post-injury/anesthesia using the Barnes maze. ... Tampa, Florida; 3The Open University, Milton Keynes, UK; 4 Litwin-Zucker, Center for Research in Alzheimer's ...
T10
Repetitive mild traumatic brain injury produces persistent memory deficits accompanied by chronic histological changes Benoit Mouzon1,2,3, Corbin Bachmeier1,3, Christopher Acker4, Austin Ferro1, Gogce Crynen1,3, Joseph Olubunmi1, Peter Davies4, Michael Mullan1,2,3, William Stewart5, Fiona Crawford1,2,3 Institute, Sarasota, Florida; 2James A. Haley Veterans’ Hospital, Tampa, Florida; 3The Open University, Milton Keynes, UK; 4 Litwin-Zucker, Center for Research in Alzheimer’s Disease, Feinstein Institute for Medical Research, Manhasset, New York; 5Dept. Neuropathology, Southern General Hospital and University of Glasgow, UK.
s-mTBI
24 Months
r-sham
s-sham
r-mTBI
Epitope aa 66-81 GFAP Iba-1 aa 150-190 pS202 pS396/404 pT231
Type Mouse mAb Polyclonal Rabbit Polyclonal Goat Mouse mAb Mouse mAb Mouse mAb Mouse mAb
Source Millipore Millipore Dako Dr.P.Davies Dr.P.Davies Dr.P.Davies Dr.P.Davies
12 Months s-mTBI
24 Months
r-sham
r-mTBI
800
Soluble-PHF1
600 400 200 0 6 Months s-sham
12 Months s-mTBI
r-sham
Soluble-RZ3
300 250 200 150
3
4
1
2
3
4
5
6
1
2
3
4
5
6
1
2
3
4
5
6
Of note, it is interesting to see that while the performance of the singly injured mice was similar at the 6 and 12 month timepoints in term of distance travelled, the effect of a single injury was more pronounced at 18 and 24 months post injury
5
6
1
2
3
4
5
6
1
2
3
4
5
6
1
2
3
4
5
6
1
2
3
4
5
6
r-mTBI
C
*
20
*
*
15
These behavioral impairments occur in the absence of tau or Aβ accumulation, but coincide with an increased gliosis ( including astrocytes, microglia) and axonal injury.
10 5 0
s-sham r-sham s-mTBI r-mTBI s-sham r-sham s-mTBI r-mTBI
s-sham r-sham s-mTBI r-mTBI
mTBI induces persisting neuroinflammation in the corpus callosum 6 Months (n=5)
Acute (n=6)
s-sham r-sham
s-mTBI
r-mTBI
mTBI is associated with ongoing axonal degeneration in the corpus callosum
12 Months (n=4)
6 Months
Acute
mTBI induces persisting astrogliosis in the corpus callosum
12 Months
Acute
12 Months
6 Months
50µm
r-mTBI
s-sham
12 Months
50µm
s-mTBI
24 Months
r-sham
r-mTBI
ELISA Aβ40
9 8 7 6 5 4 3 2 1 0
r-sham 6 month
s-mTBI
r-mTBI
12 month
No change in soluble cortical Aβ40 was observed between injured or sham animals at either 6 or 12 months post injury. (n=4/group)
14
APP *
18
***
0
12 10
*** ***
8
24h 6 Months
6
12 Months
4
**
2 0
s-sham
s-mTBI
r-sham
r-mTBI
Estimation of area of staining of the microglial marker Iba1 in the corpus callosum revealed a markedly increased expression at 6 & 12 months post r-mTBI when compared to their sham group. A moderate increase of reactive microgliosis was observed after single mTBI.* indicates significance when compared to their respective sham within the same time point. (*p
