The Society for Neuroscience
annual meeting ended last week in New Orleans, having presented over 15,000 research abstracts, hundreds of slide shows, and countless thousands of discussions and interactions. If one tries to take in the whole picture, that of 27,512 brain scientists gathered in one place at one time, it’s far too overwhelming.
The field of neuroscience is global, it’s deep and it’s wide: the main categories of research include these broad topics:
Neural Excitability, Synapses, and Glia: Cellular Mechanisms
Disorders of the Nervous System
Sensory and Motor Systems
Integrative Systems: Neuroendocrinology, Neuroimmunology and Homeostatic Challenge
Cognition and Behavior
Novel Methods and Technology Development
History, Teaching, Public Awareness, and Societal Impacts in Neuroscience
You don’t have to drill down very far to see how hyper-specialized this field has become. Spinal cord injury related research, for example, is widely represented but is a small subset of the Disorders section, which also includes very large research communities dealing with Alzheimer’s, Parkinson’s, brain cancer, autism, bi-polar disorders, opiate reactions, and issues of the aging brain. SCI is also sprinkled into several other categories, e.g. Motor Systems, Behavior, Glia, etc.
I did not attend the meeting this year but SFN offers a handy Internet roadmap
to see an enormous amount of what went on there. (Try this yourself: input a subject or specific scientist and see how much comes up.)
A few highlights of interest to the Reeve community, starting with the opening keynote session, Neuroscience and Society, featuring artist Chuck Close. Close, who is paralyzed due to a collapsed artery in 1988, is a titan of contemporary art. Moses Chao, President of SNF and former chair of the Reeve Foundation Science Advisory Council, introduced Close as “one of the most influential and acclaimed artists of our time.” The talk was titled, “My Life as a Rolling Neurological Clinic
;” (nearly two hours long, it is available online.) Close has lived with learning disabilities his entire life, plus dealing with functional loss below his chest and including his hands. He is face-blind -- he cannot recognize faces in three dimensions -- even though he has become known for his fabulous portraits (shown here is one of his many self-portraits).
Due to issues with pain, Close was not able to travel from his studio in New York City to New Orleans but appeared by a live video feed. Alongside Chao on the stage was a panel of neuroscientists, including Mary Bunge of the Miami Project and former member of the Reeve Foundation International Research Consortium on Spinal Cord Injury. The session offers a fascinating look at the process of making art, and as Close says, how “everything about my work has to do with my disabilities.” Highly recommended.
Now let’s consider a handful of the posters and abstracts from this year’s SFN. Caveat: these are generally works in progress, not peer-reviewed papers.
They are fascinating advance looks into future publications and provide a reliable snapshot of where the field may be headed.
Deep Brain Stimulation (DBS) Restores Locomotion in Rats with Partial Spinal Cord Injuries
This poster, from the Miami Project and the Mayo Clinic, Brian Noga lead investigator, showed that DBS, commonly used for movement disorders such as Parkinson’s, can enhance function of uninjured but inert nerve pathways after incomplete spinal cord injury in a rodent model. The researchers used an electrical implant to stimulate the brain region in rodents that affects locomotor activity. This jump-started the descending nerve fibers that control walking. Rats unable to step following injury began walking; other rats walked faster and longer. DBS appears to re-activate anatomically intact pathways that function poorly after injury. Said Noga: “Undamaged descending nerve pathways appear to be viable targets for improving walking following incomplete SCI,” Noga said. “These results are encouraging news, since DBS could be quickly translated into a versatile treatment depending on the nerve pathways affected.” This work was supported by the Reeve Foundation.
Underwear Wired to Deliver Tiny Electrical Currents Appears to Prevent Pressure Sores
Smart underwear called Smart-e-Pants, developed in Canada, feature a system to deliver tiny electrical currents to the buttocks to prevent the development of pressure sores in people with paralysis. Sean Dukelow of the University of Calgary reported that the tiny muscle contractions generated by the underwear mimic the subconscious fidgeting of nondisabled people, stimulating blood flow and redistributing pressure away from the sitting bones; of 33 clinical care patients who wore the underwear, none developed pressure ulcers during the two-month study period.
Recovery of Voluntary Control of Lower Limbs with Epidural Stimulation and Training after Chronic Complete Paralysis
This abstract, from Susan Harkema (Frasier Rehab in Louisville, principal investigator of the Reeve NeuroRecovery Network) and Reggie Edgerton (UCLA, member of Reeve International Research Consortium on Spinal Cord Injury) offers the first glimpse at their continued work with epidural stimulation. Three patients with complete lower limb paralysis have had epidural stimulators implanted. Each had been paralyzed for two to three years at the time of the implant. The first subject was Rob Summers, whose recovery has been well documented
. The latter two subjects were able to demonstrate voluntary control, when stimulated, at initial testing. Summers was not tested until seven months after implantation. The scientists report that daily training for voluntary control brought about recovery and progressive improvement in volitional motor control. The threshold level of the epidural stimulation progressively decreased over time, training generated increased force with a steady decline in fatigue. The mechanisms underlying these functional changes remain to be determined.
Riluzole Phase I Trial Results
This abstract presented preliminary results from the open-label acute SCI trial for the drug Riluzole, sponsored by the Reeve-funded North American Clinical Trials Network
(NACTN). Thirty-six patients with acute SCI were enrolled at six NACTN hospitals between April, 2010 and June, 2011. Riluzole was administered within 12 hours of injury for 14 days. There were no serious adverse events reported. Patients were scored on the ASIA Impairment Scale for conversion to an improved grade (e.g. ASIA A is no motor function, no sensory; converting to an ASIA B means there was neurological improvement). At three months, 36 percent of ASIA As improved (compared to 23 percent who would be expected to improve without treatment in a matched control group). For grade Bs, 77 percent improved (compared to 60 percent in controls) and for the C group, 74 percent improved (compared to 60 percent in controls). These rates of neurological recovery are promising; the patient numbers are small and early surgery may have had a therapeutic effect. A Phase II study is planned.
Breathing Carbon Monoxide May Accelerate Healing from Spinal Cord Injuries
Inhalation of carbon monoxide (CO) inhalation appears to improve recovery and reduce damage caused by a spinal cord injury. The acute treatment is thought to interfere with the inflammatory response to the injury. Yang D. Teng of Harvard Medical School and the Boston VA Healthcare System reported that four groups of paralyzed rats got increasing doses of CO over a 12 day period. The higher the dose, the more the reocovery. Said Teng, “We explored the possible use of CO as a therapy based on prior research showing that it readily crosses the blood-brain barrier, and has a protective effect on cells in the lungs.”
Stem Cells Have Potential to Treat Dysreflexia Caused by Spinal Cord Injuries
This study, from Armin Blesch of the Spinal Cord Injury Center at Heidelberg University Hospital, and colleagues from the Mark Tuszynski lab at the University of California, San Diego, showed that stem cells may help control autonomic dysreflexia by restoring damaged nerve connections that control blood pressure and heart rate in a rodent model. The scientists isolated neural stem cells from the fetal brainstem and transplanted them into the spinal cords of injured rats. “Only the animals that received transplants of fetal cells derived from the brainstem had a resting heart rate and blood pressure that was similar to normal values,” Blesch said. “When we looked at their spinal cords, we found evidence that the transplanted cells may be serving as nerve relays to reconnect the brain with centers of control for cardiovascular function.”
Remyelination of Spinal Cord Axons by Transplanted Canine Olfactory Ensheathing Cells (OEC) and Schwann Cells
This abstract, from a group at the Hannover Medical School in Germany and the Jeff Kocsis lab at Yale, showed that dog OEC cells, a type of nerve cell harvested from the olfactory bulb in the nose, remyelinated nerve axons in rats that had spinal cord injuries. The OEC were used in various combinations wtih Schwann cells. Myelin is an essential nerve fiber insulation material that is commonly lost after SCI. The clinical implications are significant as the work moves from the small animal model to larger animals, then humans.
Transplantation of Inhibitory Neuron Precursors to Improve Outcome After Spinal Cord Injury
This work, from the Arnold Kriegstein lab at the University of California, San Francisco, uses a novel stem cell strategy to reduce bladder dysfunction and neuropathic pain related to chronic SCI. The cells are derived from a region of the developing brain that gives rise to certain inhibitory interneurons. Preliminary evidence show that transplanted cells integrate into the spinal cord and assume new roles as inhibitory factors; the researchers observed a decrease in uninhibited bladder contractions in SCI mice that received cell injections. Also, a tail flick assay suggested a decrease in neuropathic pain in SCI animals eight weeks after cell transplantation.
VEGF Results in Angiogenesis, Neuroprotection, Functional Recovery and Decreased Neuropathic Pain
This abstract, from the Toronto labs of Michael Fehlings
(a principal investigator on the Reeve Foundation’s North American Clinical Trials Network
) used vascular endothelial growth factor (VEGF) as an acute neuroprotective for experimental SCI. Molecular analysis showed that it did indeed preserve nerve tissue after injury; moreover, VEGF improved hind-limb weight support, dramatically, and also reduced pain.
Peptide Discovery Releases Axons Trapped by Inhibitors
This abstract is from the Jerry Silver
lab at Case Western in Cleveland. Silver, a longtime member of the Science Advisory Council for the Reeve Foundation, has for many years studied inhibitory scar material called chondroitin-sulfate proteoglycan (CSPG) that accompanies spinal cord injury. His lab and others have found that a drug chondroitinase (aka chase) frees axons from the scar and allows them to grow. Chase might evolve as a therapy but there are delivery issues to work out. (See next citation: Silver’s group improved function in a “super-chronic” model). Meanwhile, in this abstract, Silver’s group demonstrated a way to turn off receptors that otherwise would cause CSPGs to block growth. By blocking these receptors with peptide inhibitors in a severe contusion model, they report “remarkable recovery of hindlimb function, locomotor activity, and bladder control … unprecedented levels of functional recovery following spinal cord injury, presenting a potential new avenue of treatment for paralysis.”
Chondroitinase in Super-Chronic Injury Promotes Respiratory Motor Recovery
Here, the Jerry Silver lab shows that treatment with scar-tissue busting Chase in animals one to one-and-a-half years post-injury restored diaphragm function. The abstract notes that the restored function is greater than that which returns after acute treatment; this suggests that precisely targeting inhibitory scar tissue may be an important priority even in chronic SCI patients.