Influence of γ-Hydroxybutyrate on the Relationship between Local Cerebral Glucose Utilization and Local Cerebral Blood Flow in the Rat Brain

Abstract

Summary:The relationship between local cerebral glu cose utilization (LCGU) and local CBF (LCBF) was ex amined during the action of ,(-hydroxybutyrate (GHB) (900 mg/kg i. v.) in conscious rats. GHB induced dis crepant effects on blood flow and metabolism. LCGU was markedly depressed in all structures examined, whereas LCBF was differently affected in that no related changes were observed. Global glucose utilization was markedly depressed ( -51%), whereas global blood flowThe close correlation between metabolism and blood flow in the brain has recently been assessed by direct measurement of local cerebral glucose uti lization (LCGU) and local CBF (LCBF) in a variety of cerebral structures (Sokoloff, 1978;Kuschinsky et al., 1981; McCulloch et al., 1982a;Nakai et al., 1983). The mechanism that mediates this relation ship is not yet understood. Numerous studies have been carried out to elucidate the mechanism of the hyperemia that accompanies functional activation of the brain. Under these conditions, hyperemia ap pears to be triggered by the increased release of metabolically linked vasodilator substances. A number of candidates exist for such a local meta bolic control, e.g., H+, K +, adenosine, etc. [for references see Kuschinsky and Wahl (1978) and Kuschinsky (1982)], because their extravascular concentrations increase during functional activation to levels that induce vasodilation of pial arteries. Whereas such local metabolic factors seem to be mediators of hyperemia induced by acute functional Received June 19,1984; accepted October 17, 1984. Address correspondence and reprint requests to Prof. Dr. W. Kuschinsky at Department of Physiology, University of Bonn, Nussallee 11, 0-5300 Bonn 1, F.R. G, Abbreviations used: GHB, -y-hydroxybutyrate; LCBF, local CB F; LCGU , local cerebral glucose utilization. 58was not significantly altered. The marked dissociation be tween the changes in global glucose utilization and global blood flow induced by GHB is reflected only to a minor degree in the local values inasmuch as the correlation between LCGU and LCBF was only slightly weakened and its heterogeneity was increased. Key Words: 2-Deox yglucose-Iodoantipyrine-Local blood flow -Local coupling-Local metabolism-Rat brain.activation, the question still remains as to whether these factors are also responsible for the heteroge neity of LCBF that under normal conditions is closely correlated with local metabolism (Sokoloff, 1978;Kuschinsky et al., 1981; McCulloch et al., 1982a;Nakai et al., 1983).To investigate this question, the influence of marked metabolic depression on the relationship between local cerebral metabolism and blood flow was examined. ,),-Hydroxybutyrate (GHB) was chosen as a metabolic depressant. It is a naturally occurring substance in mammalian brain (Bessman and Fishbein, 1963;Roth, 1970;Roth and Giarman, 1970). Its pharmacological effects have been re viewed recently (Snead, 1977). As shown earlier for ,),-butyrolactone (Wolfson et al., 1977), GHB in high doses apparently reduces global cerebral energy...

Differential development of tolerance to the functional and behavioral effects of repeated baclofen treatment in rats

“…Our findings of lower levels of functional brain activity following acute baclofen treatment are also in line with previous studies utilizing a different GABA B agonist, γ-hydroxybutyric acid (GHB; Crosby et al, 1983; Kuschinsky et al, 1985). Kuschinsky and colleagues reported lower rates of glucose utilization following acute GHB administration (Kuschinsky et al, 1985), in a similarly distributed network to that reported here following acute baclofen.…”

“…Kuschinsky and colleagues reported lower rates of glucose utilization following acute GHB administration (Kuschinsky et al, 1985), in a similarly distributed network to that reported here following acute baclofen. For example, functional activity in the frontal cortex, caudate, substantia nigra, thalamus and hippocampus was lower in GHB-treated animals, compared to controls.…”

Ratio‐Images Calculated From Interictal Positron Emission Tomography and Single‐Photon Emission Computed Tomography for Quantification of the Uncoupling of Brain Metabolism and Perfusion in Epilepsy

“…Specifically in epilepsy, several investigators have shown that the uncoupling of metabolism and perfusion may be an indicator for localizing the seizure origin and sites of propagation (10)(11)(12)(13)(14)(15). This uncoupling was par-ticularly evident in interictal positron emission tomography (PET) images obtained from temporal lobe epilepsy patients (16,17).…”

Ratio‐Images Calculated From Interictal Positron Emission Tomography and Single‐Photon Emission Computed Tomography for Quantification of the Uncoupling of Brain Metabolism and Perfusion in Epilepsy

“…Specifically in epilepsy, several investigators have shown that the uncoupling of metabolism and perfusion may be an indicator for localizing the seizure origin and sites of propagation (10)(11)(12)(13)(14)(15). This uncoupling was particularly evident in interictal positron emission tomography (PET) images obtained from temporal lobe epilepsy patients (16,17).…”