Local distribution and toxicity of prolonged hippocampal infusion of muscimol
- 1 December 2005
- journal article
- Published by Journal of Neurosurgery Publishing Group (JNSPG) in Journal of Neurosurgery
- Vol. 103 (6), 1035-1045
- https://doi.org/10.3171/jns.2005.103.6.1035
Abstract
Object. The activity of γ-aminobutyric acid (GABA), the principal inhibitory neurotransmitter, is reduced in the hippocampus in patients with complex partial seizures from mesial temporal sclerosis. To provide preliminary safety and distribution data on using convection-enhanced delivery of agents to treat complex partial seizures and to test the efficacy and safety of regional selective neuronal suppression, the authors infused muscimol, a GABA-A receptor agonist, directly into the hippocampus of nonhuman primates using an integrated catheter electrode. Methods. Ten rhesus monkeys were divided into three groups: 1) use of catheter electrode alone (four monkeys); 2) infusion of escalating concentrations of muscimol followed by vehicle (three monkeys); and 3) infusion of vehicle and subsequent muscimol mixed with muscimol tracer (three monkeys). Infusions were begun 5 days after catheter electrode placement and continued for 5.6 days before switching to the other agent. Head magnetic resonance (MR) images and electroencephalography recordings were obtained before and during the infusions. Brain histological studies and quantitative autoradiography were performed. Neurological function was normal in controls and when muscimol concentrations were 0.125 mM or less, whereas higher concentrations (0.5 and 1 mM) produced reversible apathy and somnolence. Fluid distribution was demonstrated on MR images and muscimol distribution was demonstrated on autoradiographs throughout the hippocampus and adjacent white matter. Conclusions. Targeted modulation of neuronal activity is a reasonable research strategy for the investigation and treatment of medically intractable epilepsy.Keywords
This publication has 45 references indexed in Scilit:
- Method for making selective lesions of the hippocampus in macaque monkeys using NMDA and a longitudinal surgical approachHippocampus, 2003
- Convection-enhanced selective excitotoxic ablation of the neurons of the globus pallidus internus for treatment of parkinsonism in nonhuman primatesJournal of Neurosurgery, 1999
- Chronic interstitial infusion of protein to primate brain: determination of drug distribution and clearance with singlephoton emission computerized tomography imagingJournal of Neurosurgery, 1997
- Motor cortical muscimol injection disrupts forelimb movement in freely moving monkeysNeuroReport, 1996
- Rapid Cessation of Focally Induced Generalized Seizures in Rats Through Microinfusion of Lidocaine Hydrochloride into the FocusEpilepsia, 1993
- Steady-state theory for quantitative microdialysis of solutes and water in vivo and in vitroLife Sciences, 1990
- Anti-epileptic effects of focal micro-injection of excitatory amino acid antagonistsJournal of Neural Transmission, 1988
- Measurement of gamma-aminobutyric acid in human cerebrospinal fluid: Radioreceptor assay using [3H]muscimolClinica Chimica Acta; International Journal of Clinical Chemistry, 1981
- Huntington'S disease: Treatment with muscimol, A GABA‐mimetic drugAnnals of Neurology, 1978
- Stereospecificity and structure-activity requirements of GABA receptor binding in rat brainBrain Research, 1977