Understanding the Role of Dysfunctional and Healthy Mitochondria in Stroke Pathology and Its Treatment

Abstract

Stroke remains a major cause of death and disability in the United States and around the world. Solid safety and efficacy profiles of novel stroke therapeutics have been generated in the laboratory, but most failed in clinical trials. Investigations into the pathology and treatment of the disease remain a key research endeavor in advancing scientific understanding and clinical applications. In particular, cell-based regenerative medicine, specifically stem cell transplantation, may hold promise as a stroke therapy, because grafted cells and their components may recapitulate the growth and function of the neurovascular unit, which arguably represents the alpha and omega of stroke brain pathology and recovery. Recent evidence has implicated mitochondria, organelles with a central role in energy metabolism and stress response, in stroke progression. Recognizing that stem cells offer a source of healthy mitochondria—one that is potentially transferrable into ischemic cells—may provide a new therapeutic tool. To this end, deciphering cellular and molecular processes underlying dysfunctional mitochondria may reveal innovative strategies for stroke therapy. Here, we review recent studies capturing the intimate participation of mitochondrial impairment in stroke pathology, and showcase promising methods of healthy mitochondria transfer into ischemic cells to critically evaluate the potential of mitochondria-based stem cell therapy for stroke patients.

Cannabinoid CB1 receptor agonist ACEA alleviates brain ischemia/reperfusion injury via CB1–Drp1 pathway

“…Mitochondria are the energy factory of cells, and mitochondrial impairment in the CNS induces neuronal injury and death, ultimately leading to neurological dysfunction. Therefore, maintaining neuronal mitochondrial function could be a promising therapeutic strategy for treating stroke 24 . Cannabinoid receptors are expressed in brain tissue, and activation of these receptors give rise to neuroprotection against brain IRI.…”

Stem Cell Therapy in Brain Ischemia: The Role of Mitochondrial Transfer

“…Mitochondria, a DNA containing cellular organelle, plays an important role in producing adenosine triphosphate (ATP), maintaining redox balance, and regulating cellular apoptosis [6,17]. After brain ischemia, mitochondrial homeostasis is impaired in neurons [18], which constitutes a comprehensive of pathological process (Fig.…”

Role of Creatine Supplementation in Conditions Involving Mitochondrial Dysfunction: A Narrative Review

“…Whereas earlier research mainly focused on mitochondrial bioenergetic roles, new studies have shown the importance of apoptotic signaling, mitochondrial biogenesis, and mitophagy in the development of cerebrovascular disease and stroke. Mitochondrial health is therefore essential for neurological survival and rehabilitation [ 198 , 199 ]. Reperfusion injury is another acute complication feared by medical doctors involving mitochondria and clinical outcomes [ 200 , 201 ].…”