Thursday, 22 November 2012

Production of Blood vessels


Angiogenesis is a prominent feature of central nervous system (CNS) disease and has roles in both the continued promotion of inflammation and the subsequent repair processes. Here we report that prostacyclin (or prostaglandin I2 (PGI2)) derived from new vessels promotes axonal remodeling of injured neuronal networks after CNS inflammation. In a localized model of experimental autoimmune encephalomyelitis (EAE), new vessels formed around the inflammatory lesion, followed by sprouting of adjacent corticospinal tract (CST) fibres. These sprouting fibres formed a compensatory motor circuit, leading to recovery of motor function. Capillary endothelial cell–derived prostacyclin bound to its receptor, the type I prostaglandin receptor (IP receptor), on CST neurons, promoting sprouting of CST fibres and contributing to the repair process. Inhibition of prostacyclin receptor signaling impaired motor recovery, whereas the IP receptor agonist iloprost promoted axonal remodeling and motor recovery after the induction of EAE. These findings reveal an important function of angiogenesis in neuronal rewiring and suggest that prostacyclin is a promising molecule for enhancing functional recovery from CNS disease.
The study suggests that angiogenesis, which is the production of new blood vessels that is a result of inflmation can induces in the corticospinal tract, which tract conducts impulses from the brain mainly the motor cortex to the spinal cord, to sprout nerve processes. The corticospinal tract is concerned specifically with discrete voluntary skilled movements, such as precise movement of the fingers and toes. The brain sends impulses to the spinal cord relaying the message. This is imperative in understanding that the left hemisphere of the brain controls the right side of the body, while the right hemisphere of the brain controls the left side of the body. The signals cross in the medulla oblongata, this process is also known as decussation. The nerve processes form new neural circuits in the spinal cord and promoted the process of rewiring and recovered function. As such animals with an MS-like disease showed some better recovery of function. This can be be promoted by iloprost which is a analogue of protocyclin Prostoglandin I. Prostacyclin chiefly prevents formation of the platelet plug involved in primary haemostasis (a part of blood clot formation). It does this by inhibiting platelet activation. It is also an effective vasodilator.  This is interesting new data that opens an avenue for repair.

Injecting PGI into EAE reminds me of an EAE experiment I did for a young Andrew Wakefield who was convinced vessel occlusion was the problem in MS and the solution was prostocylin. He and a colleague of his convinced me to do an EAE experiment involving injection on the hour every hour for 3 days wih PGI and then more treatemtn. There was effect compared to vehicle (It was not done in a way that repair would be evident). He then said he should have given me the drug variant that had a half-life of twenty minutes not the one he had given me that had a half life of 2 minutes (half disappears every 2 minutes). I was so miffed I never saw him again until he was on disgraced on TV. Teach me to be willing to give things a go.

2 comments:

  1. Are you saying Andrew Wakefield was on the right track here?

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    1. Not saying anything...but will say his idea of MMR vaccine and autism wasted allot of money and energy so were his ideas sound.

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