| Objective1. To determine whether rizatriptan and flunarizine have an effect on cortical spreading depression (CSD) and on c-Fos expression within periaqueductal grey (PAG) induced by CSD in rats.2. To establish a rat CSD model under hypoxic conditions and explore the effect of flunarizine on it.3. To explore whether cerebral mitochondria injury is contributed to CSD under normoxic conditions and hypoxic conditions and whether flunarizine has a protective effect on cerebral mitochondria.4. To explore the lesions in normal appearing white matter (NAWM) in migraine patients by diffusion tensor imaging (DTI).Methods1. The SD rats were randomly divided into five groups. Namely they were NaCl group, normal saline A (NSA) group, rizatriptan (R) group, normal saline B (NSB) group and flunarizine (F) group. The number and amplitude of CSD were measured after KCl or NaCl injection. C-Fos positive neurons of different layer within PAG were identified.2. The SD rats were randomly divided into six groups. Namely they were NaCl group, KCl group, KCl+flunarizine (KC1+F) group, anoxia+NaCl (A+NaCl) group, anoxia+KCl (A+KC1) group and anoxia+KCl+flunarizine (A+KCl+F) group. The number, amplitude, and duration of CSD were measured after KCl or NaCl injection.3. The SD rats were randomly divided into seven groups. Namely they were control (C) group, NaCl group, KCl group, KCl+flunarizine (KCl+F) group, anoxia+NaCl (A+NaCl) group, anoxia+KCl (A+KCl) group and anoxia+KCl+flunarizine (A+KCl+F) group. Rats were sacrificed by decapitation and brains were removed after KCl or NaCl injection. Transmembrane potential, oxidative respiratory function and morphous of mitochondria were detected.4. Seventeen migraineurs and sixteen healthy controls were recruited and examined with DTI. Apparent diffusion coefficient (ADC) and fractional anisotropy (FA) in the NAWM of region of interests (ROIs) were measured.Results1. The number of CSD in R group was significantly less than that in NSA group, and the amplitude of CSD in R group was significantly smaller than that in NSA group. The number of CSD in F group was significantly less than that in NSB group, and the amplitude of CSD in F group was significantly smaller than that in NSB group. There were more c-Fos-like immnoreactive neurons on each layer in NSA group and NSB group than in NaCl group. There were less c-Fos-like immnoreactive neurons on layers of E-W nucleus, nucleus trochlearis and inferior colliculus in R group than in NSA group. There were less c-Fos-like immnoreactive neurons on the layer of nucleus trochlearis in F group than in NSB group.2. The duration of CSD in A+KCl group was significantly longer than that in KCl group. The number of CSD in KCl+F group was significantly less than that in KCl group. The amplitude of CSD in KCl+F group was significantly smaller than that in KCl group. The duration of CSD in KCl+F group was significantly shorter than that in KCl group.The number of CSD in A+KCl+F group was significantly less than that in A+KCl group, and the duration of CSD in A+KCl+F group was significantly shorter than that in A+KCl group.3. Mitochondria transmembrane potential in KCl and A+KCl group was significantly lower than that in C group. Mitochondria transmembrane potential in A+KCl group was significantly lower than that in KCl group. Mitochondria transmembrane potential in KCl+F group was significantly higher than that in KCl group. Mitochondria transmembrane potential in A+KCl+F group was significantly higher than that in A+KCl group. State 3 respiration (ST3) in A+KCl group was significantly lower than that in C and NaCl group. ST3 in A+KCl+F group was significantly higher than that in A+KCl group. State 4 respiration (ST4) in A+KCl group was significantly higher than that in C and KCl group. Respiration control of rate (RCR) of A+KCl group was significantly lower than that in C group. RCR of A+KCl+F group was significantly higher than that in A+KCl group. Mitochondria morphous in C and NaCl group were normal or nearly normal. Some mitochondria in KCl and A+NaCl group were swelling. Most mitochondria in A+KCl group were swelling. There were more normal morphological mitochondria in KCl+F group than in KCl group, and there were more normal morphological mitochondria in A+KCl+F group than in A+KCl group.4. The ADC of periventricular NAWM in migraineurs was significantly higher than that of healthy controls. The FA of occipital lobe subcortical NAWM in migraineurs was significantly lower than that of healthy controls.Conclusions1. There is an inhibitory effect of rizatriptan and flunarizine on CSD, which might induce the headache through exciting the neurons in PAG.2. The repolarization of cerebral neurons and glial cells is inhibited during CSD under hypoxic conditions in rats. There is an inhibitory effect of flunarizine on CSD under hypoxic conditions. The repolarization of cerebral neurons and glial cells could be accelerated by flunarizine.3. Cerebral mitochondria injury might be contributed to CSD under normoxic condition. Aggravated cerebral mitochondria injury might be contributed to CSD under hypoxic conditions. Flunarizine can alleviate cerebral mitochondria injury contributed to CSD under normoxic and hypoxic conditions.4. Slight pathologic change may exist in periventricular NAWM and occipital lobe subcortical NAWM in migraineurs. |
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