"Resting" CBF in the epileptic baboon: correlation with ketamine dose and interictal epileptic discharges

Epilepsy Res. 2008 Nov;82(1):57-63. doi: 10.1016/j.eplepsyres.2008.07.015. Epub 2008 Sep 17.

Abstract

Background: Photosensitive epileptic (SZ) baboons demonstrate different cerebral blood flow (CBF) activation patterns from asymptomatic controls (CTL) during intermittent light stimulation (ILS). This study compares "resting" CBF between PS and CTL animals, and CBF correlations with ketamine dose and interictal epileptic discharges (IEDs) between PS and CTL animals.

Methods: Continuous intravenous ketamine was administered to eight PS and eight CTL baboons (matched for gender and weight), and maintained at subanesthetic doses (4.8-14.6 mg/kg/hr). Three resting H(2)(15)O-PET studies were attempted in each animal (CTI/Siemens HR+ scanner). Images were acquired in 3D mode (63 contiguous slices, 2.4mm thickness). PET images were co-registered with MRI images (3T Siemens Trio, T1-weighted 3D Turboflash sequence, TE/TR/TI=3.04/2100/785 ms, flip angle=13 degrees ). EEG was used to monitor depth of sedation and for quantification of IED rates. Regional CBF was compared between PS and CTL groups and correlations were analyzed for ketamine dose and IED rates.

Results: When subsets of animals of either group, receiving similar doses of ketamine were compared, PS animals demonstrated relative CBF increases in the occipital lobes and decreases in the frontal lobes. Correlation analyses with ketamine dose confirmed the frontal and occipital lobe changes in the PS animals. The negative correlations of CBF with ketamine dose and IED rate overlapped frontally. While frontal lobe CBF was also negatively correlated with IED rate, positive correlations were found in the parietal lobe.

Conclusions: "Resting" CBF differs between PS and CTL baboons. Correlation analyses of CBF and ketamine dose reveal that occipital lobe CBF increases and frontal lobe in PS animals are driven by ketamine. While frontal lobe CBF decreases may be related to ketamine's propensity to activate IEDs, positive CBF correlations with IED rate suggest involvement of the parietal lobes in their generation.

MeSH terms

  • Animals
  • Cerebrovascular Circulation / drug effects*
  • Disease Models, Animal
  • Dose-Response Relationship, Drug
  • Electroencephalography
  • Epilepsy, Reflex / genetics
  • Epilepsy, Reflex / physiopathology*
  • Female
  • Frontal Lobe / blood supply*
  • Frontal Lobe / diagnostic imaging
  • Frontal Lobe / physiopathology
  • Hypnotics and Sedatives / administration & dosage
  • Hypnotics and Sedatives / pharmacology*
  • Ketamine / administration & dosage
  • Ketamine / pharmacology*
  • Light
  • Magnetic Resonance Imaging
  • Myoclonic Epilepsy, Juvenile / genetics
  • Myoclonic Epilepsy, Juvenile / physiopathology*
  • Occipital Lobe / blood supply*
  • Occipital Lobe / diagnostic imaging
  • Occipital Lobe / physiopathology
  • Papio
  • Parietal Lobe / diagnostic imaging
  • Parietal Lobe / physiopathology
  • Photic Stimulation / adverse effects
  • Positron-Emission Tomography
  • Subtraction Technique

Substances

  • Hypnotics and Sedatives
  • Ketamine