Roblasts targeting ischemic lesions within the adult rodent brain [157]. Neurogenesis is abolished in CNTF knockout mice [158]. Astrocytic calcium waves in SVZ enhanced the self-renewal and migration capacity of neural stem cells (NSCs) and neural progenitor cells (NPCs) inside a mouse stroke model and were mediated by the Notch signaling pathway [159]. Astrocytes within the ischemic striatum form a migratory scaffold of neuroblasts from SVZ towards the ischemic area [160]. Reactive astrocytes around an ischemic lesion secreted chemokine CXCL12, which attracted neuroblast migration [161]. Our group located that AAV-mediated CXCL12 expression upregulated the proliferation of NSCs in SVZ and migration of neuroblasts for the peri-infarct area, thus promoting neurogenesis post-stroke [162]. Co-transplantation of astrocytes and NSCs into ischemic stroke rats resulted within the increased survival rate, proliferation, and neuronal differentiation on the transplanted NSCs compared with NSC transplantation alone [163]. Astrocytes are crucial players inside the TLR3 Agonist drug establishment of synaptic connectivity including control of synaptogenesis, synaptic plasticity (talked about earlier), and synapse elimination [164]. Astrocytes would be the big cellular source of IL-17A, which maintained and enhanced NPC survival and neuronal differentiation in SVZ and promoted subsequent synaptogenesis and functional recovery right after stroke [165]. Thrombospondin (TSP) 1 and two secreted from astrocytes elevated right after brain ischemia and promoted synaptogenesis and axon sprouting in vivo [166]. Heterogeneity existed inside the synaptogenic profile of astrocytes from distinctive brain regions, which may well be because of significantly varied expression of glypicans 4 and 6; hevin; and secreted protein, acidic and rich in cysteine (SPARC) [167]. Upregulation of the cholesterol-binding sigma-1 receptor in astrocytes is effective for axonal sprouting; a sigma-1 receptor agonist enhanced neurite outgrowth, promoting behavioral recovery soon after stroke [168]. A recent study showed that astrocytes can market structural remodeling of striato-cortical circuits through the release of extracellular vesicles in the tMCAO mouse model [169]. A meta-analysis of astrocytic EV proteomes revealed that proteins which regulate axon outgrowth and guidance, such as TUBB, ACTG1, RTN4, and Rab11A, are upregulated. However, upregulation of astrocytic ephrin-A5 blocked neuronal outgrowth and impaired behavioral recovery within the pMCAO mouse model, while inhibition of ephrin-A5 is NK2 Agonist MedChemExpress valuable [170]. L-lactate and L-2HG from astrocytes act on neuronal metabotropic GABAB receptors to increase cAMP signaling, therefore promoting corticospinal tract axon regeneration within the adult mouse spinal cord [171]. Evidence of astrocytes mediating axon regeneration via metabolites in stroke is still awaiting additional study. 3.3. The Stem Cell-Related Properties of Reactive Astrocytes Glial fibrillary acidic protein (GFAP), an intermediate filament protein, is commonly utilized as a marker to recognize astrocytes. Having said that, astrocyte-like NSCs in neurogenic niches also express GFAP. Subpopulations of reactive astrocytes proliferated and expressed stem cell-associated proteins like Nestin, Sox2, and RC2 just after injury [172,173]. An NSC may be a form of astrocyte; glial scar formation after injury may possibly partly be because of activated astrocyte-like NSCs differentiating into astrocytes under the control of post-stroke upregulated CNTF [174]. GLAST-positive reactive astrocytes coul.