Epilepsy is the most common neurological disorder, affecting approximately 0.5%–2% of the general population. The condition is characterized by bursts of abnormal electrical activity in the brain, which can lead to various types of clinical seizures. A higher prevalence has been recorded among men and children. Thanks to the development of technologies such as EEG, deeper research into the mechanisms of the disorder has become possible. However, existing methods like PET and SPECT are limited in their ability to measure real-time brain changes during seizures. The current study examined metabolic, electrical, ionic, and hemodynamic changes occurring in the brains of awake rats during epileptic seizures induced by the convulsant agent pentylenetetrazole (PTZ-Metrazol). Six experimental conditions were studied: To conduct the study, Multiprobe Assembly (MPA) technology was used, which enables continuous measurement of mitochondrial NADH, ion concentrations (Na+, K+, Ca²+, H+), cerebral blood flow (CBF), cerebral blood volume (CBV), electrical activity (ECoG, DC), and temperature. A statistical comparison was conducted among the first five groups, while the sixth group was presented qualitatively only. Initially, there was an increase in blood flow and NADH oxidation during seizures. However, in the later seizures, energetic deterioration occurred NADH became reduced, with no change in blood flow between seizures. There was a decrease in the number of seizures compared to the control. Metabolic function was limited, with a decrease in tissue oxygenation. Reduced the number of seizures, indicating NO’s involvement in seizure initiation. However, blood flow during seizures remained similar to the control group, suggesting the presence of an additional vasodilation mechanism. Did not prevent seizures and was even accompanied by a decrease in tissue oxygenation in the later seizures. This implies that excess oxygen is not necessarily protective. Anesthesia: Upon administration of Nembutal, seizures ceased completely, and not even isolated spikes were observed on the ECoG. Spreading Depression (SD) waves: Observed in all groups, with no difference in their frequency, indicating a stable mechanism of cortical generation. Potassium ions: No significant differences were recorded between the groups in terms of concentration levels or recovery time following seizures. This study highlights the advantage of continuous monitoring methods that simultaneously assess a wide range of brain parameters. The results indicate that the NO molecule plays a role in seizure initiation and that its inhibition may serve as an anticonvulsant mechanism. Additionally, ischemia also appears to suppress seizures through a mechanism not solely dependent on NO. Hyperoxia did not show any benefit in seizure reduction or metabolic improvement. Hemodynamic, electrical, and metabolic parameters change over time with seizure progression, indicating a gradual physiological deterioration leading toward death, which is not directly influenced by the treatments administered.

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Responses to Epileptic Activity Developed Under Various Pathophysiological Conditions

  • Avraham Mayevsky,
  • Amir Livnat,
  • Avivit Mendelman,
  • Revital Etziony

摘要

Epilepsy is the most common neurological disorder, affecting approximately 0.5%–2% of the general population. The condition is characterized by bursts of abnormal electrical activity in the brain, which can lead to various types of clinical seizures. A higher prevalence has been recorded among men and children. Thanks to the development of technologies such as EEG, deeper research into the mechanisms of the disorder has become possible. However, existing methods like PET and SPECT are limited in their ability to measure real-time brain changes during seizures. The current study examined metabolic, electrical, ionic, and hemodynamic changes occurring in the brains of awake rats during epileptic seizures induced by the convulsant agent pentylenetetrazole (PTZ-Metrazol). Six experimental conditions were studied: To conduct the study, Multiprobe Assembly (MPA) technology was used, which enables continuous measurement of mitochondrial NADH, ion concentrations (Na+, K+, Ca²+, H+), cerebral blood flow (CBF), cerebral blood volume (CBV), electrical activity (ECoG, DC), and temperature. A statistical comparison was conducted among the first five groups, while the sixth group was presented qualitatively only. Initially, there was an increase in blood flow and NADH oxidation during seizures. However, in the later seizures, energetic deterioration occurred NADH became reduced, with no change in blood flow between seizures. There was a decrease in the number of seizures compared to the control. Metabolic function was limited, with a decrease in tissue oxygenation. Reduced the number of seizures, indicating NO’s involvement in seizure initiation. However, blood flow during seizures remained similar to the control group, suggesting the presence of an additional vasodilation mechanism. Did not prevent seizures and was even accompanied by a decrease in tissue oxygenation in the later seizures. This implies that excess oxygen is not necessarily protective. Anesthesia: Upon administration of Nembutal, seizures ceased completely, and not even isolated spikes were observed on the ECoG. Spreading Depression (SD) waves: Observed in all groups, with no difference in their frequency, indicating a stable mechanism of cortical generation. Potassium ions: No significant differences were recorded between the groups in terms of concentration levels or recovery time following seizures. This study highlights the advantage of continuous monitoring methods that simultaneously assess a wide range of brain parameters. The results indicate that the NO molecule plays a role in seizure initiation and that its inhibition may serve as an anticonvulsant mechanism. Additionally, ischemia also appears to suppress seizures through a mechanism not solely dependent on NO. Hyperoxia did not show any benefit in seizure reduction or metabolic improvement. Hemodynamic, electrical, and metabolic parameters change over time with seizure progression, indicating a gradual physiological deterioration leading toward death, which is not directly influenced by the treatments administered.