A suitable model to investigate acute neurological consequences of coronavirus infection.

OBJECTIVE AND DESIGN: The present study aimed to investigate the neurochemical and behavioral effects of the acute consequences after coronavirus infection through a murine model. MATERIAL: Wild-type C57BL/6 mice were infected intranasally (i.n) with the murine coronavirus 3 (MHV-3). METHODS: Mice underwent behavioral tests. Euthanasia was performed on the fifth day after infection (5 dpi), and the brain tissue was subjected to plaque assays for viral titration, ELISA, histopathological, immunohistochemical and synaptosome analysis. RESULTS: Increased viral titers and mild histological changes, including signs of neuronal degeneration, were observed in the cerebral cortex of infected mice. Importantly, MHV-3 infection induced an increase in cortical levels of glutamate and calcium, which is indicative of excitotoxicity, as well as increased levels of pro-inflammatory cytokines (IL-6, IFN-γ) and reduced levels of neuroprotective mediators (BDNF and CX3CL1) in the mice brain. Finally, behavioral analysis showed impaired motor, anhedonia-like and anxiety-like behaviors in animals infected with MHV-3. CONCLUSIONS: In conclusion, the data presented emulate many aspects of the acute neurological outcomes seen in patients with COVID-19. Therefore, this model may provide a preclinical platform to study acute neurological sequelae induced by coronavirus infection and test possible therapies.

SARS-CoV-2 Infection and Possible Neonatal Neurological Outcomes: A Literature Review.

The virus responsible for COVID-19 is designated "severe acute respiratory syndrome coronavirus 2" (SARS-CoV-2), a highly transmissible and pathogenic coronavirus. Although people of all ages are susceptible to SARS-CoV-2 infection, clinical manifestations may vary with age. The response of neonates to SARS-CoV-2 infection or exposure differs from that of children and adults. Encephalitis due to viral infections in the central nervous system (CNS) and childhood multisystem inflammatory syndrome (MIS-C) are some of the possible neonatal consequences of SARS-CoV-2 infection. This review aims to verify possible neonatal neurological outcomes after SARS-CoV-2 infection. Overall, the cellular and molecular basis of the neurological sequelae of SARS-CoV-2 in neonates remains unclear, and attempts to elucidate the pathophysiology of COVID-19 involve a comparison with the mechanism of other viral diseases. There are a considerable number of case reports in the literature exploring neurological outcomes in the neonatal period. In this review, we present possible effects of SARS-CoV-2 in neonates, emphasizing the importance of monitoring this group. The mechanisms of SARS-CoV-2 entry into the CNS have not yet been fully elucidated, and the potential severity of SARS-CoV-2 infection in neonates, as well as the possible short- and long-term neurological sequelae, remain unclear.

The impact of perioperative stroke and delirium on outcomes after surgical aortic valve replacement.

OBJECTIVE: The effects of stroke and delirium on postdischarge cognition and patient-centered health outcomes after surgical aortic valve replacement (SAVR) are not well characterized. Here, we assess the impact of postoperative stroke and delirium on these health outcomes in SAVR patients at 90 days. METHODS: Patients (N = 383) undergoing SAVR (41% received concomitant coronary artery bypass graft) enrolled in a randomized trial of embolic protection devices underwent serial neurologic and delirium evaluations at postoperative days 1, 3, and 7 and magnetic resonance imaging at day 7. Outcomes included 90-day functional status, neurocognitive decline from presurgical baseline, and quality of life. RESULTS: By postoperative day 7, 25 (6.6%) patients experienced clinical stroke and 103 (28.5%) manifested delirium. During index hospitalization, time to discharge was longer in patients experiencing stroke (hazard ratio, 0.62; 95% confidence interval [CI], 0.42-0.94; P = .02) and patients experiencing delirium (hazard ratio, 0.68; 95% CI, 0.54-0.86; P = .001). At day 90, patients experiencing stroke were more likely to have a modified Rankin score >2 (odds ratio [OR], 5.9; 95% CI, 1.7-20.1; P = .01), depression (OR, 5.3; 95% CI, 1.6-17.3; P = .006), a lower 12-Item Short Form Survey physical health score (adjusted mean difference -3.3 ± 1.9; P = .08), and neurocognitive decline (OR, 7.8; 95% CI, 2.3-26.4; P = .001). Delirium was associated with depression (OR, 2.2; 95% CI, 0.9-5.3; P = .08), lower 12-Item Short Form Survey physical health (adjusted mean difference -2.3 ± 1.1; P = .03), and neurocognitive decline (OR, 2.2; 95% CI, 1.2-4.0; P = .01). CONCLUSIONS: Stroke and delirium occur more frequently after SAVR than is commonly recognized, and these events are associated with disability, depression, cognitive decline, and poorer quality of life at 90 days postoperatively. These findings support the need for new interventions to reduce these events and improve patient-centered outcomes.

Congenital Zika Infection and the Risk of Neurodevelopmental, Neurological, and Urinary Track Disorders in Early Childhood. A Systematic Review.

It was late 2015 when Northeast Brazil noticed a worrying increase in neonates born with microcephaly and other congenital malformations. These abnormalities, characterized by an abnormally small head and often neurological impairment and later termed Congenital Zika Syndrome, describe the severity of neurodevelopmental and nephrological outcomes in early childhood, and the implication of microcephaly at birth. The purpose of the study was to describe the neurodevelopmental outcomes in children exposed to Zika virus during fetal life, with and without microcephaly at birth. The systematic review included research studies about the neurodevelopmental outcomes with and without microcephaly, as well as nephrological outcomes in early childhood. We searched PubMed, Crossref, PsycINFO, Scopus, and Google Scholar publications and selected 19 research articles published from 2018 to 2021. Most studies have linked the severity of microcephaly in childbirth to the neurodevelopmental and urinary outcomes in early childhood. However, most children without microcephaly at birth develop typically, while others may be at risk for language impairment.

Potential Biomarkers with Plasma Cortisol, Brain-derived Neurotrophic Factor and Nitrites in Patients with Acute Ischemic Stroke.

BACKGROUND: Acute Ischemic Stroke (AIS) represents an economic challenge for health systems all over the globe. Changes of neuroactive steroids have been found in different neurological diseases. We have previously demonstrated that old patients with AIS show changes of plasma cortisol and estradiol concentrations, in that increased steroid levels are associated with a deterioration of neurological status and a worse cognitive decline. OBJECTIVE: The present study assessed in patients with AIS if changes of behavior, Brain-Derived Neurotrophic Factor (BDNF) and Nitrites (NO-2) bear a relationship with the degree of hypercortisolism. METHODS: We recruited patients hospitalized within the first 24 hours of AIS. Subjects were divided into two groups, each one composed of 40 control subjects and 40 AIS patients, including men and women. The neurological condition was assessed using the National Institute of Health Stroke Scale (NIHSS) and the cognitive status with the Montreal Cognitive Assessment (MoCA). The emotional status was evaluated using the Montgomery-Asberg Depression Rating Scale (MADRS), whereas the Modified Rankin Scale (MRS) was used to determine the functional condition. BDNF and NO-2 plasma levels were measured by ELISA and the Griess reaction method, respectively. RESULTS: We found that in AIS patients, increased plasma cortisol was negatively correlated with plasma BDNF and NO-2 levels, neurological condition, cognition, functional responses and emotional status, suggesting a relationship between the declines of clinical, behavioral and blood parameters with stress-induced cortisol elevation. CONCLUSION: Nitrites and BDNF may represent potential biomarkers for cortisol negative effects on the area of cerebral ischemia and penumbra, potentiating ischemic cell damage.