By Cesario V. Borlongan, Ole Isacson, Paul R. Sanberg
An authoritative survey of the latest clinical facts displaying how cyclosporin, FK-506, and their analogs-the neuroimmunophilins-evolved from being merely immunosuppressant "drugs" to neuroprotective "agents". The e-book specializes in fresh preclinical proof that demonstrates the neurotrophic/neuroprotective results of immunosuppressants while administered by myself or whilst mixed with neural transplantation remedy in animal types of neurological issues. It additionally discusses their efficacy and mechanisms of motion in vitro and in vivo versions of CNS ailment, and offers laboratory experiences with compelling medical symptoms for Alzheimer's ailment, Huntington's disorder, stroke, disturbing mind damage, spinal wire damage, ALS, sciatic nerve damage, and drug dependancy.
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Extra resources for Immunosuppressant Analogs in Neuroprotection
In discussions with M. Keep it was realized that this ischemic neuroprotective effect also extended to a broad spectrum of neural insults, including traumatic brain injury and neurodegeneration. This understanding led to a use patent for CsA as a neuroprotectant (131). Since then, CsA has been confirmed to be a potent neuroprotective agent in animal models of global Immunosuppressants as Neuroprotective Agents 17 ischemia (1,3,132) with ischemia for as long as 30 min (133), and focal ischemia (100,101) when it can cross the blood–brain barrier.
The authors, however, felt that CsAs inhibition of NOS should block regeneration, and not have its own neurotrophic effect and attributed the sprouting to immunosuppression blocking autoimmunity. Cell culture work from the same group in 1995 failed to show CsA neurotrophism, perhaps due to the cell line chosen, continuing their impression of the importance of autoimmunity blocking regeneration (83). In light of predating work showing CsA neurotrophism and neurite outgrowth in PC12 cells and sensory ganglia, it is not clear why there was no effect.
Gold BG, Katoh K, Storm-Dickerson T. The immunosuppressant FK506 increases the rate of axonal regeneration in rat sciatic nerve. J Neurosci 1995;15:7509–7516. 86. Gold BG. FK506 and the role of immunophilins in nerve regeneration. Mol Neurobiol 1997;15:285–306. 87. Lyons WE, George EB, Dawson TM, et al. Stimulating nerve growth with immunophilins, US Patent and Trademark Office, (2000), Patent: 6,080,753, Johns Hopkins University School of Medicine, Baltimore, MD. 26 Keep, Uchino, and Elmér 88.