Ras-Related C3 Botulinum Toxin Substrate 1 Promotes Axonal Regeneration after Stroke in Mice

Translational Stroke Research
Lin LiuJun Li

Abstract

Neurite plasticity is a critical aspect of brain functional recovery after stroke. Emerging data suggest that Ras-related C3 botulinum toxin substrate 1 (Rac1) plays a central role in axonal regeneration in the injured brain, specifically by stimulating neuronal intrinsic growth and counteracting the growth inhibitory signaling that leads to growth cone collapse. Therefore, we investigated the functional role of Rac1 in axonal regeneration after stroke.Delayed treatment with a specific Rac1 inhibitor, NSC 23766, worsened functional recovery, which was assessed by the pellet reaching test from day 14 to day 28 after stroke. It additionally reduced axonal density in the peri-infarct zone, assessed 28 days after stroke, with no effect on brain cavity size or on the number of newly formed cells. Accordingly, Rac1 overexpression using lentivirus promoted axonal regeneration and functional recovery after stroke from day 14 to day 28. Rac1 inhibition led to inactivation of pro-regenerative molecules, including mitogen-activated protein kinase kinase (p-MEK)1/2, LIM domain kinase (LIMK)1, and extracellular signal-regulated kinase (p-ERK)1/2 at 14 days after stroke. Inhibition of Rac1 reduced axonal length and number in cultured primary...Continue Reading

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Citations

Jan 2, 2020·Proceedings of the National Academy of Sciences of the United States of America·Abdullah Al MamunFudong Liu
Jul 17, 2021·Neural Regeneration Research·Bor Luen Tang

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Methods Mentioned

BETA
GTPase

Software Mentioned

SPSS
ImageJ
Zeiss

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