The current approaches to modeling the brain ischemia-reperfusion and inflammation: from animal models toward vascularized and neuroimmune cerebral organoids

Abstract

For several decades, the modeling of brain diseases in experimental animals has remained one of the key components of studying the pathogenesis of central nervous system pathology and searching for new methods of prevention and therapy. In recent years, new approaches to modeling pathological conditions in vitro have been in active development; these approaches will not only reduce the number of animal studies but also allow us to take a step toward reproducing the human-specific mechanisms of brain pathology. In this review, we characterize the most common rodent models of cerebral ischemia and reperfusion, as well as neuroinflammation inherent to neurodegeneration (in particular, Parkinson's disease), which are reproduced in vivo. This review addresses engineering and technical challenges and the prospects for the development of brain pathology models in vitro, e.g., vascularized and microglia-containing/neuroimmune cerebral organoids, which may be useful in overcoming the shortcomings and limitations of the current in vivo models.

Keywords: CNS pathology; brain in vitro models; cerebral organoids; ischemia–reperfusion; neuroinflammation.