Ischemic stroke causes secondary neurodegeneration in the thalamus ipsilateral to the
infarction site and impedes neurological recovery. Axonal degeneration of thalamocortical fibers and autophagy overactivation are involved in thalamic neurodegeneration after
ischemic stroke. However, the molecular mechanisms underlying thalamic neurodegeneration remain unclear. Sterile /Armadillo/Toll-
Interleukin receptor homology domain protein (SARM1) can induce
Wallerian degeneration. Herein, we aimed to investigate the role of SARM1 in thalamic neurodegeneration and autophagy activation after photothrombotic
infarction. Neurological deficits measured using modified neurological severity scores and adhesive-removal test were ameliorated in Sarm1-/- mice after photothrombotic
infarction. Compared with wild-type mice, Sarm1-/- mice exhibited unaltered
infarct volume; however, there were markedly reduced neuronal death and
gliosis in the ipsilateral thalamus. In parallel, autophagy activation was attenuated in the thalamus of Sarm1-/- mice after
cerebral infarction. Thalamic Sarm1 re-expression in Sarm1-/- mice increased thalamic neurodegeneration and promoted autophagy activation. Auotophagic inhibitor
3-methyladenine partially alleviated thalamic damage induced by SARM1. Moreover, autophagic initiation through
rapamycin treatment aggravated post-
stroke neuronal death and
gliosis in Sarm1-/- mice. Taken together, SARM1 contributes to secondary thalamic neurodegeneration after
cerebral infarction, at least partly through autophagy inhibition. SARM1 deficiency is a potential therapeutic strategy for secondary thalamic neurodegeneration and functional deficits after
stroke.