title: Systemic mechanisms of antiepileptic protection.
abstract: OBJECTIVE
  The objectives of this study were as follows: (1) to explore mechanisms that counteract epileptogenesis and provide antiepileptic protection in the life-threatening condition of status epilepticus; and (2) to access functional state of adaptation system and identify the roles of biochemical, humoral, and neurophysiologic factors in the antiepileptic protective system.
  
  
  METHODS
  The experimental part of this research included a series of experiments using animal models which studied the influence of apnea (hypoxia and hypercapnia) on seizure activity; in addition, the role of the prefrontal and orbitofrontal cortex in epileptogenesis and antiepileptogenesis was explored. The clinical part consisted of a series of neurophysiological studies, using a method of multistage dipole localization, and clinical models of absence epilepsy and a tumor in the Rolandic region. One more line of clinical investigations was the study of the functional state of the adaptation system. Thirty-one patients with status epilepticus, with ages 14-56, were recruited. Proteins and fractions, electrolytes, acid-base balance, and 17-oxycorticosteroids in the blood plasma and 17-21-dioxy-20-ketosteroids in the urine were examined in relation to clinical data, EEG, and MRI.
  
  
  RESULTS
  As a result of the experiments, it was determined that asphyxia has a two-phase impact on spike activity; an anticonvulsive effect of asphyxia is mediated by hypercapnia, while the orbitofrontal cortex plays the key role in the system of antiepileptic protection through its inhibition of other structures. Further, the mediobasal prefrontal lobe of the dominant hemisphere plays a significant role in antiepileptic protection, and increased levels of blood 17-corticosteroids and catecholamines are protective in the setting of stress from convulsive status epilepticus.
  
  
  CONCLUSIONS
  The system of antiepileptic protection includes humoral, biochemical, and neurophysiological mechanisms. We identified the roles of all these factors: hypercapnia, in connection with tonic convulsion, as the humoral factor and inhibitory potential of the prefrontal lobe as the main neurophysiologic factor. In the setting of convulsive status epilepticus, which maximally strains these adaptations, it is essential for endogenous levels of glucocorticoids (17-corticosteroid) and sympathoepinephrine to increase. This article is part of a Special Issue entitled "Status Epilepticus".
authors.affiliation: Moscow State University of Medicine and Dentistry named after A.I. Evdokimov, Russian Federation. Electronic address: v_karlov@barnsly.ru.
authors.forename: Vladimir
authors.initials: V
authors.lastname: Karlov
mesh_terms: D000293:Adolescent; D000328:Adult; D000818:Animals; D000927:Anticonvulsants / Q000627:therapeutic use; D005260:Female; D006801:Humans; D006935:Hypercapnia / Q000378:metabolism / Q000503:physiopathology; D056724:Immunity, Humoral / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D011817:Rabbits; D013226:Status Epilepticus / Q000378:metabolism / Q000503:physiopathology* / Q000517:prevention & control*; D055815:Young Adult
chemical_list: D000927:Anticonvulsants
keywords: Adaptation system; Animal model; Antiepileptic protection system; Epilepsy; Experiment; Humoral factor; Neurophysiologic factor; Research; Status epilepticus