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

2005, Number 1

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Salud Mental 2005; 28 (1)

Cortical mapping showing the effect of enkephalins in an epileptic focus.

Martínez A, Fernández-Mas R, Valdés-Cruz A, Magdaleno-Madrigal V, Fernández-Guadriola A

Language: Spanish
References: 44
Page: 18-27
PDF size: 273.58 Kb.


ABSTRACT

Introduction. Epileptic activity modifies the endogenous opioid system by increasing its levels at the end of the ictal phase, and in post-ictal and interictal phases. This increase originates a cortical excitatory effect which suppresses both slow wave sleep and REM. The epileptic activity is initiated with the presence of interictal epileptiform activity, which may be induced through penicillin administration into amygdaline nuclei. Interictal epileptiform activity is a widely employed tool used to determine the localization of epileptic foci characterized by the sudden presence of spikes or acute waves in an electroencephalogram (EEG). In the present work, this tool was used to study the participation of the opioid system in the installation and propagation of epileptic activity induced in temporal lobe amygdala. In the epiloptogenetic study, amygdaline interictal epileptiform activity was used to assess changes induced by opioids and an antagonist in the occurrence of interictal activity using an event histogram. Propagation was studied with the cortical topographic mapping technique, which shows EEG frequency components in a power spectrum, as well as the rhythmic EEG patterns.
The aim of the present study was to analyze the effect of enkephalins on epileptiform activity induced with penicillin in temporal lobe amygdala and its propagation to the cerebral cortex.
Method. Fifteen male Wistar rats were submitted to an acute preparation; they were anesthetized with urethane (1.2 g/kg, i.p.). A stainless steel bipolar electrode provided with a cannula was directed toward the left amygdaline basolateral nucleus and a second concentric bipolar electrode to the right amygdaline basolateral nucleus.
Two types of cortical recordings were carried out: global mapping and restricted areas. The first consisted of the placement of a 16 stainless steel electrode matrix (in which the electrodes from the vertex were removed) on the scalp, taking care that the tips of the electrodes were in contact with the cortex; this arrangement covered the whole cerebral cortex. The second involved a 4x4mm square matrix consisting of 16 equidistant electrodes placed on the cerebral cortex. The cortical recording was a result of placing this matrix in four different positions so that the whole cerebral cortex was monitored.
To monitor cortical recordings, experimental groups were injected penicillin into the amygdaline nuclei. To perform global mapping, enkephalins, [D-ala2]-methionine and [D-ala2]-leucine, were topically applied into the amygdaline nuclei and naloxone was administered systemically.
Analogical signals were recorded in a video-tape and were digitized in parallel with an HP workstation. Off-line analysis was carried as follows: a) information recorded in video-tapes was acquired in a computer designed for this purpose, using amygdaline interictal epileptiform activity to plot event histograms; b) EEG digitized signal, obtained from global mapping, was used to obtain a spectral analysis, consisting of color images maps in time and frequency domains, using RBEAM software. The recording of electrical activity obtained with the square matrix was visually analyzed only.
At the end of each experiment, animals were perfused and each brain was fixed intracardially with 10% formaldehyde. To verify the recording and sub-cortical injection sites, the rapid procedure was used.
Results. During control stages, cortical records showed slow activity in the form of spindles in all the recording channels; this was due to urethane. Penicillin administration in amygdaline nuclei induced epileptiform activity with a specific pattern: immediate appearance after penicillin application with a gradual increase in amplitude until stabilization was reached within 5-10 minutes of administration.
Analyses of global mapping in the frequency domain showed a specific mode of amygdaline interictal epileptiform activity propagation, starting in ipsilateral temporal, prefrontal and frontal cortices, appearing subsequently in contralateral prefrontal and frontal cortices, and finally in temporal cortex. In the time domain spectrum, an electric dipole generating an interictal spike was found in cerebral cortex.
Restricted areas mapping approach showed interictal epileptiform activity and its propagation along the ipsilateral fronto-temporal region. Data revealed an antero-posterior medial cortical activation spreading with decreasing intensity toward occipital regions.
Application of enkephalins-[D-ala2]-methionine and [D-ala2]-leucine produced no epileptic activity, but an increase in basal EEG of cortical epileptiform activity was detected, as well as a decrease in amplitude and frequency of amygdaline epileptiform activity. Naloxone originated a facilitatory effect, since its administration induced focal and generalized electrocorticographic seizures.
Conclusions. Focal penicillin is a reliable model of interictal spikes, paroxysms and generalized seizures. The study in rats showed a propagation of epileptic activity to prefrontal cortices prior to contralateral amygdala.
Our results showed that enkephalins produced a double effect. First, they originated an increase in basal EEG in temporal cortical areas, as well as a putative participation in propagation mechanisms. Second, they exerted an inhibitory effect on epilepsy installation mechanisms. The inhibitory effect originated by enkephalins was reverted by naloxone.


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