Increased vulnerability of NFH-LacZ transgenic mouse to traumatic brain injury-induced behavioral deficits and cortical damage.
The authors evaluated the neurobehavioral and neuropathologic sequelae after traumatic brain injury (TBI) in transgenic (TG) mice expressing truncated high molecular weight neurofilament (NF) protein fused to beta-galactosidase (NFH-LacZ), which develop Lewy body-like NF-rich inclusions throughout the CNS. TG mice and their wild-type (WT) littermates were subjected to controlled cortical impact brain injury (TG, n = 19; WT, n = 17) or served as uninjured controls (TG, n = 11; WT, n = 11). During a 3-week period, mice were evaluated with an array of neuromotor function tests including neuroscore, beam balance, and both fast and slow acceleration rotarod. Brain-injured WT and TG mice showed significant motor dysfunction until 15 days and 21 days post-injury, respectively (P<.025). Compared with brain-injured WT mice, brain-injured TG mice had significantly greater motor dysfunction as assessed by neuroscore (P<.01) up to and including 15 days post-injury. Similarly, brain-injured TG mice performed significantly worse than brain-injured WT mice on slow acceleration rotarod at 2, 8, and 15 days post-injury (P<.05), and beam balance over 2 weeks post-injury (P<.01). Histopathologic analysis showed significantly greater tissue loss in the injured hemisphere in TG mice at 4 weeks post-injury (P<.01). Together these data show that NFH-LacZ TG mice are more behaviorally and histologically vulnerable to TBI than WT mice, suggesting that the presence of NF-rich inclusions may exacerbate neuromotor dysfunction and cell death after TBI.
Department of Neurosurgery, School of Medicine, University of Pennsylvania, Philadelphia 19104-6316, USA.
M
M
Nakamura
K E
KE
Saatman
J E
JE
Galvin
U
U
Scherbel
R
R
Raghupathi
J Q
JQ
Trojanowski
T K
TK
McIntosh
D000818:Animals; D001522:Behavior, Animal; D001930:Brain Injuries / Q000235:genetics / Q000503:physiopathology*; D002540:Cerebral Cortex / Q000473:pathology / Q000503:physiopathology*; D005786:Gene Expression Regulation; D007763:Lac Operon; D051379:Mice; D008822:Mice, Transgenic; D016900:Neurofilament Proteins / Q000502:physiology*; D011993:Recombinant Fusion Proteins / Q000502:physiology
D016900:Neurofilament Proteins; D011993:Recombinant Fusion Proteins