期刊
JOURNAL OF STROKE & CEREBROVASCULAR DISEASES
卷 29, 期 12, 页码 -出版社
ELSEVIER
DOI: 10.1016/j.jstrokecerebrovasdis.2020.105255
关键词
Blood-brain barrier; claudin-5; early growth response-1; middle cerebral artery occlusion; peroxisome proliferator-activated receptor-gamma
资金
- National Natural Science Foundation of China [81770307]
- Excellent Going Abroad Experts' Training Program in Hebei Province
Background: Inflammatory response is a critical contributor to cerebral ischaemia injuries and blood brain barrier (BBB) dysfunction. Early growth response-1 (Egr-1), an oxygen-sensing transcription factor which is rapidly and markedly triggered in ischaemic events, acts as a master switch coordinating the upregulation of multiple target proinflammatory genes. Here, we explored whether peroxisome proliferator-activated receptor-gamma (PPAR gamma) activation by telmisartan can modulate Egr-1 expression and the subsequent inflammatory responses in a rat model of cerebral ischaemia. Methods: Cerebral ischaemia was induced in rats by middle cerebral artery occlusion (MCAO). Brain injury was evaluated by brain water content, infarct volume, and Evans blue dye extravasation. Egr-1 and claudin-5 levels were assessed by western blot and real-time polymerase chain reaction. Results: MCAO-provoked Egr-1 expression was time dependent, peaking at 24 h and continuing to 72 h. The elevation in Egr-1 was coupled with a reduction in claudin-5. Telmisartan treatment significantly corrected the alterations of Egr-1 and claudin-5, alleviated the neurological deficits, and reduced brain water content, infarct volume, and Evans blue dye extravasation 24 h after MCAO. However, all the benefits of telmisartan were reversed by antagonising PPAR gamma with GW9662. Conclusion: Egr-1, a proinflammatory factor, is positively associated with post-ischaemic inflammation and the associated BBB dysfunction. PPAR gamma serves as an upstream transcription factor of the Egr-1 cascade. Targeting Egr-1 may emerge as a potential strategy to suppress inflammatory responses following ischaemic stroke.
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