title: Blocking epidermal growth factor receptor attenuates reactive astrogliosis through inhibiting cell cycle progression and protects against ischemic brain injury in rats.
abstract: Excessive astrogliosis is a major impediment to axonal regeneration in CNS disorders. Overcoming this inhibitory barrier of reactive astrocytes might be crucial for CNS repair. Up-regulation and activation of epidermal growth factor receptor (EGFR) has been shown to trigger quiescent astrocytes into reactive astrocytes in response to several neural injuries. In this study, we investigated the effects of EGFR blockade in cultured astrocytes exposure to oxygen-glucose deprivation/reoxygenation (OGD/R) and in the rat middle cerebral artery occlusion (MCAO) model. Astrocytes in primary culture were used for OGD/R model and adult male Sprague-Dawley rats were used for MCAO model. Cell cycle progression of astrocytes in vitro was studied by flow cytometric analysis. Expression of phosphorylated epidermal growth factor receptor (p-EGFR), glial fibrillary acidic protein (GFAP), and cell proliferation-related molecules in vitro and in vivo were evaluated by immunostaining and western blot analysis. Neuronal apoptosis after MCAO was determined by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) method. Neurologic scores and infarct volumes post-ischemia were assessed in the rat MCAO model. Astrocytes became activated in the cultured astrocytes exposure to OGD/R and in the rat brain after MCAO, accompanied with phosphorylation of EGFR. EGFR blockade significantly decreased expression of p-EGFR, inhibited cell cycle progression of astrocytes, and reduced reactive astrogliosis in vitro and in vivo. EGFR inhibition also reduced infarct volumes and improved neurologic scores of rats after MCAO. Our findings indicated that blocking EGFR pathway might attenuate reactive astrogliosis through inhibiting cell cycle progression and protect against ischemic brain injury in rats.
authors: Department of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
authors: Qin
authors: Q
authors: Yang
authors: En-Yin
authors: EY
authors: Wang
authors: Xiao-Jiang
authors: XJ
authors: Huang
authors: Wen-Sheng
authors: WS
authors: Qu
authors: Lin
authors: L
authors: Zhang
authors: Jin-Zhi
authors: JZ
authors: Xu
authors: Wei
authors: W
authors: Wang
authors: Dai-Shi
authors: DS
authors: Tian
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D000911:Antibodies, Monoclonal / Q000494:pharmacology / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology*; D002545:Brain Ischemia / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D002453:Cell Cycle / Q000187:drug effects / Q000502:physiology*; D002478:Cells, Cultured; D000068818:Cetuximab; D066246:ErbB Receptors / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D005911:Gliosis / Q000378:metabolism / Q000473:pathology* / Q000517:prevention & control*; D008297:Male; D018696:Neuroprotective Agents / Q000494:pharmacology / Q000627:therapeutic use; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D018696:Neuroprotective Agents; C483803:Egfr protein, rat; D066246:ErbB Receptors; D000068818:Cetuximab