Área de Biología Celular, Instituto de Biomedicina, Universidad de León, 24071 León, Spain.
Brain Res Bull. 2013 May;94:90-7. doi: 10.1016/j.brainresbull.2013.02.006. Epub 2013 Feb 28.
This study analyzes how age and inflammation modify the response of the vesicular glutamate transporters (VGLUTs), VGLUT1-3 to global brain ischemia/reperfusion (I/R) in brain areas with different I/R vulnerabilities.
Global ischemia was induced in 3- and 18-month-old male Sprague-Dawley rats and CA1 and CA3 hippocampal areas, dentate gyrus and cerebral cortex of sham-operated and I/R animals were removed 48 h after insult. Real-time PCR analysis revealed that I/R challenge resulted in a significant decrease of the VGLUT mRNA levels in young animals. Western blot assays showed a lessened age-dependent response to the ischemic damage in VGLUT1 and VGLUT3, while VGLUT2 presented an age and structure-dependent response to challenge. The use of the anti-inflammatory agent meloxicam following challenge showed that COX2 inhibition promotes the expression of VGLUTs in both sham and injured animals, which results in a lessened response to I/R injury.
VGLUT1 and VGLUT3 presented an age-dependent response to ischemic damage, while this VGLUT response was age both and structure-dependent. In addition, COX-2 inhibition resulted in an increase of VGLUT1 and VGLUT2 protein amounts both in sham and injured animals together with a lessening of the transporters' response to ischemia.
本研究分析了年龄和炎症如何改变脑区对全脑缺血/再灌注（I/R）的反应，这些脑区具有不同的 I/R 易损性。
在 3 个月和 18 个月大的雄性 Sprague-Dawley 大鼠中诱导全脑缺血，并在损伤后 48 小时取出假手术和 I/R 动物的 CA1 和 CA3 海马区、齿状回和大脑皮质。实时 PCR 分析显示，I/R 挑战导致年轻动物的 VGLUT mRNA 水平显著下降。Western blot 分析显示，VGLUT1 和 VGLUT3 对缺血损伤的年龄依赖性反应减弱，而 VGLUT2 对挑战呈现出年龄和结构依赖性反应。在挑战后使用抗炎药美洛昔康表明，COX2 抑制促进了 sham 和受伤动物中 VGLUTs 的表达，从而减轻了对 I/R 损伤的反应。
VGLUT1 和 VGLUT3 对缺血损伤呈现出年龄依赖性反应，而这种 VGLUT 反应则是年龄和结构依赖性的。此外，COX-2 抑制导致 sham 和受伤动物中 VGLUT1 和 VGLUT2 蛋白量的增加，同时减轻了转运体对缺血的反应。
