title: The mast cell stabilizer sodium cromoglycate reduces histamine release and status epilepticus-induced neuronal damage in the rat hippocampus.
abstract: Experiments were designed to evaluate changes in the histamine release, mast cell number and neuronal damage in hippocampus induced by status epilepticus. We also evaluated if sodium cromoglycate, a stabilizer of mast cells with a possible stabilizing effect on the membrane of neurons, was able to prevent the release of histamine, γ-aminobutyric acid (GABA) and glutamate during the status epilepticus. During microdialysis experiments, rats were treated with saline (SS-SE) or sodium cromoglycate (CG-SE) and 30 min later received the administration of pilocarpine to induce status epilepticus. Twenty-four hours after the status epilepticus, the brains were used to determine the neuronal damage and the number of mast cells in hippocampus. During the status epilepticus, SS-SE group showed an enhanced release of histamine (138.5%, p = 0.005), GABA (331 ± 91%, p ≤ 0.001) and glutamate (467%, p ≤ 0.001), even after diazepam administration. One day after the status epilepticus, SS-SE group demonstrated increased number of mast cells in Stratum pyramidale of CA1 (88%, p < 0.001) and neuronal damage in dentate gyrus, CA1 and CA3. In contrast to SS-SE group, rats from the CG-SE group showed increased latency to the establishment of the status epilepticus (p = 0.048), absence of wet-dog shakes, reduced histamine (but not GABA and glutamate) release, lower number of mast cells (p = 0.008) and reduced neuronal damage in hippocampus. Our data revealed that histamine, possibly from mast cells, is released in hippocampus during the status epilepticus. This effect may be involved in the subsequent neuronal damage and is diminished with sodium cromoglycate pretreatment.
authors.affiliation: Department of Pharmacobiology, Center of Research and Advanced Studies, Mexico City, Mexico.
authors.forename: María Guadalupe
authors.initials: MG
authors.lastname: Valle-Dorado
authors.affiliation: Department of Pharmacobiology, Center of Research and Advanced Studies, Mexico City, Mexico.
authors.forename: César Emmanuel
authors.initials: CE
authors.lastname: Santana-Gómez
authors.affiliation: Unit for Medical Research in Neurological Diseases, National Medical Center, Mexico City, Mexico.
authors.forename: Sandra Adela
authors.initials: SA
authors.lastname: Orozco-Suárez
authors.affiliation: Department of Pharmacobiology, Center of Research and Advanced Studies, Mexico City, Mexico. Electronic address: lrocha@cinvestav.mx.
authors.forename: Luisa
authors.initials: L
authors.lastname: Rocha
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D018927:Anti-Asthmatic Agents / Q000627:therapeutic use*; D000927:Anticonvulsants / Q000627:therapeutic use; D002452:Cell Count; D002851:Chromatography, High Pressure Liquid; D004205:Cromolyn Sodium / Q000627:therapeutic use*; D004195:Disease Models, Animal; D004569:Electroencephalography; D005452:Fluoresceins / Q000378:metabolism; D018698:Glutamic Acid / Q000378:metabolism; D006624:Hippocampus / Q000187:drug effects / Q000473:pathology*; D006632:Histamine / Q000378:metabolism*; D008297:Male; D010862:Pilocarpine; D051381:Rats; D017208:Rats, Wistar; D013226:Status Epilepticus / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
chemical_list: D018927:Anti-Asthmatic Agents; D000927:Anticonvulsants; D005452:Fluoresceins; C435731:fluoro jade; D010862:Pilocarpine; D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid; D006632:Histamine; D004205:Cromolyn Sodium
keywords: Amino acids; Hippocampus; Histamine; Mast cells; Status epilepticus