Relevance of the Glutathione System in Temporal Lobe Epilepsy: Evidence in Human and Experimental Models
Table 2
Evidence of the GSH system in epilepsy patients.
Patients characteristics
Criteria
Methods
Observations
Reference
Nine patients (5 males and 4 females, age 37 ± 6 years) diagnosed with refractory TLE. Thirty-two healthy individuals without any drug treatments were used as controls. The age range and gender distribution of the control group were similar to the patient group (18 males and 14 females, age 37 ± 9 years). The patients were recruited from the National Center of Medical Genetics in Cuba.
Inclusion criteria Patients with refractory TLE, seizures for at least the last 2 years, and a minimum of two monthly complex partial seizures; failure of two major antiepileptic drugs and two monotherapy cycles and at least one polytherapy. Exclusion criteria Serious systemic illnesses, idiopathic epilepsy, simple partial seizures as the only type of seizure, being unresponsive to treatment, or active psychotic illness. Patients retained their habitual drug treatments (drugs and doses) during the entire study. Serum samples from 32 healthy individuals without any drug treatments were used as the controls. The age range and gender distribution of the control group were similar to those of the patient group (18 males and 14 females, age 37 ± 9 years).
Neurochemical determinations were performed in serum in the control group and lobectomy group using spectrophotometric methods: SOD activity was measured by the ability to inhibit autoxidation of pyrogallol; CAT activity was measured by H2O2 decomposition; and GPx was measured with H2O2 as the cumene hydroperoxide and GR and NADPH as the enzymatic and nonenzymatic indicators. Lipid peroxidation was analyzed with the MDA adduct. An anterior temporal lobectomy was performed after the presurgical evaluation. Determinations were performed at the presurgery stage as well as at 1, 6, 12, and 24 months after surgery.
The CAT enzymatic activity in the patients showed the greatest dispersion among the antioxidant enzymes and was not significantly different from that in the controls except at 6 months after surgery. The SOD activity in the patients was significantly different from the control group at each studied stage. The postsurgery stages were not significantly different from the presurgery phase. Statistically significant differences in GPx were observed when comparing the presurgery stage and the 1-month and 6-month postsurgery stages with the control group. Statistical significance for MDA occurred when comparing the presurgery, 1-month, 6-month, and 1-year stages with the control group. A tendency was observed toward normalization, with significantly different MDA levels at 1-year and 2-year postsurgery in terms of the presurgery values. In the group of patients with TLE, a negative correlation between GPx and MDA was observed at each studied stage. This correlation was also statistically significant for the control group.
Twelve patients diagnosed with intractable TLE were recruited from Hacettepe University (6 males and 6 females, 32 ± 11 years of age). The control was a male traffic accident victim. The subject was 35 years old with no known history of any central nervous system diseases and in good health.
GPx gene expression was analyzed by RT-PCR in hippocampectomy specimens.
Nineteen patients with epilepsy (12 males and 7 females, 32.7 ± 10.2 years of age). Eight healthy controls (3 males and 5 females, 28.4 ± 10.7 years of age). Eighteen patients with temporal lobe epilepsy (TLE). The patients were recruited from those admitted to the Department of Epileptology at the University Hospital in Zurich.
Inclusion criteria Focal epilepsy with an epileptogenic focus defined by an EEG with ( = 12 patients) or without ( = 7 patients) active epilepsy. The patients with active epilepsy still had seizures at the time of the examination; the patients without active epilepsy were seizure-free at the time of the examination for several months because of a surgical intervention, but they had previously experienced regular epileptic seizures. Exclusion criteria Contraindications for MR examination.
The GSH determination was performed by 1H-MRS.
Compared to the controls, there was a significant reduction (i.e., approximately 35%) of the mean GSH/water ratio in the parietooccipital regions of the patients. This reduction was found in the brain regions distal to the epileptogenic focus in structurally normal-appearing tissue in all but one patient with an epileptogenic focus in the parietal lobe. The mean GSH/water ratio was not different between the hemisphere containing the epileptogenic focus and the hemisphere without the focus.
