Nitric oxide is the predominant mediator of cerebellar hyperemia during somatosensory activation in rats.
Crus II is an area of the cerebellar cortex that receives trigeminal afferents from the perioral region. We investigated the mechanisms of functional hyperemia in cerebellum using activation of crus II by somatosensory stimuli as a model. In particular, we sought to determine whether stimulation of the perioral region increases cerebellar blood flow (BFcrb) in crus II and, if so, whether the response depends on activation of 2-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA)-kainate receptors and nitric oxide (NO) production. Crus II was exposed in anesthetized rats, and the site was superfused with Ringer. Field potentials were recorded, and BFcrb was measured by laser-Doppler flowmetry. Crus II was activated by electrical stimulation of the perioral region (upper lip). Perioral stimulation evoked the characteristic field potentials in crus II and increased BFcrb (34 +/- 6%; 10 Hz-25 V; n = 6) without changing arterial pressure. The BFcrb increases were associated with a local increase in glucose utilization (74 +/- 8%; P < 0.05; n = 5) and were attenuated by the AMPA-kainate receptor antagonist 2, 3-dihydroxy-6-nitro-7-sulfamoylbenzo-[f]quinoxaline (-71 +/- 3%; 100 microM; P < 0.01; n = 5). The neuronal NO synthase inhibitor 7-nitroindazole (7-NI, 50 mg/kg; n = 5) virtually abolished the increases in BFcrb (-90 +/- 2%; P < 0.01) but did not affect the amplitude of the field potentials. In contrast, 7-NI attenuated the increase in neocortical cerebral blood flow produced by perioral stimulation by 52 +/- 6% (P < 0.05; n = 5). We conclude that crus II activation by somatosensory stimuli produces localized increases in local neural activity and BFcrb that are mediated by activation of glutamate receptors and NO. Unlike in neocortex, in cerebellum the vasodilation depends almost exclusively on NO. The findings underscore the unique role of NO in the mechanisms of synaptic function and blood flow regulation in cerebellum.
Yang
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Laboratory of Cerebrovascular Biology and Stroke, Departments of Neurology, University of Minnesota Medical School, Minneapolis, Minnesota 55455, USA.
Chen
G
G
Ebner
T J
TJ
Iadecola
C
C
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D001933:Brain Stem / Q000378:metabolism; D002245:Carbon Dioxide / Q000097:blood; D002525:Cerebellar Cortex / Q000098:blood supply* / Q000502:physiology*; D002531:Cerebellum / Q000378:metabolism; D002560:Cerebrovascular Circulation / Q000187:drug effects / Q000502:physiology; D004558:Electric Stimulation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005947:Glucose / Q000378:metabolism; D006940:Hyperemia; D007191:Indazoles / Q000494:pharmacology*; D017078:Laser-Doppler Flowmetry; D008297:Male; D018696:Neuroprotective Agents / Q000494:pharmacology; D009569:Nitric Oxide / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D019335:Nitroarginine / Q000494:pharmacology*; D010069:Oxadiazoles / Q000494:pharmacology; D011810:Quinoxalines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012039:Regional Blood Flow / Q000187:drug effects; D013003:Somatosensory Cortex / Q000502:physiology*; D013779:Tetrodotoxin / Q000494:pharmacology
C095284:1H-(1,2,4)oxadiazolo(4,3-a)quinoxalin-1-one; D004791:Enzyme Inhibitors; D007191:Indazoles; D018696:Neuroprotective Agents; D010069:Oxadiazoles; D011810:Quinoxalines; C062865:2,3-dioxo-6-nitro-7-sulfamoylbenzo(f)quinoxaline; D002245:Carbon Dioxide; D019335:Nitroarginine; D009569:Nitric Oxide; D013779:Tetrodotoxin; D019001:Nitric Oxide Synthase; D005947:Glucose; C080122:7-nitroindazole