A size-controllable focal striatal lesion produced by local injection of glutamate in rats

• Main Authors: Jia-Ying Chuang, 莊佳穎
• Other Authors: Jon Son Kuo
• Format: Others
• Language: en_US
• Published: 2006
• Online Access: http://ndltd.ncl.edu.tw/handle/48497726076033329771

碩士 === 慈濟大學 === 藥理暨毒理學研究所 === 94 === Abstract Focal brain lesions, no mater produced by various cytotoxic agents or occlusion of cerebral artery, are primarily caused by excessive glutamate release. A controllable and reliable brain lesion size in the in vivo model was not available. Intra-striatal infusion of sodium glutamate (2-6 mmol at 1 M or 2 osm) produced dose-dependent increases in striatal lesion size as estimated with 2 % triphenyltetrazolium chloride (TTC) stain, in anesthetized male Sprague-Dawley rats (250-350 g). Although the same dose-induced lesion size varied widely in different rats, it varied very less on both sides of the same rat brain, while different dose-induced lesion sizes were markedly dose-dependent on both sides of the same rat brain. The lesion size was not significantly affected by osmotic effect of 1 M or 2 osm glutamate whose osmolarity is much higher than osmolarity (0.3 osm) of the extracellular fluid, because infusions of 2 osm glucose or NaCl produced but negligible lesions. Impairment of the behavior as evaluated by swing test, patch test, rotarod test, and rotational behavior test. The lesion-induced motor function impairment was improved by G-CSF administration. Applicability of this model in studying neuroprotective agents was attested by the findings that glutamate (4 mmol, 1 M)-induced striatal lesion was reduced by three neuroprotective agents, granulocyte colony-stimulating factor (G-CSF, 200 mg kg-1), a cytokine growth factor, and estradiol (2 mg kg-1), a female sex hormone, and an anti-inflammatory compound, oroxylin-A (30 mg kg-1). We thus developed a novel rat model in which local intra-striatal infusion of controlled doses of glutamate produced a controllable and reliable, striatal lesion size. This model is easy and convenient and may be important for application in studying neuroprotective agents.