Volume 32, Issue 4

Brain interstitial system (ISS) is a nanoscale network of continuously connected tubes and sheets surrounding each neural cell in the central nervous system. ISS usually accounts for ∼20% of the brain volume, far more than the cerebral blood vessels, which account for 3%. The neuronal function, signaling pathways, and drug delivery are all closely related to the microenvironment provided by ISS. The objective of this paper is to give the readers a clear outline of detection, anatomy, function, and applications of ISS. This review describes the techniques propelling the exploration for ISS in chronological order, physiological function and pathological dysfunction of ISS, and strategies for drug delivery based on ISS. Biophysical features are the focus of ISS research, in which the diffusion characteristics have dominated. The various techniques that explore ISS take advantage of this feature. ISS provides an essential microenvironment for the health of cells and brain homeostasis, which plays an important functional role in brain health and disease. Direct intracranial administration allows the diffusion of drugs directly through ISS to successfully bypass the blood–brain barrier that prevents most drugs from reaching the brain. With the deepening of understanding of the brain ISS, the new research model that takes into account brain cells, cerebral vessels, and ISS will provide a new perspective and direction for understanding, utilizing, and protecting the brain.

Alzheimer’s disease (AD) is a neurodegenerative disease and a common cause of dementia among elderly individuals. The disease is characterized by progressive cognitive decline, accumulation of senile amyloid plaques and neurofibrillary tangles, oxidative stress, and inflammation. Human-derived cell models of AD are scarce, and over the years, non-human-derived models have been developed to recapitulate clinical AD, investigate the disease’s pathogenesis and develop therapies for the disease. Several pharmacological compounds have been developed for AD based on findings from non-human-derived cell models; however, these pharmacological compounds have failed at different phases of clinical trials. This necessitates the application of human-derived cell models, such as induced pluripotent stem cells (iPSCs) in their optimized form in AD mechanistic studies and preclinical drug testing. This review provides an overview of AD and iPSCs. The AD-relevant phenotypes of iPSC-derived AD brain cells and the usefulness of iPSCs in AD are highlighted. Finally, the various recommendations that have been made to enhance iPSC/AD modelling are discussed.

Neurological disorders (NLDs) are among the top leading causes for disability worldwide. Dramatic changes in the epigenetic topography of the brain and nervous system have been found in many NLDs. Histone lysine acetylation has prevailed as one of the well characterised epigenetic modifications in these diseases. Two instrumental components of the acetylation machinery are the evolutionarily conserved Bromodomain and PHD finger containing (BRPF) and Bromo and Extra terminal domain (BET) family of proteins, also referred to as acetylation ‘readers’. Several reasons, including their distinct mechanisms of modulation of gene expression and their property of being highly tractable small molecule targets, have increased their translational relevance. Thus, compounds which demonstrated promising results in targeting these proteins have advanced to clinical trials. They have been established as key role players in pathologies of cancer, cardiac diseases, renal diseases and rheumatic diseases. In addition, studies implicating the role of these bromodomains in NLDs are gaining pace. In this review, we highlight the findings of these studies, and reason for the plausible roles of all BET and BRPF members in NLDs. A comprehensive understanding of their multifaceted functions would be radical in the development of therapeutic interventions.

As the coronavirus disease 2019 (COVID-19) pandemic continues to be a multidimensional threat to humanity, more evidence of neurological involvement associated with it has emerged. Neuroimmune interaction may prove to be important not only in the pathogenesis of neurological manifestations but also to prevent systemic hyperinflammation. In this review, we summarize reports of COVID-19 cases with neurological involvement, followed by discussion of possible routes of entry, immune responses against coronavirus infection in the central nervous system and mechanisms of nerve degeneration due to viral infection and immune responses. Possible mechanisms for neuroprotection and virus-associated neurological consequences are also discussed.

The coronavirus disease 2019 is still continuing and may affect stroke emergency care. We aim to investigate the impact of pandemic on stroke treatment in tertiary stroke centers in western China, and to quantitatively evaluate the worldwide influence with a meta-analysis. The original part was conducted in three tertiary stroke centers in Sichuan province. We compared emergency visits and efficiency of stroke treatment pre-, early, peak and late pandemic. Single-center analysis was further conducted in the largest local hospital and one hospital located close to the epicenter respectively. Relevant studies were searched in PubMed, Ovid Embase and Cochrane Library for English publications from December 2019 to July 2020 for systematic review. Fixed-and random-effect meta-analysis was performed to calculate the overall rates. Totally current original study showed fewer time of hospital admission and significantly higher rates of mechanical thrombectomy during the early and peak epidemic periods, compared with pre-epidemic time. The largest local hospital had significantly higher mechanical thrombectomy rates during the whole crisis and less daily admission during early and peak epidemic periods. The hospital located close to the epicenter presented higher proportions of intravenous thrombolysis since outbreak, and more favorable outcomes after reperfusion therapies than later (all P values <0.05). In meta-analysis, studies reported differences in reperfusion therapies and stroke severity but pooled results were non-significant. Overall, comprehensive measures should be implemented to keep hospital’s capacity to deliver high-quality stroke emergency care during the global pandemic. Some key messages were provided for medical practice in the crisis.