title: Multiple neurotrophic signals converge in surviving CA1 neurons of the gerbil hippocampus following transient forebrain ischemia.
abstract: Delayed cell death involving the CA1 area of the hippocampus was produced following 5 minutes of transient forebrain ischemia in gerbils. Cell death mainly affected CA1 pyramidal neurons, whereas parvalbumin-immunoreactive (parv-ir) cells were spared. Synaptophysin immunoreactivity was observed in the strata oriens and radiatum of CA1 for months, although immunoreactivity decreased in gerbils surviving 1 year post-ischemia. Golgi studies disclosed a few pyramidal neurons with dendrites, variably covered with dendritic spines, in the CA1 area of 1-year surviving gerbils. In the normal gerbil, the majority of CA1 neurons expressed brain-derived neurotrophic factor (BDNF), tyrosine protein kinase C (TrkC), fibroblast growth factor receptor 1 (Flg), transforming growth factor-alpha (TGF-alpha), and epidermal growth factor-receptor (EGF-R), but only a minority of cells were tyrosine protein kinase B (TrkB)-immunoreactive. Marked reduction in the number of BDNF-, TrkC-, Flg-, TGF-alpha-, and EGF-R-ir cells was observed in CA1 from 24 hours to 1 year after ischemia. In contrast, TrkB-ir cells survived the ischemic insult. Double-labeling immunohistochemistry disclosed that about 90% of surviving BDNF-ir and 85% of TrkB-ir neurons co-localized parvalbumin in the CA1 area. In control gerbils, only about 5% of BDNF-ir cells in CA1 co-expressed TrkB. However, TrkB co-localized in about 95% of surviving BDNF-ir neurons in CA1 in ischemic gerbils. In addition, parvalbumin was co-expressed in about 90% of TrkC-, 95% Flg-, and 85% EGF-R-ir surviving neurons in the stratum pyramidale of CA1. Finally, basic fibroblast growth factor (bFGF) was expressed by reactive astrocytes from day 4 onwards. These data show that the subpopulation of TrkB-/parv-ir neurons in CA1 survive the ischemic episode and that multiple neurotrophic signals converge in surviving neurons of the gerbil hippocampus following transient forebrain ischemia.
authors.affiliation: Unitat de Neuropatologia, Servei d'Anatomia Patològica, Hospital Princeps d'Espanya, Universitat de Barcelona, Spain.
authors.forename: I
authors.initials: I
authors.lastname: Ferrer
authors.forename: E
authors.initials: E
authors.lastname: López
authors.forename: E
authors.initials: E
authors.lastname: Pozas
authors.forename: J
authors.initials: J
authors.lastname: Ballabriga
authors.forename: E
authors.initials: E
authors.lastname: Martí
mesh_terms: D000818:Animals; D002470:Cell Survival / Q000502:physiology; D005849:Gerbillinae / Q000033:anatomy & histology / Q000502:physiology*; D006624:Hippocampus / Q000737:chemistry* / Q000166:cytology; D007150:Immunohistochemistry; D002546:Ischemic Attack, Transient / Q000473:pathology / Q000503:physiopathology*; D008297:Male; D009414:Nerve Growth Factors / Q000502:physiology*; D009416:Nerve Regeneration / Q000502:physiology; D016548:Prosencephalon / Q000098:blood supply*; D017475:Receptors, Nerve Growth Factor / Q000032:analysis; D016708:Synaptophysin / Q000032:analysis
chemical_list: D009414:Nerve Growth Factors; D017475:Receptors, Nerve Growth Factor; D016708:Synaptophysin