Neurodegeneration, Neuroprotection, and Disease-Oriented NeuroscienceResearch PaperStrategies to defeat ketamine-induced neonatal brain injury
Highlights
▶There is a growing need to develop strategies to prevent anesthesia-induced injury. ▶We describe a number of independent approaches to address therapeutic intervention. ▶Ketamine induced apoptotic injury in P7 rats. ▶NAP, vitamin D3, and low dose ketamine, all attenuated or prevented this injury. ▶Aspirin enhanced the injury.
Section snippets
Treatment groups
All in vivo procedures used in these studies were approved by the Wake Forest University Animal Care and Use Committee and in accordance with NIH guidelines. All efforts were made to reduce the numbers and suffering of animals used. Animals (Sprague–Dawley) were obtained from Harlan (Charlotte, NC, USA). Pups were maintained in the cage with the mother until the day of the experiment (water and food were available ad libitum). For all studies, at P7, pups were divided into roughly equal
Ketamine enhances or represses expression of multiple genes
We have shown elsewhere (Lema Tomé et al., 2006a, Lema Tomé et al., 2006b, Turner et al., 2010) that wholesale changes in gene expression are to be expected following NMDAR blockade. To monitor these changes in a more efficient and comprehensive manner, we turned to the powerful technique of microarray analysis. We compared gene expression in ketamine- or MK801-treated animals with that of vehicle-treated animals. We chose the time point of 8 h because peak induction of the pro-apoptotic enzyme
Discussion
With respect to anesthesia-induced brain injury in neonates, NIH, the FDA, as well as the International Anesthesiology Research Society (IARS) have urged researchers to not only define the scope of the problem but develop therapeutic strategies that target prevention. Thus, whereas past studies from our laboratory have focused on describing NMDAR blockade-induced injury as well as target mechanisms, more recent work has focused on developing ways to prevent this injury. In this article, we have
Acknowledgments
This work was supported by NIH RO1 NS051632, Wake Forest Intramural Research Support, and Mr and Mrs Tab Williams Family Neuroscience Endowment Fund. Animal handling and tissue processing performed by S.G., C.L., and C.P.T. Stereological cell counting and statistical analysis performed by all authors (except L.M. and J.C.). RNA isolation performed by C.L., and microarray procedure and analysis performed by L.M. and J.C. We are also indebted to Lou Craddock for her assistance with the microarray
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