Acute vs. Chronic Spinal Cord Injury Research
I am attending the National Neurotrauma Society meeting in Nashville. I could not help but notice how dominant traumatic brain injury (TBI) research is over spinal cord injury (SCI) research at this meeting. I founded the Neurotrauma Society about 30 years ago. During the 1990's when I ran the society, we had pretty much 50/50 SCI/TBI talks and posters at all our annual meetings. Since the 2000's, I have been traveling a great deal to Asia and did not attend many Neurotrauma meetings for over a decade. This year, because I was invited to speak at the beginning and end of the meeting, I attended the whole 3-day meeting.
Here is a list of the talks on the first day:
• David Loane, U. Maryland. Microglial phenotypes in acute brain injury and repair
• Jon Godbout, Ohio State U. M1/M2 phenotype of microglia in chronic consequence of neurological injury
• Carol Colton, Duke U. Immunosuppression in chronic neurodegenerative disease
• Demetrio Sierra-Mercado, Harvard U. Fear and extinction after brain injury in mice: potential model of post-traumatic stress disorder
• Stuart Friess, Washington U. Behavioral deficits in immature swine following rotational head injury are direction-dependent
• Patricia Washington, Georgetown U. The effect of brain injury severity on cognitive and emotional behaviors
• Ann-Christine Duhaime, Harvard. Why harmonizing preclinical TBI research matters
• Doug H. Smith, U. Penn. What are the preclinical TBI common data elements.
* Adam Ferguson, UCSF. Multivariate quantification across diverse SCI outcomes and models: Bioinformatics for Translational Research
• John Whyte, Moss Rehab. Cognitive rehabilition for mTBI: Institute of Medicine report and updates
• Kathleen Bell, U. Washington. Treatment of depression and related sensory conditions after mTBI.
• Robert Ruff, Case Western Reserve U. Clinical management of mTBI in service members.
• Sara Al-Dahir, Xavier U. Not just phenytoin kinetics: the emerging role of pharmacists in a neurotrauma unit
• Christopher Wood, U. Tennessee. Controversial issues in TBI pharmacotherapy in the clinical setting
• Philip Empey, U. Pittsburgh. The importance of understanding clinical pharmacology in neurotrauma research.
• Andrew Mayer, Mind Research Network. Prospective studies of structural and functional connectivity in mTBI
• Michael Stevens, Yale U. Probing multiple resting state networks using an ICA approach to resting state functional connectivity in mild TBI
• Patrick Bellgowan, Laureate Institute of Brain Research. Multiple fMRI contrast mechanisms for tracking mTBI recovery
As you can see, only one of 18 talks (Adam Ferguson) on the first day of the 3-day meeting was about spinal cord injury. In case this is because the first day of the meeting is on TBI, I looked the plenary talks on the second day:
• Milos Ikonomovic, U. Pittburgh. New perspectives on the link between TBI and AD, and what to do about it.
• Ali Rezai, Ohio State U. Neuromodulation for persistent vegetative states and behavior and neurocognitive disability
• Ramona Hicks, NINDS/NIH. Research status of multi-drug cominbaiton approaches to promote neurological recovery
• Gail Anderson and Michael Hoane, U. Washington and Southern Illinois U. Carbondale. Pharmacological optimization of poly-drug therapy in TBI.
• Jerome Badaut, Loma Linda U. AQP4 and JNK inhibition together improve the long term functional outcome after juvenile TBI
• James Pauly, U. Kentucky. Recovery following experimental brain injury and treatment with cyclosporin A and dietary choline supplementation: the benefits don't add up.
• Ramesh Raghupathi, Drexel U. Pathology-direct combination therapy for pediatric TBI.
• Fatim Atif, Emory U. Combination of progesterone and vitamin D in the treatment of brain injury: Will it work?
* Michael Fehlings, U. Toronto. Translational research: discovering novel treatments for spinal cord injury
* Lisa McKerracher, BioAxone. Cethrin: Results of Phas I/II clinical trial and planned pathway forward for the Phase II/III study
* Wise Young, Rutgers U. Umbilical cord blood and lithium treatment of spinal cord injury.
• Nathan Zasler, Concussion Care Centre of Virginia. Caveats and conundrums in PTHA research and practice.
• Jeanne Hoffman, U. Washington. Natural history of headache
• Melanie Elliot, Thomas Jefferson U. Trigeminal sensitization in rodent models of TBI: Immune and neuronal mechanisms.
• Amy Wagner, U. Pittsburgh. Overview of subacute/chronic neurosymptoms and other comorbidities associated with TBI
• Ramon Diaz-Arrastia, Uniformed Services U. Identification of post-TBI chronic anatomic and structural brain changes and neurodegeneration by imaging analysis.
• Kevin Wang, U. Florida. Systems biomarkers as new tools to monitor and manage subacute and chronic phases of TBI.
• James Ecklund, Inova Health System. Introduction to penetrating brain injury guidelines.
• Beverly Walters, Inova Health System. Introduction and background to penetrating brain injury in modern war and at home
• Mark Shaffrey, U. Virginia. Treatment of complications of penetrating brain injury: vascular and CSF leaks.
• Bizhan Aarabi, U. Maryland. Neuroimaging and surgical management of penetrating brain injury.
• Courtney Robertson, Johns Hopkins U. Developmental features of brain mitochondria: Considerations for pediatric TBI therapies
• Susan Margulies, U. Penn. Cyclosporin A therapy trials for pediatric TBI in a large animal model
• Jose Pineda, Washington U. Clinical considerations for mitochondrial therapies for pediatric TBI
• Col. Kenneth Curley MD, US Army Medical Research and Materiel Command. Roundtable discussion: Can we cross the chasm? Challenges in transplanting therapeutics to and through clinical trials.
So, the second day was slightly better. Out of 25 talks, three were about spinal cord injury. So, I looked at the third and last day program:
* Barbara Gimpe, Heinrich Heine U. Knowledge database: the path to understand regeneration failure.
• Nigam Shah, Stanford U. Speeding translational rsearch using bio-ontologies.
• Regenbase: A searchable knowledge base to organize regeneration knowledge via ontologies.
* Geoff Manley, UCSF. Combined TBI and SCI.
* Stephen Macciocchi, Atlanta Neuropsychology. Spinal cord injury and co-occurring traumatic brain injury.
* Michael Beattie, UCSF. Interactions between brain and spinal cord injury in a model of combined injury.
• Dr. Eugene Alford, the Methodist Hospital, Houston. Patient perspective talk.
• Xi-Chun May Lu, Walter Reed Army Institute of Research. Levetiracetam and gabapentin dose-dependently attenuate post-traumatic non-convulsive seizures in rat penetrating ballistic-like brain injury model.
• Thomas Reeve, Virginia Commonwealth U. Kv1.3 potassium channels: a role of white matter injury and a therapeutic target.
• Davd Brody, Washington U. Repetitive concussive traumatic brain injury induces tau aggregation activity in a transgenic mouse model, implication for chronic traumatic encephalopathy and Alzheimer's disease.
• Todd Killbaugh, U. Penn. Immature large animal translational treatment trial with mitochondrial targeted pharmacologic intervention for traumatic brain injury in children
• Markus Spurlock, U. Miami. Focal neurodegeneration in rat following penetrating ballistic brain injjry despite acute global metabolic pathophysiology
• Paul McMahon, U. Pittsburgh. Post-concussion symptoms and functional outcome in mild traumatic brain injury: Results from the prospective TRACK-TBI Study
• Adam Ferguson, UCSF. The utility of common data elements for traumatic brain injury in the assessment of 6-month psychological functioning
• Anna Teresa Mazzeo, U. Turin. Systemic concentrations of inflammatory mediators are associated with the duration of secondayr insults in patients with severe traumatic brain injury
• Ramon Diaz-Arrastia, Uniformed Services U. Acute biomarers of mild TBI: relationship between serum levels of ubiquitin C-terminal hydrolase and glial fibrillary acidic protein break-down products
• Amy Wagner, U. Pittsburgh. Chronic inflammation after severe traumatic brain injury: characterization and association with outcome
* Rachel Hill, U. Kentucky. Pharmacological multi-mechanistic inhibitor of lipid peroxidation improves mitchondrial function and reduces cytoskeletal degradation following contusive spinal cord injury.
* Samir Patel, U. Kentucky. Effects of continuous subcutaneous delivery of N-acetylcystein Aamide (NACA) on acute and chronic pathophysiology after spinal cord injury
* Qilin Cao, U. Texas Health Science Center. Human inducible pluripotent stem cell derived neuroanal precusor cells for spinal cord injury
* Celine Baligand, U. Florida. Skeletal muscle size and force after treadmill training in a severe contusion SCI rat model.
• Matthew Rasband, Baylor College of Medicine. Blast induced changes in the axonal initial segment
• Ping Wu, U. Texas Medical Branch, Galveston. Stem cell released GDNF promotes axonal repair after traumatic brain injury
• Stephen McCauley, Baylor College of Medicine. Role of Pre-injury resilience and mood on outcome following mild TBI
• Elisabeth Wilde, Baylor College of Medicine. Updates in diffusion tensor imaging in mild TBI.
The third day of the Neurotrauma Society meeting had eight SCI talks of a total of 25 talks. The rest were all TBI talks. So, all three days of the Neurotrauma Society meeting were dominated by TBI. On the first day, one of 18 talks (6%) were SCI. On the second day, three of 25 talks (12%) were about SCI. On the third day, eight of 25 talks (32%) were about SCI. Combined, there were 68 talks of which 12 were about SCI (18%). Of these talks, the only talk about chronic SCI was mine.
It is possible that the Neurotrauma Society this year is different from previous years because Claudia Robertson, the President, has a longstanding interest in TBI. It is possible that the program committee had more people interested in TBi than SCI. However, I think that this pattern has been going on for some time. Patricia Morton, who works with me, has been attending the Neurotrauma meetings for eight years and she says that the number of SCI talks use to be about 25% of the talks 8 years ago but now has shrunk to less than 20%.
A more reliable measure of the audience is the number of posters on SCI and TBI, since posters are submitted by participants who attend but may not be invited to speak. The distribution of posters reflects the interest and research of the participants. I am not sure how many people came but I estimate that as many as 500 people or more are attending the plenary lectures.
An analysis of 275 posters at the meeting came up with an even more lopsided distribution of topics. Eighteen of 275 posters (6.5%) were selected as finalists in the student competition. Of these 18 posters, 14 were about acute TBI, 2 were on acute SCI, 1 on chronic SCI, and 1 was on clinical TBI. So, 3 of 18 (17%) of the top student posters were on spinal cord injury. There were a total of four poster sessions (A, B, C, D). As listed in Table 1 below, the range of SCI posters ranged from 3-7% of the posters in each session. About 5% of the posters were about SCI. The rest were about TBI.
Table 1. Ratio of SCI to total posters in each poster session
Session A. 2/74 = 3%
Session B. 5/73 = 7%
Session C. 4/74 = 5%
Session D. 2/54 = 4%
All: 13/275 = 5%
Is there a lack of interest in spinal cord injury? I don't know. Even though only 5% of the posters were about SCI, 17% of the student poster finalists were about SCI. What is clear is that there is a lot more money going into TBI research than into SCI research. About a third of the TBI studies are on large animals (pigs or monkeys). All of the SCI studies were in rats or mice. Large animal studies are much more expensive than small animal studies.
Where is all the money for TBI research coming from? Judging from the talks and posters, the Department of Defense is the chief sponsor of 90% of the TBI studies. The Veterans Administration covered the rest. Also, many universities contributed TBI studies and many clinical departments were involved, including rehabilitation, radiology, neurosurgery, pediatrics. In contrast, the SCI studies were mostly covered by NIH or a few by private foundations or were from overseas. In general, the SCI studies are higher quality.
In summary, in the 2013 (the thirty-first) National Neurotrauma Society meeting held in Nashville, only 12 of 68 (18%) talks and 13 of 275 (5%) posters were about SCI. TBI clearly dominates the field of neurotrauma. Of the 12 talks, only one was on chronic spinal cord injury and that was my talk. Of the 13 posters on spinal cord injury, only one was about transplanting cells into chronic spinal cord injury.