Involvement of p38 MAPK in reactive astrogliosis induced by ischemic stroke.
Reactive astrogliosis is an essential feature of astrocytic response to all forms of central nervous system (CNS) injury and disease, which may benefit or harm surrounding neural and non-neural cells. Despite extensive study, its molecular triggers remain largely unknown in term of ischemic stroke. In the current study we investigated the role p38 mitogen-activated protein kinase (MAPK) in astrogliosis both in vitro and in vivo. In a mouse model of middle cerebral artery occlusion (MCAO), p38 MAPK activation was observed in the glia scar area, along with increased glial fibrillary acidic protein (GFAP) expression. In primary astrocyte cultures, hypoxia and scratch injury-induced astrogliosis was attenuated by both p38 inhibition and knockout of p38 MAPK. In addition, both knockout and inhibition of p38 MAPK also reduced astrocyte migration, but did not affect astrocyte proliferation. In a mouse model of permanent MCAO, no significant difference in motor function recovery and lesion volume was observed between conditional GFAP/p38 MAPK knockout mice and littermates. While a significant reduction of astrogliosis was observed in the GFAP/p38 knockout mice compared with the littermates. Our findings suggest that p38 MAPK signaling pathway plays an important role in the ischemic stroke-induced astrogliosis and thus may serve as a novel target to control glial scar formation.
Department of Pharmacology and Neuroscience, University of North Texas Health Science Center at Fort Worth, 3500 Camp Bowie Blvd, Fort Worth, TX 76107, USA.
Gourav
G
Roy Choudhury
Department of Pharmacology and Neuroscience, University of North Texas Health Science Center at Fort Worth, 3500 Camp Bowie Blvd, Fort Worth, TX 76107, USA.
Myoung-Gwi
MG
Ryou
Department of Pharmacology and Neuroscience, University of North Texas Health Science Center at Fort Worth, 3500 Camp Bowie Blvd, Fort Worth, TX 76107, USA.
Ethan
E
Poteet
Department of Pharmacology and Neuroscience, University of North Texas Health Science Center at Fort Worth, 3500 Camp Bowie Blvd, Fort Worth, TX 76107, USA.
Yi
Y
Wen
Department of Pharmacology and Neuroscience, University of North Texas Health Science Center at Fort Worth, 3500 Camp Bowie Blvd, Fort Worth, TX 76107, USA.
Runlian
R
He
Department of Pharmacology and Neuroscience, University of North Texas Health Science Center at Fort Worth, 3500 Camp Bowie Blvd, Fort Worth, TX 76107, USA.
Fen
F
Sun
Department of Neurosurgery, Beijing Tiantan Hospital, Beijing Neurosurgical Institute, Capital Medical University, Beijing 100050, China.
Fang
F
Yuan
Department of Pharmacology and Neuroscience, University of North Texas Health Science Center at Fort Worth, 3500 Camp Bowie Blvd, Fort Worth, TX 76107, USA.
Kunlin
K
Jin
Department of Pharmacology and Neuroscience, University of North Texas Health Science Center at Fort Worth, 3500 Camp Bowie Blvd, Fort Worth, TX 76107, USA; Department of Neurosurgery, Beijing Tiantan Hospital, Beijing Neurosurgical Institute, Capital Medical University, Beijing 100050, China. Electronic address: shaohua.yang@unthsc.edu.
Shao-Hua
SH
Yang
D000818:Animals; D001253:Astrocytes / Q000201:enzymology* / Q000378:metabolism; D002545:Brain Ischemia / Q000150:complications / Q000201:enzymology* / Q000378:metabolism; D002540:Cerebral Cortex / Q000201:enzymology / Q000378:metabolism / Q000473:pathology; D005911:Gliosis / Q000201:enzymology* / Q000209:etiology / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D020521:Stroke / Q000150:complications / Q000201:enzymology* / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism / Q000502:physiology*
D048051:p38 Mitogen-Activated Protein Kinases
Astrocytes; Astrogliosis; Glial fibrillary acidic protein; Ischemia; Stroke; p38 MAPK