Sabogal Angélica María, Arango César Augusto, Cardona Gloria Patricia, Céspedes Ángel Enrique
Grupo de Modelos Experimentales para las Ciencias Zoohumanas, Facultad de Ciencias Básicas, Universidad del Tolima, Ibagué, Colombia.
Fundación Valle del Lili, Cali, Colombia.
Biomedica. 2014 Apr-Jun;34(2):207-17. doi: 10.1590/S0120-41572014000200007.
Cerebral ischemia is the third leading cause of death and the primary cause of permanent disability worldwide. Atorvastatin is a promising drug with neuroprotective effects that may be useful for the treatment of stroke. However, the effects of atorvastatin on specific neuronal populations within the nigrostriatal system following cerebral ischemia are unknown.
To evaluate the effects of atorvastatin on dopaminergic and GABAergic neuronal populations in exofocal brain regions in a model of transient occlusion of the middle cerebral artery.
Twenty-eight male eight-week-old Wistar rats were used in this study. Both sham and ischemic rats were treated with atorvastatin (10 mg/kg) or carboxymethylcellulose (placebo) by gavage at 6, 24, 48 and 72 hours post-reperfusion. We analyzed the immunoreactivity of glutamic acid decarboxylase and tyrosine hydroxylase in the globus pallidus, caudate putamen and substantia nigra.
We observed neurological damage and cell loss in the caudate putamen following ischemia. We also found an increase in tyrosine hydroxylase immunoreactivity in the medial globus pallidus and substantia nigra reticulata, as well as a decrease in glutamic acid decarboxylase immunoreactivity in the lateral globus pallidus in ischemic animals treated with a placebo. However, atorvastatin treatment was able to reverse these effects, significantly decreasing tyrosine hydroxylase levels in the medial globus pallidus and substantia nigra reticulata and significantly increasing glutamic acid decarboxylase levels in the lateral globus pallidus.
Our data suggest that post-ischemia treatment with atorvastatin can have neuro-protective effects in exofocal regions far from the ischemic core by modulating the GABAergic and dopaminergic neuronal populations in the nigrostriatal system, which could be useful for preventing neurological disorders.
脑缺血是全球第三大死因及永久性残疾的主要原因。阿托伐他汀是一种具有神经保护作用的有前景的药物，可能对中风治疗有用。然而，脑缺血后阿托伐他汀对黑质纹状体系统内特定神经元群体的影响尚不清楚。
在大脑中动脉短暂闭塞模型中评估阿托伐他汀对外侧脑区多巴胺能和γ-氨基丁酸能神经元群体的影响。
本研究使用了28只8周龄雄性Wistar大鼠。假手术组和缺血组大鼠在再灌注后6、24、48和72小时通过灌胃给予阿托伐他汀（10 mg/kg）或羧甲基纤维素（安慰剂）。我们分析了苍白球、尾状核壳核和黑质中谷氨酸脱羧酶和酪氨酸羟化酶的免疫反应性。
我们观察到缺血后尾状核壳核出现神经损伤和细胞丢失。我们还发现，给予安慰剂的缺血动物内侧苍白球和黑质网状部的酪氨酸羟化酶免疫反应性增加，外侧苍白球的谷氨酸脱羧酶免疫反应性降低。然而，阿托伐他汀治疗能够逆转这些影响，显著降低内侧苍白球和黑质网状部的酪氨酸羟化酶水平，并显著提高外侧苍白球的谷氨酸脱羧酶水平。
我们的数据表明，缺血后用阿托伐他汀治疗可通过调节黑质纹状体系统中的γ-氨基丁酸能和多巴胺能神经元群体，对远离缺血核心的外侧脑区产生神经保护作用，这可能有助于预防神经障碍。
