title: Spermidine preconditioning ameliorates laurate-induced brain injury by maintaining mitochondrial stability.
abstract: Ischemic precondition plays a protective effect during cerebral ischemia. This effect partly depends on the autophagic activity. However, whether the activity of autophagy can exert the protective effects after cerebral ischemia is unclear. In this study, rats were treated with spermidine, an activator of autophagy, and injected with sodium laurate via the internal carotid artery to stimulate cerebral small vessel disease (CSVD). The effects of the spermidine precondition on brain injury were evaluated by behavioural test, histology assay, ultrastructure observation, and autophagic-related signals. Furthermore, the mitochondria of brain tissue were isolated, and mitDNA were extracted. The stability of mitDNA was analyzed by quantitative real-time PCR. Results showed that the penetrating artery of the striatum was damaged. This damage was accompanied by neural inflammation characterized by an increase in Fluoro-Jade C (FJC)-positive cells after sodium laurate injection. Spermidine pretreatment decreased the deletion of mitDNA and the autophagy hyperactivity induced by the laurate injection. Likewise, spermidine reduced the neurological deficit and FJC reactivation of striatum at 48 h after laurate injection. These results suggested sodium laurate injection through the internal carotid artery can induce the pathological features of CSVD characterized by the damage of penetrating artery, neurological deficit, mitochondrial impairment, and autophagic hyperactivity. Pretreatment with spermidine can ameliorate these outcomes. Further study indicated that the protective effect of the spermidine precondition is associated with the maintenance of mitochondrial stability and proper autophagy activity.
authors.affiliation: a Department of Neurology , People Hospital of Gansu Province , Lanzhou , P.R. China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: b School of Basic Medical Sciences, Institute of Anatomy and Histology & Embryology, Neuroscience , Lanzhou University , Lanzhou , P.R. China.
authors.forename: Jie
authors.initials: J
authors.lastname: Yin
authors.affiliation: b School of Basic Medical Sciences, Institute of Anatomy and Histology & Embryology, Neuroscience , Lanzhou University , Lanzhou , P.R. China.
authors.forename: Lang
authors.initials: L
authors.lastname: Zhang
authors.affiliation: b School of Basic Medical Sciences, Institute of Anatomy and Histology & Embryology, Neuroscience , Lanzhou University , Lanzhou , P.R. China.
authors.forename: Chu-Chu
authors.initials: CC
authors.lastname: Qi
authors.affiliation: c School of Basic Medical Sciences, Institute of Biochemistry and Molecular Biology , Lanzhou University , Lanzhou , P.R. China.
authors.forename: Ze-Lin
authors.initials: ZL
authors.lastname: Ma
authors.affiliation: c School of Basic Medical Sciences, Institute of Biochemistry and Molecular Biology , Lanzhou University , Lanzhou , P.R. China.
authors.forename: Li-Ping
authors.initials: LP
authors.lastname: Gao
authors.affiliation: b School of Basic Medical Sciences, Institute of Anatomy and Histology & Embryology, Neuroscience , Lanzhou University , Lanzhou , P.R. China.
authors.forename: De-Gui
authors.initials: DG
authors.lastname: Wang
authors.affiliation: b School of Basic Medical Sciences, Institute of Anatomy and Histology & Embryology, Neuroscience , Lanzhou University , Lanzhou , P.R. China.|d Key Laboratory of Preclinical Study for New Drugs of Gansu Province , Lanzhou University , Lanzhou , P.R. China.
authors.forename: Yu-Hong
authors.initials: YH
authors.lastname: Jing
mesh_terms: D000818:Animals; D001343:Autophagy / Q000187:drug effects*; D059345:Cerebral Small Vessel Diseases / Q000139:chemically induced / Q000517:prevention & control*; D003342:Corpus Striatum / Q000187:drug effects*; D004272:DNA, Mitochondrial / Q000187:drug effects*; D004195:Disease Models, Animal; D007848:Laurates / Q000494:pharmacology; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D013095:Spermidine / Q000494:pharmacology*
chemical_list: D004272:DNA, Mitochondrial; D007848:Laurates; D013095:Spermidine
keywords: Cerebral small vessel disease; autophagy; mitochondria; spermidine