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Crossing the blood brain barrier (BBB) is difficult, because the tight peripheral endothelia only allows molecules that are both lipid soluble and smaller than 400 daltons. Use this converter to find out how tiny of a molecular mass that is, and you will begin to recognize the difficulties. Microencapsulating neuropharmaceuticals in immunoliposomes that are already directed for the brain is considered a promising step in overcoming this difficulty.

Afergan et al recently reported on the use of two phagocytic cells of the immune system, monocytes and neutrophils, as transporters of serotonin to the brain. Serotonin, which cannot naturally penetrate the BBB, was first encapsulated in a negatively charged liposome. The liposomes endocytosed in both phagotyic cells, but at a higher uptake rate by the monocytes. Via flourescent microscopy the researchers could detect that they passed the BBB intact in rabbits, and were subsequently secreted by the phagocytic cell.

Four hours after administering the serotonin via liposomes and simply in solution, the concentration of serotonin in the brain was 0.138% +/- 0.34 for the serotonin liposomes and 0.068% +/- 0.02 for the group with serotonin in solution, which was a significant increase. Despite the improvement, the authors note that the technique is not yet clinically relevant because it was simply not potent enough. If the process could somehow be iterated upon and improved, it is possible that this method could see some daylight in the future.

References

Afergan E, Epstein H, Dahan R, Koroukhov N, Rohekar K, Danenber HD, Golomb G. 2008 Delivery of serotonin to the brain by monocytes following phagocytosis of liposoms. Journal of Controlled Release 132:84-90. doi:10.1016/j.jconrel.2008.08.017.

Cornford EM, Hyman S. 1999 Blood–brain barrier permeability to small and large molecule. Advanced Drug Delivery Reviews 132:145-163. doi:10.1016/S0169-409X(98)00082-9.

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The axons in cut nerves of a damaged body part can regenerate and even insert into a surgically attached graft. Stimulating this growth is important in medical applications as it helps to restore sensation to the affected body part.

The ability of axons to cross the surgical barrier between the proximal and distal stump is inhibited by chondroitin sulfate proteoglycans, a type of glycoprotein. These proteoglycans (and others in the Schwann cell basil lamina) have large glycosaminoglycan (GAG) side chains which inhibit growth through their large size and negative charge.

Groves et al. describe an in vivo attempt to use a number of bacterial enzymes to remove the GAG side group from the proteoglycans and thus remove the inhibition and stimulate axon growth. The enzymes they used were chondroitinase ABC, keratanase, heparinase I, and heparinase III. The researchers used thy-1-YFP-H transgenic mice because it has expresses yellow flourscent protein in the axons of motor neurons and analyzed the common fibular nerve.

In terms of the amount of regenerative sprouting, the heparinase I yielded the only significant difference from the control saline solution, however in terms of length of axon growth into the graft, chondroitinaise ABC performed the best of the enzymes.

Interestingly, when the researchers used a mixture of all of the four enzymes in equal concentrations, the resulting length of axon regeneration was significantly greater than the lengths of any of the enzymes individually. This result suggests that the different enzymes effect different facets of axonal regeneration, or that different types of neurons respond differently to different enzymes.

Reference

Groves ML, McKeon R, Werner E, Nagarsheth M, Meador W, English AW. 2005 Axon regeneration in peripheral nerves is enhanced by proteoglycan degradation. Experimental Neurology 195: 278-292. doi:10.1016/j.expneurol.2005.04.007.

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