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

年龄和性别对 α-Syn(α-突触核蛋白)敲低介导的中风后恢复的影响

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作者:Bharath Chelluboina, Taehee Kim, Suresh L Mehta, Joo-Yong Kim, Saivenkateshkomal Bathula, Raghu Vemuganti

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.

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.

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.

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.

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.

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