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. 2021 Feb;38(1):35-43.
doi: 10.1007/s10719-020-09966-4. Epub 2021 Jan 7.

Neuroprotective effect of heparin Trisulfated disaccharide on ischemic stroke

Gabrielly M D Chiarantin  1   2 , Lina M Delgado-Garcia  1   2 , Laura N Zamproni  1   2 , Marcelo A Lima  2   3 , Helena B Nader  2 , Ivarne L S Tersariol  4 , Marimélia Porcionatto  5   6
Affiliations

Neuroprotective effect of heparin Trisulfated disaccharide on ischemic stroke

Gabrielly M D Chiarantin et al. Glycoconj J. 2021 Feb.

Abstract

Cells undergoing hypoxia experience intense cytoplasmic calcium (Ca2+) overload. High concentrations of intracellular calcium ([Ca2+]i) can trigger cell death in the neural tissue, a hallmark of stroke. Neural Ca2+ homeostasis involves regulation by the Na+/Ca2+ exchanger (NCX). Previous data published by our group showed that a product of the enzymatic depolymerization of heparin by heparinase, the unsaturated trisulfated disaccharide (TD; ΔU, 2S-GlcNS, 6S), can accelerate Na+/Ca2+ exchange via NCX, in hepatocytes and aorta vascular smooth muscle cells. Thus, the objective of this work was to verify whether TD could act as a neuroprotective agent able to prevent neuronal cell death by reducing [Ca2+]i. Pretreatment of N2a cells with TD reduced [Ca2+]i rise induced by thapsigargin and increased cell viability under [Ca2+]I overload conditions and in hypoxia. Using a murine model of stroke, we observed that pretreatment with TD decreased cerebral infarct volume and cell death. However, when mice received KB-R7943, an NCX blocker, the neuroprotective effect of TD was abolished, strongly suggesting that this neuroprotection requires a functional NCX to happen. Thus, we propose TD-NCX as a new therapeutic axis for the prevention of neuronal death induced by [Ca2+]i overload.

Keywords: Calcium overload; Hypoxia; Neuroprotection; Stroke; Trisulfated disaccharide.

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References

    1. Benjamin, E.J., Blaha, M.J., Chiuve, S.E., Cushman, M., Das, S.R., Deo, R., de Ferranti, S.D., Floyd, J., Fornage, M., Gillespie, C., Isasi, C.R., Jiménez, M.C., Jordan, L.C., Judd, S.E., Lackland, D., Lichtman, J.H., Lisabeth, L., Liu, S., Longenecker, C.T., Mackey, R.H., Matsushita, K., Mozaffarian, D., Mussolino, M.E., Nasir, K., Neumar, R.W., Palaniappan, L., Pandey, D.K., Thiagarajan, R.R., Reeves, M.J., Ritchey, M., Rodriguez, C.J., Roth, G.A., Rosamond, W.D., Sasson, C., Towfighi, A., Tsao, C.W., Turner, M.B., Virani, S.S., Voeks, J.H., Willey, J.Z., Wilkins, J.T., Wu, J.H., Alger, H.M., Wong, S.S., Muntner, P., American Heart Association Statistics Committee and Stroke Statistics Subcommittee: Heart disease and stroke Statistics-2017 update: a report from the American Heart Association. Circulation. 135(10), e146–e603 (2017). https://doi.org/10.1161/CIR.0000000000000485 - DOI - PubMed - PMC
    1. Neumar, R.W.: Molecular mechanisms of ischemic neuronal injury. Ann. Emerg. Med. 36(5), 483–506 (2000). https://doi.org/10.1067/mem.2000.110995 - DOI - PubMed
    1. Kalogeris, T., Baines, C.P., Krenz, M., Korthuis, R.J.: Ischemia/Reperfusion. Compr Physiol. 7(1), 113–170 (2016). https://doi.org/10.1002/cphy.c160006 - DOI - PubMed - PMC
    1. Carini, R., Bellomo, G., Dianzani, M.U., Albano, E.: Evidence for a sodium-dependent calcium influx in isolated rat hepatocytes undergoing ATP depletion. Biochem. Biophys. Res. Commun. 202(1), 360–366 (1994). https://doi.org/10.1006/bbrc.1994.1936 - DOI - PubMed
    1. Song, H.A., Kim, Y.S., Cho, H.J., Kim, S.I., Kang, M.J., Kim, J.H., Min, H.J., Kang, J.W., Yoon, J.H., Kim, C.H.: Hypoxia modulates epithelial permeability via regulation of vascular endothelial growth factor in airway epithelia. Am. J. Respir. Cell Mol. Biol. 57(5), 527–535 (2017). https://doi.org/10.1165/rcmb.2016-0080OC - DOI - PubMed

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