Journalartikel

Jahr der Veröffentlichung: 2013

Seiten: 468-474

Zeitschrift: Neurosurgery

Bandnummer: 72

Heftnummer: 3

ISSN: 0148-396X

eISSN: 1524-4040

DOI Link: https://doi.org/10.1227/NEU.0b013e31827d0de7

Verlag: Lippincott, Williams & Wilkins

Abstract: 

BACKGROUND: Calcium (Ca2+) is a cofactor of multiple cellular processes. The mechanisms that lead to elevated cytosolic Ca2+ concentration are unclear.

OBJECTIVE: To illuminate how bloody cerebrospinal fluid (bCSF) from patients with intraventricular hemorrhage causes cell death of cultured human astrocytes.

METHODS: Cultured astrocytes were incubated with bCSF. In control experiments, native CSF was used. Cytosolic Ca2+ concentration was measured by fura-2 fluorescence. Apoptosis and necrosis were evaluated by staining with Hoechst-3342 and propidium iodide.

RESULTS: Incubation of astrocytes with bCSF provoked a steep Ca2+ concentration peak that was followed by a slow Ca2+ rise during the observation period of 50 minutes. Necrosis, but not apoptosis, was induced. Blockade of ATP-sensitive P2 receptors with suramin inhibited the bCSF-induced initial Ca2+ peak and necrosis. Blockade of P1 receptors with 8-phenyltheophylline or of N-methyl-D-aspartate receptors with D(-)-2-amino-5-phosphopentanoic acid had no significant effect. Preincubation with xestospongin D, a blocker of inositol 1,4,5-trisphosphate receptors, prevented the initial Ca2+ rise and reduced the rate of necrosis. Preemptying of the endoplasmic reticulum with thapsigargin protected astrocytes from the bCSF-induced Ca2+ peak. Inhibition of mitochondrial permeability transition pores opening with cyclosporin A reduced the rate of astrocytic necrosis significantly, although it did not influence the initial Ca2+ peak.

CONCLUSION: bCSF elicits a steep, transient Ca2+ rise when administered to human astrocytes by activation of ATP-sensitive P2 receptors and subsequent inositol 1,4,5-trisphosphate-dependent Ca2+ release from endoplasmic reticulum. This massive Ca2+ overload leads to subsequent mitochondrial permeability transition pores opening and necrosis of the cells.

Harvard-Zitierstil: Kasseckert, S., Shahzad, T., Miqdad, M., Stein, M., Abdallah, Y., Scharbrodt, W., et al. (2013) The Mechanisms of Energy Crisis in Human Astrocytes After Subarachnoid Hemorrhage, Neurosurgery, 72(3), pp. 468-474. https://doi.org/10.1227/NEU.0b013e31827d0de7

APA-Zitierstil: Kasseckert, S., Shahzad, T., Miqdad, M., Stein, M., Abdallah, Y., Scharbrodt, W., & Oertel, M. (2013). The Mechanisms of Energy Crisis in Human Astrocytes After Subarachnoid Hemorrhage. Neurosurgery. 72(3), 468-474. https://doi.org/10.1227/NEU.0b013e31827d0de7