Stroke studies in large animals: Prospects of mitochondrial transplantation and enhancing efficiency using hydrogels and nanoparticle-assisted delivery

One of the most frequent reasons for mortality and disability today is acute ischemic stroke, which occurs by an abrupt disruption of cerebral circulation. The intricate damage mechanism involves several factors, such as inflammatory response, disturbance of ion balance, loss of energy production, excessive reactive oxygen species and glutamate release, and finally, neuronal death. Stroke research is now carried out using several experimental models and potential therapeutics. Furthermore, studies are being conducted to address the shortcomings of clinical care. A great deal of research is being done on novel pharmacological drugs, mitochondria targeting compounds, and different approaches including brain cooling and new technologies. Still, there are many unanswered questions about disease modeling and treatment strategies. Before these new approaches may be used in therapeutic settings, they must first be tested on large animals, as most of them have been done on rodents. However, there are several limitations to large animal stroke models used for research. In this review, the damage mechanisms in acute ischemic stroke and experimental acute ischemic stroke models are addressed. The current treatment approaches and promising experimental methods such as mitochondrial transplantation, hydrogel-based interventions, and strategies like mitochondria encapsulation and chemical modification, are also examined in this work.