Brain Injury Impairs Prostaglandin Cerebrovasodilation

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Abstract
Previous studies have observed that ATP- and calcium-sensitive K+ (KATPnd Kca) channel function is impaired after fluid percussion brain injury (FPI). The present study was designed to characterize the effect of FPI on prostaglandin (PG)E2 and I2 pial artery dilation and the role of activation of these K+ channels in that dilation in newborn pigs equipped with a closed cranial window. FPI of moderate severity (1.9–2 atm) was produced by using a pendulum to strike a piston on a saline-filled cylinder that was fluid coupled to the brain via a hollow screw inserted through the cranium. PGE2 vasodilation was blunted by FPI (9 ± 1%, 13±1%, and 19 ± 1% vs. 2 ± 1%, 5 ± 1%, and 9 ± 1%, for 1, 10, and 100 ng/ml PGE2 before and after FPI, respectively). PGE2 dilation was associated with increased CSF cGMP and cAMP concentration and such changes in cyclic nucleotides were blunted by FPI (448 ± 10 and 793 ± 38 vs. 316 ± 11 and 403 ± 27 fmol/ml for control and PGE2 induced change in cGMP before and after FPI, respectively). PGI2-induced dilation and associated changes in CSF cyclic nucleotide concentration were similarly blunted by FPI. PGE2 dilation was attenuated by either glibenclamide or iberiotoxin, KATP and Kca channel antagonists, and coadministration of both K+ channel antagonists further decremented the dilator response (9 ± 1%, 14 ± 1%, and 21 ± 1%; vs. 4 ± 1%, 7 ± 1%, and 12 ± 1%; vs. 2 ± 1%, 4 ± 1%, and 7 ± 1%, for 1, 10, and 100 ng/ml PGE2 during control, after glibenclamide, and after combined glibenclamide and iberiotoxin, respectively). Glibenclamide and iberiotoxin had similar effects on PGI2 dilation. These data show that prostaglandin dilation is attenuated after FPI. These data also show that prostaglandin dilation is dependent on activation of both KATP and Kca channels. Further, these data suggest that attenuated prostaglandin dilation following FPI results from diminished prostaglandin-associated elevation in cyclic nucleotide concentration and impaired KATP and Kca channel function.