Mitochondrial Cyclophilin D as a Potential Therapeutic Target for Ischemia-Induced Facial Palsy in Rats.

Abstract

Many studies have demonstrated that ischemia could induce facial nerve (FN) injury. However, there is a lack of a suitable animal model for FN injury study and thus little knowledge is available about the precise mechanism for FN injury. The aims of this study were to establish a reliable FN injury model induced by blocking the petrosal artery and to investigate whether dysfunctional interaction between cyclophilin D (CypD) and mitochondrial permeability transition pore (MPTP) can mediate cell dysfunction in ischemic FN injury. The outcomes of ischemia-induced FN injury rat model were evaluated by behavioral assessment, histological observation, electrophysiology, and electron microscopy. Then the levels of CypD and protein that forms the MPTP were evaluated under the conditions with or without the treatment of Cyclosporin A (CsA), which has been found to disrupt MPTP through the binding of CypD. The blocking of petrosal artery caused significant facial palsy signs in the ischemia group but not in the sham group. Furthermore, ischemia can induce the dysfunction of facial nucleus neurons and destruction of the myelin sheath and increase the protein levels of CypD and MPTP protein compared with sham group. Interestingly, treatment with CsA significantly improved neurological function and reversed the ischemia-induced increase of CypD and MPTP proteins in ischemia group. These results demonstrated that blocking of petrosal artery in rats can induce FN injury and the mechanism may be related to the disruption of MPTP by CypD.

• Authors: Huizhen Chen, Chnagtao Liu, Jie Yin, Zhen Chen, Jinwang Xu, Duanlei Wang, Jiaqiu Zhu, Ziyuan Zhang, Yong Sun, Aimin Li
• Journal: Cellular and molecular neurobiology (Cell Mol Neurobiol) Vol. 35 Issue 7 Pg. 931-41 (Oct 2015) ISSN: 1573-6830 [Electronic] United States
• PMID: 25820785 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Cyclophilin D
• Mitochondrial Membrane Transport Proteins
• Mitochondrial Permeability Transition Pore
• Cyclosporine
• Cyclophilins

Topics

• Animals
• Cyclophilin D
• Cyclophilins (metabolism)
• Cyclosporine (administration & dosage)
• Drug Delivery Systems (methods)
• Facial Nerve (blood supply, drug effects)
• Facial Nucleus (blood supply, drug effects, metabolism)
• Facial Paralysis (drug therapy, etiology, metabolism)
• Ischemia (complications, drug therapy, metabolism)
• Male
• Mitochondria (metabolism)
• Mitochondrial Membrane Transport Proteins (metabolism)
• Mitochondrial Permeability Transition Pore
• Neural Conduction (drug effects, physiology)
• Rats