Neurobiological and physiological mechanisms of fever-related epileptiform syndromes.
Febrile seizures (FS) are the most common type of convulsive events in children. FS have been extensively studied using animal models, where rat and mice pups are placed in a hyperthermic environment. Such work has largely focused on the consequences rather than on the mechanisms of experimental febrile seizures (eFS). We have recently shown that eFS are preceded by a dramatic rise in the rate of respiration. The consequent respiratory alkalosis affecting the brain and increasing neuronal excitability is a direct cause of the eFS [1]. If a similar mechanism contributes to human FS and other fever-related epileptiform syndromes, a number of factors operating at the molecular, cellular and systems level that have not been previously thought to be involved in their etiology must be considered. These include physiological and pathophysiological factors affecting CO(2) chemosensitivity as well as cellular and systemic mechanisms of acid-base regulation. Furthermore, a critical role for brain pH in FS points to novel types of susceptibility genes, which include genes coding pH-sensitive target proteins (e.g. neuronal ion channels) and pH-regulatory proteins. We will discuss these novel ideas and putative therapies based on them.
Schuchmann
Sebastian
S
Department of Biological and Environmental Sciences, University of Helsinki, Helsinki, Finland.
Vanhatalo
Sampsa
S
Kaila
Kai
K
D000136:Acid-Base Equilibrium / Q000502:physiology; D000472:Alkalosis, Respiratory / Q000150:complications / Q000503:physiopathology*; D000818:Animals; D001921:Brain / Q000378:metabolism / Q000503:physiopathology*; D002245:Carbon Dioxide / Q000378:metabolism; D002628:Chemoreceptor Cells / Q000502:physiology; D004195:Disease Models, Animal; D020022:Genetic Predisposition to Disease / Q000235:genetics; D006801:Humans; D006985:Hyperventilation / Q000150:complications / Q000503:physiopathology*; D007223:Infant; D007473:Ion Channels / Q000235:genetics; D051379:Mice; D051381:Rats; D003294:Seizures, Febrile / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology*
D007473:Ion Channels; D002245:Carbon Dioxide