title: 17Beta-estradiol differentially protects cortical pericontusional zone from programmed cell death after traumatic cerebral contusion at distinct stages via non-genomic and genomic pathways.
abstract: Pericontusional zone (PCZ) of traumatic cerebral contusion is a target of pharmacological intervention. Our previous study indicated that 17beta-estradiol has a protective role in PCZ after traumatic cerebral contusion via the upregulation of estrogen receptor (ER) alpha mRNA induction and protein expression as well as inhibition of caspase-3 activation, suggesting that genomic signaling pathway is implicated in the protective effect of 17beta-estrodiol. Recent findings demonstrated that 17beta-estradiol also acts on the extranuclear/membrane ER to activate non-genomic signaling pathway to regulate cellular functions and exert the protective effect in the brain. It is still unclear how and whether genomic and non-genomic pathways of 17beta-estradiol are involved in the neuroprotection in PCZ. Our current study demonstrates that 17beta-estradiol activates ERK1/2 and Akt at the early stage and induces ERalpha and survivin mRNA at the late stage to modulate its protection via the suppression of caspase-3 activation in PCZ. These findings suggest that 17beta-estrodiol differentially plays its protective roles via genomic and non-genomic signaling pathways in PCZ after traumatic cerebral contusion.
authors.affiliation: Department of Neurosurgery, First Hospital of China Medical University, Shenyang, 110001, PR China. neurobao3@hotmail.com
authors.forename: Yi-Jun
authors.initials: YJ
authors.lastname: Bao
authors.forename: Li-Zhuo
authors.initials: LZ
authors.lastname: Li
authors.forename: Xin-Guo
authors.initials: XG
authors.lastname: Li
authors.forename: Yun-Jie
authors.initials: YJ
authors.lastname: Wang
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D001930:Brain Injuries / Q000188:drug therapy* / Q000378:metabolism; D053148:Caspase 3 / Q000378:metabolism; D004958:Estradiol / Q000494:pharmacology* / Q000627:therapeutic use; D047628:Estrogen Receptor alpha / Q000378:metabolism; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology* / Q000627:therapeutic use; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects; D013997:Time Factors
chemical_list: D047628:Estrogen Receptor alpha; D018696:Neuroprotective Agents; D004958:Estradiol; D053148:Caspase 3