Oligodendrocytes produce myelin, which provides insulation to axons and speeds up neuronal transmission. In ischaemic conditions, myelin is damaged, resulting in mental and physical disabilities. Recent evidence suggests that oligodendrocyte damage during ischaemia can be mediated by Transient Receptor Potential Ankyrin-1 (TRPA1), whose activation raises intracellular Ca2+ concentrations and damages compact myelin. Here, we show that TRPA1 is constitutively active in oligodendrocytes and the optic nerve, as the specific TRPA1 antagonist, A-967079, decreases basal oligodendrocyte Ca2+ concentrations and increases the size of the compound action potential (CAP). Conversely, TRPA1 agonists reduce the size of the optic nerve CAP in an A-967079-sensitive manner. These results indicate that glial TRPA1 regulates neuronal excitability in the white matter under physiological as well as pathological conditions. Importantly, we find that inhibition of TRPA1 prevents loss of CAPs during oxygen and glucose deprivation (OGD) and improves the recovery. TRPA1 block was effective when applied before, during, or after OGD, indicating that the TRPA1-mediated damage is occurring during both ischaemia and recovery, but importantly, that therapeutic intervention is possible after the ischaemic insult. These results indicate that TRPA1 has an important role in the brain, and that its block may be effective in treating many white matter diseases.

Aims People experiencing homelessness (PEH) have been identified as being increasingly susceptible to Coronavirus disease (COVID-19), with policies enacted to test, isolate, increase hygiene practices and prioritise vaccines among this population. Here, we conduct a scoping review of the current evidence-base pertaining to the prevalence and presentation of COVID-19 in PEH, COVID-vaccine hesitancy rates and government interventions enacted within the first year of the pandemic for PEH. Materials and methods A systematic search was conducted on Pubmed, Cochrane, Embase and MedRxiv databases for studies reporting primary data on COVID-19 prevalence and clinical characteristics in PEH, vaccine uptake for PEH and policies enacted targeting PEH. Study qualities were assessed with The National Heart, Lung and Blood Institute’s set of Study Quality. Results Eighty-three studies were included in our final analysis. The overall prevalence of symptomatic COVID-19 infection in PEH is estimated at 35%. The most common symptoms found were cough and shortness of breath, followed by fever. Concerns regarding vaccine hesitancy amongst PEH related to thoroughness of COVID-19 vaccine clinical trials, side effects and mistrust of the government. The main strategies implemented by governments were mass testing, adaption of healthcare service provision, provision of alternative housing, encouraging personal hygiene (hand sanitation and mask wearing), and inter-organisational communication. Discussion In our meta-analysis, 35% of PEH with a COVID-19 infection presented symptomatically; the low prevalence of symptomatic COVID-19 infection suggests widespread testing following outbreaks would be beneficial for this group of individuals. Temporary recuperation units and measures for housing stability in the pandemic, namely provision of alternative housing and stopping evictions, were found to be highly effective. High rates of vaccine hesitancy means that education and encouragement towards vaccination would be beneficial for this vulnerable population, where comorbidities are common. Finally increased focus in research should be placed on the mental health burden of COVID-19 and the pandemic on PEH moving forwards.

Oligodendrocytes produce myelin which provides insulation to axons and speeds up neuronal transmission. In ischaemic conditions myelin is damaged, resulting to mental and physical disabilities. Therefore, it is important to understand how the functionality of oligodendrocytes and myelin is affected by ischaemia. Recent evidence suggests that oligodendrocyte damage during ischaemia is mediated by TRPA1, whose activation raises intracellular Ca2+ concentrations and damages compact myelin. Here, we show that TRPA1 is tonically active in oligodendrocytes and the optic nerve, as the specific TRPA1 antagonist, A-967079, decreases basal oligodendrocyte Ca2+ concentrations and increases the size of the compound action potential. Conversely, TRPA1 agonists reduce the size of the optic nerve compound action potential, and this effect is significantly reduced by the TRPA1 antagonist. These results indicate that glial TRPA1 regulates neuronal excitability in the white matter under physiological as well as pathological conditions. Importantly, we find that inhibition of TRPA1 prevents loss of compound action potentials during oxygen and glucose deprivation (OGD) and improves the recovery. TRPA1 block was effective when applied before, during or after OGD, indicating that the damage is occurring during ischaemia, but that therapeutic intervention is possible after the ischaemic insult. These results indicate that TRPA1 has an important role in the brain, and that its block may be effective in treating oligodendrocyte loss and damage in many white matter diseases.

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