Adenovirus-mediated transfer and expression of β-Gal in injured hippocampus after traumatic brain injury in mice

P. M. Kochanek*, K. L. Janesko, L. W. Jenkins, H. Q. Yan, M. R. Kibbe, P. Robichaud, A. C. Wooditch, R. S B Clark, C. E. Dixon, D. W. Marion, T. R. Billiar

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

6 Scopus citations

Abstract

In models of focal cerebral ischemia, adenoviral gene transfer is often attenuated or delayed versus naive. After controlled cortical impact (CCI)-induced traumatic brain injury in mice, CA1 and CA3 hippocampus exhibit delayed neuronal death by 3 days, with subsequent near complete loss of hippocampus by 21 days. We hypothesized that adenoviral-mediated expression of the reporter gene β-Galactosidase (β-Gal) in hippocampus would be attenuated after CCI in mice. C57BL6 mice (n = 16) were subjected to either CCI to left parietal cortex or sham (burr hole). Adenovirus carrying the β-Gal gene (AdlacZ; 1 x 10)9 plaque-forming units [pfu]/mL) was then injected into left dorsal hippocampus. At 24 or 72 h, β-Gal expression was quantified (mU/mg protein). Separate mice (n = 10) were used to study β-Gal spatial distribution in brain sections. β-Gal expression in left hippocampus was similar in shams at 24 h (48.4 ± 4.1) versus 72 h (68.8 ± 8.8, not significant). CCI did not reduce β-Gal expression in left hippocampus (68.8 ± 8.8 versus 88.1 ± 7.0 at 72 h, sham versus CCI, not significant). In contrast, CCI reduced β-Gal expression in right (contralateral) hippocampus versus sham (p < 0.05 at both 24 and 72 h). β-Gal was seen in many cell types in ipsilateral hippocampus, including CA3 neurons. Despite eventual loss of ipsilateral hippocampus, adenovirus-mediated gene transfer was surprisingly robust early after CCI providing an opportunity to test novel genes targeting delayed hippocampal neuronal death.

Original languageEnglish (US)
Pages (from-to)73-82
Number of pages10
JournalJournal of neurotrauma
Volume18
Issue number1
DOIs
StatePublished - Jan 1 2001

Keywords

  • Controlled cortical impact
  • Gene therapy
  • Head injury
  • Vector

ASJC Scopus subject areas

  • Clinical Neurology

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