Abstract
Stroke is a life-threatening disease that leads to mortality, with survivors subjected to long-term disability. Microvascular damage is implicated as a key pathological feature, as well as a therapeutic target for stroke. In this review, we present evidence detailing subacute diaschisis in a focal ischemic stroke rat model with a focus on blood–brain barrier (BBB) integrity and related pathogenic processes in contralateral brain areas. Additionally, we discuss BBB competence in chronic diaschisis in a similar rat stroke model, highlighting the pathological changes in contralateral brain areas that indicate progressive morphological brain disturbances overtime after stroke onset. With diaschisis closely approximating stroke onset and progression, it stands as a treatment of interest for stroke. Indeed, the use of stem cell transplantation for the repair of microvascular damage has been investigated, demonstrating that bone marrow stem cells intravenously transplanted into rats 48 h post-stroke survive and integrate into the microvasculature. Ultrastructural analysis of transplanted stroke brains reveals that microvessels display a near-normal morphology of endothelial cells and their mitochondria. Cell-based therapeutics represent a new mechanism in BBB and microvascular repair for stroke.
Highlights
Stroke is currently the fifth leading cause of death in the US, and someone dies of one approximately every 4 min
No significant differences in glial fibrillary acid protein (GFAP) immune response in motor cortices between transient middle cerebral artery occlusion (tMCAO) and controls were present in both hemispheres
In middle cerebral artery occlusion (MCAO)-induced rat models, various cell types including bone marrow stromal cells [107], umbilical cord blood cells [108] and mesenchymal stem cells [109] have proven beneficial in increasing neurotrophic growth factors in the ischemic tissue, reducing apoptosis in the penumbral lesion zone, reducing ischemic damage and restoring cerebral blood flow [109,110,111,112,113]
Summary
Stroke is currently the fifth leading cause of death in the US, and someone dies of one approximately every 4 min. Cerebral functional insufficiency in chronic stroke might be due to pathological changes in brain areas remote from the initial ischemic lesion, for example, diaschisis. The investigation of subacute diaschisis in ischemic stroke rat models exhibits stroke-induced pathological disturbances in ipsilateral and contralateral brain areas, and causes microvascular damage with BBB breakdown in remote brain microvessels. Widespread microvascular alterations in ipsilateral and contralateral brain hemispheres suggests continued BBB damage in chronic ischemic stroke. Because of the rampant pathological microvascular changes in remote brain areas in both subacute and chronic ischemic diaschisis, such vascular damage presents as a therapeutic target for stroke. We discuss the potential use of EPCs as an effective cell source for BBB restoration in stroke by promoting neurovascular repair and preserving the mitochondrial morphology of the microvasculature
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