Perivascular nerves contribute to cortical spreading depression-associated hyperemia in rats.
We investigated the contribution of perivascular nerves and neurotransmitters to cortical spreading depression (CSD)-associated hyperperfusion in the rat. Chronic transection of the nasociliary nerve (NCN, 2 wk before) decreased ipsilateral CSD-associated hyperperfusion by 23 +/- 13% (mean +/- SD; n = 5, P < 0.05), whereas acute transection of the NCN or sham surgery had no effect (n = 8). When the NCN and parasympathetic nerve fibers (PSN) were both chronically transected, CSD hyperperfusion was attenuated by 55 +/- 19% (n = 5, P < 0.05). Cerebrovascular reactivity to hypercapnia was not significantly affected. Brain topical superfusion of the muscarinic receptor antagonist atropine (10(-4) M) caused a reduction of CSD hyperperfusion by 41 +/- 13% (n = 5, P < 0.05). The competitive blockade of calcitonin gene-related peptide (CGRP) receptors by CGRP-(8-37) (5 x 10(-7) M) afforded a decrease by 49 +/- 19% (n = 5, P < 0.05), without affecting CO2 reactivity (n = 4). The combined application of both CGRP-(8-37) and atropine further attenuated CSD hyperperfusion (by 69 +/- 17%, n = 5, P < 0.05). After chronic NCN and PSN transection brain topical superfusion of CGRP-(8-37) (5 x 10(-7) M) reduced CSD hyperperfusion slightly by 9.5 +/- 5% (n = 3). Atropine (10(-4) M) afforded a decrease by 17 +/- 6% (n = 3). These reductions were not statistically significant. We conclude that CSD-associated hyperperfusion is mediated in part by a depolarization of trigeminal sensory and parasympathetic nerve fibers, resulting in a release of vasoactive trigeminal and parasympathetic neurotransmitters.
Reuter
U
U
Department of Neurology, Charite Hospital, Humboldt University, 10098 Berlin, Germany.
Weber
J R
JR
Gold
L
L
Arnold
G
G
Wolf
T
T
Dreier
J
J
Lindauer
U
U
Dirnagl
U
U
D000818:Animals; D001285:Atropine / Q000494:pharmacology; D015740:Calcitonin Gene-Related Peptide / Q000494:pharmacology; D002536:Cerebral Arteries / Q000187:drug effects / Q000294:innervation* / Q000502:physiology; D002540:Cerebral Cortex / Q000187:drug effects; D002560:Cerebrovascular Circulation / Q000187:drug effects / Q000502:physiology*; D013181:Cortical Spreading Depression / Q000502:physiology*; D003714:Denervation; D006940:Hyperemia / Q000503:physiopathology*; D008297:Male; D018727:Muscarinic Antagonists / Q000494:pharmacology; D017764:Parasympathectomy; D010275:Parasympathetic Nervous System / Q000187:drug effects / Q000502:physiology*; D010446:Peptide Fragments / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D014276:Trigeminal Nerve / Q000187:drug effects / Q000502:physiology*
D018727:Muscarinic Antagonists; D010446:Peptide Fragments; C058636:calcitonin gene-related peptide (8-37); D001285:Atropine; D015740:Calcitonin Gene-Related Peptide