Objective To investigate the microstructural abnormalities of cerebral white matter in patients with medication-overuse headache with diffusion tensor imaging.Methods Diffusion tensor magnetic resonance imaging (DT-MRI) was carried out in 80 migraine patients with medication-overuse headache (case group) and 80 age-and sex-matched healthy controls (control group).Fractional anisotropy (FA) and apparent diffusion coefficient (ADC) were measured and the correlation between clinical characteristics and the changes was examined.Results ① The FA values at the bilateral orbitofrontal cortex,cingulate cortex,splenium of the corpus callosum and the right anterior limb of the capsula interna were significantly lower than those in the controls(P＜0.05).② The ADC values at the right orbitofrontal cortex,left inferior frontal gyrus and anterior cingulate cortex were significantly higher than those in the controls (P＜0.05).③ There were negative correlations between FA values at the bilateral orbitofrontal cortex and right hind legs of the capsula interna and headache course as well as frequency.There was negative correlation between FA values at the left hind legs of capsula interna and headache frequency.④ There were positive correlations between ADC values at the left orbitofrontal cortex and headache course as well as frequency.There were positive correlations between ADC values at the right orbitofrontal cortex and prior cingulate cortex and headache frequency.There was positive correlation between ADC values at the posterior cingulate cortex and headache course.Conclutions There might be an integrity change of neurofibrotic microstructures in the bilateral orbitofrontal cortex and cingulate cortex in patients with medication-overuse headache,FA values are negatively associated with headache course and frequency whereas ADC values are positively associated with headache course and frequency.

BACKGROUNDTherapeutic angiogenesis has been shown to promote blood vessel growth and improve tissue perfusion. Vascular endothelial growth factor (VEGF) plays an important role in angiogenesis. However, it has side effects that limit its therapeutic utility in vivo, especially at high concentrations. This study aimed to investigate whether an intramuscular injection of a genetically engineered zinc finger VEGF-activating transcription factor modulates the endothelial progenitor cells (EPC) and promotes therapeutic angiogenesis in a hindlimb ischemia model with type 1 diabetes.

METHODSAlloxan (intravenous injection) was used to induce type I diabetes in C57BL/6 mice (n = 58). The ischemic limb received ZFP-VEGF (125 µg ZFP-VEGF plasmid in 1% poloxamer) or placebo (1% poloxamer) intramuscularly. Mice were sacrificed 3, 5, 10, or 20 days post-injection. Limb blood flow was monitored using laser Doppler perfusion imaging. VEGF mRNA and protein expression were examined using real-time PCR and ELISA, respectively. Capillary density, proliferation, and apoptosis were examined using immunohistochemistry techniques. Flow cytometry was used to detect the EPC population in bone marrow. Two-tailed Student's paired t test and repeated-measures analysis of variance were used for statistical analysis.

RESULTSZFP-VEGF increased VEGF mRNA and protein expression at 3 and 10 days post-injection, and increased EPC in bone marrow at day 5 and 20 post-injection compared with controls (P < 0.05). ZFP-VEGF treatment resulted in better perfusion recovery, a higher capillary density and proliferation, and less apoptosis compared with controls (P < 0.05).

CONCLUSIONSIntramuscular ZFP-VEGF injection promotes therapeutic angiogenesis in an ischemic hindlimb model with type 1 diabetes. This might be due to the effects of VEGF on cell survival and EPC recruitment.

Animals ; Diabetes Mellitus, Type 1 ; metabolism ; Endothelial Progenitor Cells ; metabolism ; Flow Cytometry ; Hindlimb ; pathology ; Ischemia ; metabolism ; Male ; Mice ; Mice, Inbred C57BL ; Vascular Endothelial Growth Factor A ; genetics ; metabolism