title: Chronic mild reduction of cerebral perfusion pressure induces ischemic tolerance in focal cerebral ischemia.
abstract: OBJECTIVE
  Neurons acquire tolerance to ischemic stress when preconditioning ischemia occurs a few days beforehand. We focused on collateral development after mild reduction of perfusion pressure to find an endogenous response of the vascular system that contributes to development of ischemic tolerance.
  
  
  METHODS
  After attachment of a probe, the left common carotid artery (CCA) of C57BL/6 mice was occluded. The left middle cerebral artery (MCA) was subsequently occluded permanently on days 0, 1, 4, 14, and 28 (n=8 each). The change in cortical perfusion during MCA occlusion was recorded. A sham group of mice received only exposure of the CCA and MCA occlusion 14 days later. In apoE-knockout mice, the MCA was occluded 14 days after CCA occlusion or sham surgery. Infarct size and neurologic deficit were determined 4 days after MCA occlusion.
  
  
  RESULTS
  Mice that had 45% to 65% of baseline perfusion after CCA occlusion were used. Cortical perfusion after MCA occlusion was significantly preserved in day 14 (47+/-16%) and day 28 (46+/-7%) groups compared with day 0 (28+/-8%), day 1 (33+/-19%), day 4 (29+/-16%), and sham groups (32+/-9%). Infarct size and neurologic deficits were also attenuated in day 14 and day 28 groups compared with other groups. In apoE-knockout mice, there was no significant difference in perfusion, neurologic deficits, or infarction size between groups with and without CCA occlusion.
  
  
  CONCLUSIONS
  Chronic mild reduction of perfusion pressure resulted in preservation of cortical perfusion and attenuation of infarct size after MCA occlusion. These responses of collaterals were impaired in apoE-knockout mice.
authors.affiliation: Division of Strokology, Osaka University Graduate School of Medicine, Suita, Osaka, Japan. kitagawa@medone.med.osaka-u.ac.jp
authors.forename: Kazuo
authors.initials: K
authors.lastname: Kitagawa
authors.forename: Yoshiki
authors.initials: Y
authors.lastname: Yagita
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Sasaki
authors.forename: Shiro
authors.initials: S
authors.lastname: Sugiura
authors.forename: Emi
authors.initials: E
authors.lastname: Omura-Matsuoka
authors.forename: Takuma
authors.initials: T
authors.lastname: Mabuchi
authors.forename: Kohji
authors.initials: K
authors.lastname: Matsushita
authors.forename: Masatsugu
authors.initials: M
authors.lastname: Hori
mesh_terms: D000818:Animals; D001057:Apolipoproteins E / Q000235:genetics / Q000502:physiology*; D001921:Brain / Q000473:pathology*; D002545:Brain Ischemia / Q000628:therapy*; D002196:Capillaries / Q000473:pathology; D002339:Carotid Arteries / Q000473:pathology*; D017536:Carotid Artery, Common / Q000473:pathology*; D002544:Cerebral Infarction / Q000473:pathology; D020244:Infarction, Middle Cerebral Artery / Q000473:pathology; D007511:Ischemia / Q000473:pathology; D019194:Ischemic Preconditioning; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009474:Neurons / Q000378:metabolism; D009483:Neuropsychological Tests; D010477:Perfusion; D013997:Time Factors
chemical_list: D001057:Apolipoproteins E