Status epilepticus: Using antioxidant agents as alternative therapies (Review)

  • Authors:
    • Liliana Carmona‑Aparicio
    • Cecilia Zavala‑Tecuapetla
    • María Eva González‑Trujano
    • Aristides Iii Sampieri
    • Hortencia Montesinos‑Correa
    • Leticia Granados‑Rojas
    • Esaú Floriano‑Sánchez
    • Elvia Coballase‑Urrutía
    • Noemí Cárdenas‑Rodríguez
  • View Affiliations

  • Published online on: August 23, 2016     https://doi.org/10.3892/etm.2016.3609
  • Pages: 1957-1962
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )


Abstract

The epileptic state, or status epilepticus (SE), is the most serious situation manifested by individuals with epilepsy, and SE events can lead to neuronal damage. An understanding of the molecular, biochemical and physiopathological mechanisms involved in this type of neurological disease will enable the identification of specific central targets, through which novel agents may act and be useful as SE therapies. Currently, studies have focused on the association between oxidative stress and SE, the most severe epileptic condition. A number of these studies have suggested the use of antioxidant compounds as alternative therapies or adjuvant treatments for the epileptic state.

Overview of status epilepticus (SE)

Epilepsy generalities

Epilepsy is a group of different types of disorders that share an abnormally increased tendency to cause convulsive seizures (1). Epilepsy is a chronic neurological disorder characterized by abnormal organization of neuronal electrical activity leading to alterations in a neuronal population, which manifests in seizures, behavioral changes or impaired neuronal activity (14). The International League Against Epilepsy (ILAE) defines epilepsy as ‘a pathological condition because of the presence of two or more recurrent seizures over a period longer than 24 h unprovoked’ (5,6). The incidence of this neurological disease is high in children, stable in adults and increases in the final decades of life (711).

Classification of seizures

Based on their etiology, the seizures are classified as follows: i) Idiopathic (primary), associated with heredity; ii) symptomatic (secondary), associated with damage in the brain, including trauma, tumors, bleeding, infection, vascular malformations or metabolic abnormalities; and iii) cryptogenic, seizures with an unknown cause (1214).

Seizures are focal or generalized, depending on the location of hypersynchronic activity (1316). Focal seizures are caused by an electrical shock in a particular region of the brain, and can spread to the entire brain. Patients with focal seizures may or may not experience loss of consciousness (simple or complex seizures, respectively) (1317). Generalized seizures are those in which the altered electrical activity occurs in the two cerebral hemispheres concurrently (3,9). In this type of seizure, a generalized motor impairment with or without autonomic disruption can occur, characterized by an electroencephalogram pattern that is bilateral, synchronous and symmetrical in the hemispheres (1416).

Generalities of status epilepticus (SE)

SE is a term used to describe a condition resulting from the failure of the mechanisms associated with seizure termination, or from the initiation of mechanisms that lead to prolonged seizures (18). According to the ILAE in 2015, a recent classification of SE has been proposed based on a clinical diagnosis, and on an investigation and therapeutic approaches for each patient (19). The following operational definition of SE has been proposed: In adults and children >5 years old was defined as ≥5 min of continuous seizure or ≥2 seizures during which there is incomplete recovery of consciousness (19,20). There are 3 principal factors that determine the risk of mortality and morbidity in SE: i) Etiology of seizure (principally infection in children; trauma, metabolic disruptions or intoxication in adults); ii) age ≥60 years old; and iii) duration and development of SE (the majority of patients with SE have no history of seizures, presenting a risk of development of chronic epilepsy) (2125). Generalized convulsive SE is the most frequently observed type, however, non-convulsive SE is difficult to diagnose as it can be confused with other neurological and psychiatric disorders (26).

Etiology, initiation and propagation of SE

SE results from an alteration of the mechanisms that usually terminate a single and prolonged seizure (27). This alteration may result in constant neuronal excitation, or in failure of the inhibition mechanisms, and it has been suggested that reverberating seizure activity is induced in hippocampal structures and its progress is a sequence of distinct electrophysiological changes (28).

In temporal lobe epilepsy (TLE), an SE episode is generally considered a trigger that initiates epileptogenesis. It has been suggested that seizure initiation is produced by a dysregulation between the excitatory and inhibitory systems, leading to irregular neuronal activity (27). Furthermore, it has been suggested that protein phosphorylation, ion channel opening and closure, release of neurotransmitters and modulators and receptor desensitization occur during the first few seconds of a seizure. In addition, within seconds to minutes the movement of existing receptors to the synaptic membrane occurs. This process alters the activity of inhibitory and excitatory receptors available in the synaptic cleft (29). Furthermore, within minutes to hours, plastic changes in neuropeptide modulators occur, leading to a state of increased excitability (27).

When measured by in vivo intracerebral microdialysis, an increase in the levels of glutamate is the beginning of seizure activity in adults with TLE (3032). The same mechanism may happen during the onset of generalized seizures. Inhibitory neurotransmitters increase in the seizure site and reestablish the balance between excitation and inhibition response (31).

Neurotoxicity and neuroprotection in SE

In SE, neuronal damage is the consequence of sustained N-methyl-D-aspartate receptor stimulation that leads to apoptosis. The cell destruction that is generated in this manner can be reversed if the SE is terminated within the first hour (27). The investigation for acute or chronic therapies should be based on the patient age, gender and genetic predisposition in addition to the SE etiology. In this manner, understanding the spectrum of SE may lead to the identification of neuroprotective treatments that are specific for the developing central nervous system, to diminish the consequences of SE.

Experimental models of SE

SE models are currently used to study the transition from a single SE episode to chronic epilepsy. Experimental models are used that comprise the seizure-initiating mechanisms, and that may facilitate the identification of novel therapeutic strategies for improving the treatment of SE (26). Systemic administration of pilocarpine (a muscarinic receptor agonist), systemic or local administration of kainic acid as a potent glutamate receptor agonist or protocols that electrically stimulate specific brain areas are the animal model most used for the study of SE (3336).

Systemic or local convulsant chemicals

Systemic or intracerebral injection of pilocarpine induces seizures that originate in limbic regions. This results in structural damage and possible spontaneous recurrent seizures that resemble the etiology of human complex partial seizures, such as between human TLE and the pilocarpine model. Neurotrophins have been demonstrated to be altered in the hippocampus of patients with mesial TLE and in the hippocampus and neocortex of pilocarpine-treated rats (37,38). Furthermore, cognitive and memory deficits are commonly observed in TLE patients and are also present in pilocarpine-injected rats (26,39).

In addition, SE has been induced by intracerebral administration in the amygdala or hippocampal structures. Pilocarpine (intrahippocampal injection of 2.4 mg/µl; injected volume 1.0 µl) induces SE and spontaneous recurrent seizures with low mortality (40).

Kainic acid was one of the first compounds used in the TLE rodent model (systemic or intracerebral administration). It induces neuronal depolarization, and often generalized seizures secondary to partial seizures, commonly begin in the hippocampus. Rodents exhibit remarkable hippocampal sclerosis as a consequence of the neurological damage induced by the seizures. Kainic acid has the advantage of causing injuries that are usually restricted to the hippocampus, in comparison with pilocarpine, which can also result in lesions in neocortical areas (26,39). Lower doses of kainic acid produce low mortality and seizures rates with relatively long latent periods (40).

SE induction by electrical stimulation

Perforant path stimulation (PPS) is widely used to produce continuous seizures in rats and was established by Sloviter in 1991 (41). In this model, anesthetized rats receive discontinuous PPS for one day, which is usually caused by a bipolar stimulating electrode implanted into the angular bundle of the perforant pathway resulting in brain lesions based on the stimulated area, time and intensity of the stimulus (26). The histopathological findings are similar to the kainic acid and pilocarpine model although with less neurodegeneration.

The self-sustained limbic SE model by Lothman et al (42) is provoked by continuous and localized electrical stimulation of the hippocampus. In this model, a normalized electrical stimulus is determined by each rat and in adequate conditions (length and side of stimuli or kindling application), the SE persists for hours after ceasing the stimulus. This model induces SE without producing the excitotoxic effect observed in the kainic acid or pilocarpine models.

SE models in immature animals

Clinical studies have noted that a broad range of children have suffered an episode of convulsive SE, and that incidence varies widely globally (13–74%). Thus, animal models of SE are important for investigating whether long-lasting seizures in the developing brain can result in neuronal disorganization, epileptogenesis or cognitive impairment (22,43,44).

Pentylenetetrazol [a non-competitive γ-aminobutyric acid (GABA) antagonist] also leads to SE in immature animals when administered systemically at postnatal day 10 or 21 (45), similar to the models of kainic acid, lithium-pilocarpine and electrical stimulation protocols but with lower doses. In these models, seizure manifestation increases with age and induces neuronal loss in the hippocampus, amygdala and mediodorsal nucleus of the thalamus of a developing brain. However, the exact mechanisms have not been fully characterized. Nevertheless, young rats do not display the clear neuronal reorganization that is frequently observed in adults (26,4651).

Recently, Mareš et al (52) demonstrated that SE induced by pilocarpine at P12 and P25 produced cognitive damage that increased with age and is correlated with the portion of the injured brain, but not with seizure parameters.

Oxidative stress in status epilepticus

Oxidative stress in epilepsy

The study of different illnesses of the nervous system has focused on the imbalance between the oxidant and antioxidant system since 1990 (53,54). The first experimental evidence describing an association between oxidative stress and epilepsy was presented by Armstead et al (55) in 1989. The authors demonstrated that the enzyme superoxide dismutase (SOD) was increased in newborn pigs that were subject to seizure with bicuculline (a competitive antagonist of GABA), compared with control pigs and those pretreated with indomethacin. The authors concluded that superoxide reactive species formed by the newborn pig brain during seizures induced by bicuculline and cyclooxygenase metabolism of arachidonic acid may be generating this radical (55). Other reports have demonstrated the relevance of oxidative stress in different experimental models (5562)and patients (6068) with epilepsy. Currently, there is particular attention paid to clarifying the role and relevance of oxidative stress in epilepsy, particularly in severe cases, such as SE or other epileptic states.

In the early 2000s, oxidative stress was studied in the epileptic state. The evidence suggested that oxidative stress was important in this neurological pathology. In particular, SE induced by lithium-pilocarpine, pilocarpine, kainic acid, pilocarpine and sleep deprivation or cocaine in animal models (mouse and chick) causes an increase in reactive oxygen species, nitrite levels and lipid peroxidation production. It can also cause a reduction in antioxidant activity of certain enzymes such as nitric oxide synthases (NOS), catalase (CAT), SOD, glutathione peroxidase and glutathione reductase, in addition to reduced glutathione (GSH) levels in the hippocampus, striatum, thalamus, cortex or the whole brain. On the other hand, pretreatment with rosiglitazone (peroxisome proliferator-activated receptor γ agonist), tempol (SOD mimetic), muscimol (GABA agonist), FK506 (immunosuppressive agent) or buspirone (partial agonist of the 5-HT1A receptor) diminished the oxidative status while stimulating the antioxidant system (6981). The complete information is available upon request.

Different antioxidants for the treatment of SE

Although the use of antioxidants as a therapy against epilepsy has been described since 1970s, extensive studies on the use of antioxidants for treatment of SE have been reported since 2000. Different studies have demonstrated the use of antioxidants in SE, for the treatment of SE, indicating that pretreatment with vitamin E, vitamin C, coenzyme Q10, N-acetyl-cysteine, 7-nitroindazole, melatonin and various plant extracts or flavonoids reduces lipid oxidation and restores the activities of SOD, CAT and NOS and the levels of GSH in the rat hippocampus, striatum or cortex (82100). The complete information is available upon request.

Physiological and therapeutic relevance

These results will increase the understanding of the close connection between oxidative stress and epileptic state, and provide direct evidence of this association in the experimental models of epilepsy.

Oxidative stress in the epileptic state is a potential condition that requires recognition and management in clinical studies. Therefore, further studies dissecting physiological processes are required in order to establish the most effective and beneficial actions for clinical practice. The comprehension of these processes may lead to novel therapies and treatments that prevent or reduce brain injuries. Furthermore, anti-epileptic drugs are beneficial to the regulation, prevention or inhibition of seizures, although it has been demonstrated that long-term use increases oxidative stress in experimental models and in humans (101). The present study suggests that the use of antioxidants with conventional therapies may provide a beneficial treatment for SE, by diminishing brain oxidative stress induced by these seizures. However, further evidence is required to validate this hypothesis.

Acknowledgements

The funding was obtained from the National Institute of Pediatrics (Mexico City, Mexico; protocols 034/2013, 014/2012, 04/2013 and 016/2014). The authors would like to thank Ms. Sergio Humberto Larios-Godínez for the technical assistance.

References

1 

Fisher RS: Redefining epilepsy. Curr Opin Neurol. 28:130–135. 2015. View Article : Google Scholar : PubMed/NCBI

2 

Engel J Jr: Concepts of epilepsy. Epilepsia. 36:(Suppl 1). S23–S29. 1995. View Article : Google Scholar : PubMed/NCBI

3 

Engel J Jr and Starkman S: Overview of seizures. Emerg Med Clin North Am. 12:895–923. 1994.PubMed/NCBI

4 

Engel JJ and Pedley AT: Introduction to the epilepsiesEpilepsy, A Comprehensive Textbook. 1st. Lippincott-Raven; Philadelphia, PA: pp. 765–772. 1997

5 

International League Against Epilepsy, . Commission Report 1997. The Epidemiology of the Epilepsies: Future Directions. Epilepsia. 38:614–618. 1997.PubMed/NCBI

6 

International League Against Epilepsy (ILAE), . Guidelines for epidemiologic studies on epilepsy. Commission on epidemiology and prognosis, ILAE. Epilepsia. 34:592–596. 1993. View Article : Google Scholar : PubMed/NCBI

7 

Hauser WA, Annegers JF and Kurland LT: Incidence of epilepsy and unprovoked seizures in Rochester, Minnesota: 1935–1984. Epilepsia. 34:453–468. 1993. View Article : Google Scholar : PubMed/NCBI

8 

Dichter MA: Emerging insights into mechanisms of epilepsy: Implications for new antiepileptic drug development. Epilepsia. 35:(Suppl 4). S51–S57. 1994. View Article : Google Scholar : PubMed/NCBI

9 

Téllez-Zenteno JF and Hernández-Ronquillo L: A review of the epidemiology of temporal lobe epilepsy. Epilepsy Res Treat. 2012:6308532012.PubMed/NCBI

10 

Newton CR and Garcia HH: Epilepsy in poor regions of the world. Lancet. 380:1193–1201. 2012. View Article : Google Scholar : PubMed/NCBI

11 

Neligan A, Hauser WA and Sander JW: The epidemiology of the epilepsies. Handb Clin Neurol. 107:113–133. 2012. View Article : Google Scholar : PubMed/NCBI

12 

Annegers JF, Grabow JD, Groover RV, Laws ER Jr, Elveback LR and Kurland LT: Seizures after head trauma: A population study. Neurology. 30:683–689. 1980. View Article : Google Scholar : PubMed/NCBI

13 

International League Against Epilepsy (ILAE), . Proposal for revised clinical and electroencephalographic classification of epileptic seizures. Commission on classification and terminology of the ILAE. Epilepsia. 22:489–501. 1981. View Article : Google Scholar : PubMed/NCBI

14 

International League Against Epilepsy (ILAE), . Proposal for revised classification of epilepsies and epileptic syndromes. Commission on classification and terminology of the ILAE. Epilepsia. 30:389–399. 1989. View Article : Google Scholar : PubMed/NCBI

15 

Berg AT and Cross JH: Classification of epilepsies and seizures: Historical perspective and future directions. Handb Clin Neurol. 107:99–111. 2012. View Article : Google Scholar : PubMed/NCBI

16 

Cavanna AE, Rickards H and Ali F: What makes a simple partial seizure complex? Epilepsy Behav. 22:651–658. 2011. View Article : Google Scholar : PubMed/NCBI

17 

Fisher RS and Frost JJ: Epilepsy. J Nucl Med. 32:651–659. 1991.PubMed/NCBI

18 

Trinka E, Höfler J and Zerbs A: Causes of status epilepticus. Epilepsia. 53:(Suppl 4). S127–S138. 2012. View Article : Google Scholar

19 

Trinka E, Cock H, Hesdorffer D, Rossetti AO, Scheffer IE, Shinnar S, Shorvon S and Lowenstein DH: A definition and classification of status epilepticus - report of the ILAE task force on classification of status epilepticus. Epilepsia. 56:1515–1523. 2015. View Article : Google Scholar : PubMed/NCBI

20 

Lowenstein DH, Bleck T and Macdonald RL: It's time to revise the definition of status epilepticus. Epilepsia. 40:120–122. 1999. View Article : Google Scholar : PubMed/NCBI

21 

Towne AR, Pellock JM, Ko D and DeLorenzo RJ: Determinants of mortality in status epilepticus. Epilepsia. 35:27–34. 1994. View Article : Google Scholar : PubMed/NCBI

22 

DeLorenzo RJ, Hauser WA, Towne AR, Boggs JG, Pellock JM, Penberthy L, Garnett L, Fortner CA and Ko D: A prospective, population-based epidemiologic study of status epilepticus in Richmond, Virginia. Neurology. 46:1029–1035. 1996. View Article : Google Scholar : PubMed/NCBI

23 

Wu YW, Shek DW, Garcia PA, Zhao S and Johnston SC: Incidence and mortality of generalized convulsive status epilepticus in California. Neurology. 58:1070–1076. 2002. View Article : Google Scholar : PubMed/NCBI

24 

Rossetti AO, Hurwitz S, Logroscino G and Bromfield EB: Prognosis of status epilepticus: Role of aetiology, age, and consciousness impairment at presentation. J Neurol Neurosurg Psychiatry. 77:611–615. 2006. View Article : Google Scholar : PubMed/NCBI

25 

Fountain NB: Status epilepticus: Risk factors and complications. Epilepsia. 41:(Suppl 2). S23–S30. 2000. View Article : Google Scholar : PubMed/NCBI

26 

Martín E and Pozo M: Animal models for the development of new neuropharmacological therapeutics in the status epilepticus. Curr Neuropharmacol. 4:33–40. 2006. View Article : Google Scholar : PubMed/NCBI

27 

Nair PP, Kalita J and Misra UK: Status epilepticus: Why, what, and how. J Postgrad Med. 57:242–252. 2011. View Article : Google Scholar : PubMed/NCBI

28 

Lothman EW, Bertram EH III and Stringer JL: Functional anatomy of hippocampal seizures. Prog Neurobiol. 37:1–82. 1991. View Article : Google Scholar : PubMed/NCBI

29 

Naylor DE, Liu H and Wasterlain CG: Trafficking of GABA(A) receptors, loss of inhibition, and a mechanism for pharmacoresistance in status epilepticus. J Neurosci. 25:7724–7733. 2005. View Article : Google Scholar : PubMed/NCBI

30 

Carlson H, Ronne-Engström E, Ungerstedt U and Hillered L: Seizure related elevations of extracellular amino acids in human focal epilepsy. Neurosci Lett. 140:30–32. 1992. View Article : Google Scholar : PubMed/NCBI

31 

During MJ and Spencer DD: Extracellular hippocampal glutamate and spontaneous seizure in the conscious human brain. Lancet. 341:1607–1610. 1993. View Article : Google Scholar : PubMed/NCBI

32 

Haglid KG, Wang S, Qiner Y and Hamberger A: Excitotoxicity. Experimental correlates to human epilepsy. Mol Neurobiol. 9:259–263. 1994. View Article : Google Scholar : PubMed/NCBI

33 

Cavalheiro EA, Leite JP, Bortolotto ZA, Turski WA, Ikonomidou C and Turski L: Long-term effects of pilocarpine in rats: Structural damage of the brain triggers kindling and spontaneous recurrent seizures. Epilepsia. 32:778–782. 1991. View Article : Google Scholar : PubMed/NCBI

34 

Ben-Ari Y: Limbic seizure and brain damage produced by kainic acid: Mechanisms and relevance to human temporal lobe epilepsy. Neuroscience. 14:375–403. 1985. View Article : Google Scholar : PubMed/NCBI

35 

Sloviter RS and Damiano BP: Sustained electrical stimulation of the perforant path duplicates kainate-induced electrophysiological effects and hippocampal damage in rats. Neurosci Lett. 24:279–284. 1981. View Article : Google Scholar : PubMed/NCBI

36 

Lothman EW, Bertram EH, Kapur J and Stringer JL: Recurrent spontaneous hippocampal seizures in the rat as a chronic sequela to limbic status epilepticus. Epilepsy Res. 6:110–118. 1990. View Article : Google Scholar : PubMed/NCBI

37 

Schmidt-Kastner R, Humpel C, Wetmore C and Olson L: Cellular hybridization for BDNF, trkB, and NGF mRNAs and BDNF-immunoreactivity in rat forebrain after pilocarpine-induced status epilepticus. Exp Brain Res. 107:331–347. 1996. View Article : Google Scholar : PubMed/NCBI

38 

Holtzman DM and Lowenstein DH: Selective inhibition of axón outgrowth by antibodies to NGF in a model of temporal lobe epilepsy. J Neurosci. 15:7062–7070. 1995.PubMed/NCBI

39 

Reddy DS and Kuruba R: Experimental models of status epilepticus and neuronal injury for evaluation of therapeutic interventions. Int J Mol Sci. 14:18284–18318. 2013. View Article : Google Scholar : PubMed/NCBI

40 

Leite JP, Garcia-Cairasco N and Cavalheiro EA: New insights from the use of pilocarpine and kainate models. Epilepsy Res. 50:93–103. 2002. View Article : Google Scholar : PubMed/NCBI

41 

Sloviter RS: Feedforward and feedback inhibition of hippocampal principal cell activity evoked by perforant path stimulation: GABA-mediated mechanisms that regulate excitability in vivo. Hippocampus. 1:31–40. 1991. View Article : Google Scholar : PubMed/NCBI

42 

Lothman EW, Bertram EH, Bekenstein JW and Perlin JB: Self-sustaining limbic status epilepticus induced by ‘continuous’ hippocampal stimulation: Electrographic and behavioral characteristics. Epilepsy Res. 3:107–119. 1989. View Article : Google Scholar : PubMed/NCBI

43 

Hauser WA: The prevalence and incidence of convulsive disorders in children. Epilepsia. 35:(Suppl 2). S1–S6. 1994. View Article : Google Scholar : PubMed/NCBI

44 

Coppola A and Moshé SL: Why is the developing brain more susceptible to status epilepticus? Epilepsia. 50:(Suppl 12). S25–S26. 2009. View Article : Google Scholar

45 

Rajasekaran K, Zanelli SA and Goodkin HP: Lessons from the laboratory: The pathophysiology, and consequences of status epilepticus. Semin Pediatr Neurol. 17:136–143. 2010. View Article : Google Scholar : PubMed/NCBI

46 

Thompson K and Wasterlain C: Lithium-pilocarpine status epilepticus in the immature rabbit. Brain Res Dev Brain Res. 100:1–4. 1997. View Article : Google Scholar : PubMed/NCBI

47 

Thompson K, Holm AM, Schousboe A, Popper P, Micevych P and Wasterlain C: Hippocampal stimulation produces neuronal death in the immature brain. Neuroscience. 82:337–348. 1998. View Article : Google Scholar : PubMed/NCBI

48 

Sankar R, Shin DH, Liu H, Mazarati A, de Vasconcelos A Pereira and Wasterlain CG: Patterns of status epilepticus-induced neuronal injury during development and long-term consequences. J Neurosci. 18:8382–8393. 1998.PubMed/NCBI

49 

Kubová H, Druga R, Lukasiuk K, Suchomelová L, Haugvicová R, Jirmanová I and Pitkänen A: Status epilepticus causes necrotic damage in the mediodorsal nucleus of the thalamus in immature rats. J Neurosci. 21:3593–3599. 2001.PubMed/NCBI

50 

Silva AV, Regondi MC, Cipelletti B, Frassoni C, Cavalheiro EA and Spreafico R: Neocortical and hippocampal changes after multiple pilocarpine-induced status epilepticus in rats. Epilepsia. 46:636–642. 2005. View Article : Google Scholar : PubMed/NCBI

51 

Nairismägi J, Pitkänen A, Kettunen MI, Kauppinen RA and Kubova H: Status epilepticus in 12-day-old rats leads to temporal lobe neurodegeneration and volume reduction: A histologic and MRI study. Epilepsia. 47:479–488. 2006. View Article : Google Scholar : PubMed/NCBI

52 

Mareš P, Kubová H, Hen N, Yagen B and Bialer M: Derivatives of valproic acid are active against pentetrazol-induced seizures in immature rats. Epilepsy Res. 106:64–73. 2013. View Article : Google Scholar : PubMed/NCBI

53 

Choi BH: Oxygen, antioxidants and brain dysfunction. Yonsei Med J. 34:1–10. 1993. View Article : Google Scholar : PubMed/NCBI

54 

Bondy SC: The relation of oxidative stress and hyperexcitation to neurological disease. Proc Soc Exp Biol Med. 208:337–345. 1995. View Article : Google Scholar : PubMed/NCBI

55 

Armstead WM, Mirro R, Leffler CW and Busija DW: Cerebral superoxide anion generation during seizures in newborn pigs. J Cereb Blood Flow Metab. 9:175–179. 1989. View Article : Google Scholar : PubMed/NCBI

56 

Dalton T, Pazdernik TL, Wagner J, Samson F and Andrews GK: Temporalspatial patterns of expression of metallothionein-I and -III and other stress related genes in rat brain after kainic acid-induced seizures. Neurochem Int. 27:59–71. 1995. View Article : Google Scholar : PubMed/NCBI

57 

Dal-Pizzol F, Klamt F, Vianna MM, Schröder N, Quevedo J, Benfato MS, Moreira JC and Walz R: Lipid peroxidation in hippocampus early and late after status epilepticus induced by pilocarpine or kainic acid in Wistar rats. Neurosci Lett. 291:179–182. 2000. View Article : Google Scholar : PubMed/NCBI

58 

Folbergrová J: Oxidative stress in immature brain following experimentally-induced seizures. Physiol Res. 62:(Suppl 1). S39–S48. 2013.PubMed/NCBI

59 

Cárdenas-Rodríguez N, González-Trujano ME, Aguirre-Hernández E, Ruíz-García M, Sampieri A III, Coballase-Urrutia E and Carmona-Aparicio L: Anticonvulsant and antioxidant effects of Tilia americana var. mexicana and flavonoids constituents in the pentylenetetrazole-induced seizures. Oxid Med Cell Longev. 2014:3291722014. View Article : Google Scholar : PubMed/NCBI

60 

Cárdenas-Rodríguez N, Coballase-Urrutia E, Pérez-Cruz C, Montesinos-Correa H, Rivera-Espinosa L, Sampieri A III and Carmona-Aparicio L: Relevance of the glutathione system in temporal lobe epilepsy: Evidence in human and experimental models. Oxid Med Cell Longev. 2014:7592932014. View Article : Google Scholar : PubMed/NCBI

61 

Cárdenas-Rodríguez N, Coballase-Urrutia E, Rivera-Espinosa L, Romero-Toledo A, Sampieri A III, Ortega-Cuellar D, Montesinos-Correa H, Floriano-Sánchez E and Carmona-Aparicio L: Modulation of antioxidant enzymatic activities by certain antiepileptic drugs (valproic acid, oxcarbazepine and topiramate): Evidence in humans and experimental models. Oxid Med Cell Longev. 2013:5984932013. View Article : Google Scholar : PubMed/NCBI

62 

Carmona-Aparicio L, Pérez-Cruz C, Zavala-Tecuapetla C, Granados-Rojas L, Rivera-Espinosa L, Montesinos-Correa H, Hernández-Damián J, Pedraza-Chaverri J, Sampieri A III, Coballase-Urrutia E and Cárdenas-Rodríguez N: Overview of Nrf2 as therapeutic target in epilepsy. Int J Mol Sci. 16:18348–18367. 2015. View Article : Google Scholar : PubMed/NCBI

63 

Mahle C and Dasgupta A: Decreased total antioxidant capacity and elevated lipid hydroperoxide concentrations in sera of epileptic patients receiving phenytoin. Life Sci. 61:437–443. 1997. View Article : Google Scholar : PubMed/NCBI

64 

Liu CS, Wu HM, Kao SH and Wei YH: Phenytoin-mediated oxidative stress in serum of female epileptics: A possible pathogenesis in the fetal hydantoin syndrome. Hum Exp Toxicol. 16:177–181. 1997. View Article : Google Scholar : PubMed/NCBI

65 

Ono H, Sakamoto A and Sakura N: Plasma total glutathione concentrations in epileptic patients taking anticonvulsants. Clin Chim Acta. 298:135–143. 2000. View Article : Google Scholar : PubMed/NCBI

66 

Sudha K, Rao AV and Rao A: Oxidative stress and antioxidants in epilepsy. Clin Chim Acta. 303:19–24. 2001. View Article : Google Scholar : PubMed/NCBI

67 

Mueller SG, Trabesinger AH, Boesiger P and Wieser HG: Brain glutathione levels in patients with epilepsy measured by in vivo (1)H-MRS. Neurology. 57:1422–1427. 2001. View Article : Google Scholar : PubMed/NCBI

68 

Abuhandan M, Calik M, Taskin A, Yetkin I, Selek S and Iscan A: The oxidative and antioxidative status of simple febrile seizure patients. J Pak Med Assoc. 63:594–597. 2013.PubMed/NCBI

69 

Yu X, Shao XG, Sun H, Li YN, Yang J, Deng YC and Huang YG: Activation of cerebral peroxisome proliferator-activated receptors gamma exerts neuroprotection by inhibiting oxidative stress following pilocarpine-induced status epilepticus. Brain Res. 1200:146–158. 2008. View Article : Google Scholar : PubMed/NCBI

70 

Tsai CY, Chan JY, Hsu KS, Chang AY and Chan SH: Brain-derived neurotrophic factor ameliorates brain stem cardiovascular dysregulation during experimental temporal lobe status epilepticus. PLoS One. 7:e335272012. View Article : Google Scholar : PubMed/NCBI

71 

Milatovic D, Zivin M, Gupta RC and Dettbarn WD: Alterations in cytochrome c oxidase activity and energy metabolites in response to kainic acid-induced status epilepticus. Brain Res. 912:67–78. 2001. View Article : Google Scholar : PubMed/NCBI

72 

Costa DA, de Oliveira GA, Lima TC, dos Santos PS, de Sousa DP and de Freitas RM: Anticonvulsant and antioxidant effects of cyano-carvone and its action on acetylcholinesterase activity in mice hippocampus. Cell Mol Neurobiol. 32:633–640. 2012. View Article : Google Scholar : PubMed/NCBI

73 

Tejada S, Roca C, Sureda A, Rial RV, Gamundí A and Esteban S: Antioxidant response analysis in the brain after pilocarpine treatments. Brain Res Bull. 69:587–592. 2006. View Article : Google Scholar : PubMed/NCBI

74 

Tejada S, Sureda A, Roca C, Gamundí A and Esteban S: Antioxidant response and oxidative damage in brain cortex after high dose of pilocarpine. Brain Res Bull. 71:372–375. 2007. View Article : Google Scholar : PubMed/NCBI

75 

Dong Y, Wang S, Zhang T, Zhao X, Liu X, Cao L and Chi Z: Ascorbic acid ameliorates seizures and brain damage in rats through inhibiting autophagy. Brain Res. 1535:115–123. 2013. View Article : Google Scholar : PubMed/NCBI

76 

Hirotsu C, Matos G, Tufik S and Andersen ML: Changes in gene expression in the frontal cortex of rats with pilocarpine-induced status epilepticus after sleep deprivation. Epilepsy Behav. 27:378–384. 2013. View Article : Google Scholar : PubMed/NCBI

77 

Macêdo DS, de Vasconcelos SM, dos Santos RS, Aguiar LM, Lima VT, Viana GS and de Sousa FC: Cocaine alters catalase activity in prefrontal cortex and striatum of mice. Neurosci Lett. 387:53–56. 2005. View Article : Google Scholar : PubMed/NCBI

78 

Tawfik MK: Coenzyme Q10 enhances the anticonvulsant effect of phenytoin in pilocarpine-induced seizures in rats and ameliorates phenytoin-induced cognitive impairment and oxidative stress. Epilepsy Behav. 22:671–677. 2011. View Article : Google Scholar : PubMed/NCBI

79 

Du P, Tang HY, Li X, Lin HJ, Peng WF, Ma Y, Fan W and Wang X: Anticonvulsive and antioxidant effects of curcumin on pilocarpine-induced seizures in rats. Chin Med J (Engl). 125:1975–1979. 2012.PubMed/NCBI

80 

Freitas RM, Vasconcelos SM, Souza FC, Viana GS and Fonteles MM: Oxidative stress in the hippocampus after pilocarpine-induced status epilepticus in Wistar rats. FEBS J. 272:1307–1312. 2005. View Article : Google Scholar : PubMed/NCBI

81 

Freitas RM: Investigation of oxidative stress involvement in hippocampus in epilepsy model induced by pilocarpine. Neurosci Lett. 462:225–229. 2009. View Article : Google Scholar : PubMed/NCBI

82 

Liu ZW, Zhang T and Yang Z: Involvement of nitric oxide in spatial memory deficits in status epilepticus rats. Neurochem Res. 32:1875–1883. 2007. View Article : Google Scholar : PubMed/NCBI

83 

Ahmad M: Protective effects of curcumin against lithium-pilocarpine induced status epilepticus, cognitive dysfunction and oxidative stress in young rats. Saudi J Biol Sci. 20:155–162. 2013. View Article : Google Scholar : PubMed/NCBI

84 

Santos LF, Freitas RL, Xavier SM, Saldanha GB and Freitas RM: Neuroprotective actions of vitamin C related to decreased lipid peroxidation and increased catalase activity in adult rats after pilocarpine-induced seizures. Pharmacol Biochem Behav. 89:1–5. 2008. View Article : Google Scholar : PubMed/NCBI

85 

Júnior HV, de França Fonteles MM and de Freitas R Mendes: Acute seizure activity promotes lipid peroxidation, increased nitrite levels and adaptive pathways against oxidative stress in the frontal cortex and striatum. Oxid Med Cell Longev. 2:130–137. 2009. View Article : Google Scholar : PubMed/NCBI

86 

Liu J, Wang A, Li L, Huang Y, Xue P and Hao A: Oxidative stress mediates hippocampal neuron death in rats after lithium-pilocarpine-induced status epilepticus. Seizure. 19:165–172. 2010. View Article : Google Scholar : PubMed/NCBI

87 

de Freitas RL, Santos IM, de Souza GF, Ada R Tomé, Saldanha GB and de Freitas RM: Oxidative stress in rat hippocampus caused by pilocarpine-induced seizures is reversed by buspirone. Brain Res Bull. 81:505–509. 2010. View Article : Google Scholar : PubMed/NCBI

88 

Peternel S, Pilipović K and Zupan G: Seizure susceptibility and the brain regional sensitivity to oxidative stress in male and female rats in the lithium-pilocarpine model of temporal lobe epilepsy. Prog Neuropsychopharmacol Biol Psychiatry. 33:456–462. 2009. View Article : Google Scholar : PubMed/NCBI

89 

Atanasova M, Petkova Z, Pechlivanova D, Dragomirova P, Blazhev A and Tchekalarova J: Strain-dependent effects of long-term treatment with melatonin on kainic acid-induced status epilepticus, oxidative stress and the expression of heat shock proteins. Pharmacol Biochem Behav. 111:44–50. 2013. View Article : Google Scholar : PubMed/NCBI

90 

Tsai HL, Chang CN and Chang SJ: The effects of pilocarpine-induced status epilepticus on oxidative stress/damage in developing animals. Brain Dev. 32:25–31. 2010. View Article : Google Scholar : PubMed/NCBI

91 

Bell Aseervatham G Smilin, Sivasudha T, Suganya M, Rameshkumar A and Jeyadevi R: Trichosanthes tricuspidata modulates oxidative toxicity in brain hippocampus against pilocarpine induced status epilepticus in mice. Neurochem Res. 38:1715–1725. 2013. View Article : Google Scholar : PubMed/NCBI

92 

Nomura S, Shimakawa S, Miyamoto R, Fukui M and Tamai H: 3-Methyl-1-phenyl-2-pyrazolin-5-one or N-acetylcysteine prevents hippocampal mossy fiber sprouting and rectifies subsequent convulsive susceptibility in a rat model of kainic acid-induced seizure ceased by pentobarbital. Brain Res. 1590:65–74. 2014. View Article : Google Scholar : PubMed/NCBI

93 

Zeng LH, Zhang HD, Xu CJ, Bian YJ, Xu XJ, Xie QM and Zhang RH: Neuroprotective effects of flavonoids extracted from licorice on kainate-induced seizure in mice through their antioxidant properties. Zhe Jiang Da Xue Xue Bao. 14:1004–1012. 2013.(In Chinese).

94 

Golechha M, Chaudhry U, Bhatia J, Saluja D and Arya DS: Naringin protects against kainic acid-induced status epilepticus in rats: Evidence for an antioxidant, anti-inflammatory and neuroprotective intervention. Biol Pharm Bull. 34:360–365. 2011. View Article : Google Scholar : PubMed/NCBI

95 

Ambrogini P, Minelli A, Galati C, Betti M, Lattanzi D, Ciffolilli S, Piroddi M, Galli F and Cuppini R: Post-seizure α-tocopherol treatment decreases neuroinflammation and neuronal degeneration induced by status epilepticus in rat hippocampus. Mol Neurobiol. 50:246–256. 2014. View Article : Google Scholar : PubMed/NCBI

96 

Xavier SM, Barbosa CO, Barros DO, Silva RF, Oliveira AA and Freitas RM: Vitamin C antioxidant effects in hippocampus of adult Wistar rats after seizures and status epilepticus induced by pilocarpine. Neurosci Lett. 420:76–79. 2007. View Article : Google Scholar : PubMed/NCBI

97 

Barros DO, Xavier SM, Barbosa CO, Silva RF, Freitas RL, Maia FD, Oliveira AA, Freitas RM and Takahashi RN: Effects of the vitamin E in catalase activities in hippocampus after status epilepticus induced by pilocarpine in Wistar rats. Neurosci Lett. 416:227–230. 2007. View Article : Google Scholar : PubMed/NCBI

98 

Huang HL, Lin CC, Jeng KC, Yao PW, Chuang LT, Kuo SL and Hou CW: Fresh green tea and gallic acid ameliorate oxidative stress in kainic acid-induced status epilepticus. J Agric Food Chem. 60:2328–2336. 2012. View Article : Google Scholar : PubMed/NCBI

99 

Golechha M, Bhatia J, Ojha S and Arya DS: Hydroalcoholic extract of Emblica officinalis protects against kainic acid-induced status epilepticus in rats: Evidence for an antioxidant, anti-inflammatory, and neuroprotective intervention. Pharm Biol. 49:1128–1136. 2011. View Article : Google Scholar : PubMed/NCBI

100 

Wang SJ, Zhao XH, Chen W, Bo N, Wang XJ, Chi ZF and Wu W: Sirtuin 1 activation enhances the PGC-1α/mitochondrial antioxidant system pathway in status epilepticus. Mol Med Rep. 11:521–526. 2015.PubMed/NCBI

101 

Puttachary S, Sharma S, Stark S and Thippeswamy T: Seizure-induced oxidative stress in temporal lobe epilepsy. Biomed Res Int. 2015:7456132015. View Article : Google Scholar : PubMed/NCBI

Related Articles

Journal Cover

October-2016
Volume 12 Issue 4

Print ISSN: 1792-0981
Online ISSN:1792-1015

Sign up for eToc alerts

Recommend to Library

Copy and paste a formatted citation
x
Spandidos Publications style
Carmona‑Aparicio L, Zavala‑Tecuapetla C, González‑Trujano ME, Sampieri A, Montesinos‑Correa H, Granados‑Rojas L, Floriano‑Sánchez E, Coballase‑Urrutía E and Cárdenas‑Rodríguez N: Status epilepticus: Using antioxidant agents as alternative therapies (Review). Exp Ther Med 12: 1957-1962, 2016
APA
Carmona‑Aparicio, L., Zavala‑Tecuapetla, C., González‑Trujano, M.E., Sampieri, A., Montesinos‑Correa, H., Granados‑Rojas, L. ... Cárdenas‑Rodríguez, N. (2016). Status epilepticus: Using antioxidant agents as alternative therapies (Review). Experimental and Therapeutic Medicine, 12, 1957-1962. https://doi.org/10.3892/etm.2016.3609
MLA
Carmona‑Aparicio, L., Zavala‑Tecuapetla, C., González‑Trujano, M. E., Sampieri, A., Montesinos‑Correa, H., Granados‑Rojas, L., Floriano‑Sánchez, E., Coballase‑Urrutía, E., Cárdenas‑Rodríguez, N."Status epilepticus: Using antioxidant agents as alternative therapies (Review)". Experimental and Therapeutic Medicine 12.4 (2016): 1957-1962.
Chicago
Carmona‑Aparicio, L., Zavala‑Tecuapetla, C., González‑Trujano, M. E., Sampieri, A., Montesinos‑Correa, H., Granados‑Rojas, L., Floriano‑Sánchez, E., Coballase‑Urrutía, E., Cárdenas‑Rodríguez, N."Status epilepticus: Using antioxidant agents as alternative therapies (Review)". Experimental and Therapeutic Medicine 12, no. 4 (2016): 1957-1962. https://doi.org/10.3892/etm.2016.3609