title: α7 Nicotinic acetylcholine receptor agonist attenuates neuropathological changes associated with intracerebral hemorrhage in mice.
abstract: We have demonstrated previously that nicotine affords neuroprotective and anti-inflammatory effects against intracerebral hemorrhage (ICH)-associated neuropathological changes. The present study was undertaken to clarify whether subtype-specific agonists of nicotinic acetylcholine receptors (nAChRs) could preserve tissue integrity in mouse ICH model in vivo. ICH was induced by unilateral injection of collagenase into the striatum of male C57BL/6 mice. Daily intraperitoneal injection of α7 nAChR agonist PNU-282987 (3-10mg/kg) for 3 days, starting from 3h after induction of ICH, significantly increased the number of surviving neurons in the central and the peripheral regions of hematoma at 3 days after ICH. In contrast, α4β2 nAChR agonist RJR-2403 (2-10 mg/kg) given in the same regimen showed no significant effect. PNU-282987 and RJR-2403 did not affect either the size of hemorrhage or the extent of brain edema associated with ICH. PNU-282987 decreased the number of activated microglia/macrophages accumulating in the perihematoma region at 3 days after ICH, in a dose-dependent manner. On the other hand, the number of microglia/macrophages in the central region of hematoma at early phase of pathology (6 h after ICH) was increased by 10mg/kg PNU-282987. These results suggest that α7 nAChR agonist can provide neuroprotective effect on ICH-induced injury, independently of its anti-inflammatory actions.
authors: Department of Chemico-Pharmacological Sciences, Graduate School of Pharmaceutical Sciences, Kumamoto University, 5-1 Oe-honmachi, Chuo-ku, Kumamoto 862-0973, Japan.
authors: M
authors: M
authors: Hijioka
authors: H
authors: H
authors: Matsushita
authors: H
authors: H
authors: Ishibashi
authors: A
authors: A
authors: Hisatsune
authors: Y
authors: Y
authors: Isohama
authors: H
authors: H
authors: Katsuki
mesh_terms: D000818:Animals; D015153:Blotting, Western; D001834:Body Water / Q000378:metabolism; D001921:Brain / Q000473:pathology; D001923:Brain Chemistry / Q000187:drug effects; D001929:Brain Edema / Q000473:pathology; D002452:Cell Count; D002543:Cerebral Hemorrhage / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology*; D017364:Collagenases; D020287:In Situ Nick-End Labeling; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D017628:Microglia / Q000187:drug effects / Q000473:pathology; D009474:Neurons / Q000473:pathology; D009538:Nicotine / Q000031:analogs & derivatives / Q000627:therapeutic use; D018722:Nicotinic Agonists / Q000627:therapeutic use*; D011978:Receptors, Nicotinic / Q000187:drug effects*; D064569:alpha7 Nicotinic Acetylcholine Receptor
chemical_list: C579166:Chrna7 protein, mouse; D018722:Nicotinic Agonists; D011978:Receptors, Nicotinic; D064569:alpha7 Nicotinic Acetylcholine Receptor; C403531:nicotinic receptor alpha4beta2; C012419:metanicotine; D009538:Nicotine; D017364:Collagenases