The administration of cobra venom factor reduces post-ischemic cerebral injury in adult and neonatal rats.
The role of complement in post-ischemic cerebral injury is incompletely understood. Therefore, experiments were designed to test the effect of complement depletion on cerebral infarct volume in adult rats and cerebral atrophy in neonatal rats. Cerebral infarcts were induced in adult rats by transient filamentous occlusion of the right middle cerebral artery (MCAO). Cerebral atrophy was induced by subjecting 7-day-old rats to ligation of the right common carotid artery followed by 2.5h of hypoxia (8% O2). Forty-eight hours after MCAO, coronal sections of adult brains were obtained and stained with 2,3,5-triphenyl tetrazolium chloride. The infant rat brains were removed for analysis 6 weeks after the hypoxic-ischemic insult. Volumes of infarcts and normal hemispheric parenchyma were quantified by computer-based planimetry. Twenty-four hours prior to MCAO (adults) or hypoxia-ischemia (neonates), each animal received an i.p. injection of either 1 mcg/g body weight cobra venom factor (CVF; adult n=11; neonatal n=20) or normal saline (adult n=12; neonatal n=24). In the neonates, a second dose of CVF or saline was administered 2 days after hypoxia-ischemia. The administration of CVF significantly reduced: (1) post-ischemic cerebral infarct volume in the adults and (2) post-hypoxic-ischemic cerebral atrophy in the neonates. Therefore, complement activation augmented post-ischemic cerebral injury in adult and neonatal rats. Complement depletion induced by CVF significantly reduced post-ischemic cerebral infarct volume and atrophy in adult and neonatal rats.
Figueroa
Estuardo
E
Division of Neonatal Medicine and the Kosair Children's Hospital Research Institute, Department of Pediatrics, University of Louisville School of Medicine, 571 S. Floyd Street, Suite 300, Louisville, KY 40202-3830, USA.
Gordon
Laura E
LE
Feldhoff
Pamela W
PW
Lassiter
Herbert A
HA
D000818:Animals; D000831:Animals, Newborn; D001284:Atrophy / Q000517:prevention & control; D001921:Brain / Q000187:drug effects / Q000254:growth & development / Q000473:pathology; D020520:Brain Infarction / Q000209:etiology / Q000473:pathology / Q000517:prevention & control*; D002545:Brain Ischemia / Q000150:complications / Q000473:pathology; D004195:Disease Models, Animal; D004546:Elapid Venoms / Q000627:therapeutic use*; D009716:Numerical Analysis, Computer-Assisted; D051381:Rats; D013778:Tetrazolium Salts; D013997:Time Factors
D004546:Elapid Venoms; D013778:Tetrazolium Salts; C016310:cobra venom factor; C009591:triphenyltetrazolium