Scutellarin promotes microglia-mediated astrogliosis coupled with improved behavioral function in cerebral ischemia.
Scutellarin, an anti-inflammatory agent, has been reported to suppress microglia activation. It promotes astrocytic reaction but through activated microglia. Here we sought to determine more specifically the outcomes of scutellarin treatment in reactive astrocytes in rats subjected to middle cerebral artery occlusion (MCAO). GFAP, MAP-2 and PSD-95 expression was assessed in reactive astrocytes in scutellarin injected MCAO rats. Expression of BDNF, NT-3 and IGF-1, and cell cycle markers cyclin-D1/B1 was also evaluated. In vitro, the above-mentioned proteins were also investigated in TNC 1 and primary astrocytes, treated respectively with conditioned medium from BV-2 microglia with or without pretreatment of scutellarin and lipopolysaccharide. Behavioral study was conducted to ascertain if scutellarin would improve the neurological functions of MCAO rats. In MCAO, reactive astrocytes in the penumbral areas were hypertrophic bearing long extending processes; expression of all the above-mentioned markers was markedly augmented. When compared to the controls, TNC1/primary astrocytes responded vigorously to conditioned medium derived from BV-2 microglia treated with scutellarin + lipopolysaccharide as shown by enhanced expression of all the above markers by Western and immunofluorescence analysis. By electron microscopy, hypertrophic TNC1 astrocytes in this group showed abundant microfilaments admixed with microtubules. In MCAO rats given scutellarin treatment, neurological scores were significantly improved coupled with a marked decrease in infarct size when compared with the matching controls. It is concluded that scutellarin is neuroprotective and that it can amplify astrogliosis but through activated microglia. Scutellarin facilitates tissue remodeling in MCAO that maybe linked to improvement of neurological functions.
Department of Emergency and Critical Care, Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou, 510080, China; Department of Anatomy, Yong Loo Lin School of Medicine, 4 Medical Drive, MD10, National University of Singapore, 117594, Singapore. Electronic address: drfangming@163.com.
Ming
M
Fang
Department of Anatomy and Histology/Embryology, Kunming Medical University, 1168 West Chunrong Road, Kunming, 650500, China. Electronic address: yuanyunkm@126.com.
Yun
Y
Yuan
Department of Anatomy, Yong Loo Lin School of Medicine, 4 Medical Drive, MD10, National University of Singapore, 117594, Singapore; Defence Medical and Environmental Research Institute, DSO National Laboratories, 27 Medical Drive, 117510, Singapore. Electronic address: ljia@dso.org.sg.
Jia
J
Lu
Department of Anatomy and Histology/Embryology, Kunming Medical University, 1168 West Chunrong Road, Kunming, 650500, China. Electronic address: lihonge89@163.com.
Hong E
HE
Li
Department of Anatomy and Histology/Embryology, Kunming Medical University, 1168 West Chunrong Road, Kunming, 650500, China. Electronic address: zhaomin_kmmu@163.com.
Min
M
Zhao
Department of Anatomy, Yong Loo Lin School of Medicine, 4 Medical Drive, MD10, National University of Singapore, 117594, Singapore. Electronic address: antlea@nus.edu.sg.
Eng-Ang
EA
Ling
Department of Anatomy and Histology/Embryology, Kunming Medical University, 1168 West Chunrong Road, Kunming, 650500, China. Electronic address: wuchunyunkm@163.com.
Chun-Yun
CY
Wu
D000818:Animals; D047310:Apigenin / Q000494:pharmacology* / Q000627:therapeutic use; D002545:Brain Ischemia / Q000188:drug therapy* / Q000473:pathology; D002465:Cell Movement / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D003071:Cognition / Q000187:drug effects* / Q000502:physiology; D005911:Gliosis / Q000188:drug therapy* / Q000473:pathology; D005965:Glucuronates / Q000494:pharmacology* / Q000627:therapeutic use; D008297:Male; D017628:Microglia / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley
D005965:Glucuronates; C484876:scutellarin; D047310:Apigenin
Activated microglia; Cerebral ischemia; Neurotrophic factors; Reactive astrocytes; Scutellarin