Evaluation of anti-inflammatory diphenyldihaloketone EF24 in transient ischemic stroke model

ABSTRACT

Objectives

Revascularization is necessary in patients with ischemic stroke, however it does not address inflammation that contribute to reperfusion injury and the early growth of ischemic core. We investigated EF24, an anti-inflammatory agent, in a stroke model.

Methods

Ischemic stroke was induced in mice by occluding middle cerebral artery for 1 h followed by reperfusion. EF24 was given either 10 min post-reperfusion (EF24_Post) or 10 min before occlusion (prophylactic, EF24_Pro). Survival, ipsilateral uptake of radioactive infarct marker ¹⁸F-fluoroglucaric acid (FGA), inflammatory cytokines, and tetrazolium chloride (TTC) staining were assessed.

Results

Survival was increased in both EF24-treated groups compared to the stroke+vehicle group. Ipsilateral ¹⁸F-FGA uptake increased 2.6-fold in stroke+vehicle group compared to sham group (p < 0.05); the uptake in EF24-treated groups and sham group was not significantly different. TTC-staining also showed reduction in infarct size by EF24 treatment. Plasma IL-6, TNF-α, and corticosterone did not show significant changes among groups. However, ipsilateral tissue in stroke+vehicle mice showed increased IL-6 (>90-fold) and TNF-α (3-fold); the tissue IL-6 and TNF-α were significantly reduced in stroke+EF24_Pro and stroke+EF24_Post groups. ¹⁸F-FGA uptake significantly correlated with tissue IL-6 levels.

Conclusions

EF24 controls infarct growth and suppresses tissue inflammation in ischemic stroke, which can be monitored by ¹⁸F-FGA uptake.

KEYWORDS:

• Brain
• ischemic stroke
• EF24
• inflammation

Acknowledgements

Technical assistance by Dr. Geeta Rao, a postdoctoral fellow in the OUHSC-College of Pharmacy, is acknowledged.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

Sandra K and David L Gilliland Chair in Nuclear Pharmacy