Mitophagy in Cerebral Ischemia and Ischemia/Reperfusion Injury

Abstract

Ischemic stroke is a severe cerebrovascular disease with high mortality and morbidity. In recent years, reperfusion treatments based on thrombolytic and thrombectomy are major managements for ischemic stroke patients, and the recanalization time window has been extended to over 24 h. However, with the extension of the time window, the risk of ischemia/reperfusion (I/R) injury following reperfusion therapy becomes a big challenge for patient outcomes. I/R injury leads to neuronal death due to the imbalance in metabolic supply and demand, which is usually related to mitochondrial dysfunction. Mitophagy is a type of selective autophagy referring to the process of specific autophagic elimination of damaged or dysfunctional mitochondria to prevent the generation of excessive reactive oxygen species (ROS) and the subsequent cell death. Recent advances have implicated the protective role of mitophagy in cerebral ischemia is mainly associated with its neuroprotective effects in I/R injury. This review discusses the involvement of mitochondria dynamics and mitophagy in the pathophysiology of ischemic stroke and I/R injury in particular, focusing on the therapeutic potential of mitophagy regulation and the possibility of using mitophagy-related interventions as an adjunctive approach for neuroprotective time window extension after ischemic stroke.

A Bibliometric Analysis for Global Trends and Full View of the Autophagy in Ischemic Stroke from 2006 to 2022

“…Linking autophagy to oxidative stress and pathological features after ischemic stroke, or demonstrating mitochondrial fission during autophagy as a key component of early ischemic stroke, they have paved a number of possible paths for subsequent researchers. Related research has inspired thinking about the specific role of autophagy in ischemic stroke [29], extended the mechanism of mitochondria in the process of autophagy [30][31][32], and deepened thinking about the role of oxidative stress in ischemic stroke [33,34]. The use of bibliometric analysis enables us to investigate the pathogenesis of diseases in a more accurate way, and the model of big data also makes it more feasible to explore future research directions and focus on specific concerns [35].…”

Therapeutic Targets for Regulating Oxidative Damage Induced by Ischemia-Reperfusion Injury: A Study from a Pharmacological Perspective

“…That is why ischemic preconditioning combined with antioxidant therapies will most likely be critical regulators for ischemic stroke [ 131 ]. Current studies have focused on the pathways of oxidative stress that involve a variety of cellular pathways, receptors, and processes that can be used on focused therapy for oxidative damage, such as autophagy, mitophagy, and necrosis, which are involved in eliminating excess ROS and subsequent cell death triggered by these free radicals [ 132 , 133 ]. The endogenous protective mechanisms in the brain included the antioxidant enzyme systems and the low-molecular-weight antioxidants [ 134 ].…”

The Influence of Mitochondrial-DNA-Driven Inflammation Pathways on Macrophage Polarization: A New Perspective for Targeted Immunometabolic Therapy in Cerebral Ischemia-Reperfusion Injury

“…It has a good therapeutic effect in the acute phase of rat stroke model [ 164 ]. Some studies believe that mitochondrial autophagy will promote the glycolysis process, and mitochondrial autophagy inhibitors such as CsA can effectively inhibit the transformation of the M1 phenotype of macrophages [ 11 , 12 ]. L-Monomethylarginine (L-NMMA) is an inhibitor of nitric oxide synthase.…”

“…As a downstream effect of mitochondrial apoptosis, inflammation further destroys brain function. The opening of the mitochondrial permeability transition pore (mPTP) is deemed to be the core cause of this inflammatory disaster [ 6 , 11 , 12 ]. Cytochrome C is released to cause apoptosis.…”