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Neuroprotective effect of ketamine/xylazine on two rat models of Parkinson's disease
Ferro, M. M; Angelucci, M. E. M; Anselmo-Franci, J. A; Canteras, N. S; Da Cunha, C.
  • Ferro, M. M; Universidade Federal do Paraná. Departamento de Bioquímica e Biologia Molecular. Curitiba. BR
  • Angelucci, M. E. M; Universidade Federal do Paraná. Departamento de Farmacologia. Laboratório de Fisiologia e Farmacologia do Sistema Nervoso Central. Curitiba. BR
  • Anselmo-Franci, J. A; Universidade de São Paulo. Faculdade de Odontologia de Ribeirão Preto. Departamento de Morfologia, Estomatologia e Fisiologia. Ribeirão Preto. BR
  • Canteras, N. S; Universidade de São Paulo. Instituto de Ciências Biomédicas I. Departamento de Anatomia. São Paulo. BR
  • Da Cunha, C; Universidade Federal do Paraná. Departamento de Farmacologia. Laboratório de Fisiologia e Farmacologia do Sistema Nervoso Central. Curitiba. BR
Braz. j. med. biol. res ; 40(1): 89-96, Jan. 2007. ilus, graf
Article in English | LILACS | ID: lil-439667
ABSTRACT
There is a great concern in the literature for the development of neuroprotectant drugs to treat Parkinson's disease. Since anesthetic drugs have hyperpolarizing properties, they can possibly act as neuroprotectants. In the present study, we have investigated the neuroprotective effect of a mixture of ketamine (85 mg/kg) and xylazine (3 mg/kg) (K/X) on the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) or 6-hydroxydopamine (6-OHDA) rat models of Parkinson's disease. The bilateral infusion of MPTP (100 æg/side) or 6-OHDA (10 æg/side) into the substantia nigra pars compacta of adult male Wistar rats under thiopental anesthesia caused a modest (~67 percent) or severe (~91 percent) loss of tyrosine hydroxylase-immunostained cells, respectively. On the other hand, an apparent neuroprotective effect was observed when the rats were anesthetized with K/X, infused 5 min before surgery. This treatment caused loss of only 33 percent of the nigral tyrosine hydroxylase-immunostained cells due to the MPTP infusion and 51 percent due to the 6-OHDA infusion. This neuroprotective effect of K/X was also suggested by a less severe reduction of striatal dopamine levels in animals treated with these neurotoxins. In the working memory version of the Morris water maze task, both MPTP- and 6-OHDA-lesioned animals spent nearly 10 s longer to find the hidden platform in the groups where the neurotoxins were infused under thiopental anesthesia, compared to control animals. This amnestic effect was not observed in rats infused with the neurotoxins under K/X anesthesia. These results suggest that drugs with a pharmacological profile similar to that of K/X may be useful to delay the progression of Parkinson's disease.
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Full text: Available Index: LILACS (Americas) Main subject: Parkinson Disease / Xylazine / Substantia Nigra / Neuroprotective Agents / Anesthetics, Combined / Ketamine Limits: Animals Language: English Journal: Braz. j. med. biol. res Journal subject: Biology / Medicine Year: 2007 Type: Article Affiliation country: Brazil Institution/Affiliation country: Universidade Federal do Paraná/BR / Universidade de São Paulo/BR

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Full text: Available Index: LILACS (Americas) Main subject: Parkinson Disease / Xylazine / Substantia Nigra / Neuroprotective Agents / Anesthetics, Combined / Ketamine Limits: Animals Language: English Journal: Braz. j. med. biol. res Journal subject: Biology / Medicine Year: 2007 Type: Article Affiliation country: Brazil Institution/Affiliation country: Universidade Federal do Paraná/BR / Universidade de São Paulo/BR