Enhancing of Methotrexate Penetration Into The Brain Via The Operation of Indirect Nonanastomotic By-Pass Technique (Encephalo-Myo- Synangiosis) In Rats

Abstract

ABSTRACT The aim of this experimental study was to investigate the penetration of methotrexate into the brain parenchyma after indirect nonanastomotic by-pass surgery (encephalo-myo-synangiosis) in rats. The fourteen rats were divided into two groups as control and operated rats. Control rats were not operated but received methotrexate treatment (50 mg/kg). The operation of indirect nonanastomotic by-pass was done on operated group. After four weeks from the operation, methotrexate (50 mg/kg) was injected via intravenous route one hour before the decapitation. Parenchymal methotrexate level was estimated by using biochemical methods. The mean methotrexate level in the brain parenchyma of control group was estimated as 1.16± 0.93 µmol/L. The mean methotrexate level in the brain parenchyma of operated group was found as 2.5±0.98 µmol/L. The operation of pial synangiosis enhanced the penetration of methodrexate into the brain parenchyma in comparison with unoperated subjects. The differences between these two groups were statistically meaningful (p=0.0221). In this experimental study, we used the operation of encephalo-myo-synangiosis (EMS) for enhancing of the penetration of methotrexate into the brain. According to our results the operation of EMS enhanced the penetration of methotrexate into the brain parenchyma in the rats. 

Keywords

• Indirect nonanastomotic by-pass
• methotrexate
• brain parenchyma
• encephalo-myo-synangiosis.

References

1. Bellavance, M.A., Blanchette, M., Fortin, D. 2008. Recent advances in blood-brain barrier disruption as a CNS delivery strategy. AAPS J. 10, 166-177
2. Cloughesy, T.F., Gobin,Y.P., Black, K.L., Vinuella, F., Taft, F., Kadkhoda, B., Kabbinavar, F. 1997. Intra-arterial carboplatin chemotherapy for brain tumors: a dose escalation study based on cerebral blood flow. J. Neurooncol. 35, 121-131
3. Deeken, J.F., Löscher, W. 2007. The blood-brain barrier and cancer: transporters, treatment, and Trojan horses. Clin. Cancer Res. 13, 1663- 1674
4. Gao, K., Jiang, X. 2006. Influence of particle size on transport of methotrexate across blood brain barrier by polysorbate 80-coated polybutylcy anoacrylate nanoparticles. Int. J. Pharm. 310, 213-219
5. Griffin, T.W., Rasey, J.S., Bleyer, W.A. 1977. The effect of photon irradiation on blood brain barrier permeability to methotrexate in mice. Can- cer. 40, 1109-1111
6. Karasawa, J., Kikuchi, H., Furuse, S., Sakaki, T., Yoshida, Y. 1977. A surgical treatment of moyampya disease. Encephalo-myo-synangiosis. Neurol. Med. Chir 17, 29-37
7. Kemper, E.M., Boogerd, W., Thuis, I., Beijnen, J.H., van Tellingen, O. 2004. Modulation of the blood–brain barrier in oncology: therapeutic opportunities for the treatment of brain tumours? Cancer Treat. Rev. 30, 415-423
8. Lassman, A.B., Abrey, L.E., Shah, G.D., Panageas, K.S., Begemann, M., Malkin, M.G., Raizer, J.J. 2006. Systemic high-dose intravenous methotrexate for central nervous system metastases. J. Neurooncol. 78, 255-260

9. Newton, H.B., Slivka, M.A.,Volpi, C., Bourekas, E.C., Christoforidis, G.A., Baujan, M.A., Slone, W., Chakeres, D.W. 2003. Intra-arterial carbo platin and intravenous etoposide for the treatment of metastatic brain tumors. J. Neurooncol. 61, 35- 44
10. Orlando, L., Curigliano, G., Colleoni, M., Nole, F., Ferretti, G., Masci, G., Peruzotti, G., Minchella, I., Intra, M., Veronesi, P., Viale, G., Gol dhirsch, A. 2002. Intrathecal chemotherapy in carcinomatous meningitis from breast cancer. Anticancer Res. 22, 3057-3059 Rall, P.D. 1965. Experimental studies oft he blood brain barrier. Cancer Res. 25, 1572-1577
11. Yoshioka, N., Tominaga, S. 1998. Cerebral revascularization using muscle free flap for ischemic cerebrovascular disease in adult patients. Neu- rol. Med. Chir 38, 464-468