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Prolonged Exposure to Isoflurane Ameliorates Infarction Severity in the Rat Pup Model of Neonatal Hypoxia-Ischemia
Investigator: Adriel Fajilan, Loma Linda University School of Medicine
Mentor: Johyn H. Zhang, Md, PhD, Loma Linda University School of Medicine
The neonatal hypoxia-ischemia (HI) rat model (i.e. Rice-Vannucci model) is extensively used in studying perinatal HI and child brain injury. One major weakness of this model is its inconsistency of brain infarction amongst animals. We hypothesize that this inconsistency is caused by prolonged operation time and therefore isoflurane exposure. Neonatal HI was induced in postnatal days 7 and 10 rat pups by unilateral right common carotid ligation followed by 2.5 hours of hypoxia (8% oxygen). The incision-to-ligation (ITL) was defined as the time from initial incision (4 minutes after 2% isoflurane exposure) to completion of carotid ligation (with termination of isoflurane exposure). In the first half of the study, the ITL of each group was designated to be 5, 13, and 21 minutes. In the second half, the ITL was standardized to 4 minutes and continued isoflurane was used to create 5-, 13-, and 21-minute isoflurane exposure times for each group. Brain infarction percentages were assessed at 48 hours following surgery. Motor deficits were quantified by Rotarod testing. In the first half of the study, marked brain infarction was observed in the 5-minute ITL group whereas less infarction was observed in the 13- and 21-minute ITL groups (P<0.05). The second half demonstrated similar results; marked brain infarction was observed in the 5-minute isoflurane exposure group whereas less infarction was observed in the 13- and 21-minute isoflurane exposure groups (P<0.05). Similar tendencies were observed in Rotarod testing; the 5-minute ITL and 5-minute isoflurane exposure groups showed more marked deficits (P<0.05). This study demonstrated that brain infarction inconsistency in the neonatal HI rat pup model is related to operation time. The observed time-dependent decrease in brain infarction is correlated to the isoflurane exposure time. Therefore, shorter operation and isoflurane exposure times improve this model's consistencies of brain infarction and motor deficits.
Updated on July 21, 2011.