Stress In Epilepsy Research Articles

Psychological and pharmacological treatments of stress in epilepsy

Treatments available for stress-related disorders span a variety of psychological and pharmacological domains. These interventions have been used both separately and in combination with one another, and both appear to be mainstays of treatment. Practical considerations or patient preferences may guide decisions. The selection of an initial treatment plan may depend largely on to whom a patient presents for treatment. A patient presenting to a nonphysician mental health provider is more likely to receive psychotherapy options, while presentation to a physician provider could offer either psychotherapy or pharmacologic therapy, or both. Subsequently, the selection of specific psychotherapies, or specific pharmacologic interventions, may depend to a large degree on the clinician's training.

Oxidative stress in epilepsy with comorbid psychiatric illness

Background: Free radicals have been implicated in the development of various acute and chronic diseases of brain. The present cross sectional study was designed to illustrate the oxidative stress in epilepsy with co morbid psychiatric illness using malondialdehyde as only few studies were available in this context. Objective: To evaluate the malondialdehyde (MDA) as a marker of oxidative stress in epilepsy with psychiatric co morbidity. Materials and Methods: The present cross sectional study had 210 samples which were divided in 5 groups including age and sex matched control. The MDA formation was estimated using the level of thiobarbituric acid reactive substances (TBARS) using spectrophotometry. The statistical analysis was done by using SPSS software and results were described with unpaired T test and p value. Results: MDA levels were significantly higher in epilepsy with psychiatric co morbidity, psychosis and depression than control. On further comparison, the MDA levels were higher in persons of epilepsy with psychiatric co morbidity than with psychosis or depression. Conclusion: Level of oxidative stress was significantly higher in epilepsy with co morbid psychiatric illness as compared to control.

Targeting Oxidative Stress in Epilepsy: Study of Effect of Antioxidants on Anticonvulsant Profile of Jatamansone

Nardostachys jatamansi, commonly known as Indian nard or spike nard or nardus root, is an indigenous Indian drug used in treatment of epilepsy, hysteria, syncope and mental weakness. It has been reported to possess anticonvulsant, neuroprotective activity and antioxidant activity. In the present paper, Jatamansone, a major component of volatile oil was isolated and characterized by spectral analysis. It was evaluated for anticonvulsant activity by MES and scPTZ tests alone and in combination with well known antioxidants like alcoholic extract of Bacopa monnieri, volatile oil of Syzygium aromaticum and pure gallic acid. Results obtained have shown significant change (reduction) in the recovery time in MES screen for Bacopa monnieri and Syzygium aromaticum (39.33s and 6.66s at 1.0 h and 4.0 h) compared to (113.66s and 123.33s at 1.0 h and 4.0 h time interval) of control while gallic acid was found to show insignificant effect (126.66s and 96s) respectively. These data are compared with standard anticonvulsant drug, Phenytoin. Antioxidant data for Jatamansone and its combinations was evaluated by DPPH model. In this screen, Jatamansone has shown IC50 value of 14.80 mg/ml alone and 6.1 μg/ml in combination.

Mitochondrial oxidative stress and epilepsy in SOD2 deficient mice: Attenuation by a lipophilic metalloporphyrin

Epileptic seizures are a common feature associated with inherited mitochondrial diseases. This study investigated the role of mitochondrial oxidative stress in epilepsy resulting from mitochondrial dysfunction using cross-bred mutant mice lacking mitochondrial manganese superoxide dismutase (MnSOD or SOD2) and a lipophilic metalloporphyrin catalytic antioxidant. Video-EEG monitoring revealed that in the second to third week of postnatal life (P14-P21) B6D2F2 Sod2−/− mice exhibited frequent spontaneous motor seizures providing evidence that oxidative stress-induced mitochondrial dysfunction may contribute to epileptic seizures. To confirm the role of mitochondrial oxidative stress in epilepsy a newly developed lipophilic metalloporphyrin, AEOL 11207, with high potency for catalytic removal of endogenously generated reactive oxygen species was utilized. AEOL 11207-treated Sod2−/− mice showed a significant decrease in both the frequency and duration of spontaneous seizures but no effect on seizure severity. A significant increase in the average lifespan of AEOL 11207-treated Sod2−/− mice compared to vehicle-treated Sod2−/− mice was also observed. Indices of mitochondrial oxidative stress and damage (aconitase inactivation, 3-nitrotyrosine formation, and depletion of reduced coenzyme A) and ATP levels affecting neuronal excitability were significantly attenuated in the brains of AEOL 11207-treated Sod2−/− mice compared to vehicle-treated Sod2−/− mice. The occurrence of epileptic seizures in Sod2−/− mice and the ability of catalytic antioxidant therapy to attenuate seizure activity, mitochondrial dysfunction, and ATP levels suggest that ongoing mitochondrial oxidative stress can contribute to epilepsy associated with mitochondrial dysfunction and disease.

Decreased glutamine synthetase, increased citrulline–nitric oxide cycle activities, and oxidative stress in different regions of brain in epilepsy rat model

To understand their role in epilepsy, the nitric oxide synthetase (NOS), argininosuccinate synthetase (AS), argininosuccinate lyase (AL), glutamine synthetase (GS), and arginase activities, along with the concentration of nitrate/nitrite (NOx), thiobarbituric acid reactive substances (TBARS), and total antioxidant status (TAS), were estimated in different regions of brain in rats subjected to experimental epilepsy induced by subcutaneous administration of kainic acid (KA). The short-term (acute) group animals were killed after 2h and the long term (chronic) group animals were killed after 5days of single injection of KA (15mg/kg body weight). After decapitation of rats, the brain regions were separated and in their homogenates, the concentration of NOx, TBARS and TAS and the activities of NOS, AS, AL, arginase and glutamine synthetase were assayed by colorimetric methods. The results of the study demonstrated the increased activity of NOS and formation of NO in acute and chronic groups epilepsy. The activities of AS and AL were increased and indicate the effective recycling of citrulline to arginine. The activity of glutamine synthetase was decreased in acute and chronic groups of epilepsy compared to control group and indicate the modulation of its activity by NO in epilepsy. The activity of arginase was not changed in acute group; however it was decreased in chronic group and may favor increased production of NO in this condition. The concentration TBARS were increased and TAS decreased in acute and chronic groups of epilepsy and supports the oxidative stress in epilepsy.

Combating oxidative stress in epilepsy: Design, synthesis, quantum chemical studies and anticonvulsant evaluation of 1-(substituted benzylidene/ethylidene)-4-(naphthalen-1-yl)semicarbazides

A series of 1-(substituted benzylidene/ethylidene)-4-(naphthalen-1-yl)semicarbazides ( 3a–19a; 3b–6b) were synthesized in good yield and evaluated for their anticonvulsant and antioxidant activities. The structures of the synthesized compounds were confirmed on the basis of their spectral data and elemental analysis. All of the compounds were found to be active in MES and scPTZ tests. Quantum chemical studies were carried out on these compounds to understand the structural features essential for activity. Electronic properties were found to be the principal modulator of both anticonvulsant and antioxidant activities. A computational study was carried out for prediction of pharmacokinetic properties and none of the compounds violated Lipinski’s rule of 5, making them potentially promising agents for the treatment of epilepsy.

Mitochondrial DNA damage and impaired base excision repair during epileptogenesis

Oxidative stress and mitochondrial dysfunction are acute consequences of status epilepticus (SE). However, the role of mitochondrial oxidative stress and genomic instability during epileptogenesis remains unknown. Using the kainate animal model of temporal lobe epilepsy, we investigated oxidative mitochondrial DNA (mtDNA) damage and changes in the mitochondrial base excision repair pathway (mtBER) in the rat hippocampus for a period of 3 months after SE. Acute seizure activity caused a time-dependent increase in mitochondrial, but not nuclear 8-hydroxy-2-deoxyguanosine (8-OHdG/2dG) levels and a greater frequency of mtDNA lesions. This was accompanied by increased mitochondrial H 2O 2 production and a transient decrease in mtDNA repair capacity. The mtBER proteins 8-oxoguanine glycosylase (Ogg1) and DNA polymerase gamma (Pol γ) demonstrated elevated expression at mRNA and protein levels shortly after SE and this was followed by a gradual improvement in mtDNA repair capacity. Recurrent seizures associated with the chronic phase of epilepsy coincided with the accumulation of mtDNA damage, increased mitochondrial H 2O 2 levels, decreased expression of Ogg1 and Pol γ and impaired mtDNA repair capacity. Together, increased oxidative mtDNA damage, mitochondrial H 2O 2 production and alterations in the mtBER pathway provide evidence for mitochondrial oxidative stress in epilepsy and suggest that mitochondrial injury may contribute to epileptogenesis.

Modulation of pentylenetetrazole‐induced seizures and oxidative stress parameters by sodium valproate in the absence and presence of N‐acetylcysteine

In view of a role of oxidative stress in epilepsy and the evidence for the involvement of peroxidative injury in sodium valproate (SVP)-induced adverse effects on liver and kidneys, we investigated whether the combination of SVP with N-acetylcysteine (NAC), an antioxidant, may help us to achieve maximal efficacy in terms of seizure control, with minimal toxicity on liver and kidneys. Pentylenetetrazole (PTZ)-induced seizures were used to evaluate the anticonvulsant effect of drugs. Biochemical estimations included the determination of oxidative stress markers like thiobarbituric acid-reactive substances in brain tissue and glutathione (GSH) levels in liver and kidney tissues. Aspartate aminotransferase and alanine aminotransferase concentrations in the serum were also determined to assess liver function. In our study, NAC exhibited a nondose-dependent anticonvulsant effect. The concurrent administration of NAC with SVP significantly prolonged the latency to jerks, myoclonus and clonic generalized seizures. No significant oxidative stress was evident in brain tissue following PTZ-induced seizures, though an elevation of serum transaminase enzymes was seen. SVP at the dose studied did not produce any significant oxidative stress on the liver and kidneys, while treatment with NAC elevated liver and kidney GSH levels. The concurrent administration of NAC with SVP had beneficial effects on liver and kidney cells.

The role of counselling in an out-patient epilepsy clinic: a three year study

The majority of patients seen at special epilepsy out-patient clinics have chronic active epilepsy. As such they represent a worse than average group and may have multi-factorial difficulties. People with epilepsy stress that their main handicaps are psychological, rather than purely physical and that unresolved anxiety about seizures and their perceived impact on life are the heaviest burdens that they must endure. Those who experience a great deal of psychological t rauma may benefit greatly from the opportunity to explore, discover and clarify ways to a better sense of well-being. This is what counselling offers. A humane society that prides itself on the egalitarian provision of health care should ensure that counselling is available for those who need it. At the appropriate time in an individual's life it makes what was previously unsupportable supportable. It will not, as is sometimes feared, deskill other members of the health care team. It will just put in place what was not there before. In situations where clinicians feel that the t ime and energy they have is not available to the patient and that the counsellor's skills are more appropriate, a referral may be made. Change is facilitated when counsellor and patient establish appropriate, achievable goals, confront maladaptive beliefs and devise coping strategies. In a relatively short time a sense of control is promoted and confidence gained. The desire to help another is no guarantee of success. Counselling is an applied activity; knowledge alone is not sufficient to make an effective counsellor. The key is to apply knowledge sensitively and appropriately to facilitate an individual toward the resolution of a dilemma. Many of the problems caused by epi lepsy-which are not related to the medical or technical aspects of seizure control--are not dealt with effectively in medically orientated neurological clinics. For adults, the most widely available specialist facility is the neurological out-patient clinic. A frequent complaint is the lack of counselling and support facilities. Having epilepsy causes difficulty in a number of areas, affecting, for instance, interpersonal relations, the ability to cope with daily activities, social stigma, adjustment, difficulties with employment and with sexual relations. The relative risks of disclosure and concealment arise when searching for employment and with interpersonal relationships, where risks of rejection are feared. The need for skilled counselling in patients with active epilepsy, in addition to 'routine' therapeutic intervention, has been recognized. At the National Hospital for Neurology and Neurosurgery, London, a trained counsellor was appointed to their epilepsy clinic to provide a forum for the problems commonly experienced by sufferers to be openly discussed. In this communication I report an analysis of 83 patients counselled at the clinic since its inception in January 1989 up to December 1991.