Cns Regeneration Essay, Research Paper
CNS regenerationThe ability to regenerate the tissues of the human central nervous system(CNS) is one of the greatest projects undertaken by biomedical engineerstoday. With this eventual technology, permanent paralysis and blindnessdue to CNS injury will be a thing of the past. Central nervous systeminjuries will be repairable, an idea that was, until recently, just afanciful dream, something out of a science fiction novel. In the last few years, however, giant strides have been made to make theidea of CNS regeneration a reality within the grasp of engineers anddoctors alike. This technology has advanced to the point where successfultests are being performed on lower level adult mammals. If all continuesto go well, human implementation may soon follow. The axons of the central nervous system in adult mammals do not regeneratespontaneously after injury, mainly because of the presence ofoligodendrocytes that inhibit axonal growth. These glial cells block thegrowth of the axons in the central nervous system, preventing any kind ofregeneration within the CNS. What was discovered, through experimentation, was that lower non-mammalianvertebrates could regenerate their central nervous system after injury. Regeneration of the optic nerve occurs spontaneously in fish. Thisphenomenon has been correlated to the presence of factors that are toxicto oligodendrocytes. This substance is closely related to interleukin-2. Lower level mammals, on the other hand, are, like humans, unable toregenerate their CNS. The same experiment performed on the fish aboveyielded completely different results when done on adult mammals. Severingof the optic nerve near the eye is followed by a loss of retinal ganglioncells combined with a failure of axons to regrow into the brain. Further experimentation found that by manipulating the environment aroundthe injured retinal ganglion cells, increases the survival rate ofneurons, and make lengthy axonal regeneration, that restores nervefunction to the injured area, possible. This discovery suggested thatthat injured nerve cells in the mature mammal CNS are influenced byinteractions with their immediate environment. In certain conditions,injured central nervous system neurons can resemble normally developingneurons, and return to a functioning state. The restoration of connections in the injured CNS of adult mammals isaided by a guided channeling of the injured axons along a transplantedsegment of peripheral nerve. These neurons recover their capacity to formsynapses along their former channel. These peripheral nerve graftsincrease the survival rate of severed neurons in adult rats twentypercent. Some of these neurons returned to a fully functional form,making complete synaptic connections with other neurons. To explore further the capacity of damaged CNS neurons to initiate andsustain fiber growth, PN grafts were first applied to the spine of adultrats. After six to forty two weeks, the range in which the CNS and PNgrafts have been known to integrate, the rats spines were crushed. Investigated four to eleven weeks later, it was shown that these graftshad significantly helped the regeneration of the spinal cord. The numberand distribution of neurons in the crushed areas of the rats spines wasfound to be similar to that of the uncrushed regions. This suggests thatcentral neurons whose axons are grafted with peripheral nerve cells arecapable of renewed growth after injury. Under these experimentalconditions, CNS neurons respond to injury in a similar manner toperipheral nerve cells. Another hypothesis was made, that suggested that axons could onlyregenerate when their growing tips are surrounded by extracellular fluidcontaining proteins from the blood. An experiment was done on fetal ratexplants to test the hypothesis. The explants were cultured in serummedium for ten days, followed by an eight day period in a serum freemedium. It was found that all explants cultured in serum medium for tendays showed a greater than seventy seven percent viability. The explantsthat were kept in the serum for eight more days retained their viabilityrate, while the viability rate for the explants that were placed in theserum free environment dropped to seven and a half percent. Electron
microscope analysis, showed that tissue viability was above seventy fivepercent in all explants, indicating that serum is important only to axongrowth and not neuron survival . This data strengthened the hypothesisthat blood derived proteins were needed for prolonged regen!eration. There are certain cells, found in the peripheral nervous system, thatundertake a broad field of tasks in the peripheral nervous system. CalledSchwann cells, they regulate ensheathment and myelination, they areinvolved in extracellular matrix production, and they are alsoinstrumental in the promotion of peripheral nervous system regeneration byremyelating axons and restoring electrophysiological conduction. Alongwith astrocytes, which provide nutritional proteins for the regenerationof axons, these two cells are primarily responsible for peripheral nervoussystem regeneration. The conjecture that was made next was that these Schwann cells were thereason that the peripheral graft experiments went so well. The Schwanncells and astrocytes were helping to rebuild not only the peripheralnerves that had been crushed, but the CNS neurons as well. Another experiment was done on rats to determine whether or not theSchwann cells were responsible for the regeneration in the peripheralnervous system. Semipermeable nerve guidance channels were prepared,inserted to connect to ends of a severed peripheral nerve, and the seededwith astrocytes, Schwann cells, or a mixture of the two. The astrocytesalone, impeded regeneration, while the Schwann cells increased the amountof growth. The combination of the two worked as well, provided that theSchwann cells out numbered the astrocytes. Taking this into account, the latest move has been to attempt to createnerve guidance channels for the central nervous system. Using the all theprevious research in the field, biomedical engineers have designed andcreated a device that is being tested in animals right now. Using a nerveguidance channel filled with agarose hydrogel, a gel-like medium ideal fornerve regeneration and excellent at conducting electricity, this channelis inserted into the body at the site of CNS injury. Each separated endof the nerve is enclosed in the guidance channel, and then the channel isseeded with Schwann cells, astrocytes, proteins to nourish the growingnerve, and interleukin-2, to destroy the inhibiting Oligodendrocytes. If this works, we may soon be able to cure paralysis and some types ofblindness. Mankind will make another great stride forward in the field ofmedicine, curing another seemingly incurable affliction. This technologywill be an achievement of utmost magnitude and importance, and we will allbenefit from the realization of something that, until recently was just apipe dream. List of WorksAguayo AJ, et al. Degenerative and Regenerative Responses of InjuredNeurons in the Central Nervous System of Adult Mammals. PhilosophicalTransactions of the Royal Society of London-Series B: Biological Sciences. 331(1261):337-43, 1991 March 29. Aguayo AJ, et al. Synaptic Connections Made by Axons Regenerating in theCentral Nervous System of Adult Mammals. Journal of Experimental Biology. 153:199-224, 1990 October. Bray GM, et al. The Use of Peripheral Nerve Grafts to Enhance NeuronalSurvival, Promote Growth and Permit Terminal Reconnections in the CentralNervous System of Adult Rats. Journal of Experimental Biology. 132:5-19,1987 September. Bunge RP. The Role of the Schwann Cell in Trophic Support andRegeneration. Journal of Neurology, 242 (1 Supplement 1):S19-21, 1994December. David S, Aguayo AJ. Axonal regeneration After Crush Injury of Rat CentralNervous System Fibres Innervating Peripheral Nerve Grafts. Journal ofNeurocytology. 14(1):1-12, 1985 February. Eitan S, et al. Identification of an Interleukin 2-like Substance as aFactor Cytotoxic to Ologodendrocytes and Associated with Central NervousSystem Regeneration. Proceedings of the National Academy of Sciences ofthe United States of America. 89(12):5442-6, 1992 June 15. Guenard V, Aebischer P, Bunge RP. The Astrocyte Inhibition of PeripheralNerve Regeneration is Reversed by Schwann Cells. Experimental Neurology. 126(1):44-60, 1994 March. Oorschot DE, Jones DG. Tissue Culture Analysis of Neurite Outgrowth in thePresence and Absence of Serum: Possible Relevance for Central NervousSystem Regeneration. Journal of Neuroscience Research. 15(3):341-52, 1986.