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Órgano Oficial del Instituto Nacional de Psiquiatría Ramón de la Fuente Muñiz

2004, Number 5

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Salud Mental 2004; 27 (5)

Efecto de la estimulación del nervio vago sobre la epilepsia focal amigdalina en la rata

Martínez A, López-Ruiz E, Vega-Flores G, Fernández-Mas R, Fernández-Guardiola S

Language: Spanish
References: 45
Page: 62-72
PDF size: 662.69 Kb.


ABSTRACT

Antecedents Vagus nerve electric stimulation (VNS) is an anticonvulsant therapy used in patients with refractory epilepsy. Several methods are used to find VNS’s action mechanisms. These techniques employ experimental models of epilepsy, such as topic applications into cerebral cortex or injections of convulsive substances by different systemic ways, both in chronic and acute experiments. However, only a few studies have related the VNS and the epilepsy of the temporal lobe. When limbic seizures are produced in the amygdaloid complex, it is known that all their own sub-nuclei activate. However, during the spread or propagation of epileptiform activity, all nuclei and sites related with amygdala’s complex participate are involved. There are many reports about the relationship between development and spread topics. However, it remains unclear the effect of VNS and its relation with interictal spike's frequency, seizure epileptic behavioral stages on Racine's scale, and the number of crisis in an induced epileptic focus into temporal lobe amygdala. Aim of the study
The propose is to study how the VNS affects the development and spread of the epileptiform spike in the penicillin focus and behavioral stages induced by a topical administration of penicillin in the temporal lobe of the amygdala. Additionally we will observe the changes induced by VNS on theta rhythm.
Material and methods
Male Wistar rats were used. Rats were implanted with a guide cannula glued to a bipolar electrode in the amygdala of the temporal lobe; an electrode to the dorsal hippocampus; two epidural nails in the prefrontal cortex (for cortical record); two flexible wires in the lateral part of the neck muscles for electromyogram record, and one hook-form electrode in the left vagus nerve corresponding exactly to the larynx's level. At the end of the post-surgery recovery period (five days), the animals were divided in two groups (n=5). After one hour of recording, group I animals were administrated penicillin G sodic (Pn) in the amygdala (solution with 50 international units in 1 microliter as final volume, using a saline solution of 0.9% sodium chloride as vehicle). After one hour of the penicillin injection, the vagus nerve electrical stimulation was performed (1.2 to 3.0 mA, square pulses of 0.5 ms duration, and 30 Hz frequency) during 30 seconds with intervals of 15 minutes between each stimulation only during two hours of recording (eight VNS’s in total). The same manipulation was followed with group II, except that in this case the first VNS was performed just before the penicillin injection. Cerebral electric activity was recorded and saved for post off-line frequency analysis, during a six-hour period in both groups. Results
We compared electrographic parameters provoked by a single Pn injection vs Pn + VNS on each group of animals and considering each rat as its own control.
Vagus nerve stimulation effects on the latency and duration of the epileptiform spikes
Group I showed a 40% decrease on its latency, and a 15% duration increase when compared with its own controls. Group II showed a 37% increase on latency and a 40% decrease on duration. Vagus nerve stimulation effects over seizure stage and seizure number. Group I developed stages III and IV on Racine’s scale and higher number of seizures. Group II remained on seizure stages I and II presenting a smaller number of seizure compared to its own control records.
Vagus nerve stimulation effects on frequency of spikes Group I showed a significant increase in frequency (p<0.05), which was sustained during a long recording time. In contrast, Group II showed a decrease.
Spectral analyses of cerebral electric activity The electroencephalogram is a tool used to investigate how the vagus nerve stimulation affects the epileptic phenomenon. In this case, the spectral analysis of the electric activity of amygdala and cerebral cortex showed a high activity between 1 and 4 Hz. This high voltage prevailed after penicillin injection and during all recording time. Hippocampus showed theta rhythm periods. The VNS caused cortical desynchronization, but it was not associated with hippocampal theta rhythm elicitation.
There is a possibility that VNS induced an increased susceptibility on rats to the convulsive effects of Pn. This was manifested in significantly shorter latencies to seizures, and significantly higher incidence, and duration of seizure.
Conclusion
When performed before the Pn injection, the vagus nerve stimulation increased the latency to the appearance of spikes, as well as the frequency, but the number of seizures decreased instead. Even, only early stages, such as I and II of Racine’s scale, were seen. These data suggest that VNS softened epileptic synchronization. The frequency of the spikes, the development of stages IV and V, and also the number of seizures were dalayed. The VNS performed one hour after penicillin injection produced progressive epileptiform spike spread and changes in the behavioral seizure pattern. Frequency of spikes increased as well as seizures severity (stage III and IV). The vagus nerve stimulation did not only reduce epileptiform activity, but also induced neuronal recruiting, which is manifested as an enhancement in seizure expression.
The VNS elicited dual effects related with tissue-sensibility. This effect confirms anatomic and physiological relations among vagal afferents, amygdaloid complex and cerebral cortex due to thalamic pathways and its relations with vagus nerve, amygdaloid complex and pyramidal cells. As a matter of fact, the thalamus is the most important structure related with cerebral rhythms. For this reason we hypothesized that the thalamus plays a key role in the results showed here.


REFERENCES

  1. ASAI M, MARTINEZ A, FERNANDEZ-MAS R, FERNANDEZ-GUARDIOLA A: Penicillin-G induced interictal activity increases both opioid peptide tissue content and release in the rat brain. Neuropeptides, 29:163-170, 1995.

  2. BERTRAM EH, ZHANG DX, MANGAN P, FOUNTAIN N, REMPE D: Functional anatomy of limbic epilepsy: a proposal for central synchronization of diffusely hyperexcitable network. Epilepsy Res, 32:194-205, 1998.

  3. CARMONA L: Caracterización de los sistemas de excitación e inhibición presentes en el foco epiléptico amigdalino inducidob por la administración intracerebral de penicilina G en la rata. Tesis de Maestría en ciencias, México, 2002.

  4. FERNANDEZ-GUARDIOLA A, CONTRERAS CM, GONZALEZ-ESTRADA MT: Red nucleus multineuronal activity during the propagation and extinction of tonic-clonic generalized seizures. Bol Inst Est Med Biol (Mex), 28:265-271, 1975.

  5. FERNANDEZ-GUARDIOLA A, AYALA F: Red nucleus fast activity and signs of paradoxical sleep appearing during the extinction of experimental seizures. Electroencephalogr Clin Neurophysiol, 30: 547-555, 1971.

  6. FERNANDEZ-GUARDIOLA R, FERNANDEZ-MAS R, MARTINEZ A, GUTIERREZ R: Mapeo espacio-temporal del EEG durante el kindling amigdalino en el gato. En: Brailowsky S, Otero-Silíceo E (eds). Epilepsia Experimental. Academia Mexicana de Neurología, 2:139-148, México, 1991.

  7. FERNANDEZ-GUARDIOLA A, MARTINEZ A, FERNANDEZ-MAS R: Repeated penicillin-induced amygdala epileptic focus in freely moving cats. EEG, polysomnographic (23 h. recording) and brain mapping study. Epilepsy Res, 22:127-136, 1995.

  8. FERNANDEZ-GUARDIOLA A, MARTINEZ A, VALDES-CRUZ A, MAGDALENO-MADRIGAL VM, MARTINEZ D, FERNANDEZ-MAS R: Vagus nerve chronic stimulation in cats: effects on epileptogenesis (amygdala electrical kindling): behavioral and electrographic changes. Epilepsia, 40:822-829, 1999.

  9. FERNANDEZ-MAS R, VALDES A, MARTINEZ A, MAGDALENO V, ALMAZAN S, MARTINEZ D, FERNANDEZ-GUARDIOLA A: Visualización gráfica de las transiciones de las fases del sueño en el hombre: métodos de representación tridimensional. Salud Mental, 21:27-32, 1998.

  10. GLOOR P: Generalized epilepsy with bilateral synchronous spike and wake discharge. New findings concerning its physiological mechanisms. Electroencephalogr Clin Neurophysiol (Supl) 34:245-249, 1978.

  11. GODDARD GV, MCINTYRE DC, LEECH CK: A permanent change in brain function resulting from daily electrical stimulation. Exp Neurol, 25:295-330, 1969.

  12. GOLANOV E, REIS DJ: Neurons of nucleus of the solitary tract synchronize the EEG and elevate cerebral blood flow via a novel medullary area. Brain Res, 892:1-12, 2001.

  13. GUZMAN-FLORES C, ALCARAZ M, FERNANDEZ GUARDIOLA A. Rapid procedure to localize electrodes in experimental neurophysiology. Bol Inst Est Med Biol (Mex), 16:29-31, 1958.

  14. HAMMOND EJ, UTHMAN BM, REID SA, WILDER BJ, RAMSAY RE: Vagus nerve stimulation in humans: neurophysiological studies and electrophysiological monitoring. Epilepsia (Supl 31), 2:51-59, 1990.

  15. HASHIZUME K, TANAKA T, FUJITA T, TANAKA S: Generalized seizures induced by an epileptic focus in the mesencephalic reticular formation: Impact on the understanding of the generalizing mechanism. Stereotact Funct Neurosurg, 74:153-160, 2000.

  16. KUBA R, GUZANINOVA M, BRAZDIL M, NOVAK Z, CHRASTINA J, REKTOR I: Effect of vagal nerve stimulation on interictal epileptiform discharges: A scalp EEG study. Epilepsia, 43:1181-1188, 2002.

  17. KUMAR P, RAJU TR: Seizure susceptibility decreases with enhancement of rapid eye movement sleep. Brain Res, 922:299-304, 2001.

  18. LA GRUTTA V, SABATINO M: Focal hippocampal epilepsy: effects of caudate stimulation. Experimental Neurol, 99:38-49, 1988.

  19. LERMA J, HERRERAS O, MUÑOZ D, SOLIS JM: Interactions between hippocampal penicillin spikes and theta rhythm. Electroencephalogr Clin Neurophysiol, 57:532-540, 1984.

  20. LLAMAS A, AVENDAÑO C, REINOSO-SUAREZ F: Amygdaloid projections to prefrontal and motor cortex. Science, 195:794-796, 1977.

  21. LOCKARD JS, CONGDON WC, DUCHARM E: Feasibility and safety of vagal stimulation in monkey model. Epilepsia (Supl 31), 2:20-26, 1990.

  22. MAGDALENO-MADRIGAL VM, VALDES-CRUZ A, MARTINEZ-VARGAS D, MARTINEZ A, ALMAZAN S, FERNANDEZ-MAS R, FERNANDEZ-GUARDIOLA A: Effect of electrical stimulation of the nucleus of the solitary tract on the development of electrical amygdaloid kindling in the cat. Epilepsia, 43:964-969, 2002.

  23. MAGNES J, MORUZZI G, POMPEIANO O: Synchronization of the EEG produced by low frequency electrical stimulation of the region of the Solitary Tract. Arch Ital Biol, 99:33-61, 1961.

  24. MCLACHLAN R S: Suppression of interictal spikes and seizures by stimulation of the vagus nerve. Epilepsia, 34:918-923, 1993.

  25. MILGRAM NW, YEARWOOD T, KHRUGEL M, IVY GO, RACINE R: Changes in inhibitory processes in the hippocampus following recurrent seizures induced by systemic administration of kainic acid. Brain Res, 551:236-246, 1991.

  26. MILLER JW: The role of mesencephalic and thalamic arousal systems in experimental seizures. Prog Neurobiol, 39:155-178, 1992.

  27. MILLER JW, TURNER GM, GRAY BC: Anticonvulsant effects of the experimental induction of hippocampal theta activity. Epilepsy Res. 18:195-204, 1994.

  28. PAXINOS G, WATSON C: The Rat Brain in Stereotaxic Coordinates. Academic Press, Nueva York, 1998.

  29. PELLEGRINI A, GLOOR P: Effects of bilateral partial diencephalic lesions on cortical epileptic activity in generalized penicillin epilepsy in the cat. Exp Neurol, 66:285-308, 1979.

  30. PITKÄNEN A, JOLKKONEN E, KEMPPAINEN S: Anatomic heterogeneity of the rat amygdaloid complex. Folia Morphol, 59:1-23, 2000.

  31. RACINE RJ. Modification of seizure activity by electrical stimulation: II. Motor seizure. Electroencephalogr Clin Neurophysiol, 32:281-294, 1972.

  32. RICARDO JA, KOH ET: Anatomical evidence of direct projections from the nucleus of the solitary tract to the hypothalamus, amygdala, and other forebrain structures in the rat. Brain Res, 153:1-26, 1978.

  33. RUIZ DR, RULL RA, ROLDAN RE, FERNANDEZGUARDIOLA A: Mecanismos de propagación y extinción de la actividad convulsiva. Bol Inst Est Med Biol (Mex), 16:153-173, 1958.

  34. SAPER CB, LOEWY AD: Efferent connections of the parabrachial nucleus in the rat. Brain Res, 197:291-317, 1980.

  35. SARTER M, MARKOWITSCH HJ: Collateral innervation of the medial and lateral prefrontal cortex by amygdaloid, thalamic, and brain-stem neurons. J Comp Neurol, 224:445- 460, 1984.

  36. STERIADE M, GLOOR P, LLINAS RR, LOPES DA SILVA FH, MESULAM MM: Basic mechanisms of cerebral rhythmic activities. Electroencephalogr Clin Neurophysiol, 76:481- 508, 1990.

  37. TAKAYA M, TERRY WJ, NARITOKU DK: Vagus nerve stimulation induces a sustained anticonvulsant effect. Epilepsia, 37:1111-1116, 1996.

  38. TER HORST GJ, STREEFLAND C: Ascending projections of the solitary tract nucleus. En: Robin I, Barraco A (eds). Nucleus Solitary Tract. CRC Press, 93-103, Londres, 1994.

  39. VALDES A, MAGDALENO V, MARTINEZ D, FERNANDEZ-MAS R, ALMAZAN S, MARTINEZ A, FERNANDEZ-GUARDIOLA A: Chronic stimulation of the cat Vagus Nerve effect on sleep and behavior. Prog Neuro- Psychopharmacol Biol Psychiat, 26:113-118, 2002.

  40. VAN LUIJTELAAR G, MEEREN H, SITNIKOVA EY, WELTING J: The effects of lesions in the reticular thalamic nucleus on sleep spindles and spike-wave discharges in rats. J Sleep Research (Supl 11), 1: Abstr 463, 2002.

  41. VERTES RP, COLOM LV, FORTIN WJ, BLAND BH: Brain sites for carbachol of the hippocampal theta rhythm in the rat. Exp Brain Res, 96:419-429, 1993.

  42. WALKER RB, EASTON A, GALE K: Regulation of limbic motor seizures by GABA and Glutamate transmission in nucleus tractus solitarius. Epilepsia, 40:1051-1057, 1999.

  43. WOODBURY DM, WOODBURY JW: Effects of vagal stimulation on experimentally induced seizures in rats. Epilepsia (Supl 43), 2:7-19,1990.

  44. ZANCHETTI A, WANG S C, MORUZZI G: The effect of vagal afferent stimulation on the EEG pattern of the cat. Electroencephalogr Clin Neurophysiol, 4:357-361, 1952.

  45. ZHANG X, LE GAL LA SALLE G, RIDOUX V, YU PH, JU G: Prevention of kainic acid-induced limbic seizures and fos expression by the GABA-A receptor agonist muscimol. Eur J Neurosci, 9:29-40, 1997.




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