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Microvasc Res. 2019 Jul 5;126:103891. doi: 10.1016/j.mvr.2019.103891. [Epub ahead of print]

Tert-butylhydroquinone enhanced angiogenesis and astrocyte activation by activating nuclear factor-E2-related factor 2/heme oxygenase-1 after focal cerebral ischemia in mice.

Author information

1
Department of Neurology, The Second Hospital of Hebei Medical University, 215 Hepingxi Road, Shijiazhuang, Hebei 050000, PR China; Department of Endocrinology, The Second Hospital of Hebei Medical University, 215 Hepingxi Road, Shijiazhuang, Hebei 050000, PR China.
2
Department of Neurology, The Second Hospital of Hebei Medical University, 215 Hepingxi Road, Shijiazhuang, Hebei 050000, PR China; Hebei Key Laboratory of Vascular Homeostasis and Hebei Collaborative Innovation Center for Cardio-cerebrovascular Disease, 215 Hepingxi Road, Shijiazhuang, Hebei 050000, PR China. Electronic address: zhang6xj@aliyun.com.
3
Department of Neurology, The Second Hospital of Hebei Medical University, 215 Hepingxi Road, Shijiazhuang, Hebei 050000, PR China.
4
Department of Endocrinology, The Second Hospital of Hebei Medical University, 215 Hepingxi Road, Shijiazhuang, Hebei 050000, PR China.
5
Department of Neurology, The Second Hospital of Hebei Medical University, 215 Hepingxi Road, Shijiazhuang, Hebei 050000, PR China; Hebei Key Laboratory of Vascular Homeostasis and Hebei Collaborative Innovation Center for Cardio-cerebrovascular Disease, 215 Hepingxi Road, Shijiazhuang, Hebei 050000, PR China.

Abstract

Angiogenesis after cerebral ischemia plays a pivotal role in neurological recovery and represents a therapeutic target. The angiogenic effect of nuclear factor E2-related factor 2 (Nrf2) was identified in recent years. However, the effects of tert-butylhydroquinone, an Nrf2 inducer, on angiogenesis and astrocyte activation after stroke remain unclear. In this study, we investigated whether tert-butylhydroquinone enhanced angiogenesis and astrocyte activation through Nrf2 pathway. Wild-type (Nrf2+/+) and Nrf2-deficient (Nrf2-/-) mice were subjected to permanent distal middle cerebral artery occlusion (dMCAO). We established 6 experimental groups (sham Nrf2+/+ group, vehicle Nrf2+/+ group, tBHQ Nrf2+/+ group; sham Nrf2-/- group, vehicle Nrf2-/- group, and tBHQ Nrf2-/- group). The infarct volume, neurological function, microvessel density (MVD), astrocytic endfeet covered ratio and the expression of Nrf2, HO-1 and VEGF in the ischemic brain were measured at different time points. Compared with that observed in the vehicle Nrf2+/+ group, tBHQ significantly reduced the infarct volume, enhanced post-stroke angiogenesis and astrocytic endfeet covered ratio in the peri-infarct area. The Nrf2/HO-1/VEGF pathway was activated by tBHQ in the angiogenesis process. However, in Nrf2-/- mice, Nrf2 deficiency blocked the effects of tBHQ on angiogenesis process and neurological recovery as well as abolished the mediation of proangiogenic factors. These results suggested that tBHQ enhanced angiogenesis and astrocyte activation through activating Nrf2 pathway after cerebral ischemia.

KEYWORDS:

Angiogenesis; Astrocyte activation; Cerebral ischemia; Nuclear factor E2-related factor 2; Tert-butylhydroquinone

PMID:
31283926
DOI:
10.1016/j.mvr.2019.103891

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