Increased vulnerability of NFH-LacZ transgenic mouse to traumatic brain injury-induced behavioral deficits and cortical damage

Michio Nakamura, Kathryn E. Saatman, James E. Galvin, Uwe Scherbel, Ramesh Raghupathi, John Q. Trojanowski, Tracy K. McIntosh

Research output: Contribution to journalArticlepeer-review

41 Scopus citations


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.

Original languageEnglish
Pages (from-to)762-770
Number of pages9
JournalJournal of Cerebral Blood Flow and Metabolism
Issue number7
StatePublished - 1999


  • Inclusion body
  • Lewy body
  • Neurodegeneration
  • Neurofilament
  • Neuromotor function

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology
  • Cardiology and Cardiovascular Medicine


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