Advertisement

Mapping of cerebral energy metabolism in rats with genetic generalized nonconvulsive epilepsy

  • A. Nehlig
  • M. Vergnes
  • C. Marescaux
  • S. Boyet
Part of the Journal of Neural Transmission book series (NEURAL SUPPL, volume 35)

Summary

The quantitative 2-[14C]deoxyglucose autoradiographic method was applied to measure local cerebral metabolic rates of glucose (LCMRglc) in a model of genetic petit-mal-like seizures in a strain of Wistar rats. During the experimental period, epileptic rats exhibited synchronous spikeand-wave discharges, whereas the EEG pattern of control animals was normal. Overall, LCMRglc was consistently higher in epileptic rats than in the non-epileptic controls. The increase in LCMRglc was widespread and concerned all cerebral functional systems studied, whether they exhibit spike-and-wave discharges (neocortex and thalamus), or not (limbic system). These results are in good accordance with positron-emission tomography measurements in humans with typical childhood absence epilepsy. There appears to be a lack of anatomical correlation between areas demonstrating hypermetabolism and areas where spike-and-wave discharges are recorded. The administration of 200 mg/kg ethosuximide completely suppressed spike-and-wave discharges in epileptic rats and did not change the EEG pattern in controls. However, LCMRglc were increased to the same extent over control values in epileptic rats whether they were injected with ethosuximide or untreated. By contrast, when epileptic rats were given 2 mg/kg haloperidol, the frequency and the length of spikeand-wave discharges increased, inducing almost a permanent petit-mal status epilepticus. Haloperidol did not change EEG pattern in controls. In haloperidol-treated epileptic rats, LCMRglc decreased to levels comparable to those measured in untreated control rats. In the presence of haloperidol, LCMRglc were similar in both control and epileptic rats. Thus, the diffuse increase in cerebral energy metabolism in epileptic rats as compared to controls is not directly related to the occurrence of spike-and-wave discharges, and may rather be associated with inhibitory mechanisms involved in their termination and suppression, as well as their spread to limbic and motor structures.

Keywords

Wave Discharge Cerebral Glucose Utilization Cerebral Energy Metabolism Local Cerebral Glucose Utilization Focal Motor Seizure 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Ackermann RF, Finch DM, Babb TL, Engel J Jr (1984) Increased glucose metabolism during long-duration recurrent inhibition of hippocampal pyramidal cells. J Neurosci 4: 251–264PubMedGoogle Scholar
  2. Ben-Ari Y, Tremblay E, Riche D, Ghilini G, Naquet R (1981) Electrographic, clinical pathological alterations following systemic administration of kainic acid, bicuculline or pentetrazole: metabolic mapping using the deoxyglucose method with special reference to the pathology of epilepsy. Neuroscience 6: 1361–1391PubMedCrossRefGoogle Scholar
  3. Bernardi S, Trimble MR, Frackowiak RSJ, Wise RJS, Jones T (1983) An interictal study of partial epilepsy using positron emission tomography and the oxygen-15 inhalation technique. J Neurol Neurosurg Psychiatry 46: 473–477PubMedCrossRefGoogle Scholar
  4. Browne TR, Dreifuss FE, Dyken PR, Goode DJ, Penry JK, Porter RJ, White BG, White PT (1975) Ethosuximide in the treatment of absence (petit mal) seizures. Neurology 25: 515–524PubMedGoogle Scholar
  5. Caveness WF, Kato M, Malamut BL, Hosokawa S, Wakisaka S, O’Neill RR (1980) Propagation of focal motor seizures in the pubescent monkey. Ann Neurol 7: 213–221PubMedCrossRefGoogle Scholar
  6. Chugani HT, Ackermann RF, Chugani DC, Engel J Jr (1984) Autoradiographic studies of opioid-mediated epileptogenic phenomena in rats. In: Fariello RG, Morselli PL, Lloyd KG, Quesney LF, Engel J Jr (eds) Neurotransmitters, seizures and epilepsy II. Raven Press, New York, pp 315–325Google Scholar
  7. Chugani HT, Ackermann RF, Chugani DC, Engel J Jr (1984) Opioid-induced epileptogenic phenomena: anatomical, behavioral, and electroencephalographic features. Ann Neurol 15: 361–368PubMedCrossRefGoogle Scholar
  8. Collins RC, Kennedy C, Sokoloff L, Plum F (1976) Metabolic anatomy of focal motor seizures. Arch Neurol 33: 536–542PubMedCrossRefGoogle Scholar
  9. Engel J Jr (1988) Comparison of positron emission tomography and electroencephalo-graphy as measures of cerebral function in epilepsy. In: Pfurtscheller G, Lopes da Silva FH (eds) Functional brain imaging Hans Huber, Bern, pp 229–238Google Scholar
  10. Engel J Jr, Ludwig BI, Fetell M (1978) Prolonged partial complex status epilepticus: EEG and behavioral observations. Neurology 28: 863–869Google Scholar
  11. Engel J Jr, Kuhl DE, Phelphs ME (1982) Patterns of human local cerebral glucose metabolism during epileptic seizures. Science 218: 64–66PubMedCrossRefGoogle Scholar
  12. Engel J Jr, Kuhl DE, Phelps ME, Rausch R, Nuwer M (1983) Local cerebral metabolism during partial seizures. Neurology 33: 400–413PubMedGoogle Scholar
  13. Engel J Jr, Lubens P, Kuhl DE (1985) Local cerebral metabolic rate for glucose during petit mal absences. Ann Neurol 17: 121–128PubMedCrossRefGoogle Scholar
  14. Engel J Jr, Lubens P, Phelps M (1988) Metabolic correlates of diffuse EEG spike-andwave and absence seizures. Ann Neurol 23: 207–208PubMedCrossRefGoogle Scholar
  15. Engel J Jr, Ochs R, Gloor P (1990) Metabolic studies of generalized epilepsy. In: Avoli M, Gloor P, Kostopoulos G, Naquet R (eds) Generalized epilepsy: neurobiological approaches. Birkhäuser, Boston, pp 387–396Google Scholar
  16. Fariello RG, Golden GT, Reyes PF (1984) Metabolic correlates of GABAmimeticinduced EEG abnormalities. In: Fariello RG, Morselli PL, Lloyd KG, Quesney LF, Engel J Jr (eds) Neurotransmitters, seizures and epilepsy II. Raven Press, New York, pp 245–252Google Scholar
  17. Ferrendelli JA, Klunk WE (1982) Ethosuximide. Mechanisms of action. In: Woodbury DM, Penry JK, Pippenger CE (eds) Antiepileptic drugs. Raven Press, New York, pp 655–661Google Scholar
  18. Gur RC, Sussman NM, Alavi A, Gur RE, Rosen AD, O’Connor M, Goldberg HI, Greenberg JH, Reivich M (1982) Positron emission tomography in two cases of childhood epileptic encephalopathy ( Lennox-Gastaut syndrome ). Neurology 32: 1191–1194Google Scholar
  19. Hosokawa S, Iguchi T, Caveness WF, Kato M, O’Neill RR, Wakisaka S, Malamut BL (1980) Effects of manipulation of the sensorimotor system on focal motor seizures in the monkey. Ann Neurol 7: 222–229PubMedCrossRefGoogle Scholar
  20. Kato M, Malamut BL, Caveness, WF, Hosokawa S, Wakisaka S, O’Neill RR (1980) Local cerebral glucose utilization in newborn and pubescent monkeys during focal motor seizures. Ann Neurol 7: 204–212PubMedCrossRefGoogle Scholar
  21. Kelly PAT, McCulloch J (1982) Effects of the putative GABAergic agonists, muscimol and THIP, upon local cerebral glucose utilization. J Neurochem 39: 613–624PubMedCrossRefGoogle Scholar
  22. Kuhl DE, Engel J Jr, Phelps ME, Selin C (1980) Epileptic patterns of local cerebral metabolism and perfusion in humans determined by emission computed tomography of 18FDG and 13NH3. Ann Neurol 8: 348–360PubMedCrossRefGoogle Scholar
  23. Marescaux C, Micheletti G, Vergnes M, Depaulis A, Rumbach L, Waiter JM (1984a) A model of chronic spontaneous petit mal-like seizures in the rat: comparison with pentylenetetrazol-induced seizures. Epilepsia 25: 326–331PubMedCrossRefGoogle Scholar
  24. Marescaux C, Vergnes M, Micheletti G, Depaulis A, Rumbach L, Warter JM, Kurtz D (1984b) Une forme génétique d’absences petit-mal chez le rat Wistar. Rev Neurol 140: 63–66PubMedGoogle Scholar
  25. Micheletti G, Vergnes M, Marescaux C, Reis J, Depaulis A, Rumbach L, Warter JM (1985) Antiepileptic drug evaluation in a new animal model: spontaneous petit mal epilepsy in the rat. Arzneimittelforschung/Drug Res 35: 483–485Google Scholar
  26. Ochs RF, Gloor P, Tyler JL, Wolfson T, Worsley K, Anderman F, Diksic M, Meyer E, Evans A (1987) Effect of generalized spike-and-wave discharge on glucose metabolism measured by positron emission tomography. Ann Neurol 21: 458–464PubMedCrossRefGoogle Scholar
  27. Palacios JM, Kuhar MJ, Rapoport SI, London ED (1982) Effects of y-aminobutyric acid agonist and antagonist drugs on local cerebral glucose utilization. J Neurosci 2: 853–860PubMedGoogle Scholar
  28. Paxinos G, Watson C (1982) The rat brain in stereotaxic coordinates. Academic Press, New YorkGoogle Scholar
  29. Phelps ME, Huang SC, Hoffman EJ, Selin C, Sokoloff L, Kuhl DE (1979) Tomographic measurement of local cerebral glucose metabolic rate in humans with (F-18)2-fluoro-2-deoxy-d-glucose: validation of method. Ann Neurol 6: 371–388PubMedCrossRefGoogle Scholar
  30. Reivich M, Kuhl D, Wolf A, Greenberg J, Phelps M, Ido T, Cassella V, Fowler J, Hoffman E, Alavi A, Som P, Sokoloff L (1979) The [18F]fluoro-deoxyglucose method for the measurement of local cerebral glucose utilization in man. Circ Res 44: 127–137PubMedGoogle Scholar
  31. Sasa M, Ohno Y, Ujihara H, Fujita Y, Yoshimura M, Takaori S, Serikawa T, Yamada J (1988) Effects of antiepileptic drugs on absence-like and tonic seizures in the spontaneously epileptic rat, a double mutant rat. Epilepsia 29: 505–513PubMedCrossRefGoogle Scholar
  32. Sokoloff L (1985) Basic principles in imaging of regional cerebral metabolic rates. In: Sokoloff L (ed) Brain imaging and function. Raven Press, New York, pp 21–49Google Scholar
  33. Sokoloff L, Reivich M, Kennedy C, Des Rosiers MH, Patlak CS, Pettigrew K, Sakurada O, Shinohara M (1977) The [14C]deoxyglucose method for the measurement of local cerebral glucose utilization: theory, procedure and normal values in the conscious and anesthetized albino rat. J Neurochem 28: 897–916PubMedCrossRefGoogle Scholar
  34. Theodore WH (1988) Cerebral metabolism in absence seizures and related syndromes. In: Myslobodsky MS, Mirsky AF (eds) Elements of petit mal epilepsy. Peter Lang, New York, pp 131–157Google Scholar
  35. Theodore WH, Newmark ME, Sato S, Brooks R, Patronas M, De La Paz R, DiChiro G, Kessler RM, Margolin R, Manning RG, Channing M, Porter R (1983) [18F]Fluorodeoxyglucose positron emission tomography in refractory complex partial seizures. Ann Neurol 14: 429–437Google Scholar
  36. Theodore WH, Brooks R, Margolin R, Patronas N, Sato S, Porter RJ, Mansi L, Bairamian D, DiChiro G (1985) Positron emission tomography in generalized seizures. Neurology 35: 684–690PubMedGoogle Scholar
  37. Vergnes M, Marescaux C, Micheletti G, Reis J, Depaulis A, Rumbach L, Warter JM (1982) Spontaneous paroxysmal electroclinical patterns in rat: a model of generalized non-convulsive epilepsy. Neurosci Lett 33: 97–101PubMedCrossRefGoogle Scholar
  38. Vergnes M, Marescaux C, Depaulis A, Micheletti G, Warter JM (1987) Spontaneous spike and wave discharges in thalamus and cortex in a rat model of genetic petit mal-like seizures. Exp Neurol 96: 127–136PubMedCrossRefGoogle Scholar
  39. Vergnes M, Marescaux C, Depaulis A (1990a) Mapping of spontaneous spike and wave discharges in Wistar rats with genetic generalized non convulsive epilepsy. Brain Res 523: 87–91PubMedCrossRefGoogle Scholar
  40. Vergnes M, Marescaux C, Depaulis A (1990b) The spontaneous spike and wave discharges in Wistar rats: a model of genetic generalized non convulsive epilepsy. In: Avoli M, Gloor P, Kostopoulos G, Naquet R (eds) Generalized epilepsy: neurobiological approaches. Birkhäuser, Boston, pp 238–253Google Scholar
  41. Warter JM, Vergnes M, Depaulis A, Tranchant C, Rumbach L, Micheletti G, Marescaux C (1988) Effects of drugs affecting dopaminergic neurotransmission in rats with spontaneous petit mal-like seizures. Neuropharmacology 27: 269–274PubMedCrossRefGoogle Scholar
  42. Wolfson LI, Sakurada O, Sokoloff L (1977) Effects of y-butyrolactone on local cerebral glucose utilization in the rat. J Neurochem 29: 777–783PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag 1992

Authors and Affiliations

  • A. Nehlig
    • 1
    • 4
  • M. Vergnes
    • 2
  • C. Marescaux
    • 3
  • S. Boyet
    • 1
  1. 1.INSERM U272Université de Nancy INancyFrance
  2. 2.Centre de NeurochimieCNRSStrasbourgFrance
  3. 3.Groupe de Recherche de Physiopathologie Nerveuse, Clinique NeurologiqueHôpital CivilStrasbourgFrance
  4. 4.INSERM U272Université de Nancy INancy CedexFrance

Personalised recommendations