Page 63 - NNS 2014 Program & Abstract Book

cortex(CT) and corpus callosum(CC). After MRI, animals were per-
fused for IHC examinations of neurofilaments(SMI31), myelina-
tion(MBP), microgliosis(IBA1) and astrogliosis(GFAP).
Compared to baseline, glucose drastically decreased 50% at 1DPI
in CT(p < 0.01) and gradually decreased 30% at 8DPI in CC(p < 0.01).
Lactate in CT significantly decreased to the lowest level(* 55%) at
1DPI(p < 0.01), and gradually increased to the baseline level at 8DPI.
The Glx group in CT decreased 30% after injury at 1DPI(p < 0.05) and
remained low at both 3DPI and 8DPI(p < 0.05). Similarly in CC,
lactate and the Glx groups decreased at 1DPI(* 30%, p < 0.05),
reached the lowest at 3DPI(30%, p < 0.01), then slightly increased at
8DPI(p < 0.05). Although the trends of the IHC analysis were not
significant, a gradual decrease of SMI31 and MBP, and increase of
microgliosis and astrogliosis were observed.
Comparable to previous reports, glucose largely decreased after
trauma, and glutamate may regulate glycolysis in astrocytes and in-
fluence lactate release in supporting the increased energy demand in
the traumatized tissue. Different patterns of glutamine, lactate and
glucose interrelations were found between gray and white matter,
indicating that the interrelation patterns may be specific to the tissue
and type of TBI. The early decrease of CEST effects on all metabo-
lites suggests that the water content significantly increased from
edema after inslut. IHC results indicate that the injury was mild to
moderate in a pattern of slightly injured axon and myelin, and a slight
increase of immuno response. These results indicate that the CEST-
MRI asymmetry analysis is sensitive in reflecting the consequence of
mild TBI, even when the convention IHC stainings do not show
significant difference.
Key words
CEST MRI, glucose, glutamate, lactate, non-invasive
A2-19
TSPO-PET IMAGING AFTER TRAUMATIC BRAIN INJURY
IN MICE
Hosomi, S.1,2, Yoshiya, K.1, Watabe, T.3, Yamashita, T.2, Ogura, Y.1,
Shimazu, T.1
1Department of Traumatology and Acute Critical Medicine, Osaka
University Graduate School of Medicine, Suita, Japan
2Department of Molecular Neuroscience, Osaka University Graduate
School of Medicine, Suita, Japan
3Department of Nuclear Medicine and Tracer Kinetics, Osaka Uni-
versity Graduate School of Medicine, Suita, Japan
Positron emission tomography (PET) imaging of the translocator
protein 18 kDa (TSPO) is recognized as a clinical means to detect and
investigate neuroinflammation. It is widely considered that TSPO PET
signal reveals not only reactive microglia but also astrocyte. However,
it is still unclear how to interpret uptake of TSPO PET signals after
traumatic brain injury (TBI) which involved peripheral immune cell
recruitment.
We aimed to determine what types of cells expressed TSPO uptake
after TBI.
Controlled cortical impact (CCI) was induced in the cerebral
hemisphere of adult male C57B6/J mice. Sham and CCI operated
mice were investigated by [18F] PET from 1 day to 9 weeks after
injury. Regions of interest were placed on the injured site of the PET/
CT fused images. Max standardized uptake values (SUV max) in this
area were calculated. Furthermore, the ratio of cells infiltrated into the
injured cortex was analyzed by flow cytometry, and localization of
those cells was also analyzed by Immunohistochemistry.
TSPO uptake started to increase around the injured site after injury,
focused toward the injured core at 1 week after injury and redistributed
around the cavitation of contusion afterword. SUV max indicated a bi-
modal increase at 7 days post injury and 6 weeks post injury. Flowcyto-
metric study showed that Gr-1 + /Ly-6Chigh macrophages increased from
1 day to 3 days post injury and decreased rapidly. Immunohistochemistry
analysis showed TSPO uptake co-localized by reactive microglia.
Our results suggested the first peak of TSPO uptake at 1weeks after
injury showed the phagocytosis of cell debris and the second peak at
6 weeks post injury indicated the glial scar formation. TSPO-PET has
the possibility to be an imaging technique to monitor neuroin-
flammation after TBI.
Key words
astrocyte, microglia, PET, TSPO
A2-20
POST-TBI ALTERATIONS IN FRONTO-LIMBIC MORPHO-
METRY ARE ASSOCIATED WITH DEPRESSION
Failla, M.D.1,2, Myrga, J.M.2, Ricker, J.R.5, Conley, Y.P.3,
Ferrell, R.E.4 , Wagner, A.K.1,2
1Center for Neuroscience, University of Pittsburgh, Pittsburgh, PA,
USA
2Department of Physical Medicine and Rehabilitation, Medicine,
University of Pittsburgh, Pittsburgh, PA
3Health Promotion & Development, Nursing, University of Pitts-
burgh, Pittsburgh, PA
4Department of Human Genetics, Public Health, University of Pitts-
burgh, Pittsburgh, PA
5Department of Rehabilitation Medicine, New York University School
of Medicine, New York, NY
Post-traumatic depression (PTD) is a common neurobehavioral com-
plication following traumatic brain injury (TBI). Studies shows vol-
umetric alterations in fronto-limbic brain regions are associated with
depressive symptomology. This study examined fronto-limbic brain
morphometry in TBI as a possible biomarker of PTD susceptibility,
hypothesizing a reduction in these regions post-TBI. Structural MRI
scans were acquired 1–3 years post-TBI in 40 adults with moderate/
severe TBI and 33 age-matched controls. Regional brain volumes
were calculated using automatic segmentation software (FreeSurfer).
A subset of individuals with TBI (cases, n = 21) were assessed for
depressive symptomology using the Patient Health Questionnaire
(PHQ-9). Mann-Whitney and Spearman correlations were used as
appropriate. Data were corrected for multiple comparisons. Within
cases, volumes in the amygdala (right, p = 0.005; left, p = 0.058) and
hippocampus (bilaterally, p < 0.001) were reduced compared to con-
trols. Correlations between regional volumes also differed among
cases compared to controls. Among cases, left amygdala volume was
positively correlated with left hippocampus (r = 0.42702, p = 0.015)
and left caudal anterior cingulate volume (r = 0.36604, p = 0.0421),
while these correlations were non-significant among controls. How-
ever, bilateral amygdala volumes were less correlated with medial
orbitomedial cortex volumes in cases compared to controls. Interest-
ingly, subjects with PTD showed larger left amygdala volumes
(p = 0.005) compared to those with no depression. We suggest relative
regional atrophy within fronto-limbic circuits following TBI may
result in altered volume correlations. This relative TBI-related fronto-
limbic regional atrophy may represent a possible PTD susceptibility
following TBI. Future studies need to validate these findings in larger
populations, examining how fronto-limbic regional volumes may re-
flect fronto-limbic circuit function and relate to PTD susceptibility.
A-31