Abstract:The aim of this study was to examine neurotoxicity indocyanine green (ICG). We assessed viability of primary cerebellar granule cell culture (CGC) exposed to ICG to test two mechanisms that could be the first triggers causing neuronal toxicity: imbalance in calcium homeostasis and the degree of oligomerization of ICG molecules. We have observed this imbalance in CGC after exposure to 75-125μΜ ICG and dose and application sequence dependent protective effect of Gadovist on surviving neurons in vitro when used with ICG. Spectroscopic studies suggest the major cause of toxicity of the ICG is connected with oligomers formation. ICG at concentration of 25 μM (which is about 4 times higher than the highest concentration of ICG in the brain applied in in-vivo human studies) is not neurotoxic in the cell culture. Orlock, and C. A. Puliafito, "Adverse reactions due to indocyanine green," Ophthalmology 101(3), 529-533 (1994). 2. B. F. Hochheimer, "Angiography of the retina with indocyanine green," Arch. Ophthalmol. 86(5), 564-565 (1971). 3. J. Fishbaugh, "Retina: indocyanine green (ICG) angiography," Insight 19(3), 30-32 (1994). 4. J. Caesar, S. Shaldon, L. Chiandussi, L. Guevara, and S. Sherlock, "The use of indocyanine green in the measurement of hepatic blood flow and as a test of hepatic function," Clin. Sci. 21, 43-57 (1961). 5. A. El-Desoky, A. M. Seifalian, M. Cope, D. T. Delpy, and B. R. Davidson, "Experimental study of liver dysfunction evaluated by direct indocyanine green clearance using near infrared spectroscopy," Br. J. Surg. 1005-1011 (1999). 6. T. Ishizawa, N. Fukushima, J. Shibahara, K. Masuda, S. Tamura, T. Aoki, K. Hasegawa, Y. Beck, M. Fukayama, and N. Kokudo, "Real-time identification of liver cancers by using indocyanine green fluorescent imaging," Cancer 115(11), 2491-2504 (2009 4998-5003 (2006). 17. T. L. Jackson, "Indocyanine green accused," Br. J. Ophthalmol. 89(4), 395-396 (2005). Reson. Imaging 14(6), 619-623 (1996). 77. D. E. Ray, J. B. Cavanagh, C. C. Nolan, and S. C. Williams, "Neurotoxic effects of gadopentetate dimeglumine: behavioral disturbance and morphology after intracerebroventricular injection in rats," AJNR Am. J. Neuroradiol. 17(2), 365-373 (1996). 78. X. Feng, Q. Xia, L. Yuan, X. Yang, and K. Wang, "Impaired mitochondrial function and oxidative stress in rat cortical neurons: implications for gadolinium-induced neurotoxicity," Neurotoxicology 31(4), 391-398 (2010). 79. M. P. Mattson and Y. Goodman, "Different amyloidogenic peptides share a similar mechanism of neurotoxicity involving reactive oxygen species and calcium," Brain Res. 676(1), 219-224 (1995).
86(8),