cinnarizine and Reperfusion-Injury

To explore the relations between anti-apoptotic role of dipfluzine (DIP) and the death signaling transduction pathway initiated by CD95 molecules, and the transcription factor involved in the transcription regulation of CD95 molecules in the hippocampal CA1 region after transient forebrain ischemia.. The rat forebrain transient ischemia model was established through 15 min ischemia followed by 3 days reperfusion by using the four-vessel method. The rats were divided randomly into five groups: sham control group, ischemia/reperfusion (I/R) group, DIP treated groups (20, 40 and 80 mg x kg(-1) body weight, ig, separately). Western blotting and RT-PCR were performed to detect the expression changes of Fas, FasL, caspase 10 p20, caspase 8, I-kappaB-alpha, and p-I-kappaB-alpha molecules in protein and mRNA levels, separately, and immunohistochemistry for molecular localization of Fas and FasL in rat hippocampus.. The expression of Fas, FasL, and caspase 10 p20 in protein and mRNA levels increased after I/R, which was inhibited significantly after treatment with 20 and 40 mg x kg(-1) of DIP (P < 0.01). In 80 mg x kg(-1) of DIP group, the expression of Fas and FasL protein was not significantly different from that of I/R group (P > 0.05). The expression of caspase 8 and I-kappaB-alpha showed no significant differences in all groups (P > 0.05), and no gene expression was observed for p-I-kappaB-alpha protein in the study. DIP significantly affected molecular distribution of Fas and FasL protein in CA1 subregion of hippocampus.. DIP inhibits the death signaling transduction pathway initiated by CD95 molecules in rat hippocampal CA1 subregion, and NF-kappaB transcription factor may not be involved in the transcription regulation of CD95 molecules after transient forebrain ischemia.

Topics: Animals; Apoptosis; Brain Ischemia; Calcium Channel Blockers; Cinnarizine; Fas Ligand Protein; fas Receptor; Female; Hippocampus; Membrane Glycoproteins; Neurons; NF-kappa B; Rats; Rats, Sprague-Dawley; Reperfusion Injury; RNA, Messenger; Signal Transduction; Tumor Necrosis Factors

To evaluate the effects of dipfluzine on the expressions of E-selectin, P-selectin, and ICAM-1 and the infiltration of polymorphonuclear leukocytes in brain ischemia-reperfusion rats.. The model of focal cerebral ischemia was established with the Zea-Longa occluding suture. Dipfluzine (0.25, 0.5 and 1 mg x kg(-1)), flunarizine 0.5 mg x kg(-1) and solvent were injected separately into lingual vein at 30 min after ischemia. The occluding suture was slowly taken away to cause reperfusion at 1 h after ischemia. Rats were decapitated under anesthesia at 24 h after ischemia-reperfusion and brains were immediately removed to do the following procedures. Effects of dipfluzine on morphology of the brain tissue were observed through hematoxylin-eosin (HE) staining. By immunohistochemistry and flow cytometry technique and biochemical method, effects of dipfluzine on P-selectin, E-selectin, ICAM-1 and myeloperoxidase (MPO) were observed.. Dipfluzine could relieve pathological damages in the brain tissue after ischemia-reperfusion, and reduce the expressions of E-selectin, P-selectin and ICAM-1 and activities of MPO in dose-dependent manner.. Dipfluzine depresses the expressions of P-selectin, E-selectin, and ICAM-1, which are correlated with their effects on the activities of MPO, suggesting that dipfluzine has anti-inflammation effect in certain extent and could protect brain tissue from ischemia-reperfusion injury.

Topics: Animals; Brain Ischemia; Cerebral Cortex; Cinnarizine; Dose-Response Relationship, Drug; E-Selectin; Infarction, Middle Cerebral Artery; Intercellular Adhesion Molecule-1; Male; Neuroprotective Agents; P-Selectin; Peroxidase; Rats; Rats, Sprague-Dawley; Reperfusion Injury