The Effect of Caffeine on the Neurobehavioral and Neuropathological Outcome of the Newborn Rat

Omar SD Abu-Sa'da
Caffeine is used for the treatment of apnea of prematurity. The objective of this study was to determine the long term neuropathological and neurobehavioral effects of caffeine on the immature rat brain. Newborn rats were injected with either caffeine, or normal saline from postnatal days 3 to 7, equivalent to the human premature infant of 28-36 weeks. Behavioral tests revealed no abnormality in caffeine treated animals compared to controls. Fluro-Jade B stain of P4 rat brains showed that
more » ... s showed that caffeine caused significant neuronal cell death in some areas of the brain, compared to controls, but this alteration was transient and not present at P8. Anti-NeuN stain at P21 showed significant neuronal cell loss in CA1 and hypothalamus regions in the caffeine group, but not at P160. Anti-Neurofilament M stain at P8, P21 and P160 showed no differences between the control and caffeine groups. We conclude that use of caffeine has no significant effect on the behavioral tests measured in our newborn rat pups. While caffeine caused neuronal cell death at P4, and neuronal cell loss in CA1 and hypothalamus regions at P21, there was no long-lasting effect on neuropathological outcome. However, given these latter findings, the use of caffeine in the premature infant must still be done with caution. model, a caring mentor and a truly wise supervisor. My special appreciation goes to Dr. Po-Yin Cheung for being a co-supervisor, for supervising me during the course "Directed Reading in Clinical Medicine", and for his continuous support and advice. I would also like to thank Dr. Gregory D. Funk for being a member of the supervising committee and for many varied ways of demonstrating support and advice. My thanks go also to Arlene Figley for her excellent administrative help and to Dr. Richard Schulz for his chairing the examining committee.
doi:10.7939/r3hm8r fatcat:qwcfb7q5gzfqlkxxf4og473klq