Astrocyte Activation in Neurovascular Damage and Repair Following Ischaemic Stroke

Abstract

Transient or permanent loss of tissue perfusion due to ischaemic stroke can lead to damage to the neurovasculature, and disrupt brain homeostasis, causing long-term motor and cognitive deficits. Despite promising pre-clinical studies, clinically approved neuroprotective therapies are lacking. Most studies have focused on neurons while ignoring the important roles of other cells of the neurovascular unit, such as astrocytes and pericytes. Astrocytes are important for the development and maintenance of the blood–brain barrier, brain homeostasis, structural support, control of cerebral blood flow and secretion of neuroprotective factors. Emerging data suggest that astrocyte activation exerts both beneficial and detrimental effects following ischaemic stroke. Activated astrocytes provide neuroprotection and contribute to neurorestoration, but also secrete inflammatory modulators, leading to aggravation of the ischaemic lesion. Astrocytes are more resistant than other cell types to stroke pathology, and exert a regulative effect in response to ischaemia. These roles of astrocytes following ischaemic stroke remain incompletely understood, though they represent an appealing target for neurovascular protection following stroke. In this review, we summarise the astrocytic contributions to neurovascular damage and repair following ischaemic stroke, and explore mechanisms of neuroprotection that promote revascularisation and neurorestoration, which may be targeted for developing novel therapies for ischaemic stroke.

Functional Recovery Caused by Human Adipose Tissue Mesenchymal Stem Cell-Derived Extracellular Vesicles Administered 24 h after Stroke in Rats

“…Stimulation of angiogenesis, as observed by EV treatment, has been shown to improve neurological and motor function in animal stroke models [ 55 ], an effect currently acknowledged as an outcome of EV transfer of proteins, mRNAs, and miRNAs to endothelial cells [ 33 , 56 ] and regulating protein expression [ 57 ]. Additionally, BBB impairment in ischemic stroke, as observed here, has also been documented [ 58 , 59 , 60 ], but its involvement in EVs therapeutic strategies, as indicated in this study, has not been previously reported.…”

Inflammatory resolution and vascular barrier restoration after retinal ischemia reperfusion injury

“…For example, in the acute phase of cerebral stroke, microglia quickly react to neuronal damage leading to inflammatory cytokine and chemokine expression. Astrocytes also undergo reactive gliosis and contribute to cytokine expression and inflammation following stroke [ 24 ]. Vascular endothelial cells become activated, with increased expression of selectins and cell adhesion molecules, increased permeability and subsequent attraction, adhesion and infiltration of granulocytes, principally neutrophils, and classical pro-inflammatory monocytes (Ly6C hi in mouse), within hours after injury [ 25 ].…”

Dysfunction of the Neurovascular Unit in Ischemic Stroke: Highlights on microRNAs and Exosomes as Potential Biomarkers and Therapy

“…The aquaporin-4 (AQP4) water channels, which are highly expressed on the end-feet of astrocytes, play a key role in brain water homeostasis. Following ischemia, the increased expression of proinflammatory mediators and the resulting neurovascular inflammation lead to alterations in AQP4 expression causing cerebral edema [ 53 ]. Kitchen et al revealed that targeting AQP4 not only reduces CNS edema but also leads to accelerated functional recovery following hypoxia [ 54 ].…”