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Astrocyte Activation in Neurovascular Damage and Repair Following Ischaemic Stroke

Journal

Publisher

MDPI
DOI: 10.3390/ijms22084280

Keywords

stroke; astrocyte; neurovascular; neuroprotection; neurotoxicity; neurorestoration; neuroinflammation; secretion

Funding

  1. NSW Ministry of Health, Australia under the NSW Health EarlyMid Career Fellowships Scheme
  2. Wellcome Trust [200633/z/16/z]
  3. Wellcome Trust [200633/Z/16/Z] Funding Source: Wellcome Trust

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Ischaemic stroke can cause damage to the neurovasculature, leading to long-term motor and cognitive deficits. Current neuroprotective therapies are lacking, with many studies focusing on neurons and neglecting the important roles of other cells in the neurovascular unit, such as astrocytes.
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.

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