title: Pramipexole-Induced Hypothermia Reduces Early Brain Injury via PI3K/AKT/GSK3β pathway in Subarachnoid Hemorrhage rats.
abstract: Previous studies have shown neuroprotective effects of hypothermia. However, its effects on subarachnoid hemorrhage (SAH)-induced early brain injury (EBI) remain unclear. In this study, a SAH rat model was employed to study the effects and mechanisms of pramipexole-induced hypothermia on EBI after SAH. Dose-response experiments were performed to select the appropriate pramipexole concentration and frequency of administration for induction of mild hypothermia (33-36 °C). Western blot, neurobehavioral evaluation, Terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) and Fluoro-Jade B (FJB) staining were used to detect the effects of pramipexole-induced hypothermia on SAH-induced EBI, as well as to study whether controlled rewarming could attenuate these effects. Inhibitors targeting the PI3K/AKT/GSK3β pathway were administered to determine whether the neuroprotective effect of pramipexole-induced hypothermia was mediated by PI3K/AKT/GSK3β signaling pathway. The results showed that intraperitoneal injection of pramipexole at 0.25 body weight once per 8 hours was found to successfully and safely maintain rats at mild hypothermia. Pramipexole-induced hypothermia ameliorated SAH-induced brain cell death, blood-brain barrier damage and neurobehavioral deficits in a PI3K/AKT/GSK3β signaling-dependent manner. Therefore, we may conclude that pramipexole-induced hypothermia could effectively inhibit EBI after SAH in rats via PI3K/AKT/GSK3β signaling pathway.
authors.affiliation: Department of Neurosurgery &Brain and Nerve Research Laboratory, The First Affiliated Hospital of Soochow University, 188 Shizi Street, Suzhou 215006, China.|Department of Neurosurgery, Suzhou Kowloon Hospital Affiliated Shanghai Jiao Tong University, Suzhou, 266021, China.
authors.forename: Junwei
authors.initials: J
authors.lastname: Ma
authors.affiliation: Department of Neurosurgery &Brain and Nerve Research Laboratory, The First Affiliated Hospital of Soochow University, 188 Shizi Street, Suzhou 215006, China.
authors.forename: Zhong
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Department of Neurosurgery &Brain and Nerve Research Laboratory, The First Affiliated Hospital of Soochow University, 188 Shizi Street, Suzhou 215006, China.
authors.forename: Chenglin
authors.initials: C
authors.lastname: Liu
authors.affiliation: Department of Neurosurgery &Brain and Nerve Research Laboratory, The First Affiliated Hospital of Soochow University, 188 Shizi Street, Suzhou 215006, China.
authors.forename: Haitao
authors.initials: H
authors.lastname: Shen
authors.affiliation: Department of Neurosurgery &Brain and Nerve Research Laboratory, The First Affiliated Hospital of Soochow University, 188 Shizi Street, Suzhou 215006, China.
authors.forename: Zhouqing
authors.initials: Z
authors.lastname: Chen
authors.affiliation: Department of Neurosurgery &Brain and Nerve Research Laboratory, The First Affiliated Hospital of Soochow University, 188 Shizi Street, Suzhou 215006, China.
authors.forename: Jia
authors.initials: J
authors.lastname: Yin
authors.affiliation: Department of Neurosurgery &Brain and Nerve Research Laboratory, The First Affiliated Hospital of Soochow University, 188 Shizi Street, Suzhou 215006, China.
authors.forename: Gang
authors.initials: G
authors.lastname: Zuo
authors.affiliation: Department of Neurosurgery &Brain and Nerve Research Laboratory, The First Affiliated Hospital of Soochow University, 188 Shizi Street, Suzhou 215006, China.
authors.forename: Xiaochun
authors.initials: X
authors.lastname: Duan
authors.affiliation: Department of Neurosurgery &Brain and Nerve Research Laboratory, The First Affiliated Hospital of Soochow University, 188 Shizi Street, Suzhou 215006, China.
authors.forename: Haiying
authors.initials: H
authors.lastname: Li
authors.affiliation: Department of Neurosurgery &Brain and Nerve Research Laboratory, The First Affiliated Hospital of Soochow University, 188 Shizi Street, Suzhou 215006, China.
authors.forename: Gang
authors.initials: G
authors.lastname: Chen
mesh_terms: D000818:Animals; D017209:Apoptosis; D052160:Benzothiazoles / Q000494:pharmacology* / Q000627:therapeutic use; D001812:Blood-Brain Barrier / Q000378:metabolism; D001921:Brain / Q000098:blood supply / Q000187:drug effects / Q000473:pathology; D004353:Drug Evaluation, Preclinical; D000071679:Glycogen Synthase Kinase 3 beta / Q000378:metabolism; D007036:Hypothermia, Induced; D008297:Male; D018696:Neuroprotective Agents / Q000494:pharmacology* / Q000627:therapeutic use; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D000077487:Pramipexole; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction; D013345:Subarachnoid Hemorrhage / Q000378:metabolism / Q000473:pathology / Q000628:therapy*
chemical_list: D052160:Benzothiazoles; D018696:Neuroprotective Agents; D000077487:Pramipexole; D019869:Phosphatidylinositol 3-Kinases; D000071679:Glycogen Synthase Kinase 3 beta; C000605508:Gsk3b protein, rat; D051057:Proto-Oncogene Proteins c-akt