title: Intermittent fasting is neuroprotective in focal cerebral ischemia by minimizing autophagic flux disturbance and inhibiting apoptosis.
abstract: Previous studies have demonstrated that autophagy induced by caloric restriction (CR) is neuroprotective against cerebral ischemia. However, it has not been determined whether intermittent fasting (IF), a variation of CR, can exert autophagy-related neuroprotection against cerebral ischemia. Therefore, the neuroprotective effect of IF was evaluated over the course of two weeks in a rat model of focal cerebral ischemia, which was induced by middle cerebral artery occlusion and reperfusion (MCAO/R). Specifically, the role of autophagy modulation as a potential underlying mechanism for this phenomenon was investigated. It was demonstrated that IF reduced infarct volume and brain edema, improved neurobehavioral deficits, and rescued neuronal loss after MCAO/R. Furthermore, neuronal apoptosis was decreased by IF in the rat cortex. An increase in the number of autophagosomes (APs) was demonstrated in the cortices of IF-treated rats, using immunofluorescence staining and transmission electron microscopy. Using immunoblots, an IF-induced increase was detected in microtubule-associated protein 1 light chain 3 (LC3)-II, Rab7, and cathepsin D protein levels, which corroborated previous morphological studies. Notably, IF reduced the accumulation of APs and p62, demonstrating that IF attenuated the MCAO/R-induced disturbance of autophagic flux in neurons. The findings of the present study suggest that IF-induced neuroprotection in focal cerebral ischemia is due, at least in part, to the minimization of autophagic flux disturbance and inhibition of apoptosis.
authors.affiliation: Department of Anatomy, College of Medicine, Konyang University, Seo-gu, Daejeon 302-718, Republic of Korea.
authors.forename: Ji Heun
authors.initials: JH
authors.lastname: Jeong
authors.affiliation: Department of Anatomy, College of Medicine, Konyang University, Seo-gu, Daejeon 302-718, Republic of Korea.
authors.forename: Kwang Sik
authors.initials: KS
authors.lastname: Yu
authors.affiliation: Department of Anatomy, College of Medicine, Konyang University, Seo-gu, Daejeon 302-718, Republic of Korea.
authors.forename: Dong Ho
authors.initials: DH
authors.lastname: Bak
authors.affiliation: Department of Anatomy, College of Medicine, Konyang University, Seo-gu, Daejeon 302-718, Republic of Korea.
authors.forename: Je Hun
authors.initials: JH
authors.lastname: Lee
authors.affiliation: Department of Anatomy, College of Medicine, Konyang University, Seo-gu, Daejeon 302-718, Republic of Korea.
authors.forename: Nam Seob
authors.initials: NS
authors.lastname: Lee
authors.affiliation: Department of Anatomy, College of Medicine, Konyang University, Seo-gu, Daejeon 302-718, Republic of Korea.
authors.forename: Young Gil
authors.initials: YG
authors.lastname: Jeong
authors.affiliation: Department of Physiology, College of Medicine, Konyang University, Seo-gu, Daejeon 302-718, Republic of Korea.
authors.forename: Dong Kwan
authors.initials: DK
authors.lastname: Kim
authors.affiliation: Department of Anatomy, Brain Research Institute, College of Medicine, Chungnam National University, Jung-gu, Daejeon 301-747, Republic of Korea; LES Corporation Inc., Yuseong-gu, Daejeon 305-335, Republic of Korea.
authors.forename: Jwa-Jin
authors.initials: JJ
authors.lastname: Kim
authors.affiliation: Department of Anatomy, College of Medicine, Konyang University, Seo-gu, Daejeon 302-718, Republic of Korea.
authors.forename: Seung-Yun
authors.initials: SY
authors.lastname: Han
keywords: apoptosis; autophagic flux; intermittent fasting; middle cerebral artery occlusion/reperfusion