Journal of neurotrauma
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Journal of neurotrauma · Jul 2018
Enhancement of Brain d-Serine Mediates Recovery of Cognitive Function after Traumatic Brain Injury.
Cognitive deficits, especially memory loss, are common and devastating neuropsychiatric sequelae of traumatic brain injury (TBI). The deficits may persist for years and may be accompanied by increased risk of developing early- onset dementia. Past attempts to reverse the neuropathological effects of brain injury with glutamate-N-methyl-d-aspartate (NMDA) antagonists failed to show any benefits or worsened the outcome, suggesting that activation, rather than blockage, of the NMDA receptor (NMDAR) may be useful in the subacute period after TBI and stroke. ⋯ Moreover, the compound proved to be neuroprotective, as the hippocampal volume and the number of neurons in hippocampal regions increased. Treatment with CBIO boosted the NR1 and phospho- NR1 subunits of the NMDAR and affected the CREB, phospho-CREB, and brain-derived neurotropic factor (BDNF) pathways. These findings render CBIO a promising, novel treatment for cognitive impairment following TBI.
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Journal of neurotrauma · Jul 2018
Observational StudyFeasibility of Telemetric Intracranial Pressure Monitoring in the Neuro Intensive Care Unit.
Intracranial pressure (ICP) monitoring is crucial in the management of acute neurosurgical conditions such as traumatic brain injury (TBI). However, pathological ICP may persist beyond the admission to the neuro intensive care unit (NICU). We investigated the feasibility of telemetric ICP monitoring in the NICU, as this technology provides the possibility of long-term ICP assessment beyond NICU discharge. ⋯ Therefore, telemetric ICP monitoring in an acute neurosurgical setting is feasible. Signal quality and stability are sufficient for clinical decision making based on mean ICP. The low sampling frequency (5 Hz) does not permit analysis of intracranial pulse wave morphology, but resolution is sufficient for calculation of derived indices such as the pressure reactivity index (PRx).
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Journal of neurotrauma · Jul 2018
Transient Receptor Potential Melastatin 4 Induces Astrocyte Swelling But Not Death after Diffuse Traumatic Brain Injury.
Traumatic brain injury (TBI) is a prevalent disease with significant costs. Although progress has been made in understanding the complex pathobiology of focal lesions associated with TBI, questions remain regarding the diffuse responses to injury. Expression of the transient receptor potential melastatin 4 (Trpm4) channel is linked to cytotoxic edema during hemorrhagic contusion expansion. ⋯ Correlative H&E assessments demonstrated little evidence of hippocampal damage, suggesting that Trpm4 expression by astrocytes does not precipitate cell death following diffuse TBI. Additionally, ultrastructural assessments showed Trpm4+ astrocytes exhibited twice the soma size compared with Trpm4- astrocytes, indicating that astrocyte swelling is associated with Trpm4 expression. This study provides a foundation for future investigations into the role of Trpm4 in astrocyte swelling and edema following diffuse TBI.
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The aims of this study were to document the frequency of major and minor depressive episodes in the first year after traumatic brain injury (TBI), taking into account TBI severity and pre-morbid history of major depression, and to describe trajectories of depressive episodes. Participants were 227 adults who were hospitalized post-TBI (76% male; mean age = 41 years; 50% mild, 33% moderate, and 17% severe TBI). Major and minor depressive episodes were assessed with the Mini International Neuropsychiatric Interview at three time points (4, 8, and 12 months after TBI). ⋯ Results also revealed a wide variety of trajectories of depressive episodes across assessments. Of note, 52% of major depression cases still fulfilled diagnostic criteria 4 months later, whereas 38% of minor depression cases deteriorated to major depression at the following assessment. These findings suggest that depression is highly prevalent after TBI, and monitoring of patients with subthreshold depressive symptoms is warranted in order to prevent the development of full-blown major depressive episodes.
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Journal of neurotrauma · Jul 2018
Dimethyl Fumarate Attenuates Neuroinflammation and Neurobehavioral Deficits Induced by Experimental Traumatic Brain Injury.
Traumatic brain injury (TBI) is a serious neuropathology that causes secondary injury mechanisms, including dynamic interplay between ischemic, inflammatory, and cytotoxic processes. Fumaric acid esters (FAEs) showed beneficial effects in pre-clinical models of neuroinflammation and toxic oxidative stress, so the aim of the present work was to evaluate the potential beneficial effects of dimethyl fumarate (DMF), the most pharmacologically effective molecules among the FAEs, in a mouse model of TBI induced by controlled cortical impact (CCI). Mice were administered DMF orally at the doses of 1, 10, and 30 mg/kg 1 h and 4 h after CCI. ⋯ Further, DMF treatment up-regulated antioxidant Kelch-like ECH-associated protein 1/nuclear factor erythroid 2-related factor pathway, inducing activation of manganese superoxide dismutase and heme-oxygenase-1 and reducing 4-hydroxy-2-nonenal staining. Also, regulating the NF-κB pathway, DMF treatment decreased the severity of inflammation through a modulation of neuronal nitric oxide synthase, interleukin 1, tumor necrosis factor, cyclooxygenase 2, and myeloperoxidase activity, reducing ionized calcium-binding adapter molecule 1 and glial fibrillary acidic protein expression. Our results support the thesis that DMF may be an effective neuroprotectant after brain trauma and warrants further study.