Phycocyanobilin positively modulates inflammatory genes in acute cerebral hypoperfusion in rats

Stroke causes high mortality rates and serious disability worldwide. Ischemic penumbra rescue is the main objective of acute interventions, such as thrombolysis and neuroprotection, but they show low translational success. Increasing evidence demonstrates that inflammatory response is involved in the stroke cascade. Here we evaluated the effects of Phycocyanobilin (PCB), the C- Phycocyanin linked tetrapyrrole, on gene expression in the anterior cortex of hypoperfused brains of rats. The acute drop of cerebral blood flow in this model is comparable to ischemic penumbra, thus offering a reliable tool for studying molecular mechanisms. After the permanent bilateral common carotid arteries occlusion, the animals were treated therapeutically with saline or PCB. Samples were taken 24h after the surgery. Global gene expression was analyzed with GeneChip Rat Gene ST 1.1 from Affymetrix, and the expression of particular genes was assessed by the Fast SYBR Green RT-PCR Master Mix method. The PCB treatment significantly modulated 190 genes (93 up- and 97 down-regulated) associated to several immunological processes in both the regulatory and effector subsets. Furthermore, PCB was able to positively modulate 13 genes mostly related to a detrimental pro-inflammatory environment. Our results support the view of major inflammatory mediators in acute cerebral hypoperfusion, effectively counteracted by PCB. These results may justify the application of PCB as a new acute disease modifying drug against ischemic stroke.