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Highlights • SARS-CoV-2 may infect immature olfactory sense neurons. • Olfactory sense neurons and the blood brain barrier may allow infection of the brain. • The distribution of ACE2, or novel cellular entry proteins, will limit viral spread. • Animal models may be of limited value in studying COVID-19 and the brain. • Post-mortem histological approaches may be insufficient to study COVID-19 in the CNS., Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in Wuhan, China in December 2019. On February 11, the World Health Organization (WHO) announced the name for the new illness caused by SARS-CoV-2: COVID-19. By March 11, the outbreak of COVID-19 was declared a pandemic by the WHO. This virus has extensively altered daily life for many across the globe, while claiming hundreds of thousands of lives. While fundamentally a respiratory illness, many infected individuals experience symptoms that involve the central nervous system (CNS). It is likely that many of these symptoms are the result of the virus residing outside of the CNS. However, the current evidence does indicate that the SARS-CoV-2 virus can use olfactory neurons to travel from the periphery into the CNS, and that the virus may also enter the brain through the blood-brain barrier (BBB). We discuss how the virus may use established infection mechanisms (ACE2, TMPRSS2, and Cathepsin L), as well mechanisms still under consideration (NRP1 and BASIGIN) to infect and spread throughout the CNS. Confirming the impact of the virus on the CNS will be crucial in dealing with the long-term consequences of the epidemic.

Research indicates that relieving the cognitive and negative symptoms of schizophrenia is crucial for improving patient quality of life. However effective pharmacotherapies for cognitive and negative symptoms do not currently exist. A review of ongoing Phase III clinical trials indicates that, despite numerous compounds being investigated for cognition in schizophrenia, few are actually novel and most are not backed by empirically driven preclinical research efforts. Based on these trials, and a general disinvestment in development of novel therapies for schizophrenia, the likelihood of a major advancement in treating cognitive differences in schizophrenia does not look promising. Possible ways in which the remaining resources for development of novel treatment for schizophrenia can best be leveraged are discussed.

Many studies have shown that prolonged or repeated use of general anesthesia early in life can cause an increase in neurodegeneration and lasting changes in behavior. While short periods of general anesthesia appear to be safe, there is a concern about the neurotoxic potential of prolonged or repeated general anesthesia in young children. Unfortunately, the use of general anesthesia in children cannot be avoided. It would be a great benefit to develop a strategy to reduce or reverse anesthesia mitigated neurotoxicity. The mechanisms behind anesthesia related neurotoxicity are unknown, but evidence suggests that mitochondrial dysfunction and abnormal energy utilization are involved. Recent research suggests that a class of compounds known as carnitines may be effective at preventing anesthesia related neurotoxicity by influencing fatty acid metabolism in the mitochondria. However, it is unknown if carnitines can provide protection against changes in behavior associated with early life exposure to anesthesia. Accordingly, we evaluated the neuroprotective potential of acetyl- l -carnitine in 7-day old rats. Rat pups were exposed to 6 h of general anesthesia with sevoflurane or a control condition, with and without acetyl- l -carnitine. The oxygenation level of animals was continuously monitored during sevoflurane exposure, and any animal showing signs of hypoxia was removed from the study. Animals exposed to sevoflurane showed clear signs of neurodegeneration 2 h after sevoflurane exposure. The hippocampus, cortex, thalamus, and caudate putamen all had elevated levels of Fluoro-Jade C staining. Despite the elevated levels of Fluoro-Jade C, few behavioral changes were observed in an independent cohort of animals treated with sevoflurane. Furthermore, acetyl- l -carnitine had little impact on levels of Fluoro-Jade C staining in animals treated with sevoflurane. These data suggest that acetyl- l -carnitine may offer little protection again anesthesia related neurotoxicity in fully oxygenated animals.