Further evidence indicates that rt-PA mediates an increase in the permeability/ leakage of the BBB. Clinically, the most serious complications after rt-PA treatment are hemorrhage and blood-brain barrier breakdown. Cerebral ischemia/reperfusion leads to release of pro-inflammatory mediators which in turns leads to production of MMP by resident and infiltrating cells, which altogether increase BBB permeability. One marker for BBB permeability is MMP-9 and studies have shown that MMP-9 is responsible for rt-PA induced parenchymal hemorrhages after stroke. Our results indicate that there is a tendency of increased MMP-9 after MCAO, which is significantly reduced after rt-PA treatment given at 20 min after induction of MCAO. However, rtPA treatment after 40 min decreased the protein levels of MMP-9, but not significantly as compared to MCAO. We did not observe any increase in BBB permeability after rt-PA treatment at 20 or 40 min after MCAO. A limitation of our study is 
the lack of definitive information on the status of the Tetrahydroberberine microcirculation following treatment with rt-PA. Application of MR perfusion-weighted imaging and arterial spin labeling techniques could provide more insight into understanding the pathophysiology of perfusion changes during persistent MCA occlusion under rt-PA therapy. However, MRI may not have the spatial resolution needed to visualize and quantify changes in the microvasculature. High-resolution 3D nano-CT imaging, which allows analysis of the vasculature in microscopic detail, may be useful for quantification of alterations in the cerebral microcirculation after rt-PA therapy. The simultaneous implementation of such imaging procedures with laser Doppler monitoring of CBF was not technically feasible in our study, however. In conclusion, this study shows that rt-PA treatment decreases ischemic lesion volume, which indicates that the success of thrombolysis therapy is not limited to the recanalization of the arterial main stem occlusion. In addition, there is a clear correlation between the protein expression of inflammatory mediators, apoptosis and stress genes with the recanalization data after rt-PA treatment. Fibroblast growth factor 19 is expressed in human liver and intestine and shows different tissue distribution from its mouse ortholog, FGF15, which is only expressed in the intestine. However, both proteins function as enterohepatic hormones and they are secreted from the small intestine to regulate bile acid homeostasis in the liver. After being secreted into the portal circulation, FGF15/19 binds to its receptor, FGFR4, in the liver and activates downstream signaling pathways to suppress the transcription of the gene encoding cholesterol 7a-hydroxylase, the rate-limiting enzyme for bile acid synthesis. Moreover, FGF15/19 has been shown to promote liver tumorigenesis, energy metabolism, insulin sensitivity, and liver regeneration, but the underlying mechanisms have not been fully clarified. Pure and functional proteins produced by an efficient method can provide a valuable tool to greatly improve the research of FGF19/15. Due to easy handling, inexpensive cultivation and large-scale production, the E. coli bacterial system is a popular and well characterized prokaryotic host system for heterologous protein expression. However, the E. coli system also contains a few limitations, and expression of eukaryotic proteins in a bacterial system has been Loganin always challenging, especially when these proteins contain disulfide bonds. Disulfide bonds are very common in mammalian proteins and are crucial for proper protein folding, stability, and activity.