title: Preconditioning cortical lesions reduce the incidence of peri-infarct depolarizations during focal ischemia in the Spontaneously Hypertensive Rat: interaction with prior anesthesia and the impact of hyperglycemia.
abstract: The relationship between peri-infarct depolarizations (PIDs) and infarction was investigated in a model of preconditioning by cortical freeze lesions (cryogenic lesions, CL) in the Spontaneously Hypertensive Rat. Small (< 5 mm(3)) lesions produced 24 hours before permanent focal ischemia were protective, without impacting baseline cerebral blood flow (CBF) and metabolism. Prior CL reduced infarct volume, associated with improved penumbral CBF as previously showed for ischemic preconditioning. The brief initial procedure avoided sham effects on infarct volume after subsequent occlusion under brief anesthesia. However, under prolonged isoflurane anesthesia for perfusion monitoring both sham and CL rats showed reduced PID incidence relative to naive animals. This anesthesia effect could be eliminated by using α-chloralose during perfusion imaging. As an additional methodological concern, blood glucose was frequently elevated at the time of the second surgery, reflecting buprenorphine-induced pica and other undefined mechanisms. Even modest hyperglycemia (>10 mmol/L) reduced PID incidence. In normoglycemic animals CL preconditioning reduced PID number by 50%, demonstrating associated effects on PID incidence, penumbral perfusion, and infarct progression. Hyperglycemia suppressed PIDs without affecting the relationship between CBF and infarction. This suggests that the primary effect of preconditioning is to improve penumbral perfusion, which in turn impacts PID incidence and infarct size.
authors.affiliation: Department of Neurology, University of Tennessee Health Science Center, Memphis, Tennessee, USA.
authors.forename: Liang
authors.initials: L
authors.lastname: Zhao
authors.affiliation: Department of Neurology, University of Tennessee Health Science Center, Memphis, Tennessee, USA.
authors.forename: Thaddeus S
authors.initials: TS
authors.lastname: Nowak
mesh_terms: D000758:Anesthesia; D018685:Anesthetics, Inhalation / Q000627:therapeutic use; D018686:Anesthetics, Intravenous / Q000627:therapeutic use; D000818:Animals; D002525:Cerebellar Cortex / Q000098:blood supply / Q000473:pathology* / Q000503:physiopathology; D002544:Cerebral Infarction / Q000150:complications* / Q000209:etiology / Q000473:pathology* / Q000503:physiopathology; D002560:Cerebrovascular Circulation; D002698:Chloralose / Q000627:therapeutic use; D013181:Cortical Spreading Depression; D004195:Disease Models, Animal; D005615:Freezing; D006943:Hyperglycemia / Q000150:complications*; D019194:Ischemic Preconditioning; D007530:Isoflurane / Q000627:therapeutic use; D008297:Male; D011918:Rats, Inbred SHR
chemical_list: D018685:Anesthetics, Inhalation; D018686:Anesthetics, Intravenous; D002698:Chloralose; D007530:Isoflurane