Platelet-activating factor receptor antagonism targets neuroinflammation in experimental epilepsy

Epilepsia. 2011 Mar;52(3):551-61. doi: 10.1111/j.1528-1167.2010.02920.x. Epub 2011 Jan 4.


Purpose: Temporal lobe epilepsy is associated with the inflammatory process related to the basic mechanisms that lead to seizure susceptibility and brain damage. Platelet-activating factor (PAF), a potent, short-lived phospholipid mediator of inflammation, participates in physiologic signaling in the brain. However, after seizures, PAF accumulates in the brain and activates intracellular signaling related with inflammation-mediated excitotoxicity and hippocampal hyperexcitability. The objective of this study is to evaluate the effect of PAF antagonism on hippocampal hyperexcitability, seizure susceptibility, and neuroprotection using the kindling paradigm and pilocarpine-induced seizure damage models.

Methods: The PAF antagonist, LAU-0901 (60 mg/kg, i.p.), or vehicle, was administrated each day of kindling or daily during the 4 weeks after status epilepticus (SE). We analyzed seizure severity, electrical activity, cellular damage, and inflammation in the hippocampi of both treated groups.

Key findings: LAU-0901 limits the progression of kindling and attenuates seizure susceptibility 1 week after the kindling procedure. In addition, under the seizure-damage conditions studied here, we observed that LAU-0901 induces hippocampal neuroprotection and limits somatostatin interneuronal cell loss and inflammation.

Significance: Our results indicate that modulation of PAF overactivity attenuates seizure susceptibility, hippocampal hyperexcitability, and neuroinflammation.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Death / drug effects
  • Cytokines / metabolism*
  • Dihydropyridines / pharmacology*
  • Dinoprostone / metabolism
  • Disease Models, Animal*
  • Epilepsy, Temporal Lobe / immunology*
  • Epilepsy, Temporal Lobe / pathology
  • Hippocampus / drug effects*
  • Hippocampus / immunology*
  • Hippocampus / pathology
  • Kindling, Neurologic / drug effects*
  • Kindling, Neurologic / immunology*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Neuroprotective Agents / pharmacology*
  • Platelet Activating Factor / metabolism
  • Platelet Membrane Glycoproteins / antagonists & inhibitors*
  • Pyramidal Cells / drug effects
  • Pyramidal Cells / immunology
  • Pyramidal Cells / pathology
  • Rats
  • Rats, Wistar
  • Receptors, G-Protein-Coupled / antagonists & inhibitors*


  • Cytokines
  • Dihydropyridines
  • LAU 0901
  • Neuroprotective Agents
  • Platelet Activating Factor
  • Platelet Membrane Glycoproteins
  • Receptors, G-Protein-Coupled
  • platelet activating factor receptor
  • Dinoprostone