, the experimental brain deformation data currently used to validate these models are limited. The objective of this study was to develop a methodology for the investigation of in situ three-dimensional brain deformation during pure rotational loading of the head, using sonomicrometry. ⋯ All tests were completed within 56 h postmortem. Overall, the combined experimental and sonomicrometry methods were demonstrated to reliably and repeatedly capture three-dimensional dynamic deformation of an intact human brain. These methods provide a framework for using sonomicrometry to acquire multidimensional experimental data required for FE model development and validation, and will lend insight into the deformations sustained by the brain during impact.
-
Journal of neurotrauma · Mar 2018
Intranasally Delivered Wnt3a Improves Functional Recovery after Traumatic Brain Injury by Modulating Autophagic, Apoptotic and Regenerative Pathways in the Mouse Brain.
Traumatic brain injury (TBI) is a prevalent disorder, but no effective therapies currently exist. An underlying pathophysiology of TBI includes the pathological elevation of autophagy. β-Catenin, a downstream mediator of the canonical Wnt pathway, is a repressor of autophagy. The Wnt/β-catenin pathway plays a crucial role in cell proliferation and neuronal plasticity/repair in the adult brain. ⋯ This chronic Wnt3a therapy augmented neurogenesis (0.52 ± 0.09 and 1.25 ± 0.13 BrdU+/NeuN+ co-labeled cells in TBI+Saline mice and TBI+Wnt3a mice, respectively; p < 0.01, n = 6/group) and angiogenesis (0.26 ± 0.07 and 0.74 ± 0.13 BrdU+/GLUT1+ co-labeled cells in TBI+Saline and TBI+Wnt3a mice, respectively; p = 0.014, n = 6/group). The treatment improved performance in the rotarod test and adhesive removal test. Targeting the Wnt pathway implements a unique combination of protective and regenerative approaches after TBI.
-
Journal of neurotrauma · Feb 2018
Correlation of Concussion Symptom Profile with Head Impact Biomechanics: A Case for Individual-Specific Injury Tolerance.
Concussion is a brain injury induced by biomechanical forces that is broadly defined as a complex pathophysiological process affecting the brain. The intricate link between biomechanical input and concussion injury response is poorly understood. We aimed to test the hypothesis that greater biomechanical forces would result in the presentation of more concussion-related symptoms that would take longer to resolve. ⋯ While concussive impacts did not stand out relative to impacts that did not result in injury, concussive impacts were among the most severe for each individual player. This suggests tolerance to head acceleration might be individual-specific, meaning similar biomechanical inputs can produce different injury presentations between individuals. Future investigations should consider individual-specific analyses of tolerance to head acceleration and injury response.
-
Journal of neurotrauma · Feb 2018
Sex Differences in Thermal, Stress, and Inflammatory Responses to Minocycline Administration in Rats with Traumatic Brain Injury.
Persistent inflammation, mediated in part by increases in cytokines, is a hallmark of traumatlc brain injury (TBI). Minocycline has been shown to inhibit post-TBI neuroinflammation in male rats and mice, but has not been tested in females. Here, we studied sex differences in thermal, stress, and inflammatory responses to TBI and minocycline. ⋯ In females, but not males, hippocampal IL-6 content increased post-CCI compared with sham-injured controls, whereas IL-1β content was augmented by minocycline. Hippocampal TNF-α was unaffected by CCI and minocycline. These results demonstrate sex differences in immediate thermal and long-lasting stress and cytokine responses to CCI, and only short-term protective effects of minocycline on hyperthermia.