title: Serotonin depletion can enhance the cerebrovascular responses induced by cortical spreading depression via the nitric oxide pathway.
abstract: Serotonin (5-HT) is an important neurotransmitter involved in the control of neural and vascular responses. 5-HT depletion can induce several neurological disorders, including migraines. Studies on a cortical spreading depression (CSD) migraine animal model showed that the cortical neurons sensitivity, vascular responses, and nitric oxide (NO) production were significantly increased in 5-HT depletion. However, the involvement of NO in the cerebrovascular responses in 5-HT depletion remains unclear. This study aimed to investigate the role of NO in the CSD-induced alterations of cerebral microvessels in 5-HT depletion. Rats were divided into four groups: control, control with L-NAME treatment, 5-HT depleted, and 5-HT depleted with L-NAME treatment. 5-HT depletion was induced by intraperitoneal injection with para-chlorophenylalanine (PCPA) 3 days before the experiment. The CSD was triggered by KCl application. After the second wave of CSD, N-nitro-l-arginine methyl ester (L-NAME) or saline was intravenously injected into the rats with or without L-NAME treatment groups, respectively. The intercellular adhesion molecules-1 (ICAM-1), cell adhesion molecules-1 (VCAM-1), and the ultrastructural changes of the cerebral microvessels were examined. The results showed that 5-HT depletion significantly increased ICAM-1 and VCAM-1 expressions in the cerebral cortex. The number of endothelial pinocytic vesicles and microvilli was higher in the 5-HT depleted group when compared to the control. Interestingly, L-NAME treatment significantly reduced the abnormalities observed in the 5-HT depleted group. The results of this study demonstrated that an increase of NO production is one of the mechanisms involved in the CSD-induced alterations of the cerebrovascular responses in 5-HT depletion.
authors.affiliation: 1Department of Pathology, Faculty of Medicine, Chulalongkorn University , Bangkok , Thailand.
authors.forename: Chonlawan
authors.initials: C
authors.lastname: Saengjaroentham
authors.forename: Weera
authors.initials: W
authors.lastname: Supornsilpchai
authors.forename: Wilawan
authors.initials: W
authors.lastname: Ji-Au
authors.forename: Anan
authors.initials: A
authors.lastname: Srikiatkhachorn
authors.forename: Supang
authors.initials: S
authors.lastname: Maneesri-le Grand
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D002560:Cerebrovascular Circulation / Q000187:drug effects / Q000502:physiology*; D013181:Cortical Spreading Depression / Q000187:drug effects / Q000502:physiology*; D004195:Disease Models, Animal; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D008297:Male; D008694:Methamphetamine / Q000031:analogs & derivatives / Q000494:pharmacology; D046529:Microscopy, Electron, Transmission; D055806:Microvessels / Q000473:pathology / Q000648:ultrastructure; D008881:Migraine Disorders / Q000139:chemically induced / Q000473:pathology / Q000503:physiopathology*; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology / Q000633:toxicity; D011189:Potassium Chloride; D051381:Rats; D017208:Rats, Wistar; D012701:Serotonin / Q000172:deficiency*; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism
chemical_list: D004791:Enzyme Inhibitors; D019010:Vascular Cell Adhesion Molecule-1; C073090:chlormethamphetamine; D018799:Intercellular Adhesion Molecule-1; D012701:Serotonin; D008694:Methamphetamine; D011189:Potassium Chloride; D019331:NG-Nitroarginine Methyl Ester
keywords: cortical spreading depression; endothelial cell; serotonin depletion; ultrastructural changes