title: Kainic acid-induced albumin leak across the blood-brain barrier facilitates epileptiform hyperexcitability in limbic regions.
abstract: Systemic administration of kainic acid (KA) is a widely used procedure utilized to develop a model of temporal lobe epilepsy (TLE). Despite its ability to induce status epilepticus (SE) in vivo, KA applied to in vitro preparations induces only interictal-like activity and/or isolated ictal discharges. The possibility that extravasation of the serum protein albumin from the vascular compartment enhances KA-induced brain excitability is investigated here.
  
  
  
  Epileptiform activity was induced by arterial perfusion of 6 μm KA in the in vitro isolated guinea pig brain preparation. Simultaneous field potential recordings were carried out bilaterally from limbic (CA1, dentate gyrus [DG], and entorhinal cortex) and extralimbic regions (piriform cortex and neocortex). Blood-brain barrier (BBB) breakdown associated with KA-induced epileptiform activity was assessed by parenchymal leakage of intravascular fluorescein-isothiocyanate albumin. Seizure-induced brain inflammation was evaluated by western blot analysis of interleukin (IL)-1β expression in brain tissue.
  
  
  
  KA infusion caused synchronized activity at 15-30 Hz in limbic (but not extralimbic) cortical areas, associated with a brief, single seizure-like event. A second bolus of KA, 60 min after the induction of the first ictal event, did not further enhance excitability. Perfusion of serum albumin between the two administrations of KA enhanced epileptiform discharges and allowed a recurrent ictal event during the second KA infusion.
  
  
  
  Our data show that arterial KA administration selectively alters the synchronization of limbic networks. However, KA is not sufficient to generate recurrent seizures unless serum albumin is co-perfused during KA administration. These findings suggest a role of serum albumin in facilitating acute seizure generation.
authors.affiliation: Unit of Clinical Epileptology and Experimental Neurophysiology, Carlo Besta Neurological Institute Foundation, Milan, Italy.
authors.forename: Francesco M
authors.initials: FM
authors.lastname: Noé
authors.affiliation: Unit of Clinical Epileptology and Experimental Neurophysiology, Carlo Besta Neurological Institute Foundation, Milan, Italy.
authors.forename: Elisa
authors.initials: E
authors.lastname: Bellistri
authors.affiliation: Unit of Molecular Neuroanatomy and Pathogenesis, Carlo Besta Neurological Institute Foundation, Milan, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Colciaghi
authors.affiliation: Unit of Clinical Epileptology and Experimental Neurophysiology, Carlo Besta Neurological Institute Foundation, Milan, Italy.
authors.forename: Barbara
authors.initials: B
authors.lastname: Cipelletti
authors.affiliation: Unit of Molecular Neuroanatomy and Pathogenesis, Carlo Besta Neurological Institute Foundation, Milan, Italy.
authors.forename: Giorgio
authors.initials: G
authors.lastname: Battaglia
authors.affiliation: Unit of Clinical Epileptology and Experimental Neurophysiology, Carlo Besta Neurological Institute Foundation, Milan, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: de Curtis
authors.affiliation: Unit of Clinical Epileptology and Experimental Neurophysiology, Carlo Besta Neurological Institute Foundation, Milan, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Librizzi
mesh_terms: D000418:Albumins / Q000378:metabolism*; D000818:Animals; D001812:Blood-Brain Barrier / Q000187:drug effects*; D002199:Capillary Permeability / Q000187:drug effects; D004195:Disease Models, Animal; D004569:Electroencephalography; D018690:Excitatory Amino Acid Agonists / Q000009:adverse effects*; D005260:Female; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D006168:Guinea Pigs; D053583:Interleukin-1beta / Q000378:metabolism; D007608:Kainic Acid / Q000009:adverse effects*; D008032:Limbic System / Q000187:drug effects / Q000503:physiopathology*; D018613:Microscopy, Confocal; D010751:Phosphopyruvate Hydratase / Q000378:metabolism; D012640:Seizures / Q000139:chemically induced*; D012709:Serum Albumin / Q000494:pharmacology; D013057:Spectrum Analysis; D013347:Subcellular Fractions / Q000378:metabolism
chemical_list: D000418:Albumins; D018690:Excitatory Amino Acid Agonists; D005904:Glial Fibrillary Acidic Protein; D053583:Interleukin-1beta; D012709:Serum Albumin; D010751:Phosphopyruvate Hydratase; D007608:Kainic Acid
keywords: Beta-gamma activity; IL-1 beta; In vitro guinea pig brain preparation; Neuronal network synchronization; Status epilepticus