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Tissue scarring upon cerebral ischemia entails a cascade of multifaceted cellular and molecular mechanisms that govern the remodeling of the neurovascular unit, which integrates neuronal, glial, and vascular functions. The process encompasses inflammation, glial reactivity, vascular reactivity, and neuronal remodeling. In this chapter we cover three major aspects involved in tissue scarring after cerebral ischemia. First, we outline the primary cellular mechanisms underlying glial scar formation, emphasizing on the interactions between astrocytes, microglia, and mural cells, including pericytes and fibroblasts at the injury core and perilesional areas. Next, we address the key routes of extracellular matrix deposition by reactive and fibrogenic cells, including proteoglycans, tenascins, fibronectin, and collagen. Finally, we discuss the promises and challenges of manipulating tissue scarring as a strategy to promote brain structural remodeling and neurological recovery.
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