Effects of anesthesia on functional activation of cerebral blood flow and metabolism

Abstract

Functional brain mapping based on changes in local cerebral blood flow (lCBF) or glucose utilization (lCMRglc) induced by functional activation is generally carried out in animals under anesthesia, usually ␣-chloralose because of its lesser effects on cardiovascular, respiratory, and reflex functions. Results of studies on the role of nitric oxide (NO) in the mechanism of functional activation of lCBF have differed in unanesthetized and anesthetized animals. NO synthase inhibition markedly attenuates or eliminates the lCBF responses in anesthetized animals but not in unanesthetized animals. The present study examines in conscious rats and rats anesthetized with ␣-chloralose the effects of vibrissal stimulation on lCMRglc and lCBF in the whisker-to-barrel cortex pathway and on the effects of NO synthase inhibition with N G -nitro-L-arginine methyl ester (L-NAME) on the magnitude of the responses. Anesthesia markedly reduced the lCBF and lCMRglc responses in the ventral posteromedial thalamic nucleus and barrel cortex but not in the spinal and principal trigeminal nuclei. L-NAME did not alter the lCBF responses in any of the structures of the pathway in the unanesthetized rats and also not in the trigeminal nuclei of the anesthetized rats. In the thalamus and sensory cortex of the anesthetized rats, where the lCBF responses to stimulation had already been drastically diminished by the anesthesia, L-NAME treatment resulted in loss of statistically significant activation of lCBF by vibrissal stimulation. These results indicate that NO does not mediate functional activation of lCBF under physiological conditions. whisker-to-barrel cortex pathway ͉ cerebral glucose utilization ͉ deoxy[ 14 C]glucose ͉ functional brain imaging ͉ iodo[ 14 C]antipyrine N euronal functional activation is normally associated with increases in local cerebral glucose utilization (lCMR glc ) and blood flow (lCBF) in anatomic units of the activated neural pathways. These associations are now widely exploited to map regions of the brain involved in specific neural and cognitive processes. The mechanisms underlying the functional activation of lCMR glc are reasonably well understood. Glucose utilization is increased by functional activation in direct proportion to the increases in spike frequency in the afferent inputs to the activated areas, and the increases are localized in neuropil and not perikarya (1, 2). The increases in lCMR glc appear to result mainly from activation of Na ϩ ,K ϩ -ATPase activity (2, 3), needed to restore ionic gradients in the neuronal elements degraded by the spike activity. Neuropil contains not only axonal and dendritic processes but also astroglial processes, and glutamate stimulates glucose utilization in astroglia, also due in part to activation of Na ϩ ,K ϩ -ATPase activity by coupled uptake of Na ϩ ions with the glutamate released during functional activation (4, 5). Glucose utilization is also increased to support the ATPdependent conversion to glutamine of the glutamate taken up by the astroglia (6).The mechan...

In vivo quantification of localized neuronal activation and inhibition in the rat brain using a dedicated high temporal-resolution β + -sensitive microprobe

“…The lCMRglc value determined by the ␤-MICROPROBE for the somatosensory cortex is comparable to the values obtained by using 2-deoxy-D-[ 14 C]glucose autoradiography: 67 Ϯ 2 mol͞100 ml per min under thiopental sodium anesthesia and 118 Ϯ 3 mol͞100 ml per min in the conscious-restrained state (1). The lCMRglc in striatum derived from the ␤-MICROPROBE measurements is similar to that estimated with FDG autoradiography (21) and somewhat higher to that determined by using FDG micro-PET, for which partial volume effects lead to underestimation of lCMRglc as reported by Moore et al (22).…”

Direct, noninvasive measurement of brain glycogen metabolism in humans

“…This rate was approximately half that observed in rat brain after 2 h of glucose administration (Choi et al, 1999). It is interesting to note that metabolic rates in the conscious rat brain are typically two to three times faster than those in humans (Gruetter et al, 2001;Nakao et al, 2001). Independent of the precise value of the label turnover rate, the present study clearly demonstrates that metabolism of bulk brain glycogen is very slow.…”

Alpha-chloralose is a suitable anesthetic for chronic focal cerebral ischemia studies in the rat: A comparative study

“…Our choice of anesthetic dose was based on cerebral metabolism studies. Dudley and colleagues (Dudley et al, 1982) reported that a 60mg/kg single dose of α-chloralose reduces the cerebral glucose utilization rate to 35−47% of that in the awake preparation in the cortex, and Nakao et al (2001) found thata 50mg/kg bolus followed by a 40 mg/kg/h maintenance dose reduced glucose utilization to 36% in the sensory motor cortex. These reductions in cerebral glucose metabolism in the cortex are very similar to the reductions observed with isoflurane at the concentrations used in the present study (Krafft et al, 2000;Ori et al, 1986).…”