FULL-LENGTH ORIGINAL RESEARCH
Platelet-activating factor receptor antagonism targets neuroinflammation in experimental epilepsy
Article first published online: 4 JAN 2011
Wiley Periodicals, Inc. © 2011 International League Against Epilepsy
Volume 52, Issue 3, pages 551–561, March 2011
How to Cite
Musto, A. E. and Samii, M. (2011), Platelet-activating factor receptor antagonism targets neuroinflammation in experimental epilepsy. Epilepsia, 52: 551–561. doi: 10.1111/j.1528-1167.2010.02920.x
- Issue published online: 11 MAR 2011
- Article first published online: 4 JAN 2011
- Accepted October 14, 2010; Early View publication January 4, 2011.
- Platelet-activating factor;
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.