title: Cortical spreading depolarization stimulates gliogenesis in the rat entorhinal cortex.
abstract: Recently, we showed that cortical spreading depolarizations (CSDs) are a potent trigger of hippocampal neurogenesis. Here, we evaluated CSD-induced cytogenesis in the entorhinal cortex (EC), which provides the major afferent input to the dentate gyrus. Cortical spreading depolarizations were induced by epidural application of 3 mol/L KCl, controls received equimolar NaCl. Cytogenesis was analyzed at different time points thereafter by means of intraperitoneal 5-bromodeoxyuridine injections (day 2, 4, or days 1 to 7) and immunohistochemistry. Recurrent CSD significantly increased numbers of newborn cells in the ipsilateral EC. The majority of these cells expressed glial markers. Microglia proliferation was maximal at day 2, whereas NG2 glia and astrocytes responded for a prolonged period of time (days 2 to 4). Newborn glia remained detectable for 6 weeks after CSD. Whereas we furthermore detected newborn cells immunopositive for doublecortin, a marker for immature neuronal cells, we found no evidence for the generation of new neurons in the EC. Our results indicate that CSD is a potent gliogenic stimulus, leading to rapid and enduring changes in the glial cellular composition of the affected brain tissue. Thus, CSD facilitates ongoing structural remodeling of the directly affected cortex that might contribute to the pathophysiology of CSD-related brain pathologies.
authors.affiliation: Hans Berger Department of Neurology, Jena University Hospital, Jena, Germany.
authors.forename: Anja
authors.initials: A
authors.lastname: Urbach
authors.affiliation: Hans Berger Department of Neurology, Jena University Hospital, Jena, Germany.
authors.forename: Judith
authors.initials: J
authors.lastname: Brueckner
authors.affiliation: 1] Hans Berger Department of Neurology, Jena University Hospital, Jena, Germany [2] Center for Sepsis Control and Care, Jena University Hospital and Friedrich Schiller University Jena, Jena, Germany.
authors.forename: Otto W
authors.initials: OW
authors.lastname: Witte
mesh_terms: D000818:Animals; D000963:Antimetabolites / Q000008:administration & dosage; D001973:Bromodeoxyuridine / Q000008:administration & dosage; D049109:Cell Proliferation; D019343:Citric Acid; D013181:Cortical Spreading Depression; D000089662:Doublecortin Protein; D004338:Drug Combinations; D018728:Entorhinal Cortex / Q000166:cytology* / Q000502:physiology*; D005290:Ferric Compounds; D007267:Injections; D008297:Male; D009457:Neuroglia / Q000166:cytology*; D011189:Potassium Chloride / Q000008:administration & dosage; D051381:Rats; D017208:Rats, Wistar; D013012:Sorbitol
chemical_list: D000963:Antimetabolites; C000714848:Dcx protein, rat; D000089662:Doublecortin Protein; D004338:Drug Combinations; D005290:Ferric Compounds; C008170:citric acid, iron, sorbitol drug combination; D019343:Citric Acid; D013012:Sorbitol; D011189:Potassium Chloride; D001973:Bromodeoxyuridine