Page 40 - NNS 2014 Program & Abstract Book

viability, functional recovery, and glial activation. Briefly, adult male rats
were subjected to a moderate contusion SCI and PET imaging with
[18F]Fluorodeoxyglucose (18F-FDG), which was performed prior to in-
jury and at 6 and 24 h and 15 days post-injury (dpi). Locomotor function
was assessed at 2 and 14 dpi using the Basso, Beattie, and Breshnahan
(BBB) scale, the ladder walk and modified cat walk tasks. Histology was
performed at 16 dpi. Using region of interest (ROI) analysis with ref-
erence region normalization, 18F-FDG PET imaging revealed that
moderate contusion SCI significantly depressed glucose uptake in com-
parison with sham-injured and naı¨ve controls at 6 h post-injury, followed
by a gradual return to post-injury uptake by 15 dpi. Further, the degree of
depressed glucose uptake at 6 h post-injury was correlated with lesion
volume (p = .0071) and functional impairment at both acute (BBB
function, 2 dpi, p = .0085) and delayed time points (ladder walk, 15 dpi,
p =.0252). These results show that moderate SCI results in an observable
depression in spinal cord glucose uptake using 18F-FDG PET that may be
predictive of histological and functional outcomes.
Key words
contusion injury model, glucose uptake, PET imaging, spinal cord,
spinal cord injury
T1-17
HIGHER MEAN ARTERIAL BLOOD PRESSURES FOL-
LOWING HUMAN SPINAL CORD INJURY CORRELATE
WITH GREATER NEUROLOGICAL RECOVERY
Hawryluk, G.W., Whetstone, W., Saigal, R., Ferguson, A., Talbott, J.,
Bresnahan, J., Pan, J., Dhall, S., Beattie, M., Manley, G.
Brain and Spinal Cord Injury Center, UCSF, San Francisco, USA
Current guidelines for the care of patients with acute spinal cord
injuries (SCIs) recommends maintaining MAP values of 85–90 mmHg
following SCI, however little evidence supports this recommendation.
We sought to better inform the relationship between MAP values and
neurological recovery.
Physiological data was collected every minute (q1) from ICU monitors
on 100 SCI patients over a 6 y period. 73 of these patients had AIS grades
determined by physical examination on admission and at time of hospital
discharge. The proportion of MAP values below threshold were calculated
for values from 120 mmHg to 40 mmHg in 1mmHg increments; these
thresholds were explored within 1 d, 3 d, 5 d and 7 d of ICU admission.
A total of 994,875 q1 minute arterial line blood pressure mea-
surements were recorded for the included patients amidst 1,688,194
minutes of recorded observation. Higher MAP values in the first 7 d
were consistently associated with greater neurological recovery. The
proportion of MAP values below a threshold of 85 – 90 mmHg ro-
bustly distinguished patients achieving a 1-point AIS grade im-
provement from those achieving 2 or 3 points of improvement.
Patients with no AIS grade improvement had a greater proportion of
MAP recordings below 100 mmHg than those who improved one AIS
grade. Number of measures below 85 mmHg were significantly dif-
ferent in each outcome group (p < 0.0001).
This study provides strong evidence supporting a correlation between
MAP values and neurological recovery. It does not, however, demon-
strate a causal relationship. It supports the notion of MAP thresholds in
SCI recovery and the highest MAP values correlated with the greatest
degree of neurological recovery. The results are concordant with cur-
rent guidelines in suggesting that MAP thresholds > 85mmHg may be
appropriate following acute SCI.
Key words
blood pressure, outcome, spinal cord injury
T1-18
THE EFFECTS OF MYELIN RETRACTION AND DETACH-
MENT ON SIGNAL CONDUCTION IN A COMPUTATIONAL
MODEL OF DAMAGED AXONS
Daneshi Kohan, E.1,2, Delva, M.L.1, Sparrey, C.J.1,2
1Simon Fraser University, Surrey, Canada
2ICORD, Vancouver, Canada
Mapping the relationship between injury mechanics, structural damage
and functional outcomes in patients with spinal cord injury is important
for identifying potential treatment targets. Computational models of the
CNS augment animal and in vitro models by providing tools to evaluate
the effects of specific structural changes after injury on function. Mild
stretch injury of axons was shown to induce retraction and detachment of
myelin around the nodes of Ranvier resulting in the exposure of fast
potassium channels in the juxtaparanodal areas and reduction of the
periaxonal resistivity. The aim of this study was to determine the effects
of myelin retraction and detachment on action potential propagation along
axons. A single motor neuron axon (j =10 um) based on the McIntyre’s
model of a mammalian motor nerve (McIntyre 2002) was modeled in
NEURON. Fast potassium channels were implemented in the juxtapar-
anodal areas. To simulate the effect of myelin retraction, a damaged
demyelinated area was inserted between the nodes (0.5 um) and shortened
paranodal areas. The effect of myelin detachment has been simulated by a
reduction in periaxonal resistivity (70 ohm-cm) in the paranodal and
juxtaparanodal areas. Changes in action potential amplitude and con-
duction velocity were measured for isolated changes in nodal length,
periaxonal resistivity, and potassium channel activity and simultaneous
alternation of all injury parameters. Our results show that increasing the
nodal length up to 1.5 um to simulate myelin retraction decreased the
conduction velocity by 15% compared to the intact axons (40m/s) and
induced a small change ( <3%) in action potential amplitude. Reducing
either of paranodal or juxtaparanodal resistivity by 99% reduced con-
duction velocity by 45% and 35% respectively whereas peak action po-
tential changed less than 25%. However, 70% simultaneous reduction in
both paranodal and juxtaparanodal periaxonal resistivity stopped action
potential generation. The post-injury axonal functionality is most affected
by the detachment of myelin in the paranodal and juxtaparanodal regions
when retraction and detachment are modeled simultaneously.
Key words
axonal injury, computational modeling, function, myelin
T1-19
NORBNI DOSE-DEPENDENTLY BLOCKS THE ADVERSE
EFFECTS OF INTRATHECAL MORPHINE ADMINISTRA-
TION FOLLOWING SCI
Aceves, M., Hook, M.A.
Texas A&M Health Science Center & Texas A&M Institute for
Neuroscience, Department of Neuroscience and Experimental
Therapeutics, College Station, United States
Opioids are one of few effective analgesics for the treatment of pain
following spinal cord injury (SCI). Unfortunately, we have shown that
morphine administered in the acute phase of SCI, irrespective of the route
of administration, compromises recovery of locomotor function, in-
creases mortality and pain reactivity, and suppresses weight gain in a
rodent contusion model (Hook et al., 2007, 2009, 2011). These adverse
effects appear to depend on activation of the kappa opioid receptor
(KOR). Selective activation of the KOR, using GR89696, undermined
locomotor recovery and decreased weight gain. In the current study, we
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