The effect of concentration and duration of normobaric oxygen in reducing caspase-3 and -9 expression in a rat-model of focal cerebral ischaemia

Brain Res. 2015 Aug 27:1618:205-11. doi: 10.1016/j.brainres.2015.05.027. Epub 2015 May 30.

Abstract

The aim of this study was to determine the effect of different concentrations of normobaric oxygen (NBO) on neurological function and the expression of caspase-3 and -9 in a rat model of acute cerebral ischaemia. Sprague-Dawley rats (n=120) were randomly divided into four groups (n=30 per group), including 3 groups given NBO at concentrations of 33%, 45% or 61% and one control group given air (21% oxygen). After 2h of ischaemic occlusion, each group was further subdivided into six subgroups (n=5) during reperfusion according to the duration (3, 6, 12, 24, 48 or 72h) and concentration of NBO (33%, 45% or 61%) or air treatment. The Fluorescence Quantitative polymerase chain reaction (PCR) and immunohistochemistry were used to detect caspase-3 and -9 mRNA and protein relative expression respectively. The Neurologic Impairment Score (NIS) was significantly lower in rats given 61% NBO ≥3h after reperfusion when compared to the control group (P<0.05, Mann-Whitney U). NBO significantly reduced caspase-3 and -9 mRNA and protein expression when compared to the control group at all NBO concentrations and time points (P<0.05, ANOVA). The expression of caspase-3 and -9 was lower in the group given 61% NBO compared any other group, and this difference was statistically significant when compared to the group given 33% NBO for ≥48h and the control group (both P<0.05, ANOVA). These findings indicate that NBO may inhibit the apoptotic pathway by reducing caspase-3 and -9 expression, thereby promoting neurological functional recovery after stroke.

Keywords: Apoptosis; Cerebral ischaemic–reperfusion; Ischaemic rat model; Normobaric oxygen.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Brain Ischemia / therapy*
  • Caspase 3 / genetics
  • Caspase 3 / metabolism*
  • Caspase 9 / genetics
  • Caspase 9 / metabolism*
  • Disease Models, Animal
  • Dose-Response Relationship, Drug
  • Gene Expression Regulation / drug effects*
  • Male
  • Neurologic Examination
  • Oxygen / administration & dosage*
  • RNA, Messenger / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Statistics, Nonparametric

Substances

  • RNA, Messenger
  • Caspase 3
  • Caspase 9
  • Oxygen