title: Cinepazide Maleate Improves Cognitive Function and Protects Hippocampal Neurons in Diabetic Rats with Chronic Cerebral Hypoperfusion.
abstract: To determine the combined effect of type 2 diabetes (T2D) and chronic cerebral hypoperfusion (CCH) on learning and spatial memory, we developed a rat model of CCH by permanent occlusion of bilateral common carotid arteries (2-vessel occlusion (2VO)) in high-fat diet (HFD)-fed rats injected with low-dose streptozotocin (STZ). Furthermore, we examined the effect of cinepazide maleate (CM) on cognitive deficits and brain damage in this rat model. Rats were maintained on HFD for 6 weeks and then injected with 35 mg/kg STZ to induce T2D. Sham or 2VO surgery was performed in non-diabetic or diabetic (DM) rats to obtain four groups: blank, DM, CCH, and DM-CCH groups. Cognitive function was tested by the Morris water maze (MWM) test. To determine the effects of the vasodilator cinepazide maleate (CM) on cognitive deficits and brain damage, DM-CCH rats were administered with 10 mg/kg CM or saline daily for 14 d. Neuronal damage in DM-CCH rats was associated with increased expression of glial fibrillary acidic protein (GFAP) and β-secretase 1 (BACE1), but decreased expression of choline acetyltransferase (ChAT). Moreover, the levels of all these proteins were significantly alleviated by CM treatment. These results suggest that T2D exacerbated CCH-induced brain damage and cognitive impairment, and CM ameliorated these effects.
authors.affiliation: Department of Neurology, Shanghai Jiaotong University Affiliated Sixth People's Hospital.
authors.forename: Yumei
authors.initials: Y
authors.lastname: Li
authors.forename: Ting
authors.initials: T
authors.lastname: Zhang
authors.forename: Xiaojie
authors.initials: X
authors.lastname: Zhang
authors.forename: Wenying
authors.initials: W
authors.lastname: Zou
authors.forename: Xian
authors.initials: X
authors.lastname: Gong
authors.forename: Jianliang
authors.initials: J
authors.lastname: Fu
mesh_terms: D053829:Amyloid Precursor Protein Secretases / Q000378:metabolism; D000818:Animals; D016282:Aspartic Acid Endopeptidases / Q000378:metabolism; D001921:Brain / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D002545:Brain Ischemia / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism; D002795:Choline O-Acetyltransferase / Q000378:metabolism; D003071:Cognition / Q000187:drug effects*; D003072:Cognition Disorders / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000150:complications / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000150:complications* / Q000378:metabolism; D059305:Diet, High-Fat; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D006624:Hippocampus; D007858:Learning / Q000187:drug effects*; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D009474:Neurons; D018696:Neuroprotective Agents / Q000494:pharmacology / Q000627:therapeutic use; D010879:Piperazines / Q000494:pharmacology / Q000627:therapeutic use*; D017207:Rats, Sprague-Dawley; D065852:Spatial Memory / Q000187:drug effects; D014665:Vasodilator Agents / Q000494:pharmacology / Q000627:therapeutic use
chemical_list: D005904:Glial Fibrillary Acidic Protein; D018696:Neuroprotective Agents; D010879:Piperazines; D014665:Vasodilator Agents; C026896:cinepazide; D002795:Choline O-Acetyltransferase; D053829:Amyloid Precursor Protein Secretases; D016282:Aspartic Acid Endopeptidases; C509281:Bace1 protein, rat