Electrophysiological evaluation of the anti-oxidants glutathione and a-lipoic acid action in an animal model of cerebral ischemia

Avaliação eletrofisiológica da ação dos antioxidantes glutation e ácido a-lipóico em um modelo animal de isquemia cerebral

THESES

ELECTROPHYSIOLOGICAL EVALUATION OF THE ANTI-OXIDANTS GLUTATHIONE AND a-LIPOIC ACID ACTION IN AN ANIMAL MODEL OF CEREBRAL ISCHEMIA. (ABSTRACT)^*. THESIS. FORTALEZA, 2000.

OTONI CARDOSO DO VALE^**

An animal model for brain ischemia was developed. An electroencephalographic analysis of several band frequency absolute amplitudes has been performed in order to demonstrate the effects on cerebral electric activity induced by ischemia, following common carotid arteries bilateral obliteration in Wistar rats, anaesthetized with urethane.

The waves were recorded from subcutaneous electrodes on left frontal (F3), right frontal (F4), left parietal (P3), right parietal (P4) and vertex (Cz) regions. This electrophysiological analysis consisted of the absolute amplitude means evaluation of the several frequency spectra (alpha, beta₁, beta₂, beta₃, theta and delta). The cerebral electrical activity was picked up by an appropriate hardware and a software system for analysis.

It has been verified a highly significant reduction of the absolute amplitude means of the spectrum waves (p<0.015) after both common carotid arteries occlusion. The infusion of 1.2 mM reduced glutathione solution into the cephalic segment of the left common carotid artery of Wistar rats significantly reverted the depression of the absolute amplitudes of the several spectral frequencies of the electroencephalogram (p<0.05) induced by obliteration of both common carotid arteries.

The infusion of 0.12 mM reduced glutathione or saline solution into the cephalic segment of the left common carotid artery of the same animals did not reverted significantly the depression of the electroencephalographic wave absolute amplitudes induced by obliteration of both common carotid arteries. The occlusion of left common carotid artery in urethane anaesthetized Wistar rats caused less significant absolute amplitude reduction than both carotid arteries occlusion and the absolute amplitude recovery with intracarotid 1.2 mM reduced glutathione infusion was less evident. The left intracarotid infusion of 0.12 mM reduced glutathione in rats with bilateral common carotid arteries occlusion reverted the ischemic absolute amplitude reduction of only right frontal beta₁ hypersynchronic activity (p<0.05), but induced NREM sleep electrophysiological activity (p<0.05).

The intracarotid infusion of 2.1 mM L-cystine or 1.2 mM L-glutamine in rats with both common carotid arteries occlusion did not cause consistent absolute amplitude modifications of the electroencephalographic spectral waves. The intracarotid infusion of 3,03 mM a-lipoic acid in rats with both common carotid arteries occlusion caused initial reduction and partial final absolute amplitude recuperation of several spectral band frequencies (p<0.05); the intracarotid infusion of 6.06 mM a-lipoic acid significantly reverted the ischemic depression of the absolute amplitudes of frontal theta and right parietal delta spectra; the intracarotid infusion of 60.6 mM a-lipoic acid significantly increased the absolute amplitude ischemic-induced depression of almost all spectral electroencephalographic waves (p<0.05).

Finally, it has been demonstrated that intracarotid 1.2 mM reduced glutathione and 6.06 mM a-lipoic acid in rats with both common carotid arteries occlusion increased the intracerebral level of reduced glutathione (p<0.05).

It was concluded that an appropriated electroencephalographic analysis of Wistar rats with both carotid arteries occlusion is a valuable study model of cytotoxic effects of cerebral ischemia and could be used to verify the cytoprotector reduced glutathione effect and both pro-oxidant and oxidant a-lipoic acid action, as well as other drug effect studies.

KEY WORDS: ischemia, glutathione, a-lipoic acid, cerebral electric activity.

**Address: Rua Vicente Linhares 614 / 700, 60135-270 Fortaleza CE, Brasil.

*

Avaliação eletrofisiológica da ação dos antioxidantes glutation e ácido a-lipóico em um modelo animal de isquemia cerebral (Resumo). Tese de Doutorado. Universidade Federal do Ceará (Área: Neurofarmacologia). Orientador: Manassés Claudino Fonteles.

Publication Dates

• Publication in this collection
  19 July 2002
• Date of issue
  June 2002