NNS 2015 Program & Abstract Book

Chronic pain after SCI may present as hyperalgesia, allodynia, and/or

spontaneous pain and is often resistant to conventional pain therapy.

Identifying better interventions to manage SCI-PAIN requires im-

proved understanding of the pathophysiological mechanisms in-

volved. After SCI, a key pathophysiological mechanism appears to be

cell cycle activation (CCA). We have shown previously that central or

systemic early administration of a selective CCA inhibitor reduced

CCA, glial changes, and limited SCI-induced hyperesthesia. Here we

compared the effects of early versus late treatment with pan-CDK

inhibitor flavopiridol on allodynia as well as presence of spontane-

ously face pain. Adult C57BL/6 male mice subjected to moderate SCI

were treated with daily IP injections of flavopiridol (1 mg/kg), be-

ginning 3 h or 5 weeks after injury and continually for 7 days,

mechanical/thermal allodynia as well as mouse grimace scale (MGS)

test, a measure of spontaneous pain, were evaluated. We showed that

the von Frey hair force, thresholds response to thermal stimulation,

and locomotor function were significant improved in early flavopir-

idol-treated mice when compared to vehicle group. MGS based on ear

position, orbital tightening, and nose bulge was transiently increased

at day 1 post-injury for all groups. The mice with SCI showed robust

and extended increases of MGS up to 3 weeks. Early administration of

flavopiridol significantly reduced MGS at week 1 and returned to the

baseline level at week 2. Late flavopiridol injection significantly

limited hyperesthesia at 7 days after treatment with no effects on

locomotion. Thus, our data suggest that cell cycle modulation may

provide an effective therapeutic strategy to improve reduce both hy-

peresthesia and motor dysfunction after SCI. These findings would

also markedly expand the potential therapeutic window for such pain.

Keywords: spinal cord injury, hyperesthesia, mechanical/thermal

stimulation, the mouse grimace scale, neuropathic pain

C6 Poster Session VI - Group C: Electophysiology

C6-01

DELAYED PRIMARY BLAST-INDUCED ELIMINATION OF

LONG-TERM POTENTIATION IN RAT ORGANOTYPIC

HIPPOCAMPAL SLICE CULTURES

Edward Vogel III

, Cameron R. Bass

, David F. Meaney

, Barclay

Morrison III

Columbia University in the City of New York, Department of Bio-

medical Engineering, New York, USA

Duke University, Department of Biomedical Engineering, Durham,

USA

University of Pennsylvania, Department of Biomedical Engineering,

Philadelphia, USA

Blast-induced traumatic brain injury (TBI) is the signature wound of

the conflicts in Iraq and Afghanistan. This study investigated the time-

course of primary blast loading on electrophysiological function

within rat organotypic hippocampal slice cultures. Blast injury was

initiated with a compressed-gas driven shock tube. Electro-

physiological recordings were acquired at either 60 minutes, 1, 2, 4, 6,

or 10 days following injury using 60-channel microelectrode arrays.

Functional recordings were collected following either a sham, mild

(336 kPa/0.84 ms/87 kPa

ms) or moderate injury (424 kPa/2.31 ms/

248 kPa

ms). Long-term potentiation was induced in CA1, via the

Schaffer collateral pathway, using 100 Hz tetanic current stimuli. LTP

induction was calculated as percent potentiation above baseline based

on the last 10 minutes of pre- and post-induction baseline recordings.

We observed that neither blast level reduced LTP at 1 hour post-

injury; however, both blast intensities significantly reduced LTP be-

tween 1 and 6 days post-injury. LTP recovered in mild blast-exposed

cultures at 10 days post-injury, but not in moderate blast exposed

cultures. We conclude that primary blast injury does not eliminate

LTP immediately post-injury, but rather between 1 and 24 hours after

injury. There is potential for natural recovery of LTP following blast,

but only at 10 days following a mild blast exposure. LTP deficits may

be the source of memory loss commonly observed in TBI patients.

Future research will elucidate the cellular mechanisms responsible for

this delayed disruption of LTP following primary blast injury.

Keywords: Blast, TBI, In Vitro, Electrophysiology, Hippocampus

C6-02

EFFECT TBI ON SLEEP AFTER LATERAL FLUID-

PERCUSSION INJURY IN RATS

Pedro Andrade

, Asla Pitkanen

UEF, Department of Neurobiology, Kuopio, Finland

Introduction:

Transitional stage between wakefulness and non-REM

sleep is the period when the brain is most prone for generating epi-

leptic seizures whereas REM sleep is the most antiepileptic state of

the sleep-wake cycle. Our objective was to test a hypothesis that the

occurrence of spike-and-wave discharges (SWDs), present in a sub-

population of rats, affects the sleep architecture after TBI.

Methodology:

TBI was induced with lateral fluid-percussion injury

(FPI) in 12 adult Spraque-Dawley rats. Eleven sham-operated rats

served as controls. Starting at 7 months post-TBI, animals were

continuously video-EEG monitored to assess sleep. A 24-h continuous

EEG recording was divided in 2947 epochs (30 sec each), and scored

according to the recommendations American Academy of Sleep

Medicine (2007) with slight modifications. Sleep pattern was analyzed

separately during lights-on and lights-off periods.

Results:

When all animals with TBI or sham-operation were

compared, we found no differences in S2, S3, REM, or wake stages.

When rats with (SWD

) or without (SWD-) SWDs were analyzed

separately, we found that during lights-off period the TBI-SWD

group (n

9) spent less time in REM sleep than the TBI-SWD- (n

(61%, p

0.02) or the control-SWD

group (n

3)(82%, p

0.03).

Similarly, the control-SWD

group (n

8) showed reduced REM

sleep during lights-off period as compared to control-SWD- group

(74%, p

0.05). The duration of stage II (p

0.05) or stage III

0.05) sleep did not differ between any of the TBI and control

groups. Analysis of hypnograms revealed that the architecture of sleep

was less structured in rats TBI than in controls.

Conclusion:

Our data show that occurrence of SWDs is associated

with reduced REM sleep both in controls and TBI animals during

lights-off period, and the effect is even more pronounced after TBI.

These data suggest that cortico-thalamic activity, driving the SWDs,

modulates sleep architecture during the lights-off period.

Keywords: Sleep, Circadian Rhythm, spike-and-wave discharges,

TBI

C6-03

ELECTROPHYSIOLOGICAL PHENOTYPING OF HUMAN

NEURONS IN SLICES AND DISSOCIATED CULTURE

Alexandra Ulyanova

, Jae-Hee Lee

, Steven Brem

, Timothy Lucas

Donald O’Rourke

, Michael Grovola

, Jinhui Wang

, Youngji Na

Jennifer Singh

, Douglas Smith

, Junhyong Kim

, James Eberwine

Jai-Yoon Sul

, Sean Grady

, John Wolf

1,2

University of Pennsylvania, Neurosurgery, Philadelphia, USA

A-85