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Pericyte hypoxia-inducible factor-1 (HIF-1) drives blood-brain barrier disruption and impacts acute ischemic stroke outcome
- Source :
- Tsao, Chih-Chieh; Baumann, Julia; Huang, Sheng-Fu; Kindler, Diana; Schroeter, Aileen; Kachappilly, Nicole; Gassmann, Max; Rudin, Markus; Ogunshola, Omolara O (2021). Pericyte hypoxia-inducible factor-1 (HIF-1) drives blood-brain barrier disruption and impacts acute ischemic stroke outcome. Angiogenesis, 24(4):823-842.
- Publication Year :
- 2021
-
Abstract
- Pericytes play essential roles in blood-brain barrier integrity and their dysfunction is implicated in neurological disorders such as stroke although the underlying mechanisms remain unknown. Hypoxia-inducible factor-1 (HIF-1), a master regulator of injury responses, has divergent roles in different cells especially during stress scenarios. On one hand HIF-1 is neuroprotective but on the other it induces vascular permeability. Since pericytes are critical for barrier stability, we asked if pericyte HIF-1 signaling impacts barrier integrity and injury severity in a mouse model of ischemic stroke. We show that pericyte HIF-1 loss of function (LoF) diminishes ischemic damage and barrier permeability at 3 days reperfusion. HIF-1 deficiency preserved barrier integrity by reducing pericyte death thereby maintaining vessel coverage and junctional protein organization, and suppressing vascular remodeling. Importantly, considerable improvements in sensorimotor function were observed in HIF-1 LoF mice indicating that better vascular functionality post stroke improves outcome. Thus, boosting vascular integrity by inhibiting pericytic HIF-1 activation and/or increasing pericyte survival may be a lucrative option to accelerate recovery after severe brain injury.
Details
- Database :
- OAIster
- Journal :
- Tsao, Chih-Chieh; Baumann, Julia; Huang, Sheng-Fu; Kindler, Diana; Schroeter, Aileen; Kachappilly, Nicole; Gassmann, Max; Rudin, Markus; Ogunshola, Omolara O (2021). Pericyte hypoxia-inducible factor-1 (HIF-1) drives blood-brain barrier disruption and impacts acute ischemic stroke outcome. Angiogenesis, 24(4):823-842.
- Notes :
- application/pdf, info:doi/10.5167/uzh-204220, English, English
- Publication Type :
- Electronic Resource
- Accession number :
- edsoai.on1443037804
- Document Type :
- Electronic Resource