title: NOC/oFQ contributes to age-dependent impairment of NMDA-induced cerebrovasodilation after brain injury.
abstract: This study characterized the effects of fluid percussion brain injury (FPI) on N-methyl-D-aspartate (NMDA)-induced vasodilation and determined the role of nociceptin/orphanin FQ (NOC/oFQ) in such changes as a function of age and time postinsult. FPI elevated cerebrospinal fluid (CSF) NOC/oFQ from 70 +/- 3 to 444 +/- 56 pg/ml ( approximately 10(-10) M) within 1 h and to 1,931 +/- 112 pg/ml within 8 h, whereas values returned to control levels within 168 h in the newborn pig. In contrast, FPI elevated CSF NOC/oFQ from 77 +/- 4 to 202 +/- 16 pg/ml within 1 h and values returned to control levels within 8 h in the juvenile pig. Topical NOC/oFQ (10(-10) M) had no effect on pial artery diameter but attenuated NMDA (10(-8), 10(-6) M)-induced dilation (9 +/- 1 and 16 +/- 1 vs. 5 +/- 1 and 10 +/- 1%) in both age groups. In the newborn, NMDA-induced pial artery dilation was reversed to vasoconstriction within 1 h post-FPI and responses remained impaired for 72 h, but such vasoconstriction was attenuated by pretreatment with [F/G]NOC/oFQ(1-13)-NH(2) (10(-6) M, 1 mg/kg iv), an NOC/oFQ antagonist (9 +/- 1 and 16 +/- 1 vs. -7 +/- 1 and -12 +/- 1 vs -2 +/- 1 and -3 +/- 1% for control, FPI, and FPI pretreated with the NOC/oFQ antagonist). In contrast, in the juvenile, NMDA-induced vasodilation was only attenuated within 1 h post-FPI and returned to control within 8 h. Such dilation was also partially restored by the NOC/oFQ antagonist. These data indicate that NOC/oFQ contributes to impaired NMDA pial artery dilation after FPI. These data suggest that the greater NOC/oFQ release in the newborn versus the juvenile may contribute to age-related differences in FPI effects on excitatory amino acid-induced pial dilation.
authors.affiliation: Departments of Anesthesia and Pharmacology, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA. armsteaw@mail.med.upenn.edu
authors.forename: W M
authors.initials: WM
authors.lastname: Armstead
mesh_terms: D000375:Aging / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D000831:Animals, Newborn; D001160:Arterioles / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects; D001930:Brain Injuries / Q000378:metabolism*; D002560:Cerebrovascular Circulation / Q000187:drug effects; D004195:Disease Models, Animal; D018846:Excitatory Amino Acids / Q000378:metabolism / Q000494:pharmacology; D005260:Female; D018698:Glutamic Acid / Q000378:metabolism / Q000494:pharmacology; D008297:Male; D016202:N-Methylaspartate / Q000378:metabolism* / Q000494:pharmacology; D009292:Narcotic Antagonists; D018847:Opioid Peptides / Q000134:cerebrospinal fluid / Q000378:metabolism* / Q000494:pharmacology; D010446:Peptide Fragments / Q000494:pharmacology; D010841:Pia Mater / Q000098:blood supply / Q000187:drug effects; D011957:Receptors, Opioid; D013552:Swine; D014661:Vasoconstriction / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects; D014949:Wounds, Nonpenetrating; D000094942:Nociceptin Receptor; D000097629:Nociceptin
chemical_list: D018846:Excitatory Amino Acids; D018698:Glutamic Acid; D016202:N-Methylaspartate; D009292:Narcotic Antagonists; D018847:Opioid Peptides; D010446:Peptide Fragments; D011957:Receptors, Opioid; D000094942:Nociceptin Receptor; D000097629:Nociceptin; C417048:(F-G)NOC oFQ(1-13)-NH2