Effects of intrathecal methotrexate on spinal cord and meninges of rabbits

• Grant number: 11/08971-0
• Support type: Regular Research Grants
• Duration: July 01, 2011 - June 30, 2012
• Field of knowledge: Health Sciences - Medicine - Surgery
• Principal researcher: Eliana Marisa Ganem
• Grantee: Eliana Marisa Ganem
• Home Institution: Faculdade de Medicina (FMB). Universidade Estadual Paulista (UNESP). Campus de Botucatu. Botucatu , SP, Brazil

Abstract

Cancer is a disease characterized by deviation of the control mechanisms that regulate the survival, proliferation and differentiation of cells. The surgery, chemotherapy and radiotherapy treatments are commonly used in cancer patients. Chemotherapy may be curative even for certain cancers spread, both macroscopic and microscopic. The chemotherapeutic agents such as methotrexate are considered effective anticancer drugs. He who belongs to the class of antimetabolites, which act on the intermediary metabolism of proliferating cells was introduced into clinical practice for over 50 years and has pharmacological action by antagonism to folic acid. By being increasingly used in cancer treatment protocols, and with progressively higher doses, the occurrence of toxicity of methotrexate for central nervous tissue is increased. The exact mechanism triggering neurotoxicity has not been elucidated. Clinical manifestation of neurotoxicity after subarachnoid administration is chemical arachnoiditis and occurs in approximately 50% of patients. Some authors have associated it also cauda equina syndrome. The aim of the research will evaluate the effects that methotrexate administered via spinal determine on the spinal cord, nerve roots and meninges of rabbits. Methodology: After approval of the Ethics Committee on Animal Experiments will be used 30 young adult rabbits, male, race Group Genetic Botucatu with weights between 3500 and 4500g and length of the spine between 38 and 40 cm provided by the vivarium of the Faculty of Medicine Botucatu. The animals will be divided into 3 groups (G): G1 spinal puncture, G2 and G3 saline methotrexate. After intravenous anesthesia with ketamine and xilaziana will be held addressing the subarachnoid space (25G Quincke needle 2), the intervertebral space between the first and second sacral vertebra guided by ultrasound. The animals from G2 and G3 receive the corresponding solutions in volume corresponding to 12 mg.m2 body surface of methotrexate (approximately 0.1 ml) or corresponding volume of saline and the G1 will be conducted only spinal puncture. This procedure is repeated four times at intervals of 7 days. The animals will be clinically evaluated regarding sensitivity and motor function for 30 days after which they will be killed by decapitation under anesthesia and withdrawing to the lumbar and sacral spinal cord for histologic examination by light microscopy and immunohistochemistry (beta-amyloid protein).OuvirLer foneticamente (AU)