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

In models of focal cerebral ischemia, adenoviral gene transfer is often att enuated or delayed versus naive. After controlled cortical impact (CCI)-ind uced traumatic brain injury in mice, CA1 and CA3 hippocampus exhibit delaye d neuronal death by 3 days, with subsequent near complete loss of hippocamp us by 21 days. We hypothesized that adenoviral-mediated expression of the r eporter gene beta -Galactosidase (beta -Gal) in hippocampus would be attenu ated after CCI in mice. C57BL6 mice (n = 16) were subjected to either CCI t o left parietal cortex or sham (burr hole). Adenovirus carrying the beta -G al gene (AdlacZ; 1 x 10(9) plaque-forming units [pfu]/mL) was then injected into left dorsal hippocampus. At 24 or 72 h, beta -Gal expression was quan tified (mU/mg protein). Separate mice (n = 10) were used to study beta -Gal spatial distribution in brain sections. beta -Gal expression in left hippo campus was similar in shams at 24 h (48.4 +/- 4.1) versus 72 h (68.8 +/- 8. 8, not significant). CCI did not reduce beta -Gal expression in left hippoc ampus (68.8 +/- 8.8 versus 88.1 +/- 7.0 at 72 h, sham versus CCI, not signi ficant). In contrast, CCI reduced beta -Gal expression in right (contralate ral) hippocampus versus sham (p < 0.05 at both 24 and 72 h). <beta>-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.