Hot Topics in Cellular Neuropathology II: Promoting Neuronal Plasticity in the Injured Central Nervous System

Progress in Cellular Neuropathology is strongly facilitated by paradigm changes. Paradigm changes shift the way we look at neurological diseases. They promote new experimental approaches, from which translational advances in clinical neurosciences may result. Clinical neurosciences were predominated for ~80 years by the doctrine of the Spanish neuropathologist Santiago Ramon y Cajal (1852–1934), the discoverer of the axonal growth cone. In meticulous neuropathological studies, Ramon y Cajal has made fundamental contributions to clinical neurosciences by pursuing the concept of neurons as contiguous entities. Photographs of his silver nitrate stainings, which he advanced based on Camillo Golgi's (1843–1926) protocols, are legendary. Besides others, Ramon y Cajal postulated that adult central nervous system (CNS) neurons are able to sprout and create new axonal growth cone connections, which he considered as structural correlate of memory formation and learning (Sherrington, 1935). In response to CNS injury on the contrary, using autopsies of patients who died post-CNS injury, Ramon y Cajal observed surprisingly little axonal growth across and beyond brain or spinal cord lesions. Ramon y Cajal concluded that CNS axons of adult human neurons exhibit limited potential for white matter tract regeneration and sprouting (Ramon y Cajal, 1928). This neuroregeneration failure he made responsible for deficient neurological recovery in CNS injured patients.