Down-Regulation of Platelet-Activating Factor Receptor Gene Expression During Focal Reversible Cerebral Ischemia in Rats

Abstract

Platelet-activating factor (PAF) is an endogenous potent phospholipid mediator in stroke and related to the post-ischemic brain damage. The aim of this study was to investigate the regulation and mechanisms of PAF receptor gene expression in the perifocal regions of cerebral infarction after middle cerebral artery occlusion/reperfusion. Sixty mature Wistar rats were randomly divided into 12 groups: sham-operated control group, simple ischemia 90 min group, 6, 12, 18 h, 1 day (1 d), 2, 3, 4, 5, 6, 7 d reperfusion groups. After the right middle cerebral artery occluded, the rats were suffered from ischemia for 90 min, and then reperfusion was allowed for different time courses. Reverse transcription-polymerase chain reaction (RT-PCR) and radioimmunoassay were applied to evaluate the PAF receptor messenger RNA (mRNA) expression and PAF levels in the perifocal regions of cerebral infarction respectively. RT-PCR analysis revealed that PAF receptor mRNA was 0.95 +/- 0.15 in control group. However, following ischemia-reperfusion, the levels of PAF receptor mRNA progressively decreased until 2 d of reperfusion (0.54 +/- 0.10), then returned to control group's levels gradually. Compared with the control group's (582 +/- 72 pg/g wet weight), the PAF concentrations of simple ischemic and 6, 12, 18 h, 1, 2 d reperfusion group were significantly higher than that of any other groups. These results indicate that PAF receptor gene expression may be subject to down-regulation in the perifocal regions of cerebral infarction after cerebral ischemia-reperfusion and relative to the increase of endogenous PAF concentrations.

A Possible Role for Platelet-Activating Factor Receptor in Amyotrophic Lateral Sclerosis Treatment

“…A PAFR knockout mice model used in a transient global cerebral ischemia and reperfusion experiment showed that the lack of PAFR improves neurological deficits and decreases the percentage of necrotic cavities ( 44 ). PAF concentration was increased in perifocal regions of cerebral infarction after middle cerebral artery occlusion in rat and expression of PAFR was decreased following ischemia-reperfusion ( 45 ). In model of acute ischemic stroke on middle cerebral ischemia occlusion, rats pretreated with ginkgolide K had less infarction volume and oxidative stress index, such as superoxide dismutase and nitric oxide synthase were reversed to their normal levels in serum and in the cerebral ischemic section ( 46 ).…”

Protective effect of tea polyphenols on the blood-brain barrier

“…Collagen IV is a major component of the basement membrane of the BBB and its degradation may lead to the disruption of integrity of the BBB and an increase in the permeability of the BBB. Collagen IV may further affect the outflow of water and neutrophils from vasculature, and influence the production of cerebral edema [8]. The major function of MMP-9 is to degrade collagen IV to lead to the breakdown of the BBB [7].…”

“…The undermined BBB may lead to increased brain permeability, brain edema formation, aggravated infarction and hemorrhagic transformation [8][9][10]. Tea polyphenols (TP), polyphenolic compounds in tea, especially the epicatechin (flavan-3-ol compound), have strong antioxidant capacity [11].…”