Should We Lose Sleep Over Sleep Disturbances After Sports-Related Concussion? A Scoping Review of the Literature.

OBJECTIVE: A single, severe traumatic brain injury can result in chronic sleep disturbances that can persist several years after the incident. In contrast, it is unclear whether there are sleep disturbances after a sports-related concussion (SRC). Considering growing evidence of links between sleep disturbance and neurodegeneration, this review examined the potential links between diagnosed SRCs and sleep disturbances to provide guidance for future studies. METHODS: The scoping review undertook a systematic search of key online databases (Scopus, MEDLINE, SportDiscus, and Web of Science) using predetermined search terms for any articles that examined sleep after concussion. A screening criterion using agreed inclusion and exclusion criteria was utilized to ensure inclusion of relevant articles. DESIGN: This scoping review is guided by the PRSIMA Scoping Review report. RESULTS: Ten studies met the inclusion criteria, reporting on 896 adults who had experienced an SRC. Comparison with 1327 non-SRC adults occurred in 8 studies. Nine studies subjectively examined sleep, of which all but one study reported sleep disturbances after an SRC. Three studies objectively measured sleep, with 2 studies indicating large coefficients of variation of sleep duration, suggesting a range of sleep responses after an SRC. The only study to examine overnight polysomnography showed no differences in sleep metrics between those with and without an SRC. No studies examined interventions to improve sleep outcomes in people with concussion. CONCLUSIONS: This scoping review indicates preliminary evidence of sleep disturbances following an SRC. The heterogeneity of methodology used in the included studies makes consensus on the results difficult. Given the mediating role of sleep in neurodegenerative disorders, further research is needed to identify physiological correlates and pathological mechanisms of sleep disturbances in SRC-related neurodegeneration and whether interventions for sleep problems improve recovery from concussion and reduce the risk of SRC-related neurodegeneration.

Evaluating spatiotemporal microstructural alterations following diffuse traumatic brain injury.

BACKGROUND: Diffuse traumatic brain injury (TBI) is known to lead to microstructural changes within both white and grey matter detected in vivo with diffusion tensor imaging (DTI). Numerous studies have shown alterations in fractional anisotropy (FA) and mean diffusivity (MD) within prominent white matter tracts, but few have linked these to changes within the grey matter with confirmation via histological assessment. This is especially important as alterations in the grey matter may be predictive of long-term functional deficits. METHODS: A total of 33 male Sprague Dawley rats underwent severe closed-head TBI. Eight animals underwent tensor-based morphometry (TBM) and DTI at baseline (pre-TBI), 24 hours (24 h), 7, 14, and 30 days post-TBI. Immunohistochemical analysis for the detection of ionised calcium-binding adaptor molecule 1 (IBA1) to assess microglia number and percentage of activated cells, ß-amyloid precursor protein (APP) as a marker of axonal injury, and myelin basic protein (MBP) to investigate myelination was performed at each time-point. RESULTS: DTI showed significant alterations in FA and RD in numerous white matter tracts including the corpus callosum, internal and external capsule, and optic tract and in the grey-matter in the cortex, thalamus, and hippocampus, with the most significant effects observed at 14 D post-TBI. TBM confirmed volumetric changes within the hippocampus and thalamus. Changes in DTI were in line with significant axonal injury noted at 24 h post-injury via immunohistochemical analysis of APP, with widespread microglial activation seen within prominent white matter tracts and the grey matter, which persisted to 30 D within the hippocampus and thalamus. Microstructural alterations in MBP+ve fibres were also noted within the hippocampus and thalamus, as well as the cortex. CONCLUSION: This study confirms the widespread effects of diffuse TBI on white matter tracts which could be detected via DTI and extends these findings to key grey matter regions, with a comprehensive investigation of the whole brain. In particular, the hippocampus and thalamus appear to be vulnerable to ongoing pathology post-TBI, with DTI able to detect these alterations supporting the clinical utility in evaluating these regions post-TBI.

The amyloid precursor protein derivative, APP96-110, is efficacious following intravenous administration after traumatic brain injury.

Following traumatic brain injury (TBI) neurological damage is ongoing through a complex cascade of primary and secondary injury events in the ensuing minutes, days and weeks. The delayed nature of secondary injury provides a valuable window of opportunity to limit the consequences with a timely treatment. Recently, the amyloid precursor protein (APP) and its derivative APP96-110 have shown encouraging neuroprotective activity following TBI following an intracerebroventricular administration. Nevertheless, its broader clinical utility would be enhanced by an intravenous (IV) administration. This study assessed the efficacy of IV APP96-110, where a dose-response for a single dose of 0.005mg/kg- 0.5mg/kg APP96-110 at either 30 minutes or 5 hours following moderate-severe diffuse impact-acceleration injury was performed. Male Sprague-Dawley rats were assessed daily for 3 or 7 days on the rotarod to examine motor outcome, with a separate cohort of animals utilised for immunohistochemistry analysis 3 days post-TBI to assess axonal injury and neuroinflammation. Animals treated with 0.05mg/kg or 0.5mg/kg APP96-110 after 30 minutes demonstrated significant improvements in motor outcome. This was accompanied by a reduction in axonal injury and neuroinflammation in the corpus callosum at 3 days post-TBI, whereas 0.005mg/kg had no effect. In contrast, treatment with 0.005m/kg or 0.5mg/kg APP96-110 at 5 hours post-TBI demonstrated significant improvements in motor outcome over 3 days, which was accompanied by a reduction in axonal injury in the corpus callosum. This demonstrates that APP96-110 remains efficacious for up to 5 hours post-TBI when administered IV, and supports its development as a novel therapeutic compound following TBI.