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Furosemide and mannitol suppression of epileptic activity in the human brain.

Publication ,  Journal Article
Haglund, MM; Hochman, DW
Published in: J Neurophysiol
August 2005

Most research on basic mechanisms of epilepsy and the design of new antiepileptic drugs has focused on synaptic transmission or action potential generation. However, a number of laboratory studies have suggested that nonsynaptic mechanisms, such as modulation of electric field interactions via the extracellular space (ECS), might also contribute to neuronal hypersynchrony and epileptogenicity. To date, a role for nonsynaptic modulation of epileptic activity in the human brain has not been investigated. Here we studied the effects of molecules that modulate the volume and water content of the ECS on epileptic activity in patients suffering from neocortical and mesial temporal lobe epilepsy. Electrophysiological and optical imaging data were acquired from the exposed cortices of anesthetized patients undergoing surgical treatment for intractable epilepsy. Patients were given a single intravenous injection containing either 20 mg furosemide (a cation-chloride cotransporter antagonist) or 50 g mannitol (an osmolyte). Furosemide and mannitol both significantly suppressed spontaneous epileptic spikes and electrical stimulation-evoked epileptiform discharges in all subjects, completely blocking all epileptic activity in some patients without suppressing normal electroencephalographic activity. Optical imaging suggested that the spread of electrical stimulation-evoked activity over the cortex was significantly reduced by these treatments, but the magnitude of neuronal activation near the stimulating electrode was not diminished. These results suggest that nonsynaptic mechanisms play a critical role in modulating the epileptogenicity of the human brain. Furosemide and other drugs that modulate the ECS might possess clinically useful antiepileptic properties, while avoiding the side effects associated with the suppression of neuronal excitability.

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Published In

J Neurophysiol

DOI

ISSN

0022-3077

Publication Date

August 2005

Volume

94

Issue

2

Start / End Page

907 / 918

Location

United States

Related Subject Headings

  • Time Factors
  • Spectrum Analysis
  • Neurology & Neurosurgery
  • Middle Aged
  • Mannitol
  • Male
  • Injections, Intravenous
  • Humans
  • Furosemide
  • Female
 

Citation

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Haglund, M. M., & Hochman, D. W. (2005). Furosemide and mannitol suppression of epileptic activity in the human brain. J Neurophysiol, 94(2), 907–918. https://doi.org/10.1152/jn.00944.2004
Haglund, Michael M., and Daryl W. Hochman. “Furosemide and mannitol suppression of epileptic activity in the human brain.J Neurophysiol 94, no. 2 (August 2005): 907–18. https://doi.org/10.1152/jn.00944.2004.
Haglund MM, Hochman DW. Furosemide and mannitol suppression of epileptic activity in the human brain. J Neurophysiol. 2005 Aug;94(2):907–18.
Haglund, Michael M., and Daryl W. Hochman. “Furosemide and mannitol suppression of epileptic activity in the human brain.J Neurophysiol, vol. 94, no. 2, Aug. 2005, pp. 907–18. Pubmed, doi:10.1152/jn.00944.2004.
Haglund MM, Hochman DW. Furosemide and mannitol suppression of epileptic activity in the human brain. J Neurophysiol. 2005 Aug;94(2):907–918.

Published In

J Neurophysiol

DOI

ISSN

0022-3077

Publication Date

August 2005

Volume

94

Issue

2

Start / End Page

907 / 918

Location

United States

Related Subject Headings

  • Time Factors
  • Spectrum Analysis
  • Neurology & Neurosurgery
  • Middle Aged
  • Mannitol
  • Male
  • Injections, Intravenous
  • Humans
  • Furosemide
  • Female