title: Nimodipine protects cultured spinal cord neurones from depolarization-induced inhibition of neurite outgrowth.
abstract: In the nervous system calcium ions play a crucial role in the regulation of growth cone motility, cell migration and neurite outgrowth. High intracellular Ca2+ concentrations severely disturb Ca(2+)-regulated processes and may lead to neuronal death. We studied whether the Ca(2+)-antagonist nimodipine could prevent inhibition of neurite outgrowth which occurs in depolarized cultures of rat foetal spinal neurones. Spinal cord slices were depolarized in culture with 50 mM K+. Nimodipine (0.01-10 microM) was added before depolarization. After 5 and 7 days the effect of treatment was determined by: (a) blind scoring of neurite outgrowth under phase contrast; and (b) measuring neurofilament (NF) protein with an ELISA. Neurite outgrowth was markedly decreased after depolarization, but was restored to control values by nimodipine (0.1 microM). Depolarization also led to a decrease in total NF content (18%). The NF content of depolarized slices incubated with 0.1 microM nimodipine was the same as in the controls. Thus, depolarization-induced Ca2+ entry into spinal neurones inhibits neurite outgrowth from spinal neurones. Low concentrations of nimodipine prevented this inhibition. As nimodipine had no effect on neurite outgrowth in control cultures, we conclude that nimodipine does not act as a neurotrophic factor but rather as a neuroprotective agent.
authors.affiliation: Department of Neurology, Utrecht University, The Netherlands.
authors.forename: P R
authors.initials: PR
authors.lastname: Bär
authors.forename: G H
authors.initials: GH
authors.lastname: Renkema
authors.forename: C M
authors.initials: CM
authors.lastname: Veraart
authors.forename: E M
authors.initials: EM
authors.lastname: Hol
authors.forename: W H
authors.initials: WH
authors.lastname: Gispen
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D016501:Neurites / Q000187:drug effects*; D016900:Neurofilament Proteins / Q000032:analysis; D009553:Nimodipine / Q000494:pharmacology*; D011188:Potassium / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D013116:Spinal Cord / Q000187:drug effects*
chemical_list: D016900:Neurofilament Proteins; D009553:Nimodipine; D011188:Potassium