Studies have shown that mesenchymal stem cell-derived exosomes can enhance neural plasticity and improve cognitive impairment. The purpose of this study was to investigate the effects of mesenchymal stem cell-derived exosomes on neurogenesis and cognitive capacity in a mouse model of Alzheimer’s disease. Alzheimer’s disease mouse models were established by injection of beta amyloid 1−42 aggregates into dentate gyrus bilaterally. Morris water maze and novel object recognition tests were performed to evaluate mouse cognitive deficits at 14 and 28 days after administration. Afterwards, neurogenesis in the subventricular zone was determined by immunofluorescence using doublecortin and PSA-NCAM antibodies. Results showed that mesenchymal stem cells-derived exosomes stimulated neurogenesis in the subventricular zone and alleviated beta amyloid 1−42-induced cognitive impairment, and these effects are similar to those shown in the mesenchymal stem cells. These findings provide evidence to validate the possibility of developing cell-free therapeutic strategies for Alzheimer’s disease. All procedures and experiments were approved by Institutional Animal Care and Use Committee (CICUAL) (approval No. CICUAL 2016-011) on April 25, 2016.

Brain changes have been reported in the first weeks after SARS-CoV-2 infection. However, limited literature exists about brain alterations in post-COVID syndrome, a condition increasingly associated with cognitive impairment. The present study aimed to evaluate brain functional and structural alterations in patients with post-COVID syndrome, and assess whether these brain alterations were related to cognitive dysfunction. Eighty-six patients with post-COVID syndrome and 36 healthy controls were recruited and underwent neuroimaging acquisition and a comprehensive neuropsychological assessment. Cognitive and neuroimaging examinations were performed 11 months after the first symptoms of SARS-CoV-2. Whole-brain functional connectivity analysis was performed. Voxel-based morphometry was performed to evaluate grey matter volume, and diffusion tensor imaging was carried out to analyse white-matter alterations. Correlations between cognition and brain changes were conducted and Bonferroni corrected. Post-COVID syndrome patients presented with functional connectivity changes, characterized by hypoconnectivity between left and right parahippocampal areas, and between bilateral orbitofrontal and cerebellar areas compared to controls. These alterations were accompanied by reduced grey matter volume in cortical, limbic and cerebellar areas, and alterations in white matter axial and mean diffusivity. Grey matter volume loss showed significant associations with cognitive dysfunction. These cognitive and brain alterations were more pronounced in hospitalized patients compared to non-hospitalized patients. No associations with vaccination status were found. The present study shows persistent structural and functional brain abnormalities 11 months after the acute infection. These changes are associated with cognitive dysfunction and contribute to a better understanding of the pathophysiology of the post-COVID syndrome.

It is well known that the central nervous system (CNS) has a limited regenerative capacity and that many therapeutic molecules cannot cross the blood brain barrier (BBB). The use of biomaterials has emerged as an alternative to overcome these limitations. For many years, biomedical applications of chitosan have been studied due to its remarkable biological properties, biocompatibility, and high versatility. Moreover, the interest in this biomaterial for CNS biomedical implementation has increased because of its ability to cross the BBB, mucoadhesiveness, and hydrogel formation capacity. Several chitosan-based biomaterials have been applied with promising results as drug, cell and gene delivery vehicles. Moreover, their capacity to form porous scaffolds and to bear cells and biomolecules has offered a way to achieve neural regeneration. Therefore, this review aims to bring together recent works that highlight the potential of chitosan and its derivatives as adequate biomaterials for applications directed toward the CNS. First, an overview of chitosan and its derivatives is provided with an emphasis on the properties that favor different applications. Second, a compilation of works that employ chitosan-based biomaterials for drug delivery, gene therapy, tissue engineering, and regenerative medicine in the CNS is presented. Finally, the most interesting trends and future perspectives of chitosan and its derivatives applications in the CNS are shown.