Phenothiazines Enhance Mild Hypothermia-induced Neuroprotection via PI3K/Akt Regulation in Experimental Stroke

Physical hypothermia has long been considered a promising neuroprotective treatment of ischemic stroke, but the treatment’s various complications along with the impractical duration and depth of therapy significantly narrow its clinical scope. In the present study, the model of reversible right midd...

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Bibliographic Details
Published in:Scientific reports 2017-08, Vol.7 (1), p.7469-11, Article 7469
Main Authors: An, Hong, Duan, Yunxia, Wu, Di, Yip, James, Elmadhoun, Omar, Wright, Joshua C., Shi, Wenjuan, Liu, Kaiyin, He, Xiaoduo, Shi, Jingfei, Jiang, Fang, Ji, Xunming, Ding, Yuchuan
Format: Article
Language:English
Subjects:
1-Phosphatidylinositol 3-kinase
13/2
64
692/420
692/617/375/534
82
82/1
82/29
82/80
96/1
96/2
96/21
AKT protein
Animals
Antipsychotic Agents - administration & dosage
Antipsychotic Agents - pharmacology
Antipsychotics
Apoptosis
Apoptosis-inducing factor
BAX protein
Bcl-2 protein
Bcl-x protein
Cerebral blood flow
Chlorpromazine
Chlorpromazine - administration & dosage
Chlorpromazine - pharmacology
Combined Modality Therapy
Disease Models, Animal
Humanities and Social Sciences
Hypothermia
Hypothermia, Induced - methods
Ischemia
Kinases
Male
multidisciplinary
Neostriatum
Neurological diseases
Neuroprotection
Phenothiazine
Phenothiazines - administration & dosage
Phenothiazines - pharmacology
Phosphatidylinositol 3-Kinases - metabolism
Phosphorylation - drug effects
Promethazine
Promethazine - administration & dosage
Promethazine - pharmacology
Proto-Oncogene Proteins c-akt - metabolism
Rats
Rats, Sprague-Dawley
Rectum
Science
Science (multidisciplinary)
Signal Transduction - drug effects
Stroke
Stroke - metabolism
Stroke - therapy
Treatment Outcome
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Summary:Physical hypothermia has long been considered a promising neuroprotective treatment of ischemic stroke, but the treatment’s various complications along with the impractical duration and depth of therapy significantly narrow its clinical scope. In the present study, the model of reversible right middle cerebral artery occlusion (MCAO) for 2 h was used. We combined hypothermia (33–35 °C for 1 h) with phenothiazine neuroleptics (chlorpromazine & promethazine) as additive neuroprotectants, with the aim of augmenting its efficacy while only using mild temperatures. We also investigated its therapeutic effects on the Phosphatidylinositol 3 kinase/Protein kinase B ( PI3K / Akt ) apoptotic pathway. The combination treatment achieved reduction in ischemic rat temperatures in the rectum, cortex and striatum significantly ( P  
ISSN:2045-2322
2045-2322
DOI:10.1038/s41598-017-06752-5