The influence of anticonvulsant drugs on cerebral aspartate aminotransferase activity in mice with predisposition to audiogenic seizures.
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Biomedical subjects
Publications and source records attributed to D Haţegan.
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A polygraphic study on resistance to habituation of the somatic, autonomic and EEG components of the orienting reaction elicited by a repetitive auditory stimulus was performed in 39 epileptics with therapy-resistant generalized seizures (TRGS) and in 119 matched subjects in two control groups. The study showed a significantly higher resistance to habituation of the orienting reaction in epileptics with TRGS vs. the normal subjects of control group I. A significantly higher resistance to habituation was also noted in epileptics with therapy-controlled generalized seizures of control group II. The correlational analysis of data showed that the severity of these habituation disturbances in epileptics with TRGS depended on the patients' age, type of electroclinical seizures, pretrial seizure frequency, type of resting EEG, administered treatment (no. of administered antiepileptic drugs/patient), daily dose, as well as on the serum level of these drugs. The multivariate regression analysis showed that the most significant predictive variables for the habituation disturbances were the pretrial seizure frequency, type of electroclinical seizures, daily dose of administered antiepileptic drugs and their serum level. The data also evidenced that the antiepileptic treatment improves the interictal habituation disturbances, the effect being the more marked as the treatment was more sustained. The above-mentioned habituation changes in epileptics with TRGS should be ascribed to some disturbances in nervous excitability.
Forty Wistar rats were injected with a solution of lidocaine (90 mg/kg s.c.) 5 days per week for 30-40 days. In 36 of the animals, attacks of stiffness were obtained. After a period of disordered movements, the animals, remained completely immobile with the hindlimbs rigidly extended. The attacks of stiffness lasted from 10 to 60 minutes. The hemisection of the spinal cord at the thoracic level suppressed the rigidity of the ipsilateral leg. Electrical recording with electrodes applied to the cortex or implanted in the depth of the temporal lobe failed to reveal paroxysmal activity. These data could not confirm the results of other authors reporting typical epileptic seizures after lidocaine kindling. Despite essential differences, epileptic kindling and lidocaine-kindled stiffness attacks are both manifestations of the central nervous system plasticity. Therefore it appears that pharmacologically induced plasticity is a more general process than epileptic kindling.
In most of the 129 patients with a recent stroke by cerebral hemorrhage or infarction a note-worthy acute-phase response was found, as demonstrated by important quantitative alterations of blood levels of several acute-phase proteins (APP). These alterations were different in patients with cerebral hemorrhage as compared to those with cerebral infarction. The alterations due to cerebral infarction were not different according to the site of the infarction in brain, i.e. in the brain territories irrigated by the carotid artery system or by the basilar artery system. The APP alterations do not depend on the sex of patients or on the time elapsed from stroke-onset to blood collection.
From 129 patients with a recent stroke 105 survived and 24 died within 3 weeks from stroke-onset. At around 40 hours after the latter, the blood-levels of the acute-phase proteins ceruloplasmin and albumin did not forecast the death of the respective patients, but, in contradistinction, the level of fibrinogen was significantly higher in those who eventually died, than in those who survived. Therefore, a higher level of fibrinogen could be a risk-factor for death after stroke.
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A polygraphic study of the somatic, autonomic and EEG components of the orienting reaction elicited by an auditory stimulus was performed in 39 epileptics with therapy-resistant generalized seizures (TRGS) and in 119 matched subjects in two control groups. The study showed a significant interictal hyperresponsivity in epileptics with TRGS vs. the normal subjects of control group I, which consisted in a marked increase of the intensity of the orienting reaction components. This hyperresponsivity was also more marked than that noted in epileptics with therapy-controlled generalized seizures of control group II. The correlation analysis of data showed that the severity of these responsiveness disturbances in epileptics with TRGS depended on the patients' age, type of electroclinical seizures, pretrial seizure frequency, type of resting EEG, administered treatment (no. of administered antiepileptic drugs/patient), daily dose, as well as on the serum level of these drugs. The multivariate regression analysis showed that the most significant predictive variables for the responsiveness disturbances were the pretrial seizure frequency, type of electroclinical seizures, daily dose of administered antiepileptic drugs and their serum level. The data also evidenced that the antiepileptic treatment improves the interictal responsiveness disturbances, the effect being the more marked as the treatment was more sustained. The above-mentioned responsiveness changes in epileptics with TRGS should be ascribed to some disturbances in nervous excitability.
Hippocampic and brain stem levels of amino acids were determined in audiogenic seizure-susceptible rats following habituation by repeated exposure to the acoustic stimulus. The biochemical determinations were performed in the brains of 42 habituated animals and 23 not habituated seizure susceptible rats used as controls. It was found that the habituation process is associated with: a) increased levels of aspartate in hippocampus and pons; b) significantly decreased levels of glycine in the hippocampus and pons; c) decreased concentration of glutamate in the pons; d) no significant changes in the GABA concentrations in hippocampus and brain stem. The changes of the excitatory and inhibitory amino acids in the brain of the habituated rats cannot explain the fall in epileptic susceptibility associated with habituation.
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The beta-glycerophosphatase (GP), p-nitrophenyl phosphatase (PNFP) and beta-glucuronidase (BG) activities in four neocortical rabbit areas have been determined in six successive electrocorticographic stages of postnatal ontogenetic development of epileptic reactivity. The lysosomal enzyme activity decreases gradually from rabbits aged 1 day to adult ones and is similar within the four neocortical areas. The activity of the three lysosomal enzymes is not parallel. Statistically significant decreases in beta-glycerophosphatase activity are present in rabbits at the age of 30 days versus adult age in all the areas investigated while beta-glucuronidase is higher at the same developmental stage only in beta retrosplenial (III) and motor (II) areas. Correlation of the electrophysiological and biochemical data cannot provide explanation for the particular phenomena of the epileptogenic reactivity in rabbit cerebral neocortex.
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