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T1-03
COMPUTATIONAL MODELING AND VALIDATION OF
BRAIN DEFORMATION IN HUMAN VOLUNTEERS WITH
RELEVANCE TO TRAUMATIC BRAIN INJURY
Shailesh Ganpule
1
, Nitin Daphalapurkar
1
, Andrew Knutsen
2
, Dzung
L. Pham
2
, K.T. Ramesh
1
1
Johns Hopkins University, Hopkins Extreme Materials Institute,
Baltimore, USA
2
The Henry M. Jackson Foundation for the Advancement of Military
Medicine, Radiology and Imaging Sciences, Bethesda, USA
Background:
Knowledge of how brain deforms under physical forces
is critical for understanding mechanics of TBI and for developing
methods of prevention. The objective of this work is to compare
deformation field obtained from the computer simulations with the
experimental measurements of full-field deformation field in human
brains.
Methods:
To this end, we have developed subject-specific com-
putational models of the human brain in human volunteers for which
experimentally measured in vivo brain deformations are also avail-
able. For computational modeling of each subject, we incorporate
information on brain morphology and white matter anisotropy from
acquired T1-weighted and DTI scans, respectively. Computational
simulations are performed using the Material Point Method (MPM).
Loading conditions for the simulations are obtained directly from the
experiments. The experiments involved sub-injurious rotational ac-
celeration of the head about the inferior/superior axis with a peak
angular accelerations of 200–250 rad/s
2
. Dynamic deformation in each
subject was measured using tagged MRI during the accelerations.
Results:
The results of simulations are compared against the ex-
perimentally measured in vivo deformations (displacement and strain
fields). Good agreement was seen between the simulations and the
experiments in terms of predicted deformation patterns. Simulation
results suggest that in these cases the brain deformation is dominated
by shearing modes with peak shearing strains on the order of 4–6% in
various substructures of the brain. It is also observed that global
shearing of a brain tissue leads to local stretching in various sub-
structures of the brain. Subject specific changes in morphology and
anisotropy of brain tissue had an effect on the predicted local defor-
mation pattern, although the global deformation pattern remained
similar.
Conclusion:
By combining state-of-the-art neuroimaging tech-
niques with the computational mechanics based analysis, we elucidate
mechanics of brain deformation in a living human brain.
Keywords: Brain Biomechanics, Computational Model, Tagged
MRI, Validation
T1-04
ADOLESCENT BRAIN INJURY INDUCES CHRONIC MESO-
LIMBIC NEUROINFLAMMATION THAT COINCIDES WITH
ENHANCED ADDICTION-LIKE BEHAVIOR IN MICE
Steven Merkel
1,2
, Christopher Tallarida
2,4
, Roshanak Razmpour
1
,
Evan Lutton
1
, Yuri Persidsky
1,2
, Scott Rawls
2,4
, Servio Ramirez
1–3
1
Temple University School of Medicine, Department of Pathology and
Laboratory Medicine, Philadelphia, USA
2
Temple University School of Medicine, Center for Substance Abuse
Research, Philadelphia, USA
3
Shriners Hospitals, Pediatric Research Center, Philadelphia, USA
4
Temple University School of Medicine, Department of Pharmacol-
ogy, Philadelphia, USA
Substance use disorder is one of the most prevalent clinical psychiatric
diagnoses among traumatic brain injury (TBI) patients. Recent epide-
miological data suggests that 1) patients sustaining adolescent TBIs
experience greater behavioral issues with substance abuse than control
subjects, and 2) a history of TBI appears to be a possible risk factor
contributing to the onset of cocaine use. Notably, virtually no data exists
examining whether the preference for illicit drugs of abuse is affected
by adolescent brain injury. Using the controlled cortical impact model
of TBI coupled with the conditioned place preference (CCP) assay, we
test the hypothesis that brain injury during adolescence exacerbates the
reinforcing properties of cocaine in adulthood by affecting function of
the reward pathway. Six-week old, male C57BL/6 mice sustained a
single impact TBI of varying severity (mild or moderate) to the right
somatosensory cortex. CPP pre-testing began 2 weeks post-TBI, fol-
lowed by 6 days of intraperitoneal cocaine administration (10mg/kg).
The place preference shift was significantly enhanced in all treatment
groups receiving cocaine compared to saline controls; furthermore, a
moderate TBI during adolescence caused a significant increase in the
place preference shift compared to non-surgical cocaine controls. Few
reports have examined the presence and potential of mesolimbic neu-
ropathology following brain injury. Using GFAP and IBA-1 immuno-
fluorescence, we have observed persistent neuroinflammatory responses
in the nucleus accumbens and ventral tegmental area following TBI.
These results suggest that sustaining a moderate TBI during adoles-
cence may augment addiction-like behavior in adulthood possibly re-
lated to mesolimbic neuroinflammation.
Keywords: Controlled Cortical Impact, Conditioned Place Pre-
ference, Cocaine, Mesolimbic Nuclei, Astrocyte, Microglia
T1-05
COGNITIVE DEFICITS DEVELOP 30D AFTER TBI AND ARE
EXAGGERATED BY MICROGLIA-ASSOCIATED RE-
ACTIVITY TO PERIPHERAL IMMUNE CHALLENGE
Megan Muccigrosso
1
, Joni Ford
1
, Chris Burnsides
1
, Ashley Fenn
1
,
Phillip Popovich
1
, Jonathan Lifshitz
2
, Rohan Walker
3
, Daniel
Eiferman
1
, Jonathan Godbout
1
1
The Ohio State University, Neuroscience, Columbus, USA
2
Arizona University, Barrow Neurological Institute, Phoenix, USA
3
The University of Newcastle, Biomedical Sciences, New Castle,
Australia
Traumatic brain injury (TBI) elicits immediate neuroinflammatory
events that contribute to acute cognitive, motor, and behavioral dis-
turbance. Despite resolution of these acute complications, cognitive
impairment can develop after TBI. We have reported that a moderate
midline fluid-percussion injury leads to a population of ‘‘primed’’
(MHCII
+
) microglia that develop and persist 1 month after injury.
Moreover, these primed microglia are hyper-reactive to immune
challenge and this is associated with amplified neuroinflammation and
onset of depressive-like behavior. Therefore, the objective of this
study was to determine the degree to which microglia priming and
immune-reactivity causes cognitive impairment. Using the Barnes
maze, a hippocampal-dependent learning-memory task, we show that
a diffuse TBI interrupts retrograde memory acutely 7d after injury.
Yet 7d after injury there were no acute deficits in anterograde learn-
ing. By 30d after TBI, however, significant anterograde learning im-
pairments developed in TBI mice in the acquisition of the memory
task. Moreover these cognitive deficits at 30d after TBI were exag-
gerated by peripheral immune challenge. For instance, 72h after LPS
injection, TBI-LPS mice had more errors, increased time to find the
escape, and spent less time in the escape quadrant during the probe
trial. These deficits were not associated with alteration in the number
A-3