Ablation of astrocytic laminin impairs vascular smooth muscle cell function and leads to hemorrhagic stroke

Astrocytes express laminin and assemble basementmembranes (BMs) at their endfeet, which ensheaththe cerebrovasculature. The function of astrocyticlaminin in cerebrovascular integrity is unknown. We showthat ablation of astrocytic laminin by tissue-specific Cremediatedrecombination disrupted endfeet BMs and ledto hemorrhage in deep brain regions of adult mice, resemblinghuman hypertensive hemorrhage. The lack ofastrocytic laminin led to impaired function of vascularsmooth muscle cells (VSMCs), where astrocytes have acloser association with VSMCs in small arterioles, andwas associated with hemorrhagic vessels, which exhibitedVSMC fragmentation and vascular wall disassembly.Acute disruption of astrocytic laminin in the striatum ofadult mice also impaired VSMC function, indicating thatlaminin is necessary for VSMC maintenance. In vitro, bothastrocytes and astrocytic laminin promoted brain VSMCdifferentiation. These results show that astrocytes regulateVSMCs and vascular integrity in small vessels of deepbrain regions. Therefore, astrocytes may be a possibletarget for hemorrhagic stroke prevention and therapy.