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Clodronate inhibits the secretion of proinflammatory cytokines and NO by isolated microglial cells and reduces the number of proliferating glial cells in excitotoxically injured organotypic hippocampal slice cultures.
Exp Neurol 2004; 189(2):241-51EN

Abstract

Treatment of excitotoxically injured organotypic hippocampal slice cultures (OHSC) with clodronate is known to result in the inhibition of microglial activation. We hypothesized that this is due to direct effects of clodronate on microglial cells, and investigated microglial proliferation in OHSC, and cytokine and NO secretion in isolated microglial cells. N-methyl-D-aspartate (NMDA) lesioning of OHSC resulted in a massive increase in the number of proliferating, bromo-desoxy-uridine (BrdU)-labeled cells that was reduced to control levels after treatment with clodronate (0.1, 1, 10 microg/ml). Triple-labeling revealed that clodronate abrogated the proliferation of both glial fibrillary acidic protein (GFAP)-labeled astrocytes and Griffonia simplicifolia isolectin B4 (IB4)-labeled microglial cells. Furthermore, isolated microglial cells were treated with clodronate after stimulation with lipopolysaccharide (LPS) or macrophage colony stimulating factor (M-CSF). Clodronate (0.01, 0.1, 1 microg/ml) significantly down-regulated the LPS-stimulated microglial secretion of tumor necrosis factor (TNF)-alpha, Interleukin (IL)-1beta and NO, but not of IL-6. In contrast, clodronate significantly reduced the microglial IL-6-release induced by M-CSF, indicating different intracellular pathways. The number and morphology of isolated microglial cells did not change significantly after treatment with clodronate. In summary, the number of proliferating microglial cells and astrocytes after excitotoxic injury is reduced to control levels after treatment with clodronate. Furthermore, clodronate inhibits microglial secretion of proinflammatory cytokines and NO. Clodronate could therefore prove to be a useful tool in the investigation of interactions between damaged neurons and microglial cells.

Authors+Show Affiliations

Institute of Anatomy II, Johann Wolfgang Goethe-University, Theodor-Stern-Kai 7, D-60590 Frankfurt am Main, Germany.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

15380476

Citation

Dehghani, Faramarz, et al. "Clodronate Inhibits the Secretion of Proinflammatory Cytokines and NO By Isolated Microglial Cells and Reduces the Number of Proliferating Glial Cells in Excitotoxically Injured Organotypic Hippocampal Slice Cultures." Experimental Neurology, vol. 189, no. 2, 2004, pp. 241-51.
Dehghani F, Conrad A, Kohl A, et al. Clodronate inhibits the secretion of proinflammatory cytokines and NO by isolated microglial cells and reduces the number of proliferating glial cells in excitotoxically injured organotypic hippocampal slice cultures. Exp Neurol. 2004;189(2):241-51.
Dehghani, F., Conrad, A., Kohl, A., Korf, H. W., & Hailer, N. P. (2004). Clodronate inhibits the secretion of proinflammatory cytokines and NO by isolated microglial cells and reduces the number of proliferating glial cells in excitotoxically injured organotypic hippocampal slice cultures. Experimental Neurology, 189(2), pp. 241-51.
Dehghani F, et al. Clodronate Inhibits the Secretion of Proinflammatory Cytokines and NO By Isolated Microglial Cells and Reduces the Number of Proliferating Glial Cells in Excitotoxically Injured Organotypic Hippocampal Slice Cultures. Exp Neurol. 2004;189(2):241-51. PubMed PMID: 15380476.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Clodronate inhibits the secretion of proinflammatory cytokines and NO by isolated microglial cells and reduces the number of proliferating glial cells in excitotoxically injured organotypic hippocampal slice cultures. AU - Dehghani,Faramarz, AU - Conrad,Ariane, AU - Kohl,Angelika, AU - Korf,Horst-Werner, AU - Hailer,Nils P, PY - 2004/01/12/received PY - 2004/04/20/revised PY - 2004/06/03/accepted PY - 2004/9/24/pubmed PY - 2004/10/29/medline PY - 2004/9/24/entrez SP - 241 EP - 51 JF - Experimental neurology JO - Exp. Neurol. VL - 189 IS - 2 N2 - Treatment of excitotoxically injured organotypic hippocampal slice cultures (OHSC) with clodronate is known to result in the inhibition of microglial activation. We hypothesized that this is due to direct effects of clodronate on microglial cells, and investigated microglial proliferation in OHSC, and cytokine and NO secretion in isolated microglial cells. N-methyl-D-aspartate (NMDA) lesioning of OHSC resulted in a massive increase in the number of proliferating, bromo-desoxy-uridine (BrdU)-labeled cells that was reduced to control levels after treatment with clodronate (0.1, 1, 10 microg/ml). Triple-labeling revealed that clodronate abrogated the proliferation of both glial fibrillary acidic protein (GFAP)-labeled astrocytes and Griffonia simplicifolia isolectin B4 (IB4)-labeled microglial cells. Furthermore, isolated microglial cells were treated with clodronate after stimulation with lipopolysaccharide (LPS) or macrophage colony stimulating factor (M-CSF). Clodronate (0.01, 0.1, 1 microg/ml) significantly down-regulated the LPS-stimulated microglial secretion of tumor necrosis factor (TNF)-alpha, Interleukin (IL)-1beta and NO, but not of IL-6. In contrast, clodronate significantly reduced the microglial IL-6-release induced by M-CSF, indicating different intracellular pathways. The number and morphology of isolated microglial cells did not change significantly after treatment with clodronate. In summary, the number of proliferating microglial cells and astrocytes after excitotoxic injury is reduced to control levels after treatment with clodronate. Furthermore, clodronate inhibits microglial secretion of proinflammatory cytokines and NO. Clodronate could therefore prove to be a useful tool in the investigation of interactions between damaged neurons and microglial cells. SN - 0014-4886 UR - https://www.unboundmedicine.com/medline/citation/15380476/Clodronate_inhibits_the_secretion_of_proinflammatory_cytokines_and_NO_by_isolated_microglial_cells_and_reduces_the_number_of_proliferating_glial_cells_in_excitotoxically_injured_organotypic_hippocampal_slice_cultures_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S001448860400233X DB - PRIME DP - Unbound Medicine ER -