Allopregnanolone and progesterone decrease cell death and cognitive deficits after a contusion of the rat pre-frontal cortex
Section snippets
Animals
A total of 48 adult male Sprague-Dawley rats weighing approximately 280–350 g served as subjects. All procedures involving animals conformed to guidelines set forth in the “Guide for the Care and Use of Laboratory Animals” (National Academy of Sciences, 1996) and were approved by the Emory University Institutional Animal Care and Use Committee (IACUC of Emory University protocol 101–99). Approved protocols meeting NIH guidelines require that investigators take all necessary steps to minimize
Neurosteroid effect on caspase-3 activity at the lesion site
Twenty-four hours after injury, logarithm transfor-mation of caspase-3 activity data showed a significant difference among groups (F(5,35)=3.583, P<0.05) and injured rats given vehicle or ALLOP (4 mg/kg) were the only ones to show significantly higher caspase-3 activity compared with shams (P<0.05; Table 1).
Neurosteroid effect on DNA fragmentation
One day after the injury, post hoc tests failed to show a significant difference between groups (F(5,17)=2.452, P=0.094). No significant difference between shams and lesion rats given
Discussion
These results suggest, in general, that ALLOP and PROG produce long-term memory improvements after a bilateral injury to the pre-frontal cortex in rats. In addition, animals treated with either neurosteroid at 24 h post-injury showed a decrease of caspase-3 activity, and at 19 days after the injury, a decrease of cell death in the MDN of the thalamus, a region distal to the lesion site. Generally, rats given ALLOP (8 mg/kg) were similar in performance to their sham-operated counterparts. The
Acknowledgements
This work was supported by NIH grants 1 R01 NS40825, 1 R01 NS38664, and a gift from GeneralCologneRe.
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