Brain injury biomarkers do not predict delirium in acutely ill older patients: a prospective cohort study.

Delirium is a common, serious, and often preventable neuropsychiatric emergency mostly characterized by a disturbance in attention and awareness. Systemic insult and inflammation causing blood-brain-barrier (BBB) damage and glial and neuronal activation leading to more inflammation and cell death is the most accepted theory behind delirium's pathophysiology. This study aims to evaluate the relationship between brain injury biomarkers on admission and delirium in acutely ill older patients. We performed a prospective cohort study which analyzed plasma S100B levels at admission in elderly patients. Our primary outcome was delirium diagnosis. Secondary outcomes were association between S100B, NSE and Tau protein and delirium diagnosis and patients' outcomes (admissions to intensive care, length of hospital stay, and in-hospital mortality). We analyzed 194 patients, and 46 (24%) developed delirium, 25 on admission and 21 during hospital stay. Median of S100B at admission in patients who developed delirium was 0.16 and median was 0.16 in patients who didn't develop delirium (p: 0.69). Levels S100B on admission did not predict delirium in acutely ill elderly patients.Trial registration: The study was approved by the local institutional review board (CAPPESq, no. 77169716.2.0000.0068, October 11, 2017) and registered in Brazilian Clinical Trials Registry (ReBEC, no. RBR-233bct).

Lower peripheral blood Toll-like receptor 3 expression is associated with an unfavorable outcome in severe COVID-19 patients.

The role of innate immunity in COVID-19 is not completely understood. Therefore, this study explored the impact of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection on the expression of Pattern Recognition Receptors (PRRs) in peripheral blood cells and their correlated cytokines. Seventy-nine patients with severe COVID-19 on admission, according to World Health Organization (WHO) classification, were divided into two groups: patients who needed mechanical ventilation and/or deceased (SEVERE, n = 50) and patients who used supplementary oxygen but not mechanical ventilation and survived (MILD, n = 29); a control group (CONTROL, n = 17) was also enrolled. In the peripheral blood, gene expression (mRNA) of Toll-like receptors (TLRs) 3, 4, 7, 8, and 9, retinoic-acid inducible gene I (RIGI), NOD-like receptor family pyrin domain containing 3 (NLRP3), interferon alpha (IFN-α), interferon beta (IFN-ß), interferon gamma (IFN-γ), interferon lambda (IFN-λ), pro-interleukin(IL)-1ß (pro-IL-1ß), and IL-18 was determined on admission, between 5-9 days, and between 10-15 days. Circulating cytokines in plasma were also measured. When compared to the COVID-19 MILD group, the COVID-19 SEVERE group had lower expression of TLR3 and overexpression of TLR4.

A new function for Prokineticin 2: Recruitment of SVZ-derived neuroblasts to the injured cortex in a mouse model of traumatic brain injury.

Traumatic brain injury is an important cause of global morbidity and mortality. After an initial injury, there is a cascade of cellular and molecular events that ultimately lead to cell death. Therapies aim to both counteract these mechanisms and replenish the lost cell population in order to improve recovery. The adult mammal brain has at least two neurogenic regions that maintain physiological functions: the subgranular zone of the dentate gyrus in the hippocampus, which produces neurons that integrate locally, and the subventricular zone (SVZ) adjacent to the lateral ventricles, which produces neuroblasts that migrate through the rostral migratory stream (RMS) to the olfactory bulbs. Brain injuries, as well as neurodegenerative diseases, induce the SVZ to respond by increasing cell proliferation and migration to the injured areas. Here we report that cells migrate from the SVZ and RMS to the injured cortex after traumatic brain injury in mice, and that the physiological RMS migration is not impaired. We also show that Prokineticin 2 (PROK2), a chemokine important for the olfactory bulb neurogenesis, expressed exclusively by cortical microglia in the cortex as early as 24 h after injury. We then show that administration of a PROK2 receptor antagonist decreases the number of SVZ cells that reach the injured cortex, while injection of recombinant PROK2 into the cortex of uninjured mice attracts SVZ cells. We also demonstrate that cells expressing PROK2 in vitro directionally attract SVZ cells. These data suggest that PROK2 could be utilized in regeneration efforts for the acutely injured mammalian cortex.