Ischemic stroke in humans imposes a substantial burden on health care organizations and personal care providers due to the absence of effective therapy that can prevent or halt the development of post-ischemic dementia. As a result, many patients become bedridden and require 24-hour care. Thus, the progressive and irreversible neurodegeneration following ischemia leads to severe long-term outcomes. For this reason, there is great emphasis on better understanding the neuropathogenesis of the post-ischemic brain. Experimental and clinical studies have shown that ischemia leads to progressive neurodegeneration of the brain, which results in impaired cognitive functions and the development of full-blown Alzheimer's disease-type dementia. Elevated levels of tau protein and amyloid have been found in post-ischemic brains, which transform into amyloid plaques and neurofibrillary tangles, respectively. Furthermore, other pathological phenomena have been identified, such as calcium accumulation, decreased acetylcholine levels, excitotoxicity, blood-brain barrier permeability and inflammation. These processes lead to massive neuronal cell death and brain atrophy. Moreover, it has been noted that post-ischemic neurodegenerative processes continue well beyond the acute stage and are irreversible. Previous studies indicate that protein misfolding, aggregation, and damage to multiple organelles are the main pathological phenomena in neurons after ischemia. Autophagy is a key process for the large-scale degradation of protein aggregates and damaged organelles, and existing data indicate that autophagy plays a dual role after ischemia (pro-survival and pro-death). In this review, we focus on the importance of autophagy and mitophagy gene expression at the onset of clinical symptoms (acute phase), during disease progression, and at lesion maturation (chronic phase) after cerebral ischemia. We present the current knowledge on alterations in autophagy genes and the function of autophagy in post-ischemic cerebral neurodegeneration.
Pluta et al. (Thu,) studied this question.