Page 81 - NNS 2014 Program & Abstract Book

B1-14
IMPAIRED NEUROGENESIS IN A RAT MODEL OF TRAU-
MATIC BRAIN INJURY
Micci, M.A., Boone, D.R., Porter, R., Yusuf, C., Bishop, E.,
Hellmich, H., Prough, D.S.
UTMB, Department of Anesthesiology, Galveston, USA
Following traumatic brain injury (TBI), incomplete replacement of lost
neurons by endogenous cells in the dentate gyrus (DG) of the hippo-
campus, summed to ongoing neurodegeneration, results in a range of
cognitive dysfunctions that significantly affect the quality of life for post-
traumatic brain injury survivors. The aim of this work was to study the
process of neurogenesis in the rat hippocampus following moderate TBI.
We used adult male Sprague-Dawley rats and the fluid percussion
injury model of TBI. Laser capture microdissected samples collected
from the DG were analyzed using the ‘‘Neurogensis RT2 Profiler PCR
array kit (Qiagen). Further analysis of the DG was performed by
immunofluoresence using specific antibodies against neuronal pro-
genitor cells and granule neurons.
Gene expression analysis showed that 2 weeks following moderate
TBI, the expression of several genes known to play a role in neuronal
differentiation, migration and survival was significantly reduced as
compared to naı¨ve rats. At the same time, we found a significant increase
in the expression of both the ligand for the NOTCH receptor, DLL1, and
the transcription factor STAT3, both known to be involved in promoting
gliogenesis while suppressing neurogenesis. Further analysis of rat brain
sections showed that the number of neuronal progenitor cells expressing
DCX was significantly increased after TBI in both the ipsilateral and
controlateral sites while the number of cells expressing both DCX and
the mature neuronal marker NeuN was significantly reduced.
Our data show that although an increase of neural progenitor cells
in the DG is observed after TBI, the maturation and integration of
newly formed neurons is significantly reduced. Moreover, the increase
in the expression of DLL1 and STAT3 in the SGZ strongly suggests
that the suppression of neurogenesis is accompanied by a concurrent
increase in gliogenesis. Underrstanding the mechanisms underlying
impaired neurogenesis after TBI will aid the development of novel
therapeutic interventions for the treatment of TBI survivors.
Key words
gene expression, hippocampus, neurogenesis, TBI
B1-15
ENVIRONMENTAL ENRICHMENT RESTORES COGNITIVE
PERFORMANCE IN AN ATTENTIONAL SET-SHIFTING
TEST AFTER TRAUMATIC BRAIN INJURY
Bondi, C.O.1, Cheng, J.P.1, Tennant, H.M.1, Lajud, N.2, Monaco,
C.M.1, Leary, J.B.1, Kline, A.E.1
1Physical Medicine and Rehabilitation, Safar Center for Resuscitation
Research, Center for Neuroscience, University of Pittsburgh, Pitts-
burgh, USA
2Laboratorio de Neuroendocrinologia, CIBIMI-IMSS, Morelia, Mexico
Cognitive impairment associated with prefrontal cortical dysfunction
is a major component of disability in traumatic brain injury (TBI)
survivors. Specifically, deficits in executive function and behavioral
flexibility are present across all injury severities. While impairments
in spatial learning have been extensively reported, experimental
models of TBI investigating more complex cognitive disabilities are
relatively scarce. We have begun to employ the attentional set-shifting
test (AST), a complex cognitive paradigm analogous to the Wisconsin
Card Sorting Test, which is used to measure strategy-switching defi-
cits in patients with frontal lobe damage. Previously, we demonstrated
that a controlled cortical impact (CCI) injury (2.8 mm cortical de-
formation at 4 m/s) produced significant impairments in executive
function and cognitive flexibility in the AST (Bondi et al., 2014,
J Neurotrauma). The current study evaluated whether environmental
enrichment (EE), a preclinical model of neurorehabilitation, would
restore cognitive performance post-injury. Thirty-one isoflurane-an-
esthetized male rats received a CCI or sham injury and then were
randomly assigned to TBI and sham groups that were further divided
into EE and standard housing (n = 6-10/group). When tested at 4
weeks post-surgery, TBI impaired extradimensional set-shifting and
stimulus reversal learning and increased total response errors and set
loss errors (i.e., after 50% or more of the contingency rule has been
achieved) (p < 0.05), which replicated previous findings from our
laboratory. Moreover, EE exposure significantly attenuated the det-
rimental effects of TBI on cognitive performance in the AST, sug-
gesting that EE may be a viable preclinical model of cognitive
rehabilitation (p < 0.05). These novel findings demonstrate that exec-
utive function and behavioral flexibility deficits in our CCI model are
sensitive to the beneficial effects of EE. Ongoing studies are evalu-
ating pharmacological and cognitive rehabilitation therapies as a
clinically relevant combinational paradigm, as well as elucidating
mechanisms underlying the neuropsychological deficits.
Key words
attentional set-shifting, brain trauma, controlled cortical impact, en-
vironmental enrichment, functional recovery, pharmacotherapies
B1-16
LONGITUDINAL RECOVERY OF REACTION TIME IN
ACUTE AND CHRONIC CONCUSSION PATIENTS
Zeiger, M., Fischer, J., Choe, M., McArthur, D., Yudovin, S., Giza, C.
University of California Los Angeles, Brain Injury Research Center,
Los Angeles, US
Clinical reaction time (RT) is a valuable tool in a multifaceted sports
concussion assessment battery. Eckner et al have shown that assess-
ment of simple reaction time utilizing the RTclin drop-stick is a re-
liable clinical test with high specificity and sensitivity to the acute
effects of concussion. Previous studies have demonstrated that RTclin
is effective in distinguishing concussive effects when compared to
baseline data. This study aimed to examine the use of RTclin in the
early (£ 30 days) and late (> 30 days) post-injury time periods in the
absence of baseline values. Furthermore, we sought to determine
whether recovery of function differed between groups.
A group of 53 concussed patients (30 early, 23 late) were evaluated
at UCLA Sports-Concussion clinic. RTclin scores were recorded at
the initial clinic visit and at one clinical follow-up for each patient.
Mean RTclin scores were calculated as an average fall time prior to
catch for eight trials with an 80 cm measuring stick.
Using Welch two sample t-test (p = 0.05) and a Yuen robust analysis
(p = 0.05), reaction times of the entire group significantly improved be-
tween visits, from 243.91 ms (29.15 cm) to 230.53 ms (26.04 cm). Linear
mixed effects modeling shows statistically significant effects due to clinic
visit (initial vs follow-up), post-injury group (late vs early), days since
injury, and their interactions. Further, multimodal inference places the
highest emphasis on clinic visit, group, and group by visit interaction.
RTclin improvements were observed from initial visit to follow-up
regardless of time since injury, and in both early and late patients.
However, patients improved more if seen during the early post-injury
period, and seen closer to date of injury. These results suggest RTclin
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