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Effects of intrathecal methotrexate on spinal cord and meninges of rabbits.

Grant number: 11/02291-7
Support Opportunities:Scholarships in Brazil - Scientific Initiation
Effective date (Start): May 01, 2011
Effective date (End): November 30, 2012
Field of knowledge:Health Sciences - Medicine - Surgery
Principal Investigator:Eliana Marisa Ganem
Grantee:Felipe Gilberto Valerini
Host Institution: Faculdade de Medicina (FMB). Universidade Estadual Paulista (UNESP). Campus de Botucatu. Botucatu , SP, Brazil


Summary Cancer is a disease characterized by deviation of the control mechanisms that regulate survival, proliferation and differentiation of cells. The surgery, chemotherapy and radiotherapy treatments are commonly used in oncology patients., AChemotherapy may be curative even for certain cancers spread, both macroscopic and microscopic. The chemotherapeutic agents such as methotrexate anticancer drugs are considered effective. He who belongs to the class of antimetabolites, acting on the intermediary metabolism of proliferating cells, was introduced in clinical practice for over 50 years and has the pharmacological action by the antagonism folic acid. By being increasingly used in cancer treatment protocols, and progressively higher doses, the occurrence of toxicity for central nervous tissue methotrexate is increased. The exact mechanism triggering neurotoxicity was not elucidated. Clinical manifestation of neurotoxicity after administration via Spinal arachnoiditis is a chemical and occurs in approximately 50% of patients. Some authors also associate the cauda equina syndrome. The aim of the research will evaluate the effects of methotrexate administered via spinal determine on spinal cord, nerve roots and meninges of rabbits. Methodology: After approval of the Ethics Committee on Animal Experiments will be used 30 rabbits young adult males, racial group Genetic Botucatu weights between 3500 and 4500 ge length of the spine between 38 and 40 cm provided by the vivarium Faculdade de Medicina de Botucatu. The animals will be divided into 3 groups (G): G1 spinal puncture, G2 and G3 saline methotrexate. After intravenous anesthesia xilaziana with ketamine and the approach will be conducted from the subarachnoid space (needle Quincke 22 December / 2 G) in the intervertebral space between the forearm and the 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 only be made only to spinal puncture. This procedure is repeated four times at intervals of 7 days. The animals are evaluated clinically, as the sensory and motor for 30 days after which they will be sacrificed by decapitation under anesthesia and removal of the lumbar and sacral spinal cord for histology by light microscopy and immunohistochemistry (protein beta-amylase).

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