NNS 2015 Abstract Book

the formation of biobridges designed to stabilize the ECM structure and to

harness the ECM’s ability to dampen neuroinflammation stand as potent

TBI therapeutics. Second, we advance a novel mechanism of ‘‘nuclear

sequestration of inflammatory cell death signals’’ (i.e., withholding cell

death signals in the nucleus to inhibit their propagation to the cytoplasm),

which could potentially enhance cell survival and rescue damaged cells in

the TBI brain. The transit of large proteins (

42kD) through the nuclear

pore requires carrier proteins, with Exportin 1 (XPO1) identified as amajor

carrier protein and recently shown to be dramatically upregulated in neural

cells juxtaposed to inflammatory cells following TBI. In collaborationwith

Karyopharm Therapeutics, we demonstrated that a novel class of potent,

small molecule, brain penetrating inhibitors of XPO1, termed Selective

Inhibitor of Nuclear Export (SINE) compounds, can sequester cell sur-

viving signals (e.g., FOXP1, AKT), as well as cell death signals (NFkB)

within the nucleus after TBI, resulting in reduced inflammation and im-

proved behavioral recovery in SINE-treated TBI animals. Altogether,

stabilizing the ECM and fostering nuclear sequestration of cell death

signals pose as innovative anti- inflammatory response in TBI.

Keywords: Inflammation, Neurotransplantation, Regeneration &

Plasticity, Cell Death, Stem Cells, Small Molecules

S02 AGE and SCI

S02-01

FORTY YEARS OF LIVING WITH SPINAL CORD INJURY -

PHYSICAL AND PSYCHOSOCIAL CHANGES OVER TIME

Susan Charlifue

Craig Hospital, Research Department, Englewood, USA

With improved survival and life expectancy, clinicians are facing not

only the anticipated conditions that accompany aging with spinal cord

injury (SCI), but also must address the more common conditions as-

sociated with normal human aging. Individuals aging with SCI have a

thinner margin of health, the potential earlier onset of additional chronic

conditions, and face the risk of experiencing more severe consequences

of those conditions before appropriate medical intervention is sought.

The findings from a longitudinal study of aging with SCI conducted in

the United Kingdom demonstrate a variety of physical and psychosocial

changes experienced by a group of individuals injured prior to 1971.

Key themes of importance to clinicians have been identified, including

the physical, practical and emotional impact of the process of aging

with SCI. Physical changes over the study period of 20 years (1990–

2010) focus on cardiovascular risk factors, bowel and bladder changes

and skin integrity. From a psychological perspective, the changing

patterns of life satisfaction, perceived stress, depressive symptomatol-

ogy and global quality of life reported by the study participants are

described. Finally, changes over time in community participation as

well as the participants’ perceptions of environmental barriers and fa-

cilitators that they experience are discussed.

Keywords: secondary health conditions, psychosocial issues

S02-02

MUSCLE CHANGES WITH SPINAL CORD INJURY AND

AGE

Christine Thomas

, Bradley DeForest, Yang Liu, Robert Grumbles

University of Miami, The Miami Project to Cure Paralysis, Miami,

USA

Muscle strength varies widely after human spinal cord injury (SCI). For

muscles innervated from the lesion epicenter, evoked forces range from

zero (complete muscle denervation) up to usual muscle strength. Age at

SCI matters – muscles are stronger when SCI occurs at a younger age

(

25 years). The mechanisms contributing to these changes in muscle

strength remain unclear. Motoneuron death is common after SCI, but is

younger spinal cord more resilient to trauma? Do more motoneurons

survive in younger individuals? Are the axons of surviving motoneurons

better able to sprout to innervate more muscle fibers? All of these pro-

cesses would facilitate muscle strength. This trauma has consequential

and long-term effects on musculoskeletal biology. In daily tasks, muscles

weakened by SCI are inescapably overused. Does chronic overuse pre-

dispose motoneurons to death? If so, this may contribute to the new

muscle weakness and fatigue reported when individuals with SCI reach

40–45 years. Further, remediating motoneuron death by neuron trans-

plantation may restore muscle innervation and allow use of patterned

electrical stimulation of neurons to restore function. But what role does

transplant age or aging itself play in functional restoration? These issues

will be explored because of their long term impact on function.

Keywords: muscle weakness, motoneuron death, chronic overuse,

aging, muscle innervation, neuron transplantation

S02-03

ACCELERATED AGING AFTER SCI

Rachel Cowan

University of Miami Miller School of Medicine, Neurosurgery/Miami

Project to Cure Paralysis, Miami, USA

Clinicians and Researchers who treat and study persons with spinal cord

injury (SCI) generally believe that people with SCI ‘age’ faster than the

non-disabled population. The core evidence for this ‘accelerated’ or

‘premature’ aging is the earlier onset of ‘chronic diseases’; the greater

prevalence of chronic diseases; and the greater mortality rate and reduced

lifespan of persons with SCI. Impairments of body structures and func-

tions due to the SCI as well as the increased stressors of living with SCI

are suspected to be the drivers of ‘accelerated’ aging. The biological

processes underlying and indexing the clinical evidence have yet to be

quantified. This presentation will review the evidence supporting the

theory of ‘accelerated’ aging of persons with SCI, identify factors that

may ‘drive’ the accelerated aging process, and present the proposed

cellular & molecular hallmarks of aging.

Keywords: Aging, SCI

S03 Novel and Emerging Imaging for Detection and

Diagnosis of TBI

S03-01

MAGNETIC RESONANCE IMAGING OF MILD TRAUMATIC

BRAIN INJURY

Andrew Mayer

1–3

The Mind Research Network/Lovelace Biomedical and Environ-

mental Research Institute, Cognitive Neuroscience, Albuquerque,

USA

University of New Mexico School of Medicine, Department of Neu-

rology, Albuquerque, USA

University of New Mexico, Department of Psychology, Albuquerque,

USA

There has been a sea change regarding the potential physiological con-

sequences of mild traumatic brain injury (mTBI) over the past 5–10 years.

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