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
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
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
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: