Mitochondrial Quality Control in Cerebral Ischemia–Reperfusion Injury

Wu, Mimi; Gu, Xiaoping; Ma, Zhengliang

doi:10.1007/s12035-021-02494-8

Cited by 60 publications

(24 citation statements)

References 192 publications

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“…This damage is variously known as ischaemia–reperfusion injury, hypoxia–reperfusion injury, or reoxygenation injury. It is widely observed acutely [ 1 ], for instance following an acute mycocardial infarction [ 2–4 ], stroke [ 5 , 6 ], in emergency medicine [ 7 ], and during the ex vivo incubation of organs as part of transplant surgery [ 8–11 ]. It is considered (see below) that the main mechanisms involve the production, especially during the reperfusion, of various partially reduced reactive oxygen species (ROS) [ 12 , 13 ], not least by an over-reduced mitochondrial respiratory chain that was formed during the hypoxic phase (see Figure 1 for a simplified representation of ischaemia–reperfusion injury (I–R I)).…”

Section: Introductionmentioning

confidence: 99%

The potential role of ischaemia–reperfusion injury in chronic, relapsing diseases such as rheumatoid arthritis, Long COVID, and ME/CFS: evidence, mechanisms, and therapeutic implications

Kell

2022

Biochemical Journal

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Ischaemia–reperfusion (I–R) injury, initiated via bursts of reactive oxygen species produced during the reoxygenation phase following hypoxia, is well known in a variety of acute circumstances. We argue here that I–R injury also underpins elements of the pathology of a variety of chronic, inflammatory diseases, including rheumatoid arthritis, ME/CFS and, our chief focus and most proximally, Long COVID. Ischaemia may be initiated via fibrin amyloid microclot blockage of capillaries, for instance as exercise is started; reperfusion is a necessary corollary when it finishes. We rehearse the mechanistic evidence for these occurrences here, in terms of their manifestation as oxidative stress, hyperinflammation, mast cell activation, the production of marker metabolites and related activities. Such microclot-based phenomena can explain both the breathlessness/fatigue and the post-exertional malaise that may be observed in these conditions, as well as many other observables. The recognition of these processes implies, mechanistically, that therapeutic benefit is potentially to be had from antioxidants, from anti-inflammatories, from iron chelators, and via suitable, safe fibrinolytics, and/or anti-clotting agents. We review the considerable existing evidence that is consistent with this, and with the biochemical mechanisms involved.

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Section: Introductionmentioning

confidence: 99%

The potential role of ischaemia–reperfusion injury in chronic, relapsing diseases such as rheumatoid arthritis, Long COVID, and ME/CFS: evidence, mechanisms, and therapeutic implications

Kell

2022

Biochemical Journal

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“…Ischemia-induced brain increased mitochondrial ROS and weakened ETC complexes, affecting mitochondrial constituents and ROS accumulation . Mitochondrial ROS, which impacts mitochondrial function and is one of the hallmarks of reperfusion injury, was found in the frontal cortex region of the mitochondria. , P5 treatment reduced mitochondrial ROS, boosting the activity of the ETC complexes in stroke rats. P5’s antioxidant properties appear to have scavenged ROS in the mitochondria and refilled the ETC complex enzymes.…”

Section: Discussionmentioning

confidence: 96%

Pregnenolone Attenuates the Ischemia-Induced Neurological Deficit in the Transient Middle Cerebral Artery Occlusion Model of Rats

et al. 2022

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Neurosteroids are apparent to be connected in the cerebral ischemic injury for their potential neuroprotective effects. We previously demonstrated that progesterone induces neuroprotection via the mitochondrial cascade in the cerebral ischemic stroke of rodents. Here, we sought to investigate whether or not pregnenolone, a different neurosteroid, can protect the ischemic injury in the transient middle cerebral artery occlusion (tMCAO) rodent model. Male Wistar rats were chosen for surgery for inducing stroke using the tMCAO method. Pregnenolone (2 mg/kg b.w.) at 1 h postsurgery was administered. The neurobehavioral tests and (TTC staining) 2, 3, 5-triphenyl tetrazolium chloride staining were performed after 24 h of the surgery. The mitochondrial membrane potential and reactive oxygen species (ROS) were measured using flow cytometry. Oxygraph was used to examine mitochondrial bioenergetics. The spectrum of neurobehavioral tests and 2, 3, 5-triphenyltetrazolium chloride staining showed that pregnenolone enhanced neurological recovery. Pregnenolone therapy after a stroke lowered mitochondrial ROS following ischemia. Our data demonstrated that pregnenolone was not able to inhibit mitochondrial permeability transition pores. There was no effect on mitochondrial bioenergetics such as oxygen consumption and respiratory coupling. Overall, the findings demonstrated that pregnenolone reduced the neurological impairments via reducing mitochondria ROS but not through the inhibition of the mitochondria permeability transition pore (mtPTP).

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“…Mitochondrial dynamics including fusion, fission, selective degradation, and transport processes are important for immunity, apoptosis, and the cell cycle (An et al, 2021 ; Carinci et al, 2021 ; Wu et al, 2021 ; Yang et al, 2022 ). Zhou et al reviewed the molecular mechanisms of mitochondrial dynamics and its role in ischemic stroke.…”

Section: Mitochondrial Dynamics and Mitochondrial Dysfunction In Strokementioning

confidence: 99%

Editorial: Mitochondrial Dysfunction in Stroke

Yan

Wang

Huang

et al. 2022

Front. Aging Neurosci.

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Mitochondrial Quality Control in Cerebral Ischemia–Reperfusion Injury

Cited by 60 publications

References 192 publications

The potential role of ischaemia–reperfusion injury in chronic, relapsing diseases such as rheumatoid arthritis, Long COVID, and ME/CFS: evidence, mechanisms, and therapeutic implications

The potential role of ischaemia–reperfusion injury in chronic, relapsing diseases such as rheumatoid arthritis, Long COVID, and ME/CFS: evidence, mechanisms, and therapeutic implications

Pregnenolone Attenuates the Ischemia-Induced Neurological Deficit in the Transient Middle Cerebral Artery Occlusion Model of Rats

Editorial: Mitochondrial Dysfunction in Stroke

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