Age and meloxicam modify the response of the glutamate vesicular transporters (VGLUTs) after transient global cerebral ischemia in the rat brain

AimsThis 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.ResultsGlobal 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.ConclusionsVGLUT1 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.

► Both age and inflammation play critical roles in the response to ischemia.
► We have analyzed the role of vesicular glutamate transporters in cerebral ischemia.
► The transcription of VGLUTs is modified in an age and inflammation-dependent way.