Traumatic Brain Injury (TBI) remains a leading cause of morbidity and mortality among all ages; despite the advances, understanding pathophysiological responses after TBI is still complex, involving multiple mechanisms. Previous reviews have focused on potential targets; however, the research on potential targets has continuously grown in the last five years, bringing even more alternatives and elucidating previous mechanisms. Knowing the key and updated pathophysiology concepts is vital for adequate management and better outcomes. This article reviews the underlying molecular mechanisms, the latest updates, and future directions for pathophysiology-based TBI management.

Fragile X syndrome (FXS) is a neurodevelopmental disorder associated with a wide range of cognitive, behavioral and medical problems. It arises from the silencing of the fragile X mental retardation 1 (FMR1) gene, and consequently, in the absence of its encoded protein, FMRP (Fragile X Mental Retardation Protein). FMRP is a ubiquitously expressed and multifunctional RNA-binding protein, primarily considered as a translational regulator. Pre-clinical studies of the past two decades have therefore focus on this function to relate FMRP’s absence to the molecular mechanisms underlying FXS physiopathology. Based on these data, successful pharmacological strategies were developed to rescue fragile X phenotype in animal models. Unfortunately, these results did not translate into human, as clinical trials using same therapeutic approaches did not reach the expected outcomes. These failures highlight the need to put into perspectives the different functions of FMRP in order to get a more comprehensive understanding of FXS pathophysiology. In this review, FMRP’s involvement on noteworthy molecular mechanisms are pointed out; ultimately contributing to various biochemicals alterations composing the fragile X phenotype.

Severe disease and uremia are risk factors for neurological complications of coronavirus disease-2019 (COVID-19). An in-depth analysis of a case series was conducted to describe the neurological manifestations of patients with COVID-19 and gain pathophysiological insights that may guide clinical decision-making – especially with respect to the cytokine release syndrome (CRS). Extensive clinical, laboratory, and imaging phenotyping was performed in five patients. Neurological presentation included confusion, tremor, cerebellar ataxia, behavioral alterations, aphasia, pyramidal syndrome, coma, cranial nerve palsy, dysautonomia, and central hypothyroidism. Neurological disturbances were remarkably accompanied by laboratory evidence of CRS. SARS-CoV-2 was undetectable in the cerebrospinal fluid. Hyperalbuminorachy and increased levels of the astroglial protein S100B were suggestive of blood-brain barrier (BBB) dysfunction. Brain MRI findings comprised evidence of acute leukoencephalitis (n = 3, of whom one with a hemorrhagic form), cytotoxic edema mimicking ischemic stroke (n = 1), or normal results (n = 2). Treatment with corticosteroids and/or intravenous immunoglobulins was attempted – resulting in rapid recovery from neurological disturbances in two cases. Patients with COVID-19 can develop neurological manifestations that share clinical, laboratory, and imaging similarities with those of chimeric antigen receptor-T cell-related encephalopathy. The pathophysiological underpinnings appear to involve CRS, endothelial activation, BBB dysfunction, and immune-mediated mechanisms.