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Master's Dissertation
DOI
https://doi.org/10.11606/D.17.2019.tde-10102018-160616
Document
Author
Full name
Pâmella da Silva Beggiora
E-mail
Institute/School/College
Knowledge Area
Date of Defense
Published
Ribeirão Preto, 2018
Supervisor
Committee
Lopes, Luiza da Silva (President)
Catalão, Carlos Henrique Rocha
Lachat, João José
Santos, Marcelo Volpon
Title in Portuguese
Neuroproteção em ratos hidrocefálicos tratados ou não cirurgicamente: a Memantina como uma alternativa farmacológica
Keywords in Portuguese
Derivação liquórica
Fármacos neuroprotetores
Hidrocefalia
Memantina
Abstract in Portuguese
A hidrocefalia é um desequilíbrio no fluxo ou absorção do líquido cefalorraquidiano, resultando em uma dilatação no sistema ventricular. O tratamento da hidrocefalia usualmente utilizado é cirúrgico (shunt), mas nem todos os pacientes podem ser submetidos ao tratamento cirúrgico imediatamente após o diagnóstico. Com isso, medidas neuroprotetoras vêm sendo testadas a fim de minimizar as lesões teciduais envolvidas. A Memantina é antagonista não competitivo do receptor N-metil-D-aspartato (NMDA), que revelou ação neuroprotetora na Doença de Alzheimer. O objetivo desse trabalho foi avaliar a resposta neuroprotetora da Memantina em animais tratados ou não com derivação liquórica. Foram utilizados ratos machos Wistar submetidos à hidrocefalia através de injeção intracisternal de caulim, divididos em cinco grupos: controle (n=10), hidrocefálicos sem tratamento (n=10), hidrocefálicos tratados com Memantina intraperitoneal (20mg/kg/dia) (n=10), hidrocefálicos derivados (n=10), hidrocefálicos derivados tratados com Memantina (n=10). Para avaliação do tratamento foram realizados testes de comportamento (open field, monitor automático de atividade, water maze e reconhecimento de objeto), estudos histológicos e imunoistoquímicos. O tratamento da Memantina resultou em importante melhora no desenvolvimento sensoriomotor (p<0,05), maior agilidade e exploração do ambiente, preservação da memória espacial e de reconhecimento e maior capacidade de aprendizagem (p<0,05). Reduziu a reação astrocitária no córtex e na matriz germinativa (p<0,05) por imunomarcação do GFAP. Conclui-se que a Memantina oferece efeitos benéficos às estruturas que foram afetadas pelo aumento ventricular e pode ser considerada uma terapia adjuvante ao tratamento cirúrgico da hidrocefalia.
Title in English
Neuroprotection in hydrocephalic rats, surgically treated or not: the memantine as a pharmacological alternative
Keywords in English
Hydrocephalus
Memantine
Neuroprotective drugs
Shunt
Abstract in English
Hydrocephalus is an imbalance in the flow or absorption of cerebrospinal fluid, resulting in a dilation of the ventricular system. The treatment of hydrocephalus usually used is surgical (shunt), but not all patients can undergo surgical treatment immediately after diagnosis. With this, neuroprotective measures have been tested in order to minimize the tissue lesions involved. Memantine is a non-competitive N-methyl-D-aspartate (NMDA) receptor antagonist, which revealed neuroprotective action in Alzheimer's disease. The aim of this study was to evaluate the neuroprotective response of Memantine in animals treated with or without a shunt. Male Wistar rats were submitted to hydrocephalus by intracisternal injection of kaolin, divided into five groups: control (n = 10), hydrocephalus without treatment (n = 10), hydrocephalus treated with intraperitoneal Memantine (20mg / kg / day) (n = 10), hydrocephalus treated with shunt (n = 10), hydrocephalus treated with shunt plus Memantine (n = 10). To evaluate the treatment, behavior tests (open field, automatic activity monitor, water maze and object recognition), histological and immunohistochemical studies were performed. The treatment with Memantine resulted in a significant improvement in sensorimotor development (p <0.05), greater agility and exploration of the environment, preservation of spatial and recognition memory, and greater learning ability (p <0.05). Reduced astrocytic reaction in the cortex and germ matrix (p <0.05) by GFAP immunolabeling. It is concluded that Memantine offers beneficial effects to the structures that have been affected by the ventricular increase and can be considered an adjuvant therapy to the surgical treatment of hydrocephalus.
 
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Publishing Date
2019-01-03
 
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