title: The role of protein kinase C in ischemic tolerance induced by hyperoxia in rats with stroke.
abstract: Recent studies suggest that normobaric hyperoxia (HO) protects the rat brain from ischemia reperfusion (IR) injury. Protein kinase C (PKC) is a key signaling molecule involved in protection against IR injury but its role in protective effect of HO in brain injury in unknown. In this study we attempted to see if PKC is involved in the effect of HO. Rats were divided into four main experimental groups. The first two were exposed to 95 % oxygen (HO) in a chamber 4 h/day for 6 consecutive days. Each of these groups had a control group exposed to 21 % oxygen. To investigate the role of PKC during HO, chelerythrin chloride (CHEL, 1 mg/kg/day), a PKC inhibitor, or its vehicle was given to animals for 6 days. After 24 h, the rats were subjected to 60 min of right middle cerebral artery occlusion (MCAO). After 24 h reperfusion neurological deficit scores, infarct volume, brain edema and blood-brain Barrier (BBB) permeability were assessed. HO decreased the infarct volume and brain edema in comparison with controls. PKC inhibition was associated with a significant increase in infarct size in both HO and control animals. PKC inhibition was unable to change brain edema in the experimental groups. Both HO and PKC inhibition reduced the BBB permeability within 24 h post occlusion of middle cerebral artery. Although both HO and PKC inhibition were associated with inhibition of BBB permeability during ischemic brain injury in rats, the neuroprotective effect of HO was independent of PKC in the MCAO model.
authors.affiliation: Department of Physiology, School of Medical Sciences, Tarbiat Modares University, Tehran, Iran.
authors.forename: Firoozeh
authors.initials: F
authors.lastname: Alavian
authors.affiliation: Department of Physiology, School of Medical Sciences, Tarbiat Modares University, Tehran, Iran.
authors.forename: Sohrab
authors.initials: S
authors.lastname: Hajizadeh
authors.affiliation: Department of Biology, Shahid Beheshti University, Tehran, Iran.
authors.forename: Mohammad Reza
authors.initials: MR
authors.lastname: Bigdeli
authors.affiliation: Department of Physiology, School of Medical Sciences, Tarbiat Modares University, Tehran, Iran.
authors.forename: Mohammad
authors.initials: M
authors.lastname: Javan
keywords: PKC; chelerythrin chloride; ischemic preconditioning; neuroprotection; normobaric hyperoxia; stroke