Chronic cerebrovascular abnormalities in a mouse model of repetitive mild traumatic brain injury.
To investigate the status of the cerebrovasculature following repetitive mild traumatic brain injury (r-mTBI).



TBI is a risk factor for development of various neurodegenerative disorders. A common feature of neurodegenerative disease is cerebrovascular dysfunction which includes alterations in cerebral blood flow (CBF). TBI can result in transient reductions in CBF, with severe injuries often accompanied by varying degrees of vascular pathology post-mortem. However, at this stage, few studies have investigated the cerebrovasculature at chronic time points following repetitive mild brain trauma.



r-mTBI was delivered to wild-type mice (12 months old) twice per week for 3 months and tested for spatial memory deficits (Barnes Maze task) at 1 and 6 months post-injury. At 7 months post-injury CBF was assessed via Laser Doppler Imaging and, following euthanasia, the brain was probed for markers of cerebrovascular dysfunction and inflammation.



Memory impairment was identified at 1 month post-injury and persisted as late as 6 months post-injury. Furthermore, significant immunopathological insult, reductions in global CBF and down-regulation of cerebrovascular-associated markers were observed.



These results demonstrate impaired cognitive behaviour alongside chronic cerebrovascular dysfunction in a mouse model of repetitive mild brain trauma.
a The Roskamp Institute , Sarasota , FL , USA.|b The Open University , Department of Life Sciences , Milton Keynes , UK.|c James A. Haley Veteran's Administration Center , Tampa , FL , USA.
Cillian E
CE
Lynch
a The Roskamp Institute , Sarasota , FL , USA.|b The Open University , Department of Life Sciences , Milton Keynes , UK.|c James A. Haley Veteran's Administration Center , Tampa , FL , USA.
Gogce
G
Crynen
a The Roskamp Institute , Sarasota , FL , USA.|b The Open University , Department of Life Sciences , Milton Keynes , UK.|c James A. Haley Veteran's Administration Center , Tampa , FL , USA.
Scott
S
Ferguson
a The Roskamp Institute , Sarasota , FL , USA.|b The Open University , Department of Life Sciences , Milton Keynes , UK.|c James A. Haley Veteran's Administration Center , Tampa , FL , USA.
Benoit
B
Mouzon
a The Roskamp Institute , Sarasota , FL , USA.|b The Open University , Department of Life Sciences , Milton Keynes , UK.|c James A. Haley Veteran's Administration Center , Tampa , FL , USA.
Daniel
D
Paris
a The Roskamp Institute , Sarasota , FL , USA.|b The Open University , Department of Life Sciences , Milton Keynes , UK.|c James A. Haley Veteran's Administration Center , Tampa , FL , USA.
Joseph
J
Ojo
a The Roskamp Institute , Sarasota , FL , USA.
Paige
P
Leary
a The Roskamp Institute , Sarasota , FL , USA.|b The Open University , Department of Life Sciences , Milton Keynes , UK.|c James A. Haley Veteran's Administration Center , Tampa , FL , USA.
Fiona
F
Crawford
a The Roskamp Institute , Sarasota , FL , USA.|b The Open University , Department of Life Sciences , Milton Keynes , UK.|c James A. Haley Veteran's Administration Center , Tampa , FL , USA.
Corbin
C
Bachmeier
D000199:Actins / Q000378:metabolism; D000818:Animals; D001812:Blood-Brain Barrier / Q000503:physiopathology; D000070642:Brain Injuries, Traumatic / Q000150:complications*; D002135:Calcium-Binding Proteins / Q000378:metabolism; D002560:Cerebrovascular Circulation / Q000502:physiology*; D002561:Cerebrovascular Disorders / Q000209:etiology*; D003072:Cognition Disorders / Q000209:etiology; D004195:Disease Models, Animal; D015536:Down-Regulation / Q000502:physiology*; D005260:Female; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D007797:Laminin / Q000378:metabolism; D008297:Male; D018782:Maze Learning; D008569:Memory Disorders / Q000209:etiology; D051379:Mice; D008810:Mice, Inbred C57BL; D008840:Microfilament Proteins / Q000378:metabolism; D020797:Receptor, Platelet-Derived Growth Factor beta / Q000378:metabolism; D064568:S100 Calcium Binding Protein beta Subunit / Q000097:blood
C558396:Acta2 protein, mouse; D000199:Actins; C491049:Aif1 protein, mouse; D002135:Calcium-Binding Proteins; D005904:Glial Fibrillary Acidic Protein; D007797:Laminin; D008840:Microfilament Proteins; D064568:S100 Calcium Binding Protein beta Subunit; D020797:Receptor, Platelet-Derived Growth Factor beta
Repetitive mild traumatic brain injury; cerebrovascular