Stroke · 2026
Loss of Pericytic Integrin-β1 Exacerbates Blood-Brain Barrier Damage and Hemorrhagic Brain Injury.
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Culha-Taskin Irem, Nasrollahi Ava, Yao Yao
Аннотация
BACKGROUND: Pericytes play essential roles in blood-brain barrier regulation and stroke pathogenesis. Given that pericytes are embedded in the ECM (extracellular matrix), it is speculated that ECM-receptor interactions are involved in these functions. Integrin-β1, the most common integrin subunit that can engage multiple ECM proteins, is highly expressed in pericytes. The function of pericytic integrin β1, however, remains unknown.
METHODS: To address this question, we generated brain pericyte-specific integrin-β1 knockout mice by crossing the Atp13a5 (ATPase type 13A5)-CreER with the Itgb1 floxed mice and characterized their phenotypes under homeostatic conditions and after intracerebral hemorrhage.
RESULTS: Under homeostatic conditions, pericyte-specific integrin-β1 knockout mice were grossly normal and failed to show blood-brain barrier disruption or pericyte/astrocyte defects. In the collagenase-induced intracerebral hemorrhage model, however, the pericyte-specific integrin-β1 knockout mice exhibited larger hematoma volume, enhanced brain edema, aggravated blood-brain barrier damage caused by both paracellular and transcellular mechanisms, reduced pericyte number/coverage and aquaporin-4 coverage, increased neuronal death, elevated gliosis, and worsened neurological outcomes. Interestingly, hypertensive pericyte-specific integrin-β1 knockout mice demonstrated similar changes in the autologous blood model of intracerebral hemorrhage.
CONCLUSIONS: These results suggest that brain pericyte-derived integrin-β1 is dispensable under homeostatic conditions but plays a protective role in intracerebral hemorrhage, likely through repairing blood-brain barrier damage and regulating gliosis.
METHODS: To address this question, we generated brain pericyte-specific integrin-β1 knockout mice by crossing the Atp13a5 (ATPase type 13A5)-CreER with the Itgb1 floxed mice and characterized their phenotypes under homeostatic conditions and after intracerebral hemorrhage.
RESULTS: Under homeostatic conditions, pericyte-specific integrin-β1 knockout mice were grossly normal and failed to show blood-brain barrier disruption or pericyte/astrocyte defects. In the collagenase-induced intracerebral hemorrhage model, however, the pericyte-specific integrin-β1 knockout mice exhibited larger hematoma volume, enhanced brain edema, aggravated blood-brain barrier damage caused by both paracellular and transcellular mechanisms, reduced pericyte number/coverage and aquaporin-4 coverage, increased neuronal death, elevated gliosis, and worsened neurological outcomes. Interestingly, hypertensive pericyte-specific integrin-β1 knockout mice demonstrated similar changes in the autologous blood model of intracerebral hemorrhage.
CONCLUSIONS: These results suggest that brain pericyte-derived integrin-β1 is dispensable under homeostatic conditions but plays a protective role in intracerebral hemorrhage, likely through repairing blood-brain barrier damage and regulating gliosis.