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Neuroscience. 2019 May 12;410:140-149. doi: 10.1016/j.neuroscience.2019.05.005. [Epub ahead of print]

Sestrin2 overexpression attenuates focal cerebral ischemic injury in rat by increasing Nrf2/HO-1 pathway-mediated angiogenesis.

Author information

1
Department of Pathology, Chongqing Medical University, Chongqing, People's Republic of China; Institute of Neuroscience, Chongqing Medical University, Chongqing, People's Republic of China.
2
Department of Pathology, Chongqing Medical University, Chongqing, People's Republic of China; Institute of Neuroscience, Chongqing Medical University, Chongqing, People's Republic of China. Electronic address: zhaoyong668@cqmu.edu.cn.

Abstract

Sestrin2 (Sesn2) is a stress response protein which expresses neuroprotective characteristics in some neurodegenerative disorders. However, the impact of Sesn2 on the clinical outcome of stroke is unclear. The nuclear factor-erythroid 2 related factor 2/heme oxygenase-1 (Nrf2/HO-1) pathway is a key factor in angiogenesis, which aids in attenuating cerebral ischemia damage. In this study the investigators examine the effects of Sesn2 on cerebral ischemia damage by increasing angiogenesis through the Nrf2/HO-1 signaling pathway. Healthy adult Sprague-Dawley (SD) rats were exposed to photochemical cerebral ischemia while AAV injection was used to overexpress Sesn2. At 5 days after photochemical embolization, the investigators observed a reduction in neurological problems, decreased infarct volume, and diminished neuronal injury in the Sesn2 overexpression samples compared to the controls. To further explore these defensive mechanisms, the investigators also silenced Nrf2. While Sesn2, Nrf2, HO-1, and VEGF were significantly increased following cerebral ischemia, overexpression of Sesn2 further increased their expression. After silencing Nrf2, the opposite effect was observed. These results imply that Sestrin2 may activate the Nrf2 / HO-1 pathway, leading to enhanced angiogenesis following photothrombotic cerebral ischemia.

KEYWORDS:

Nrf2/HO-1; Sestrin2; VEGF; angiogenesis

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