What limits neuronal regeneration in the central nervous system?

Neuronal regeneration in the central nervous system (CNS) is primarily limited by the activation of glial scars. When neurons are damaged, glial cells proliferate and form a dense scar tissue, which physically and chemically inhibits the growth of new axons. This scar tissue not only creates a barrier that prevents axonal regrowth but also releases inhibitory molecules that further discourage regeneration. For instance, some of the molecules produced by reactive astrocytes and other glial cells can trigger signaling pathways that promote cell death or inhibit growth, such as semaphorins and chondroitin sulfate proteoglycans.

Other factors, while relevant, do not have the same critical impact on regeneration within the CNS. While the inability of neurons to divide relates to regenerative capacity, it is not the sole reason for the lack of repair, as some non-neuronal cells can proliferate. Neurotransmitters play essential roles in synaptic communication, but they do not limit regeneration in the same manner that glial scars do. Furthermore, blood flow is crucial for overall health and function but does not directly inhibit neuronal regeneration as severely as the formation of glial scars does. Thus, the presence of these scars is the most significant barrier to neuronal