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Neurochem Res. 2018 Jul;43(7):1339-1347. doi: 10.1007/s11064-018-2549-0. Epub 2018 May 16.

ALDH2 Protects Against Ischemic Stroke in Rats by Facilitating 4-HNE Clearance and AQP4 Down-Regulation.

Author information

1
The Department of Anesthesiology, The Fourth Affiliated Hospital, Harbin Medical University, Yiyuan Street 37, Harbin, 150001, China.
2
The Department of Anesthesiology, The Fourth Affiliated Hospital, Harbin Medical University, Yiyuan Street 37, Harbin, 150001, China. sihuaqi_2012@163.com.

Abstract

Aldehyde dehydrogenase 2 (ALDH2) is a new therapeutic target in the central nervous system. However, the association between ALDH2 and brain edema following ischemic stroke (IS) remains unclear. The present study was investigated to whether active ALDH2 can attenuate brain edema by using a rat model of IS, with the aim of clarifying the underlying mechanisms involved. Rats were administered the ALDH2 agonist Alda-1, vehicle or the ALDH2 inhibitor cyanamide (CYA) 15 min prior to a 1.5 h middle cerebral artery occlusion (MCAO) surgery. The effects of ALDH2 were subsequently investigated 24 h after reperfusion by evaluating neurological function, infarct sizes, brain edema volumes, 4-hydroxy-2-nonenal (4-HNE) levels, and aquaporin 4 (AQP4) protein expression. The results demonstrated that increasing ALDH2 activity significantly improved neurological deficits, reduced infarct sizes, and attenuated brain edema after MCAO. Alda-1 administration led to decreased 4-HNE levels and inhibited AQP4 protein expression in the peri-infarct section of the brain. Whereas, CYA administration increased 4-HNE levels, AQP4 expression, and simultaneously aggravated brain edema following MCAO. In conclusion, increasing ALDH2 activity can improve brain edema, infarct volumes, and reduce neurological impairment in a rat IS model. The therapeutic benefits of ALDH2 are related to 4-HNE clearance and AQP4 down-regulation.

KEYWORDS:

4-HNE; ALDH2; Aquaporin 4; Brain edema; Middle cerebral artery occlusion

PMID:
29767275
DOI:
10.1007/s11064-018-2549-0
[Indexed for MEDLINE]

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