Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Ramiro Barcellos, 2600, anexo, Santana, Porto Alegre, RS 90035-003, Brazil.
Neurol Sci. 2012 Oct;33(5):985-97. doi: 10.1007/s10072-011-0872-1. Epub 2011 Dec 14.
Chronic cerebral hypoperfusion contributes to a cognitive decline related to brain disorders. Its experimental model in rats is a permanent bilateral common carotid artery occlusion (2VO). Overstimulation of the glutamatergic system excitotoxicity due to brain energetic disturbance in 2VO animals seems to play a pivotal role as a mechanism of cerebral damage. The nucleoside guanosine (GUO) exerts extracellular effects including antagonism of glutamatergic activity. Accordingly, our group demonstrated several neuroprotective effects of GUO against glutamatergic excitotoxicity. Therefore, in this study, we evaluated a chronic GUO treatment effects in rats submitted to 2VO. We evaluated the animals performance in the Morris water maze and hippocampal damage by neurons and astrocytes immunohistochemistry. In addition, we investigated the cerebrospinal fluid (CSF) brain derived neurotrophic factor (BDNF) and serum S100B levels. Additionally, the purine CSF and plasma levels were determined. GUO treatment did not prevent the cognitive impairment promoted by 2VO. However, none of the 2VO animals treated with GUO showed differences in the hippocampal regions compared to control, while 20% of 2VO rats not treated with GUO presented loss of pyramidal neurons and increased glial labeling cells in CA1 hippocampal region. In addition, we did not observe differences in CSF BDNF nor serum S100B levels among the groups. Of note, both the 2VO surgery and GUO treatment changed the purine CSF and plasma profile. In conclusion, GUO treatment did not prevent the cognitive impairment observed in 2VO animals, but our data suggest that GUO could be neuroprotective against hippocampal damage induced by 2VO.
慢性脑灌注不足导致与脑疾病相关的认知能力下降。其在大鼠中的实验模型是永久性双侧颈总动脉闭塞（2VO）。由于 2VO 动物的脑能量障碍导致的谷氨酸能系统过度刺激兴奋性毒性似乎起着作为脑损伤机制的关键作用。核苷鸟苷（GUO）发挥细胞外作用，包括拮抗谷氨酸能活性。因此，我们的小组证明了 GUO 对谷氨酸能兴奋性毒性的几种神经保护作用。因此，在这项研究中，我们评估了 2VO 大鼠中慢性 GUO 治疗的效果。我们通过神经元和星形胶质细胞免疫组织化学评估动物在 Morris 水迷宫中的表现和海马损伤。此外，我们研究了脑脊液（CSF）脑源性神经营养因子（BDNF）和血清 S100B 水平。此外，还测定了嘌呤 CSF 和血浆水平。GUO 治疗不能预防 2VO 引起的认知障碍。然而，与对照组相比，没有接受 GUO 治疗的 2VO 动物中的任何一个在海马区域都没有差异，而未接受 GUO 治疗的 2VO 大鼠中有 20％在 CA1 海马区域出现了锥体神经元丧失和胶质标记细胞增加。此外，我们没有观察到各组 CSF BDNF 或血清 S100B 水平的差异。值得注意的是，2VO 手术和 GUO 治疗都改变了嘌呤 CSF 和血浆谱。总之，GUO 治疗不能预防 2VO 动物观察到的认知障碍，但我们的数据表明 GUO 可能对 2VO 引起的海马损伤具有神经保护作用。
