Impact of Age and Sex on α-Syn (α-Synuclein) Knockdown-Mediated Poststroke Recovery

BACKGROUND AND PURPOSE:Increased expression of α-Syn (α-Synuclein) is known to mediate secondary brain damage after stroke. We presently studied if α-Syn knockdown can protect ischemic brain irrespective of sex and age. METHODS:Adult and aged male and female mice were subjected to transient middle c...

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Published in:Stroke (1970) 2020-10, Vol.51 (10), p.3138-3141
Main Authors: Chelluboina, Bharath, Kim, Taehee, Mehta, Suresh L., Kim, Joo-Yong, Bathula, Saivenkateshkomal, Vemuganti, Raghu
Format: Article
Language:English
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Summary:BACKGROUND AND PURPOSE:Increased expression of α-Syn (α-Synuclein) is known to mediate secondary brain damage after stroke. We presently studied if α-Syn knockdown can protect ischemic brain irrespective of sex and age. METHODS:Adult and aged male and female mice were subjected to transient middle cerebral artery occlusion. α-Syn small interfering RNA (siRNA) was administered intravenous at 30 minutes or 3 hour reperfusion. Poststroke motor deficits were evaluated between day 1 and 7 and infarct volume was measured at day 7 of reperfusion. RESULTS:α-Syn knockdown significantly decreased poststroke brain damage and improved poststroke motor function recovery in adult and aged mice of both sexes. However, the window of therapeutic opportunity for α-Syn siRNA is very limited. CONCLUSIONS:α-Syn plays a critical role in ischemic brain damage and preventing α-Syn protein expression early after stroke minimizes poststroke brain damage leading to better functional outcomes irrespective of age and sex.
ISSN:0039-2499
1524-4628
DOI:10.1161/STROKEAHA.120.028978