Temporal changes in edema, Na⁺, K⁺, and Ca⁺⁺ in focal cortical stroke: GM1 ganglioside reduces ischemic injury

Abstract

Cortical focal ischemia in the rat was induced by middle cerebral artery occlusion (MCAo) together with permanent occlusion of the ipsilateral common carotid artery (CCAo) and a temporary (1 hr) occlusion of the contralateral CCA. By using a defined cortical tissue sampling procedure at 3, 6, 24, 72, 96, and 120 hr after the MCAo + CCAo, patterns of edema and ion (Na+, K+, and Ca++) changes in a primary and three peri-ischemic cortical areas are described. Ionic imbalances and edema formation have distinct patterns, are time dependent, and are different when comparing primary and peri-ischemic areas. Calcium increases to "neurotoxic" levels appear temporally independent of edema formation, reaching magnitudes 20 times greater than basal levels in the primary infarct area. Na+ increases correlate with increases in water, while K+ losses do not appear to be directly related to edema formation of Na+ and Ca++ increases. K+ losses are only significant in the primary infarct area. Rats treated with GM1 ganglioside (10 mg/kg, i.m.) daily showed significant reductions in edema, Na+ and Ca++ increases. These ganglioside effects were evident as early as 24 hr after the ischemic injury. Ca++ increases, which was maximal at 72 hr after the ischemic injury, was reduced by greater than 50% in GM1-treated animals. The mechanism by which GM1 is an effective neuroprotective agent may be evidenced by its effects on Ca++ influx/efflux processes in injury.

Temporal changes in superoxide dismutase, glutathione peroxidase, and catalase levels in primary and peri-ischemic tissue

“…We have been studying ischemic injury (cortical focal ischemic) in the rat (Tamura et al, 1981;Chen et al, 1986;Karpiak et al, 1990bKarpiak et al, , 1991 and have described the time-dependent changes that occur in edema formation and tissue ions changes (Na+, K+, and Ca++) , membrane fatty acids , and plasma membrane ATPases (Mahadik et al, 1992) in primary and peri-ischemic tissue. The ATPase activity losses are indicators of altered plasma membrane structure and failure of function (Tanaka and Teruya, 1973;Schwartz et al, 1976;Kimelberg, 1977).…”

Avanços no uso de células-tronco em ortopedia

“…Methylprednisolone administered within the first eight hours after the trauma was the first agent to produce a significant improvement in the recovery from spinal cord trauma in human beings (4,(35)(36)(37)(38)(39)(40)(41)(42)(43)(44)(45)(46) . Other drugs, like tirilazad (47)(48)(49) and GM-1 (50)(51)(52)(53)(54)(55)(56)(57) have presented promising preliminary results. These advances may provide a great improvement in the quality of life of patients with spinal cord injuries, if they are brought into clinical practice.…”

Estudo dos efeitos do monossialogangliosídeo (GM1) administrado pela via transdérmica por laser a baixa temperatura, após lesão medular experimental em ratos

“…Trata-se de um neuroprotetor, antineurotóxico, anti-inflamatório, indispensável para a excitabilidade neuronal de fibras mielínicas e amielínicas. O GM1 atua no desenvolvimento, crescimento, diferenciação e maturação neuronal, além de diminuir a intensidade da degeneração waleriana (Roisen et al, 1981;Geisler et al, 1991;Karpiak et al, 1991;Walker e Harris, 1993;Coombs et al, 1993;Constantini e Young, 1994;Schneider et al, 1995;Vogelsberg et al, 1997;Taoka e Okajima, 1998;Hadjiconstantinou e Neff, 1998;Oliveira e Langone, 2000;Fang et al, 2000;Silva et al, 2000;Weber et al, 2000;Geisler et al, 2001;Goettl et al, 2003;Barros Filho e Silva Filho, 2003;Fighera et al, 2006;Thuret et al, 2006;Furian et al, 2007;Ledeen e Wu, 2007;Ilyas e Chen, 2007;Sokolova et al, 2007;Qiao et al, 2008;Duchemin et al, 2008;Chinnock e Roberts, 2009 (Nelson et. al., 1991;Benson e Namjoshi, 2008;Bachhav et al, 2010;Bachhav et al, 2011;Kalluri e Banga, 2011 Enfatizam que a via de administração transdérmica é atraumática, indolor e não invasiva.…”

“…Estudou-se a dexametasona, o transplante de células fetais e as células-tronco, o GM1, a metilprednisolona, a eritropoetina, as neurotropinas, as vitaminas, dentre outras (Ducker e Hamit, 1969;De La Torre, et al, 1975;Roisen et al, 1981;Young e Flamm, 1982;Karpiak et al, 1991;Wyss-Coray et al, 1997;Jeffery et al, 1999;Barros Filho, 2000;Sribnick et al, 2005;Thuret et al, 2006;Ilyas e Chen, 2007;Akdemir et al, 2008;Cristante et al, 2009a).…”

“…Ele é responsável por diversas funções no metabolismo, no desenvolvimento, na maturação e na regeneração celular, e um importante neuroprotetor com funções anti-inflamatórias. O GM1 é fundamental para a modulação elétrica e na excitabilidade neuronal, na redução dos efeitos tóxicos da alta concentração de cálcio e sódio e na melhora da atividade colinérgica (Karpiak et al, 1991;Coombs et al, 1993;Vogelsberg et al, 1997;Hadjiconstantinou e Neff, 1998;Oliveira e Langone, 2000;Fang et al, 2000;Silva et al, 2000;Weber et al, 2000;Fighera et al, 2006;Furian et al, 2007;Ledeen e Wu, 2007;Sokolova et al, 2007;Qiao et al, 2008;Duchemin et al, 2008 A dose de GM1 adotada neste estudo (30 mg/kg) está condizente com outros estudos experimentais (Goettl et al, 2003;Carvalho et al, 2008). Nelson et al (1991) publicam, pela primeira vez, estudo que comprova a capacidade do laser de realizar ablação do estrato córneo da pele, possibilitando a absorção mais eficiente de substâncias químicas.…”