title: Alleviation of ischemia-induced brain edema by activation of the central histaminergic system in rats.
abstract: We have reported that facilitation of central histaminergic activity prevents the development of ischemia-induced brain injury. Since cerebral edema is a major cause of brain damage, we studied effects on brain edema of postischemic administration of L-histidine, a precursor of histamine, and thioperamide, a histamine H(3)-receptor antagonist, both of which enhance central histaminergic activity. Focal cerebral ischemia for 2 h was provoked by transient occlusion of the right middle cerebral artery in rats, and the water content and infarct size were determined 24 h after reperfusion. Changes in the extracellular concentration of histamine were examined in the striatum by a microdialysis procedure, and effects of these compounds were evaluated. Repeated administration of L-histidine (1000 mg/kg x 2, i.p.), immediately and 6 h after reperfusion, reduced the increase in the water contents in ischemic regions. Simultaneous administration of thioperamide (5 mg/kg, s.c.) with L-histidine (1000 mg/kg, i.p.) completely prevented edema formation and alleviated brain infarction, although a single dose of L-histidine, immediately after reperfusion, showed no benefits. The striatal histamine level was gradually increased after reperfusion as well as during ischemia. Simultaneous administration of thioperamide with L-histidine markedly increased the brain histamine concentration, and the value increased up to 230% of that in the saline group 5 - 6 h after reperfusion. L-Histidine alone did not affect the increase in the histamine output after ischemia. These findings suggest that further activation of the central histaminergic system after initiation of cerebral ischemia prevents development of ischemia-induced brain edema.
authors.affiliation: Department of Anesthesiology and Resuscitology, Ehime University Graduate School of Medicine, Shitsukawa, Touon, Ehime, Japan. iriyumi2006@yahoo.co.jp
authors.forename: Yumi
authors.initials: Y
authors.lastname: Irisawa
authors.forename: Naoto
authors.initials: N
authors.lastname: Adachi
authors.forename: Keyue
authors.initials: K
authors.lastname: Liu
authors.forename: Tatsuru
authors.initials: T
authors.lastname: Arai
authors.forename: Takumi
authors.initials: T
authors.lastname: Nagaro
mesh_terms: D000818:Animals; D001772:Blood Cell Count; D001834:Body Water / Q000187:drug effects / Q000378:metabolism; D001923:Brain Chemistry / Q000187:drug effects; D001929:Brain Edema / Q000188:drug therapy* / Q000209:etiology* / Q000473:pathology; D002545:Brain Ischemia / Q000150:complications* / Q000188:drug therapy* / Q000473:pathology; D002540:Cerebral Cortex / Q000473:pathology; D016207:Cytokines / Q000096:biosynthesis; D006632:Histamine / Q000502:physiology*; D017442:Histamine Agonists / Q000627:therapeutic use*; D006633:Histamine Antagonists / Q000627:therapeutic use*; D006639:Histidine / Q000627:therapeutic use*; D020244:Infarction, Middle Cerebral Artery / Q000473:pathology / Q000517:prevention & control; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D017551:Microdialysis; D017072:Neostriatum / Q000473:pathology; D010880:Piperidines / Q000627:therapeutic use*; D051381:Rats; D017208:Rats, Wistar; D013482:Superoxide Dismutase / Q000378:metabolism
chemical_list: D016207:Cytokines; D017442:Histamine Agonists; D006633:Histamine Antagonists; D010880:Piperidines; D006639:Histidine; D008315:Malondialdehyde; D006632:Histamine; D013482:Superoxide Dismutase; C052075:thioperamide