Hyperbaric oxygen preconditioning attenuates hemorrhagic transformation through increasing PPARγ in hyperglycemic MCAO rats

Abstract

Hyperbaric oxygen preconditioning (HBO-PC) has been demonstrated to attenuate hemorrhagic transformation (HT) after middle cerebral artery occlusion (MCAO) in hyperglycemic rats. However, the mechanisms remain to be illustrated. Recently, HBO-PC has been shown to activate peroxisome proliferator-activated receptor-gamma (PPARγ) by increasing 15d-PGJ2 in primary cultured neurons. We hypothesize that HBO-PC reduces HT by suppressing inflammation through increasing 15d-PGJ2 and activating PPARγ in hyperglycemic MCAO rats. HBO (2.5 ATA) was administrated for 1 hour daily for 5 consecutive days. The PPARγ inhibitor GW9662 was administrated intraperitoneally to designated animals. Infarction volume, hemorrhage volume, neurological scores and mortality were analyzed. The levels of 15d-PGJ2, PPARγ, TNF-α and IL-1β, tight junction proteins as well as the activity of MMP-2 and MMP-9 were evaluated 24 hours after MCAO. HBO-PC reduced HT, improved neurological function, down-regulated inflammatory molecules and inhibited the activation of MMP-9 by increasing 15d-PGJ2 and PPARγ at 24 hours after MCAO. The results suggested HBO-PC might be an alternative measure to decrease HT in ischemic stroke.

Hyperbaric Oxygen Preconditioning Attenuates Hemorrhagic Transformation Through Reactive Oxygen Species/Thioredoxin-Interacting Protein/Nod-Like Receptor Protein 3 Pathway in Hyperglycemic Middle Cerebral Artery Occlusion Rats

“…Inflammation may play a critical role in the pathophysiology of hyperglycemia-enhanced hemorrhagic transformation. Recently, our studies found that HBO preconditioning preserved the integrity of blood-brain barrier by suppressing inflammation through the activation of the peroxisome proliferator-activated receptor-γ pathway (23)(24)(25)(26). In this study, we focus on the NLRP3 inflammasome, which have a reported detrimental effect in the ischemic stroke and intracerebral hemorrhage models (10,11,27,28).…”

NADPH oxidase inhibitor improves outcome of mechanical reperfusion by suppressing hemorrhagic transformation

“…We prolonged the MCAO time to 5 h to create severe ischemia. To further compromise BBB functions and integrity, we created acute hyperglycemia in our animal model to increase the severity of HT 19. Indeed, most of the HTs in this animal model were parenchymal hematomas, the suppression of which led to an improved neurological score.…”

“…At 19 h after reperfusion (24 h after the onset of ischemia) the rats were sacrificed and the brains were harvested for measurements. To increase the extent of cerebral hemorrhage after ischemia/reperfusion, 50% dextrose was injected intraperitoneally at 6 mL/kg before MCAO and at 1.5 ml/kg afterwards to induce acute hyperglycemia in all rats (see online supplementary figure S1) 19…”

NADPH oxidase inhibitor regulates microRNAs with improved outcome after mechanical reperfusion

“…Seventy-five rats were from the initial stage of the study and 31 additional rats were randomly assigned to these three groups to increase the number in each group to reduce the variance of the following measurements. The infarct volume, neurological deficit score, and HT of these rats were assessed blindly according to the Stroke Therapy Academic Industry Roundtable (STAIR) criteria 8 15. Four survival rats were added to three groups for 2,3,5-triphenyltetrazolium chloride (TTC) staining to improve the quantification of infarct volume and HT.…”