In vivo activation of endocannabinoid system in temporal lobe epilepsy with hippocampal sclerosis.

The endocannabinoid system modulates neuronal excitability, protects neurons against hyperexcitability and is involved in epileptogenesis in animal models of mesial temporal lobe epilepsy with hippocampal sclerosis. We performed in vivo positron emission tomography imaging of the type 1 cannabinoid receptor in patients with mesial temporal lobe epilepsy with hippocampal sclerosis. Twelve patients with refractory mesial temporal lobe epilepsy due to hippocampal sclerosis received a [(18)F]MK-9470 scan to assess type 1 cannabinoid receptor availability in vivo. Parametric modified standard uptake values were used as quantitative measure of type 1 cannabinoid receptor availability and images were spatially normalized to standard space. Voxel-based analysis was performed comparing patients with hippocampal sclerosis to controls and correlations between type 1 cannabinoid receptor status and seizure characteristics were done using volumes of interest. Type 1 cannabinoid receptor positron emission tomography was co-registered with subtraction ictal single photon emission computed tomography co-registered to magnetic resonance imaging of a complex partial seizure (n = 9). An increased type 1 cannabinoid receptor availability in the ipsilateral temporal lobe was observed, which correlated negatively with the latency since last seizure before scanning and positively to the number of seizures in the month before scanning. A decreased type 1 cannabinoid receptor availability was present in the superior insular cortex, ipsilateral more than contralateral. The ipsilateral insular region displayed a mild ictal hyperperfusion in the transition zone of subtraction ictal single photon emission computed tomography co-registered to magnetic resonance imaging temporal lobe hyperperfusion-frontal lobe hypoperfusion during complex partial seizures. Type 1 cannabinoid receptor availability showed opposite changes in different brain regions that are involved during complex partial seizures in refractory mesial temporal lobe epilepsy with hippocampal sclerosis. The increase in type 1 cannabinoid receptor availability at the seizure onset zone might be a protective mechanism of neurons against hyperexcitability and seizure activity, or contribute to the process of epileptogenesis, or both. The decreased type 1 cannabinoid receptor availability in the insula may play a role in surround inhibition and prevention of seizure propagation.

[1]  W. van Paesschen,et al.  Neuronuclear assessment of patients with epilepsy. , 2008, Seminars in nuclear medicine.

[2]  D. Spencer,et al.  Characteristics of medial temporal lobe epilepsy: I. Results of history and physical examination , 1993, Annals of neurology.

[3]  S. Masino,et al.  Control of Cannabinoid CB1 Receptor Function on Glutamate Axon Terminals by Endogenous Adenosine Acting at A1 Receptors , 2010, The Journal of Neuroscience.

[4]  T. Babb,et al.  The clinical-pathogenic mechanisms of hippocampal neuron loss and surgical outcomes in temporal lobe epilepsy. , 1995, Brain : a journal of neurology.

[5]  B. Martin,et al.  The Endogenous Cannabinoid System Regulates Seizure Frequency and Duration in a Model of Temporal Lobe Epilepsy , 2003, Journal of Pharmacology and Experimental Therapeutics.

[6]  R. E. Blair,et al.  Activation of the Cannabinoid Type-1 Receptor Mediates the Anticonvulsant Properties of Cannabinoids in the Hippocampal Neuronal Culture Models of Acquired Epilepsy and Status Epilepticus , 2006, Journal of Pharmacology and Experimental Therapeutics.

[7]  Masahiko Watanabe,et al.  Downregulation of the CB1 Cannabinoid Receptor and Related Molecular Elements of the Endocannabinoid System in Epileptic Human Hippocampus , 2008, The Journal of Neuroscience.

[8]  Patrick Dupont,et al.  Correlations of interictal FDG-PET metabolism and ictal SPECT perfusion changes in human temporal lobe epilepsy with hippocampal sclerosis , 2006, NeuroImage.

[9]  Anne T. Berg,et al.  Epidemiology in Epilepsy. , 2001, Epilepsy currents.

[10]  N. Naderi,et al.  Evaluation of interactions between cannabinoid compounds and diazepam in electroshock-induced seizure model in mice , 2008, Journal of Neural Transmission.

[11]  B. Martin,et al.  Assessment of the role of CB1 receptors in cannabinoid anticonvulsant effects. , 2001, European journal of pharmacology.

[12]  P. Consroe.  Brain Cannabinoid Systems as Targets for the Therapy of Neurological Disorders , 1998, Neurobiology of Disease.

[13]  O. Devinsky,et al.  Alcohol and Marijuana: Effects on Epilepsy and Use by Patients with Epilepsy , 2001, Epilepsia.

[14]  S Shinnar,et al.  THE EPIDEMIOLOGY OF EPILEPSY: Past, Present, and Future , 1996 .

[15]  Patrick Dupont,et al.  [18F]MK-9470, a positron emission tomography (PET) tracer for in vivo human PET brain imaging of the cannabinoid-1 receptor , 2007, Proceedings of the National Academy of Sciences.

[16]  Karl F. Hubner,et al.  A Weight Index for the Standardized Uptake Value in 2-Deoxy-2-[F-18]fluoro-d-glucose-Positron Emission Tomography , 2007, Molecular Imaging and Biology.

[17]  I. Soltesz,et al.  Presynaptic, Activity-Dependent Modulation of Cannabinoid Type 1 Receptor-Mediated Inhibition of GABA Release , 2006, The Journal of Neuroscience.

[18]  M. Eder,et al.  CB1 Cannabinoid Receptors and On-Demand Defense Against Excitotoxicity , 2003, Science.

[19]  Alexander Hammers,et al.  Upregulation of opioid receptor binding following spontaneous epileptic seizures. , 2007, Brain : a journal of neurology.

[20]  Guy Bormans,et al.  Kinetic analysis of the cannabinoid-1 receptor PET tracer [18F]MK-9470 in human brain , 2010, European Journal of Nuclear Medicine and Molecular Imaging.

[21]  François Mauguière,et al.  Seizure-related short-term plasticity of benzodiazepine receptors in partial epilepsy: a [11C]flumazenil-PET study. , 2005, Brain : a journal of neurology.

[22]  J. Rossier,et al.  Functional CB1 receptors are broadly expressed in neocortical GABAergic and glutamatergic neurons. , 2007, Journal of neurophysiology.

[23]  Neda Bernasconi,et al.  Cortical thickness analysis in temporal lobe epilepsy , 2010, Neurology.

[24]  B. Lutz.  On-demand activation of the endocannabinoid system in the control of neuronal excitability and epileptiform seizures. , 2004, Biochemical pharmacology.

[25]  Ivan Soltesz,et al.  Prevention of Plasticity of Endocannabinoid Signaling Inhibits Persistent Limbic Hyperexcitability Caused by Developmental Seizures , 2007, The Journal of Neuroscience.

[26]  R. Nicoll,et al.  Endocannabinoid Signaling in the Brain , 2002, Science.

[27]  S. Sombati,et al.  Endocannabinoids block status epilepticus in cultured hippocampal neurons. , 2007, European journal of pharmacology.

[28]  L. Petrocellis,et al.  Endocannabinoids: endogenous cannabinoid receptor ligands with neuromodulatory action , 1998, Trends in Neurosciences.

[29]  Patrick Dupont,et al.  Gender-dependent increases with healthy aging of the human cerebral cannabinoid-type 1 receptor binding using [18F]MK-9470 PET , 2008, NeuroImage.

[30]  A. Hoffman,et al.  Mechanisms of Cannabinoid Inhibition of GABAASynaptic Transmission in the Hippocampus , 2000, The Journal of Neuroscience.

[31]  M. Kano,et al.  Presynaptic Cannabinoid Sensitivity Is a Major Determinant of Depolarization-Induced Retrograde Suppression at Hippocampal Synapses , 2002, The Journal of Neuroscience.

[32]  Sandra M. Sanabria-Bohórquez,et al.  Erratum to: Kinetic analysis of the cannabinoid-1 receptor PET tracer [18F]MK-9470 in human brain , 2010, European Journal of Nuclear Medicine and Molecular Imaging.

[33]  P Dupont,et al.  SPECT perfusion changes during complex partial seizures in patients with hippocampal sclerosis. , 2003, Brain : a journal of neurology.

[34]  F. Mauguière,et al.  The role of the insular cortex in temporal lobe epilepsy , 2000, Annals of neurology.

[35]  W. Hauser,et al.  The Epidemiology of Epilepsy in Rochester, Minnesota, 1935 Through 1967 , 1975, Epilepsia.

[36]  B. Martin,et al.  Evidence for a physiological role of endocannabinoids in the modulation of seizure threshold and severity. , 2002, European journal of pharmacology.

[37]  Jacqueline A. French,et al.  Characteristics of medial temporal lobe epilepsy , 1993 .