Brescia SCI Conference
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Laurance Johnston, Ph.D

The 4th International Symposium on Experimental Spinal Cord Repair and Regeneration took place March 25 – 27, 2002 in Brescia, Italy, about 50 miles east of Milan between the Italian Alps foothills and the Po Plain. 

The University of Brescia’s Professor Giorgio Brunelli, a preeminent spinal cord injury (SCI) surgeon, organized the symposium and extended much culturally imbued hospitality to the participants. For example, celebrated soprano Katia Ricciarelli presented a memorable operatic concert. Laurance Johnston with Giorgio Brunelli

Approximately 40 speakers from Europe and North America offered a multidisciplinary diversity of SCI research and therapeutic approaches, ranging from basic neuroscience to innovative surgical procedures. Due to space constraints, this article summarizes only a few highlights.

Nerve Growth Factor:

The symposium emphasized the contributions of many Italian scientists, including Dr. Rita Levi-Montalcini, the 1986 Nobel Laureate in medicine. While working at St. Louis’ Washington University 50 years ago, Levi-Montalcini discovered nerve growth factor, one of the 20th century’s major neurobiological breakthroughs. The discovery has not only profoundly influenced today’s SCI research but also helped undercut the then-axiomatic assumption that regeneration after SCI was impossible. Her insightful remarks and engaging personality indicated no lack of this nerve growth factor in spite of being 93.

Clinical Trials Update:

Dr. Wise Young (Piscataway, NJ) provided an overview of an ever-growing number of promising SCI interventions, including those that have entered the clinical-trial evaluation process. Among these procedures are the use of various neuronal growth factors that have been discovered since Levi-Montalcini’s initial breakthrough; alternating electrical currents; antibody blockers of inhibitors that prevent regeneration; various remyelination and 4-aminopyridine-facilitated approaches that enhance conduction; transplanted stem cells that can transform into new neuronal cells; immunological approaches; and etc. (see, clicking on CareCure Community for more detailed summaries).

Immunological Approaches:

Dr. Michal Schwartz (Rehovot, Israel), scientific founder of Proneuron, an SCI-focused biotechnology company, discussed immunological approaches that minimize neurological damage after injury. Inspired by Hippocrates’ ancient wisdom that “natural forces within us are the true healers of disease,” Schwartz uses the body’s inherent healing mechanisms to develop therapeutic approaches that proactively augment naturally occurring autoimmune processes. These approaches use the patients’ own immune cells (called macrophages and T-lymphocytes), to minimize post-injury secondary damage and promote neuronal regeneration.

Although immune cells are scarce in “immune-privileged” central nervous system (CNS) tissue, to a limited degree they accumulate at the injury site, providing some neuroprotective and neuroregenerative potential. Schwartz manipulates this autoimmune response to greatly boost its healing potential.

Patients in the acute injury phase have been recruited for Proneuron-sponsored phase-one clinical trials by (see  As a result of Schwartz’ research, future SCI healthcare may see patients receiving a damage-reducing, regeneration-promoting vaccination after injury. As a consequence, the SCI pipeline may be further closing at the source.

Rerouted Nerves:

Professor Brunelli, the symposium’s organizer, is pioneering promising surgical procedures for restoring function after SCI. Specifically, he is one of the first to surgically reroute peripheral nerves (i.e., those outside of the spinal cord and brain) to bypass the injury site, reestablishing a functional neuronal connection from the brain to previously dormant body areas (see PN April, 2002 & September 2001).

Building on much animal research, Brunelli has developed several rerouting variations to restore some function in patients with SCI. In the first, he redirected and connected the wrist’s ulnar nerve, which emanates above the injury site, to nerves that control leg muscle functioning below the injury site.

In the second variation, Brunelli has used the peroneal nerve (a nerve to the leg that emanates below the injury site) as a bridge from the spinal cord above the injury site to the nerves of the gluteus and quadriceps muscles, obtaining a direct connection of CNS with these leg muscles.

The former procedure provoked less controversy because it involves connecting two peripheral nerves, which due to their inherent regenerative potential increases the likelihood of functional connections. Because the latter procedure involves establishing more-difficult connections between the spinal cord and peripheral neurons, some scientists felt that additional documentation (e.g., gene studies), were necessary before the observed restored function could be attributed to this specific intervention. Since the upper motor neuron (nerves within the spinal cord controlling movement) and lower motor neurons (nerves that leave the cord to connect to muscles) use different neurotransmitters (a chemical released from a neuron ending that interacts with an adjacent neuron or muscle cell), gene research should provide more definitive information on the mechanism of action of this function-restoring procedure.

Scar Reduction:

Dr. Susanne Hermanns (Dusseldorf, Germany) discussed biochemical interventions that make the post-injury scar more permeable to neuronal axons attempting to regrow through the injury site. Using rats, Hermanns has shown that these interventions can inhibit the biosynthesis and deposition at the injury site of collagen, a key component of scar tissue. This creates a more permissive environment for transected axons to migrate through the injury site.

Olfactory Ensheathing Cells:

Dr. Susan Barnett (Glasgow, UK) reviewed research on transplanting olfactory ensheathing cells (OEC’s) into the injury site. OEC’s are specialized glial cells (i.e., those that provide physical and metabolic support for neurons) associated with olfactory system neurons. Unlike other CNS neurons, these neurons have considerable reOlfactory Ensheathing Cellgenerative ability due to OEC production of new insulating myelin sheaths around axons and promotion of axonal regrowth.

OEC’s also have considerable regeneration-promoting properties when transplanted into the SCI injury site. Not only to they remyelinate and promote regeneration of SCI transected axons, but studies suggest OEC’s can restore some functional recovery. For example, Dr. Patrick Gauthier (Marseilles, France) discussed how OEC transplantation into the traumatic high cervical injury site could restore respiratory function in rats.

It’s the Blood Supply!

Dr. Henry Crock (London, UK) provided an overview of the paramount, yet often under-appreciated, role of the spinal cord’s blood supply.  He reminded the audience how important this supply was in nurturing the neurons that we are struggling to regenerate. 

“Don’t throw away the walking stick of spinal injury,” Crock noted, emphasizing that both arterial and venous cord circulation is the primary thing that needs to be addressed in SCI.

For example, in post-injury SCI management, Crock stressed that surgeons must be careful in spinal stabilization so as not to aggravate paralysis through compromising existing blood supply. Furthermore, he suggested that our research efforts to develop new therapies might be more productive if emphasis was placed on mechanisms that would increase spinal-cord blood circulation.

Several other speakers noted such circulation-promoting mechanisms in their talks.  For example, Dr. Harry Goldsmith’s (Reno, Nev.) omental transposition procedure - in which the gut’s highly vascularized omental tissue is surgically transposed to the injury site - exerts its restorative effects partially through stimulating new blood vessels into the spinal cord region (see PN, March 2001). 

While discussing Eastern-healing therapies, Dr. Laurance Johnston (Boulder, Colo.) noted how acupuncture is hypothesized to restore function after SCI through improving circulation around the cord (see PN, September, 1998).

Also consistent with this theme, Dr. Weihong Pan’s (New Orleans) research focused on the changes in the blood spinal-cord barrier (BSCB) that occurs after injury. The extra tight cellular junctions that exist in CNS-associated capillaries create the BSCB, which inhibits large molecules from passing from the blood into the cerebrospinal fluid.

By studying the uptake of an immunological molecule that exerts regenerative effects at low concentrations, Pan has shown that post-injury BSCB disruption is reversible and varies depending upon the affected spinal region. Her studies suggest that the dynamic regulation of BSCB could play a pivotal role in spinal cord regeneration.

Functional Electrical Stimulation (FES):

Many speakers focused on the use of various forms of FES to stimulate paralyzed muscles. From the US, Drs. Michael Keith and Harry Hoyen (Cleveland, Ohio) reviewed their efforts to develop increasingly technologically sophisticated and physiologically integrated FES neuroprostheses for restoring hand and upper-arm function.

European scientists have especially embraced diverse FES applications as part of their rehabilitation and research programs. For example, Dr. Hans Van der Aa, (Enschede, Netherlands), discussed the long-term effectiveness of the implanted Brindley device, which stimulates paralysis-affected, bladder-controlling sacral nerve roots.

In another example, Dr. Fin Biering-Sorensen (Copenhagen, Denmark) discussed the results of a multi-institutional European study, examining the effects of FES on individuals with incomplete SCI. Although no increase in walking endurance was found, FES training enhanced gait and overall walking quality. Biering-Sorensen also reported that FES cycling for 30 minutes three times a week over a year increased bone density by 10%. However, if the cycling session was, in turn, reduced to once a week, the regained density was lost.


Celebrated science-fiction author Arthur C. Clarke has stated  “When a scientist states that something is possible, he is almost certainly right; when he states that something is impossible, he is very probably wrong.“

Given Clarke’s observation, the growing optimism that was percolating to the surface in-spite of the speakers’ inherent conservative nature portends much promise for the future.

Adapted from article appearing in Paraplegia News, August, 2002 (For subscriptions, contact

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