title: Differential effects of gaseous versus injectable anesthetics on changes in regional cerebral blood flow and metabolism induced by l-DOPA in a rat model of Parkinson's disease.
abstract: Preclinical imaging of brain activity requires the use of anesthesia. In this study, we have compared the effects of two widely used anesthetics, inhaled isoflurane and ketamine/xylazine cocktail, on cerebral blood flow and metabolism in a rat model of Parkinson's disease and l-DOPA-induced dyskinesia. Specific tracers were used to estimate regional cerebral blood flow (rCBF - [14C]-iodoantipyrine) and regional cerebral metabolic rate (rCMR - [14C]-2-deoxyglucose) with a highly sensitive autoradiographic method. The two types of anesthetics had quite distinct effects on l-DOPA-induced changes in rCBF and rCMR. Isoflurane did not affect either the absolute rCBF values or the increases in rCBF in the basal ganglia after l-DOPA administration. On the contrary, rats anesthetized with ketamine/xylazine showed lower absolute rCBF values, and the rCBF increases induced by l-DOPA were masked. We developed a novel improved model to calculate rCMR, and found lower metabolic activities in rats anesthetized with isoflurane compared to animals anesthetized with ketamine/xylazine. Both anesthetics prevented changes in rCMR upon l-DOPA administration. Pharmacological challenges in isoflurane-anesthetized rats indicated that drugs mimicking the actions of ketamine/xylazine on adrenergic or glutamate receptors reproduced distinct effects of the injectable anesthetics on rCBF and rCMR. Our results highlight the importance of anesthesia in studies of cerebral flow and metabolism, and provide novel insights into mechanisms mediating abnormal neurovascular responses to l-DOPA in Parkinson's disease.
authors.affiliation: Basal Ganglia Pathophysiology Unit, Department of Experimental Medical Science, Lund University, Lund, Sweden. Electronic address: zisis.bimpisidis@med.lu.se.
authors.forename: Zisis
authors.initials: Z
authors.lastname: Bimpisidis
authors.affiliation: Department of Clinical Sciences, Nephrology, Lund University, Lund, Sweden.
authors.forename: Carl M
authors.initials: CM
authors.lastname: Öberg
authors.affiliation: Basal Ganglia Pathophysiology Unit, Department of Experimental Medical Science, Lund University, Lund, Sweden.
authors.forename: Natallia
authors.initials: N
authors.lastname: Maslava
authors.affiliation: Basal Ganglia Pathophysiology Unit, Department of Experimental Medical Science, Lund University, Lund, Sweden. Electronic address: angela.cenci_nilsson@med.lu.se.
authors.forename: M Angela
authors.initials: MA
authors.lastname: Cenci
authors.affiliation: Anesthesiology and Intensive Care, Department of Clinical Medical Science, Lund University, Lund, Sweden.
authors.forename: Cornelia
authors.initials: C
authors.lastname: Lundblad
mesh_terms: D000777:Anesthetics / Q000494:pharmacology; D000818:Animals; D001479:Basal Ganglia / Q000187:drug effects*; D002560:Cerebrovascular Circulation / Q000187:drug effects* / Q000502:physiology; D004409:Dyskinesia, Drug-Induced; D020820:Dyskinesias / Q000378:metabolism; D005740:Gases; D007530:Isoflurane / Q000494:pharmacology*; D007649:Ketamine / Q000378:metabolism; D007980:Levodopa / Q000494:pharmacology*; D010300:Parkinson Disease / Q000188:drug therapy*; D051381:Rats
chemical_list: D000777:Anesthetics; D005740:Gases; D007980:Levodopa; D007649:Ketamine; D007530:Isoflurane
keywords: Brain imaging; Cerebrovascular responsiveness; Clonidine; Cortico-basal ganglia networks; Isoflurane; Ketamine/xylazine; MK-801; Movement disorders