Abstract
Stroke is a devastating condition characterized by widespread cell death after disruption of blood flow to the brain. The poor regenerative capacity of neural cells limits substantial recovery and prolongs disruptive sequelae. Current therapeutic options are limited and do not adequately address the underlying mitochondrial dysfunction caused by the stroke. These same mitochondrial impairments that result from acute cerebral ischemia are also present in retinal ischemia. In both cases, sufficient mitochondrial activity is necessary for cell survival, and while astrocytes are able to transfer mitochondria to damaged tissues to rescue them, they do not have the capacity to completely repair damaged tissues. Therefore, it is essential to investigate this mitochondrial transfer pathway as a target of future therapeutic strategies. In this review, we examine the current literature pertinent to mitochondrial repair in stroke, with an emphasis on stem cells as a source of healthy mitochondria. Stem cells are a compelling cell type to study in this context, as their ability to mitigate stroke-induced damage through non-mitochondrial mechanisms is well established. Thus, we will focus on the latest preclinical research relevant to mitochondria-based mechanisms in the treatment of cerebral and retinal ischemia and consider which stem cells are ideally suited for this purpose.
Highlights
Stroke is currently the fifth leading cause of death in the United States and can cause disabling neurological deficits including cognitive impairment, hemiparesis, sensory disturbance, and aphasia [1]
Injured cerebral tissue releases cytokines, chemokines, cellular adhesion molecules, and matrix metalloproteases (MMPs), which increases the permeability of the blood–brain barrier (BBB) and attracts peripheral leukocytes to infiltrate and upregulate inflammation [4,7]
Like the neurological and cognitive deficit associated with cerebral stroke, retinal ischemia is characterized by visual impairment caused by lack of blood flow to the eye which results in a cascade of apoptotic events, oxidative stress, and mitochondria dysfunction in retinal ganglion cells [8]
Summary
Stroke is currently the fifth leading cause of death in the United States and can cause disabling neurological deficits including cognitive impairment, hemiparesis, sensory disturbance, and aphasia [1]. Despite an emphasis on implementing effective acute and chronic stroke care made by the American Heart Association and American Stroke Association, there are only two FDA-approved treatment options available for acute stroke: tissue plasminogen activator (tPA) and endovascular thrombectomy. Their use is limited by the short therapeutic time window and risk for additional damage. Like the neurological and cognitive deficit associated with cerebral stroke, retinal ischemia is characterized by visual impairment caused by lack of blood flow to the eye which results in a cascade of apoptotic events, oxidative stress, and mitochondria dysfunction in retinal ganglion cells [8]. Inflammation dissipates in the chronic phase, which culminates in tissue repair
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