Research ReportNeuroprotective effects of compound FLZ in an ischemic model mediated by improving cerebral blood flow and enhancing Hsp27 expression

- Rats received FLZ treatment orally after MCAO onset.
- FLZ significantly reduced the infarct volume and improve behavioral deficits.
- FLZ improved regional CBF from 30% to over 50% of baseline during ischemia.
- High dose FLZ reduced regional CBF during hyperemia by 30%.
- FLZ markedly induced Hsp27 over-expression and reduced HSP70 over-expression.

Compound FLZ is a synthetic novel derivate of natural squamosamide, which has potent neuroprotective effects based on our previous study. We are now aiming to investigate the effects of FLZ on cerebral blood flow (CBF), infarct volume, neurological function, heat shock protein 70 (Hsp70), and Hsp27 expression in transient focal ischemia. For this goal, an animal model of middle cerebral artery occlusion (MCAO) for 2 h followed by reperfusion was used, and animals received low or high doses of FLZ (150 or 300 mg/kg), orally 10 min after MCAO onset. The results show that the infarct volume was 32.7% for the vehicle control group, and reduced to 17.6 and 12.8% for the low and high dose FLZ-treated groups, respectively. FLZ treatment also significantly improved the neurobehavioral score from 2.6 in the vehicle control group to 1.0 and 0.9 in the low and high dose groups, respectively. Further, FLZ significantly induced Hsp27 over-expression and reduced over-expression of HSP70, a sensitive marker of acute ischemia, in ipsilateral cortex by a dose-dependent manner. In addition, CBF was quantified using laser-Doppler flowmetry. During ischemia, regional CBF (rCBF) was improved from approximately 30% to over 50% of the baseline and the reperfusion-induced hyperemia was reduced in both FLZ dosage groups. Particularly, high dose FLZ reduced rCBF during hyperemia by 30%. In conclusion, FLZ (150 and 300 mg/kg) can significantly reduce the infarct volume and improve neurobehavioral deficits in a rat MCAO model, most likely through improving CBF in the penumbra and enhancing Hsp27 expression.