Article

Experimental febrile seizures are precipitated by a hyperthermia-induced respiratory alkalosis.

Department of Biological and Environmental Sciences, University of Helsinki, Viikinkaari 1 (POB 65), 00014 Helsinki, Finland.
Nature Medicine (Impact Factor: 28.05). 08/2006; 12(7):817-23. DOI: 10.1038/nm1422
Source: PubMed

ABSTRACT Febrile seizures are frequent during early childhood, and prolonged (complex) febrile seizures are associated with an increased susceptibility to temporal lobe epilepsy. The pathophysiological consequences of febrile seizures have been extensively studied in rat pups exposed to hyperthermia. The mechanisms that trigger these seizures are unknown, however. A rise in brain pH is known to enhance neuronal excitability. Here we show that hyperthermia causes respiratory alkalosis in the immature brain, with a threshold of 0.2-0.3 pH units for seizure induction. Suppressing alkalosis with 5% ambient CO2 abolished seizures within 20 s. CO2 also prevented two long-term effects of hyperthermic seizures in the hippocampus: the upregulation of the I(h) current and the upregulation of CB1 receptor expression. The effects of hyperthermia were closely mimicked by intraperitoneal injection of bicarbonate. Our work indicates a mechanism for triggering hyperthermic seizures and suggests new strategies in the research and therapy of fever-related epileptic syndromes.

0 Bookmarks
 · 
133 Views
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Febrile seizures (FS) are generally defined as seizures taking place during fever. Long-term prognosis, including development of epilepsy and malformation of cognitive function, has been demonstrated after infantile FS. However, the mechanism that triggers seizures in hyperthermic environment is still unclear. We here found that the body temperature of rat pups that experienced experimental FS was markedly decreased (∼28°C) after they were removed from the hyperthermic environment. Both the seizure generation and the temperature drop after seizure attack were abolished by either pretreatment with chlorpromazine (CPZ), which impairs the thermoregulation, or by an electrolytic lesion of the preoptic area and anterior hypothalamus (PO/AH). However, the non-steroidal anti-inflammatory drug celecoxib did not affect the seizure incidence and the decrease in body temperature after seizure attack. In addition, pentobarbital prevented the generation of seizures, but did not reverse the decrease of body temperature after FS. Therefore, our work indicates that an over-regulation of body temperature occurs during hyperthermic environment, and that the dysfunction of thermoregulation in the PO/AH following hyperthermia contributes to the generation of FS.
    Neuroscience Letters 08/2014; · 2.06 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Dissolved inorganic carbon (DIC) content of aqueous systems is a key function of the pH, of the total alkanility (TA), and of the partial pressure of CO2. However, common analytical techniques used to determine the DIC content in water are unable to operate under high CO2 pressure. Here, we propose to use Raman spectroscopy as a novel alternative to discriminate and quantitatively monitor the three dissolved inorganic carbon species CO2(aq), HCO3(-), and CO3(2-) of alkaline solutions under high CO2 pressure (from P = 0 to 250 bar at T = 40 °C). In addition, we demonstrate that the pH values can be extracted from the molalities of CO2(aq) and HCO3(-). The results are in very good agreement with those obtained from direct spectrophotometric measurements using colored indicators. This novel method presents the great advantage over high pressure conventional techniques of not using breakable electrodes or reference additives and appears of great interest especially in marine biogeochemistry, in carbon capture and storage and in material engineering under high CO2 pressure.
    Analytical Chemistry 09/2014; · 5.83 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Abstract: Epilepsy is a chronic neurological condition characterized by recurrent seizures that affects millions of people worldwide. Comprehension of the complex mechanisms underlying epileptogenesis and seizure generation in temporal lobe epilepsy and other forms of epilepsy cannot be fully acquired in clinical studies with humans. As a result, the use of appropriate animal models is essential. Some of these models replicate the natural history of symptomatic focal epilepsy with an initial epileptogenic insult, which is followed by an apparent latent period and by a subsequent period of chronic spontaneous seizures. Seizures are a combination of electrical and behavioral events that are able to induce chemical, molecular, and anatomic alterations. In this review, we summarize the most frequently used models of chronic epilepsy and models of acute seizures induced by chemoconvulsants, traumatic brain injury, and electrical or sound stimuli. Genetic models of absence seizures and models of seizures and status epilepticus in the immature brain were also examined. Major uses and limitations were highlighted, and neuropathological, behavioral, and neurophysiological similarities and differences between the model and the human equivalent were considered. The quest for seizure mechanisms can provide insights into overall brain functions and consciousness, and animal models of epilepsy will continue to promote the progress of both epilepsy and neurophysiology research.
    Neuropsychiatric Disease and Treatment 09/2014; 10:1693-1705. · 2.00 Impact Factor

Full-text (2 Sources)

Download
62 Downloads
Available from
May 27, 2014