Inhibition of protein kinase C? reverses increased blood-brain barrier permeability during hyperglycemic stroke and prevents edema formation in vivo.

ABSTRACT: We investigated the effect of circulating factors and protein kinase C? on blood-brain barrier permeability and edema during hyperglycemic stroke.Male Wistar rats that were hyperglycemic by streptozotocin (50 mg/kg) for 5 to 6 days underwent middle cerebral artery occlusion (MCAO) for 2 hours with 2 hours of reperfusion. Blood-brain barrier permeability was measured in middle cerebral arteries that were ischemic (MCAO) or nonischemic (CTL) and perfused with plasma (20% in buffer) from MCAO or CTL animals. A separate set of MCAO vessels was perfused with the protein kinase C? inhibitor CGP53353 (0.5 ?mol/L) and permeability measured. Lastly, hyperglycemic rats were treated intravenously with CGP53353 (10 or 100 ?g/kg or vehicle 15 minutes before reperfusion and edema formation measured by wet:dry weights (n=6/group).MCAO vessels had increased permeability compared with controls regardless of the plasma perfusate. Permeability (water flux, ?m(3)×10(8)) of CTL vessel/CTL plasma (n=8), CTL vessel/MCAO plasma (n=7), MCAO vessel/CTL plasma (n=6), and MCAO vessel/MCAO plasma (n=6) was 0.98±0.11, 1.13±0.07, 1.36±0.02, and 1.34±0.06; P<0.01). Inhibition of protein kinase C? in MCAO vessels (n=6) reversed the increase in permeability (0.92±0.1; P<0.01). In vivo, hyperglycemia increased edema versus normoglycemia after MCAO (water content=78.84%±0.11% versus 81.38%±0.21%; P<0.01). Inhibition of protein kinase C? with 10 or 100 ?g/kg CGP53353 during reperfusion prevented the increased edema in hyperglycemic animals (water content=79.54%±0.56% and 79.99%±0.43%; P<0.01 versus vehicle).These results suggest that the pronounced vasogenic edema that occurs during hyperglycemic stroke is mediated in large part by activation of protein kinase C?.

SUBMITTER: Cipolla MJ 

PROVIDER: S-EPMC3202059 | biostudies-literature | 2011 Nov

REPOSITORIES: biostudies-literature