Journal of neurotrauma
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Journal of neurotrauma · Jun 2019
Continuous Thermal Diffusion-Based Cerebral Blood Flow Monitoring in Adult Traumatic Brain Injury: A Scoping Systematic Review.
Thermal diffusion flowmetry (TDF) is an appealing candidate for monitoring of cerebral blood flow (CBF) in neurocritical-care patients as it provides absolute measurements with a high temporal resolution, potentially allowing for bedside intervention that could mitigate secondary injury. We performed a systematic review of TDF-regional(r)CBF measurements and their association with (1) patient functional outcome, (2) other neurophysiological parameters, and (3) imaging-based tissue outcomes. We searched MEDLINE, EMBASE, SCOPUS, BIOSIS, GlobalHealth, and the Cochrane Databases from inception to October 2018 and relevant conference proceedings published over the last 5 years. ⋯ In conclusion, despite being based on a relatively weak body of evidence, the available literature suggests a link between consistently abnormal TDF-rCBF values, intracranial hypertension, and poor functional outcome. TDF-rCBF also appears to correlate well with regional measurements of brain tissue oxygenation. Currently, such monitoring should be considered experimental, requiring much further evaluation prior to widespread adoption.
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Journal of neurotrauma · Jun 2019
The Role of CB2 Receptor in the Recovery of Mice after Traumatic Brain Injury.
Cannabis is one of the most widely used plant drugs in the world today. In spite of the large number of scientific reports on medical marijuana, there still exists much controversy surrounding its use and the potential for abuse due to the undesirable psychotropic effects. However, recent developments in medicinal chemistry of novel non-psychoactive synthetic cannabinoids have indicated that it is possible to separate some of the therapeutic effects from the psychoactivity. ⋯ HU-910 and HU-914 were selected in the present study to evaluate their potential effect in the pathophysiology of traumatic brain injury (TBI). In mice and rats subjected to closed-head injury and treated with these novel compounds, we showed enhanced neurobehavioral recovery, inhibition of tumor necrosis factor α production, increased synaptogenesis, and partial recovery of the cortical spinal tract. We propose these CB2 agonists as potential drugs for development of novel therapeutic modality to TBI.
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Journal of neurotrauma · Jun 2019
ReviewHow to Translate Time; the Temporal Aspects of Rodent and Human Pathobiological Processes in Traumatic Brain Injury.
Traumatic brain injury (TBI) triggers multiple pathobiological responses with differing onsets, magnitudes, and durations. Identifying the therapeutic window of individual pathologies is critical for successful pharmacological treatment. Dozens of experimental pharmacotherapies have been successfully tested in rodent models, yet all of them (to date) have failed in clinical trials. ⋯ Limitations toward determining conversion rates for various pathobiological processes include the use of differing outcome measures in experimental and clinical TBI studies and the rarity of longitudinal studies. In order to better translate time and close the translational gap, we suggest 1) using clinically relevant outcome measures, primarily in vivo imaging and blood-based proteomics, in experimental TBI studies and 2) collecting data at multiple post-injury time points with a frequency exceeding the expected information content by two or three times. Combined with a big data approach, we believe these measures will facilitate the translation of promising experimental treatments into clinical use.
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Journal of neurotrauma · Jun 2019
Multicenter Study Observational StudyThe Temporal Relationship of Mental Health Problems and Functional Limitations following mTBI: A TRACK-TBI and TED Study.
Mental health problems, such as depression and anxiety, are often associated with functional limitations after traumatic brain injury (TBI), prompting researchers to explore which of these TBI-related sequelae tends to precede the other. Past studies among patients with injuries ranging in severity have predominantly reported that functional impairments predict subsequent psychological concerns, rather than the other way around; however, it remains unclear whether this directionality holds for individuals with mild TBI (mTBI). The present study utilized a cross-lagged panel design within a structural equation modeling analytical framework to explore the longitudinal relationships of symptoms of depression and anxiety to functional status among 717 adult mTBI patients, with assessments occurring at 2 weeks and 3 months post-injury. ⋯ This pattern was particularly pronounced among patients with normal head computed tomography (CT) results; however, results were less clear cut among those subjects whose injuries were accompanied by intracranial abnormalities detected on CT imaging, suggesting the possibility of a more reciprocal relationship in the case of CT-positive mTBI. These results may serve to partially explain the incidence of persistent functional limitations observed among subsets of mTBI patients in past studies. Findings likewise highlight the importance of assessment and treatment for mental health problems after mTBI as an important factor to promote psychological well-being and functional recovery.
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Journal of neurotrauma · Jun 2019
Downstream TRPM4 Polymorphisms are associated with Intracranial Hypertension and Statistically Interact with ABCC8 Polymorphisms in a Prospective Cohort of Severe Traumatic Brain Injury.
Sulfonylurea-receptor-1(SUR1) and its associated transient-receptor-potential cation channel subfamily-M (TRPM4) channel are key contributors to cerebral edema and intracranial hypertension in traumatic brain injury (TBI) and other neurological disorders. Channel inhibition by glyburide is clinically promising. ABCC8 (encoding SUR1) single-nucleotide polymorphisms (SNPs) are reported as predictors of raised intracranial pressure (ICP). ⋯ Both clustered downstream, spanning a region encoding the channel pore and interacting with SUR1. If validated, this may guide risk stratification and eventually inform treatment-responder classification for SUR1-TRPM4 inhibition in TBI. Larger studies are warranted.