Genetic inactivation of SARM1 axon degeneration pathway improves outcome trajectory after experimental traumatic brain injury based on pathological, radiological, and functional measures.

ABSTRACT: Traumatic brain injury (TBI) causes chronic symptoms and increased risk of neurodegeneration. Axons in white matter tracts, such as the corpus callosum (CC), are critical components of neural circuits and particularly vulnerable to TBI. Treatments are needed to protect axons from traumatic injury and mitigate post-traumatic neurodegeneration. SARM1 protein is a central driver of axon degeneration through a conserved molecular pathway. Sarm1-/- mice with knockout (KO) of the Sarm1 gene enable genetic proof-of-concept testing of the SARM1 pathway as a therapeutic target. We evaluated Sarm1 deletion effects after TBI using a concussive model that causes traumatic axonal injury and progresses to CC atrophy at 10 weeks, indicating post-traumatic neurodegeneration. Sarm1 wild-type (WT) mice deve

SUBMITTER: Bradshaw DV 

PROVIDER: S-EPMC8130449 | biostudies-literature | 2021 May

REPOSITORIES: biostudies-literature