The 12-kDa FK506-binding Protein Involvement in Neuroprotection Provided by Dantrolene in Ischemic/Reperfused Rat Cerebral Cortex
Authors: Zhao-Hui Guo, Feng Li,
Yan-Mei Zhu, Jin Fu,
Ming Yang, Zhi-Yong San, Wei-Zhi Wang
Authors - sphere of activity: Department of Neurology, the Second Affiliated Hospital of Harbin Medical University, China *Contributed equally to this research
Article: Cesk Slov Neurol N 2011; 74/107(1): 49-53
Category: Review Article
Number of articles displayed: 513x
To investigate any neuroprotection provided by dantrolene and the mechanism involved in its action.
Materials and methods:
A middle cerebral artery occlusion (MCAO) model was followed and the expressions of 12-kDa FK506-binding protein (FKBP12) and ryanodine receptor were assessed by fluorescent double staining. Infarct volume was assessed by triphenyltetrazolium chloride (TTC) and toluidine blue staining.
The study showed that FKBP12 was upregulated in the dantrolene group compared with the control group at each corresponding time point; RyR co-expressed with FKBP12, although its staining only increased slightly from 1 h to 24 h. We also found that treatment with dantrolene 1 h and 4 h after MCAO did not reduce infarct volumes (p >0.05); however, treatment with dantrolene 24 h after MCAO reduced infarct volumes and had a significant effect on the infarct volume (p <0.05), indicating that inhibition of ryanodine receptor (RyR) leads to cytoprotection.
FKBP12 may play an important role in the processes of neuronal survival or death following cerebral ischemia, and dantrolene may exert its neuroprotective effects by upregulating FKBP12 and thereby decreasing infarct volume.
FKBP12 – ryanodine receptor – dantrolene – cerebral ischemia
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