title: The omega-3 fatty acid-derived neuroprotectin D1 limits hippocampal hyperexcitability and seizure susceptibility in kindling epileptogenesis.
abstract: OBJECTIVE
  Temporal lobe epilepsy, one of the most common epilepsy syndromes, is characterized by hippocampal hyperexcitability and progressive seizure susceptibility. Omega-3 fatty acids are involved in neuronal excitability and have anticonvulsant properties. We studied the effect of docosahexaenoic acid (DHA) or its derived lipid mediator, neuroprotectin D1 (NPD1, 10R,17S-dihydroxy-docosa-4Z,7Z,11E,13E,15Z,19Z-hexaenoic acid), in evoked seizures using a rapid kindling model of temporal lobe epilepsy.
  
  
  METHODS
  DHA or NPD1 was administered in rodents with or without kindling acquisition. Locomotor seizures and evoked epileptiform hippocampal activity immediately after hippocampal stimulations were analyzed.
  
  
  RESULTS
  DHA or NPD1 limits hippocampal electrically induced hyperexcitability. Seizures induced by kindling triggered NPD1 synthesis in the hippocampus. Supplying its precursor, DHA, or direct injection of NPD1 into the third ventricle resulted in attenuation of kindling progression and hippocampal hyperexcitability.
  
  
  CONCLUSIONS
  The significance of NPD1 in temporal lobe epilepsy could open new pathways for understanding the initiation and propagation of seizures and the role this lipid mediator plays in the neuronal network.
authors.affiliation: Neuroscience Center of Excellence, Louisiana State University Health Sciences Center, School of Medicine, New Orleans, Louisiana, USA.
authors.forename: Alberto E
authors.initials: AE
authors.lastname: Musto
authors.forename: Per
authors.initials: P
authors.lastname: Gjorstrup
authors.forename: Nicolas G
authors.initials: NG
authors.lastname: Bazan
mesh_terms: D000818:Animals; D001703:Biophysics; D004195:Disease Models, Animal; D004281:Docosahexaenoic Acids / Q000008:administration & dosage* / Q000378:metabolism; D004333:Drug Administration Routes; D004558:Electric Stimulation / Q000009:adverse effects; D004569:Electroencephalography / Q000379:methods; D004833:Epilepsy, Temporal Lobe / Q000188:drug therapy* / Q000209:etiology / Q000473:pathology*; D006624:Hippocampus / Q000187:drug effects* / Q000502:physiology; D007696:Kindling, Neurologic / Q000187:drug effects / Q000502:physiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018696:Neuroprotective Agents / Q000008:administration & dosage* / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar
chemical_list: D018696:Neuroprotective Agents; C487679:protectin D1; D004281:Docosahexaenoic Acids