scientists are investigating and researching different ways to modify CNS´s
environment in order to alter cell´s behaviour and induce the axon´s
reconstruction process upregulating the inhibitory factors, hoping to one day
be able to reverse brain and spinal cord injuries.
and large, after considering all things, it can be appreciated the fact that
one of the factors that more conditions neuroregeneration are the different
cell types that can be found as well as the environment that surrounds them and
the CNS and PNS for instance.
the embryonic evolution of the CNS and PNS is based on different pathways, the
surrounding environment would differ too, giving therefore rise to specifically
cell types with a precise survival capacity and regeneration potential based on
cell’s reaction as a genetic factor (“Boundless anatomy and physiology”).
contrast between the CNS and PNS that was exposed in the essay may have emerged
from an early embryo differentiation as CNS is formed by the neural tube
structure and its assembly, whereas the PNS is primarily constituted by the
establishment of the neural crest. PNS is composed of pluripotent cells leading
to the development of a huge variety of cell type that would induce the
formation of the neural crest, which would posteriorly be converted into the
ganglia and glia, sympathetic and parasympathetic neurones.
spite of all the molecules that inhibit axon restoration development in the
CNS, there are some factors that may also induce neuronal growth. One of these
molecules is known as the cyclic adenosine monophosphatase (cAMP), usually referred
to as a neuronal second messenger involved in neuron development. cAMP level is
normally altered when a PNS injury occurs, but it can be increased in the CNS
throughout an intra-ganglionic injection of dibutyryl Camp, which would mime the
growth effect in the lesion, stimulating sensory axons reconstruction.
Rolipram, for example, increments cAMP quantity inducing thus regeneration
(Bomze et. al 2001).
other inhibitory factors as well as alternative inhibitory pathways involving
signalling can be found outside the glia or the myelin such as, for example, the
evidence proposed by recent research considering the epidermal growth factor
receptor as being one of the components that would promote regeneration
deficiency. Additionally, if we refer to the intrinsic development and growth
of the damaged neuron, as it was stated before, one of the molecules that would
support the process but achieves distinct levels of upregulation are the RAGs
and, as in the CNS its expression is low, regeneration failure would be the result
(Pernold, K. et. al 2007).
When the CNS is injured, an astroglial wound
is formed impeding the restoration process to take place, leading to a physical
obstacle composed principally by CSPGs molecules, that after being regulated by
astrocytes that have been previously reactivated, would consequently be
excreted in the extracellular membrane space and bound to it. Unfortunately, a
receptor for this molecule has not been determined yet, but a variety of
studies shows that a factor able to interfere with CSPG would stimulate and
improve CNS regeneration (Asher, R. et. al 2000).
are mainly related to oligodendrocytes and include components such as Nogo-A,
MAG (myelin-associated glycoprotein), OMgp (oligodendrocyte myelin
glycoprotein), associated with Nogo-66 receptor 1 factor which activates
neuronal growth inhibition and, even though MAG factors limit axonal
regeneration, it was stated that their inhibitory role is not as effective as
the one Nogo factors undergo (Atwal et. al 2008).
are two main classes of molecules that would inhibit CNS regeneration:
myelin-associated inhibitors (MAIs) and chondroitin sulphate proteoglycans
(CSPGs). There are also some autonomous factors related to cells that lead to
regeneration failure, which means that even without inhibitory molecules, CNS
axons would still not be able to recover as easily as the peripheral ones
because its neurons do not regulate properly the growth associated genes (Bomze
et. al 2001).
it was mentioned previously, the environment is a factor that has a big impact in
the regeneration process and it plays an important role in understanding why
axonal reconstruction is limited in the CNS.