Nowadays, and making the molecules active instead.
Nowadays, scientists investigatedifferent ways to modify CNS´s environment in order to alter cell´s behaviourand induce the axon´s reconstruction process upregulating the inhibitoryfactors and making the molecules active instead.By and large, after consideringall things, it can be appreciated the fact that one of the factors that moreconditions neuroregeneration are the cell types that can be found and arerelated to the environment that surrounds the CNS and PNS for instance. As the embryonic evolution of theCNS and PNS is based on different pathways, the surrounding environment woulddiffer too, giving therefore rise to specifically cell types with a precisesurvival capacity and regeneration potential based on cell’s reaction as agenetic factor (“Boundless anatomy and physiology”).The contrast between the CNS andPNS that was exposed in the essay may have emerged from an early embryo differentiationas CNS is formed by the neural tube structure and its assembly, whereas the PNSis primarily constituted by the establishment of the neural crest. PNS iscomposed of pluripotent cells leading to the development of a huge variety ofcell type that would induce the formation of the neural crest, which would posteriorlybe converted into the ganglia and glia, sympathetic and parasympatheticneurones. In spite of all the molecules thatinhibit axon restoration development in the CNS, there are some factors thatmay also induce neuronal growth. One of these molecules is known as the cyclicadenosine monophosphatase (cAMP), usually referred to as a neurological secondmessenger that affects the neuron development. cAMP level is usually alteredwhen a PNS injury occurs, but it can be increased in the CNS throughout anintra-ganglionic injection of dibutyryl Camp, which would mime the growtheffect in the lesion, stimulating sensory axons reconstruction.
Rolipram, forexample, increments cAMP quantity inducing thus regeneration (Bomze et. al2001). Some other inhibitory factors aswell as alternative inhibitory pathways involving signalling can be foundoutside the glia or the myelin such as, for example, the evidence proposed byrecent studies considering the epidermal growth factor receptor as being one ofthe components that would promote regeneration deficiency. Additionally, if werefer to the intrinsic development and growth of the damaged neuron, as it wasstated before, one of the molecules that would support the process but achievesdistinct levels of upregulation is the RAGs and, as in the CNS its expressionis quite moderate, the effect it has is associated with regeneration failure(Pernold, K. et.
al 2007). Whenthe CNS is injured, an astroglial wound is formed impeding the restorationprocess to take place, leading to a physical obstacle composed principally byCSPGs molecules, that after being regulated by astrocytes that have beenpreviously reactivated, would consequently be excreted in the extracellularmembrane space and bound to it. Unfortunately, a receptor for this molecule hasnot been determined yet, but a variety of studies shows that a factor able tointerfere with CSPG would stimulate and improve CNS regeneration (Asher, R. et.al 2000).
MAIs are mainly related tooligodendrocytes and include factors such as Nogo-A, MAG (myelin-associatedglycoprotein), OMgp (oligodendrocyte myelin glycoprotein), associated withNogo-66 receptor 1 factor which activates neuronal growth inhibition and, eventhough MAG factors limit axonal regeneration, it was stated that theirinhibitory role is not as effective as the one Nogo factors undergo (Atwal et.al 2008).There are two main classes ofmolecules that would inhibit CNS regeneration: myelin-associated inhibitors(MAIs) and chondroitin sulphate proteoglycans (CSPGs). There are also someautonomous factors related to cells that lead to regeneration failure, whichmeans that even without inhibitory molecules, CNS axons would still not be ableto recover as easily as the peripheral ones because its neurons do not regulateproperly the growth associated genes (Bomze et. al 2001). As it was mentioned previously,the environment is a factor that has a big impact in the regeneration processand it plays an important role in understanding why axonal reconstruction islimited in the CNS.