Regional differences in mechanisms of cerebral circulatory response to neuronal activation

Abstract

. Regional differences in mechanisms of cerebral circulatory response to neuronal activation. Am J Physiol Heart Circ Physiol 280: H821-H829, 2001.-Vibrissal stimulation raises cerebral blood flow (CBF) in the ipsilateral spinal and principal sensory trigeminal nuclei and contralateral ventroposteromedial (VPM) thalamic nucleus and barrel cortex. To investigate possible roles of adenosine and nitric oxide (NO) in these increases, local CBF was determined during unilateral vibrissal stimulation in unanesthetized rats after adenosine receptor blockade with caffeine or NO synthase inhibition with N G -nitro-L-arginine methyl ester (L-NAME) or 7-nitroindazole (7-NI). Caffeine lowered baseline CBF in all structures but reduced the percent increase during stimulation only in the two trigeminal nuclei. L-NAME and 7-NI lowered baseline CBF but reduced the percent increase during stimulation only in the higher stations of this sensory pathway, i.e., L-NAME in the VPM nucleus and 7-NI in both the VPM nucleus and barrel cortex. Combinations of caffeine with 7-NI or L-NAME did not have additive effects, and none alone or in combination completely eliminated functional activation of CBF. These results suggest that caffeine-sensitive and NO-dependent mechanisms are involved but with different regional distributions, and neither fully accounts for the functional activation of CBF. adenosine; nitric oxide; caffeine; 7-nitroindazole; N G -nitro-Larginine NUMEROUS STUDIES HAVE ESTABLISHED that neuronal functional activation is associated with increases in both cerebral energy metabolism and blood flow (CBF) in components of the activated neural pathway (8,18,(30)(31)(32). The increases in energy metabolism evoked by functional activation have been shown to be proportional to the increases in spike frequency in the afferent inputs to the activated areas (13, 32) and to be due mainly to activation of Na ϩ -K ϩ -ATPase activity (21, 32). The mechanisms mediating the increases in CBF during functional activation remain, however, largely undefined. A popular hypothesis proposed by Roy and Sherrington (27) was that CBF is intrinsically regulated by products of energy metabolism to meet the altered metabolic demands associated with functional activity. This hypothesis received support from subsequent findings that CBF is raised by increased CO 2 tension, lowered pH, and decreased oxygen tension, all expected consequences of increased tissue metabolism, and reduced by changes in these chemical factors in the opposite direction, to be expected with decreased metabolism (14). Since then, many other endogenous agents that affect cerebral blood vessels, e.g., nitric oxide (NO), adenosine, adenine nucleotides, K ϩ , prostaglandins, vasoactive intestinal peptide, etc., have been identified and considered as possible candidates, but not one of them, alone or in combination with others, has yet been proven to account fully or even to be essential for the enhancement of CBF by neuronal activation.Inhibition of cerebral glucose utilization by hypo...

Differential Effects of NMDA and AMPA Glutamate Receptors on Functional Magnetic Resonance Imaging Signals and Evoked Neuronal Activity during Forepaw Stimulation of the Rat

“…Such a hypothesis (of NO mediation) is supported by our recent observation that administration of 7-nitroindazole (7-NI), a specific blocker of the nNOS, mildly reduced the SEPs components, whereas both PWI and BOLD responses were strongly reduced (Burke et al, 2002). These results are also consistent with the numerous studies reporting that 7-NI significantly reduces the CBF response to whisker stimulation in the somatosensory cortex in both awake (Gotoh et al, 2001) and anesthetized (Cholet et al, 1997) rats.…”

Interaction of nitric oxide, 20-HETE, and EETs during functional hyperemia in whisker barrel cortex

“…These observations are consistent with the concept that endogenously produced NO largely suppresses the synthesis or downstream 20-HETE effects independent of the level of cGMP. It should also be appreciated that the interactions among signaling pathways described in the present study may differ in magnitude in the unanesthetized state where NOS inhibition exerts a relatively small effect on the evoked CBF response (22).…”

Cerebral Blood Flow Regulation by Nitric Oxide: Recent Advances

“…Intraperitoneal injections of 7-NI, an in vivo inhibitor of the neuronal isoform of NOS, lowered baseline cerebral blood flow in unanesthetized rats (Montécot et al, 1997;Gotoh et al, 2001), cerebral capillary flow in anesthetized rats (Hudetz et al, 1998), and global cerebral blood flow in cats (Hayashi et al, 2002). In anesthetized dogs, unilateral denervation of vasodilator nerves from the pterygopalatine ganglion to the artery constricted middle cerebral and posterior communicating arteries.…”