The Role of Autophagy in the Regulation of Neuroinflammation in Acute Ischemic Stroke (Review of Literature)

Abstract

Postischemic neuroinflammation is a critical pathophysiological process within the entire scheme of cerebral ischemia, covering early damage and the period of tissue repair. It is characterized by microglial and astroglial activation with increased expression of inflammatory mediators and is accompanied by impaired innate and adaptive immune responses. In acute ischemic stroke (IS), neuroinflammation is caused by the response of resident immune cells of microglia and peripheral immunocompetent cells infiltrating the brain tissue, which penetrate the blood-brain barrier (BBB) into the lesion. Recent studies have shown the important role of the NLRP3-mediated inflammation in the death of neurons and glial cells in acute IS. The review presents the main mechanisms of activation of NLRP3-mediated inflammation in acute IS, leading to the caspase-1 formation and the IL-1β and IL-18 release, which are involved in the initiation and progression of inflammation in the brain parenchyma. The literature data on the role of autophagy in the inhibition of postischemic neuroinflammation are summarized. Autophagy can suppress neuroinflammation through a wide range of the autophagy - related proteins. The role of autophagy as a negative regulator of NLRP3-mediated inflammation in acute IS is analyzed. Data on the participation of autophagic proteins Beclin-1, LC3, and p62 in the suppression of NLRP3 inflammation due to the induction of basic mitophagy are presented. Prospects for modulating autophagy aimed at suppressing postischemic neuroinflammation, including the inhibition of NLRP3-inflammasome, have been noted. The review was based on sources from international and national data bases: Scopus, Web of Science, Springer, RINC.

Regulation of microglia polarization after cerebral ischemia

“…Therefore, impaired autophagy in microglia can contribute to the neuroinflammation ( Houtman et al, 2019 ). Autophagy can act as a negative regulator of inflammation in acute cerebral ischemia by participating in the inhibition of NLRP3-mediated neuroinflammation through the involvement of Beclin1, LC3, and p62 ( Fu et al, 2020 ; Huang et al, 2021 ; Lugovaya et al, 2022 ).…”

Autophagy in ischemic stroke: role of circular RNAs

“…Presently, the exact role of neuronal autophagy is still unclear when neuronal autophagy is induced by various intrinsic and extrinsic insults including ischemia/reperfusion (I/R), nutrient deficiencies, neurotoxins excitotoxic stimuli, and inflammation [13,27,28]. On the one hand, under these stressful conditions, mild to moderate induction of autophagy can maintain neuronal homeostasis, clear the aggregated protein and damaged mitochondria, preserve the energy balance, and alleviate the endoplasmic reticulum stress, referred to as adaptive autophagy [29].…”

Therapeutic strategies targeting the NLRP3‑mediated inflammatory response and pyroptosis in cerebral ischemia/reperfusion injury (Review)

“…However, rapid reperfusion can lead to further damage to areas of the brain, a condition known as cerebral ischemia/reperfusion injury (CIRI) (5,6). Nevertheless, there are a number of possible mechanisms by which CIRI can occur, including inflammatory response (7), ca 2+ overload (8), overproduction of reactive oxygen species (ROS) (9), neuronal damage caused by glutamate (10) and mitochondria induced-autophagy (11). Of these mechanisms, neuroinflammation serves a key role in CIRI, including via local cytokine upregulation and leukocyte infiltration (12).…”