Research

The spinal cord is part of the central nervous system (C.N.S.) which elongates into the vertabral canal. In the spinal cord there are (besides many other anatomicalstructures) millions of nerve fibers which transmit to the lower motoneurons the commands coming from the upper motor neuron (brain).When the cord is interrupted the commands from the brain are abolished as well as are the sensory informations going to the brain from the periphery. The lower motorneurons survive but are disconnected from the brain and released from the control of the tonus so that muscles become spastics with clonuses. Also neurological disturbancies of the bladder and of the bellies occur which give severe disconfort in everyday activities.
Some sexual activity remains but the absence of sensibility gives a peculiar new sexual life which introduces an unpleasant and intricate mutual adaptation. Luckely pregnancy is possible as well as the eiculation of fertile sperme so to allow young paraplegics to have children.
Research has proved that upper motor neurons are able to regenerate their axons which however cannot progress beyond the lesion. Peripheral nerve fibers, on the contrary, can regenerate and progress up to their targets thanks to the presence of the Schwann cells (which are lacking in the C.N.S.). S.C.I.s have been considered incurable for centuries. It was a”dogma” teached to the students of the medical schools and to the paraplegics since the beginning. But various dogma proved to be false along the centuries. The incurability does not depend on the cord but on our ignorance of its physiopathology. S.C.I.s are known since the ancient Egiptians.The first experiments on monkeyes were done in Rome by Galenus during the second century after Christ but 18th centuries had to pass before new research started. The spinal cord after severance does not allow theaxons of the upper neurons to descend towards the lower neurons and to excitate them.

The reason of this “non-permissivness” are not known yet. In 1979-80 1 cm of cord was removed at T XI level in rats and the gap was filled in with autologuos grafts of peripheral nerves. The grafts were rehinabited by the axons regrowing from the upper neruons but the progresion of the axons stopped as soon as in contact againwith the C.N.S. environnement. To overcome this non-permissivness, since 1981 varioussurgical protocols have been used by the researchers ofhe Foundation for the Research of Spinal Cord Lesion,aimed to connect the regrowing axons to the muscularnerves by means of autologous grafts, excluding the lower motorneurons. The upper motoneurons were able to elongate the cytoskeleton of their axons up to the muscles.
After the rats research 4 groups of monkeyes (macacafascicularis) were operated on. Magnetic stimulation of the brain (external and after craniotomy) demostrated good muscolar responses. E.M.G. also showed good responses with different latenciesaccording to the different sites of the stimulation.

Morphometrical analysis showed good axonal density, good severance area and good myelination of the fibers. While waiting for the permission of the National Ethicalcommittee to transfer to human beings this protocol, the team of the foundation transferred the ulnar nervefrom the upper to the lower limbs (in fact nerve transfers are in use for decades and did not necessitate special permission).
At the begging the patient must think to move the arms to get movement of the lower limbs, then, thank to the brain plasticity, the patient was able to move the lower limbs by thinking to do that.
After months of re-education the patient was able to walk 50-70 steps a time with the help of a walker.
Then having obtained the permission of the Ethical Committee 3 patients have been operated on by C.N.S.-P.N.S. connections according to the last animal protocol. In 2004 the first patient was able to walk for several minute with tetrapode sticks and to stand several hours. In nature all the muscles receive innervation by the lower motoneurons which on turn are excitated by the upper ones. By means of the C.N.S.-P.N.S. connections they receive innervation from the upper motoneurons while the lower ones are excluded.

Furthermore the muscles receive axons coming from different cortical area of the brain (in fact the C.N.S.- P.N.S. connection is random). That notwithstanding the animals and the patients perform selective voluntary movemnts without co-contractions.
Research was contiunued with the co-operation of the section of Pharmacology, Toxicology and Experimental therapy of the Medical School of the Brescia University (Prof. PF. Spano, and Prof. M. Pizzi), with the department of byomedical Sciences and Byotechnologies and the section of Genetics Biology, same university (Prof. S. Barlati and dott.A. Barbon) and with the department of Neurosciences and Neurophysiopathology of the general Hospital of Brescia (dott. B. Guarneri).
The result of the last 3 years of research have been published in June 2005 by the Journal of the National Accademy of Science of the U.S.A.: P.N.A.S., 2005, 102, 24, 8752-8757. While in nature all the muscles functions thanks to the stimuli coming from the lower motoneurons of the cord which use Achetilcolin as neurotransmitter, after thesurgery carried on by the team which try to constitutethe E.S.C.R.I., muscles function due to the excitation coming from the upper motoneuron which used a different transmitter: the Glutamate.