Abstract TP270: Correlation Between Prostaglandin D2 DP1 Receptor Effects on Cerebral Blood Flow and Stroke Outcomes
Background and Purpose: The association of PGD2 with vasculature and blood makes it a prime candidate to be investigated in stroke. We have shown earlier that DP1-/- have greater brain damage after MCAO and excitotoxicity. Here, we test whether DP1 agonist BW245C treatment after stroke improves cerebral blood flow (CBF), consequently minimizing anatomical and functional deficits.
Methods: First, to determine if BW245C can change basal CBF, WT and DP1-/- mice were given a single i.p. injection of vehicle or 0.02, 0.2, 2.0mg/kg BW245C, and CBF was recorded for 2h. Next, to determine whether BW245C can prevent brain damage after MCAO, WT and DP1-/- mice were subjected to 60min MCAO and 96h reperfusion. Immediately at reperfusion, mice were given a single i.p. injection of vehicle or 0.02, 0.2, 2.0mg/kg BW245C. These mice were also tested for various functional outcomes. Further, to determine if BW245C can improve CBF after stroke, BW245C was given during occlusion and changes in penumbra and core CBF were continuously recorded. Finally, to address potential compensatory mechanisms, effect of BW245C on stroke outcomes was also tested in DP1-/-.
Results: BW245C treatment significantly increased the basal CBF in WT whereas in DP1-/- it remained unchanged. The infarction volume was significantly (p<0.05) reduced to 38.7±8.1% in 0.2mg/kg BW245C treatment group as compared with the control group (51.2±7.1%) and vehicle group (52.7±8.6%). The BW245C treatment also reduced the functional deficits significantly. Interestingly, BW245C also resulted in considerable increases in penumbra and core CBF immediately before reperfusion. Analysis revealed a strong correlation between attenuation in infarction and CBF improvement in penumbra immediately at reperfusion (p<0.02) and at 60min after reperfusion (p<0.005). The infarction in DP1-/- was significantly higher (66.3±11.4%) than the WT control mice (51.2±7.1%), and BW245C treatment didn’t change the final outcome in DP1-/-.
Conclusions: Overall the data suggests that stimulation of the DP1 receptor after stroke improves CBF, and minimizes brain damage and functional deficits. This ongoing work is providing novel mechanistic pathways to better explain the neuroprotective mechanisms of DP1 receptor in stroke.
- © 2012 by American Heart Association, Inc.