Protection of flunarizine on cerebral mitochondria injury induced by cortical spreading depression under hypoxic conditions.

Fengpeng Li,Enchao Qiu,Shengyuan Yu,Zhao Dong,Ruozhuo Liu,Shiwen Wu

doi:10.1007/s10194-011-0300-1

Abstract

A rat cortical spreading depression (CSD) model was established to explore whether cerebral mitochondria injury was induced by CSD under both normoxic and hypoxic conditions and whether flunarizine had a protective effect on cerebral mitochondria. SD rats, which were divided into seven groups, received treatment as follows: no intervention (control Group I); 1 M NaCl injections (Group II); 1 M KCl injections (Group III); intraperitoneal flunarizine (3 mg/kg) 30 min before KCl injections (Group IV); 14% O2 inhalation before NaCl injections (Group V); 14% O2 inhalation followed by KCl injections (Group VI); 14% O2 inhalation and intraperitoneal flunarizine followed by KCl injections (Group VII). Following treatment, brains were removed for the analysis of mitochondria transmembrane potential (MMP) and oxidative respiratory function after recording the number, amplitude and duration of CSD. The duration of CSD was significantly longer in Group VI than that in Group III. The number and duration of CSD in Group VII was significantly lower than that in Group VI. MMP in Group VI was significantly lower than that in Group III, and MMP in Group VII was significantly higher than that in Group VI. State 4 respiration in Group VI was significantly higher than that in Group III, and state 3 respiration in Group VII was significantly higher than that in Group VI. Respiration control of rate in Group VII was also significantly higher than that in Group VI. Thus, we concluded that aggravated cerebral mitochondria injury might be attributed to CSD under hypoxic conditions. Flunarizine can alleviate such cerebral mitochondria injury under both normoxic and hypoxic conditions.

Highlights

Cortical spreading depression (CSD) is a self-propagating wave of cellular depolarization that has been implicated in migraine and in progressive neuronal injury after stroke and head trauma.cortical spreading depression (CSD) which was first described by Leao [1], comprises a wave of reversible EEG suppression that propagates at a rate of 2–3 mm/min across the cortical surface, accompanied by a negative deflection of the direct current (DC) potential and a severe disruption in ion homeostasis [2, 3]
A rat cortical spreading depression (CSD) model was established to explore whether cerebral mitochondria injury was induced by CSD under both normoxic and hypoxic conditions and whether flunarizine had a protective effect on cerebral mitochondria
SD rats, which were divided into seven groups, received treatment as follows: no intervention; 1 M NaCl injections (Group II); 1 M KCl injections (Group III); intraperitoneal flunarizine (3 mg/kg) 30 min before KCl injections (Group IV); 14% O2 inhalation before NaCl injections (Group V); 14% O2 inhalation followed by KCl injections (Group VI); 14% O2 inhalation and intraperitoneal flunarizine followed by KCl injections (Group VII)

Summary

Introduction

Cortical spreading depression (CSD) is a self-propagating wave of cellular depolarization that has been implicated in migraine and in progressive neuronal injury after stroke and head trauma.CSD which was first described by Leao [1], comprises a wave of reversible EEG suppression that propagates at a rate of 2–3 mm/min across the cortical surface, accompanied by a negative deflection of the direct current (DC) potential and a severe disruption in ion homeostasis [2, 3]. Recovery from CSD depends upon ion pump activity to cause an increase in metabolic activity and oxygen demand [4,5,6]. This chain of events is partially compensated by an increase in cerebral blood supply [6, 7]. This coupling will be disturbed in tissues which lack oxygen. Several prominent mitochondrial alterations, including changes in mitochondrial respiratory function and mitochondrial membrane potential (MMP) [8], accompanied by hypoxia can contribute to cell death. In turn, can cause an increase in the flow of calcium from the extracellular fluid to the intracellular space, resulting in calcium

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