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Abstract
A previous study showed that hippocampal BDNF mRNA decreased in 17 day old (D17) rats, relative to agematched naive rats, at day 1, 3, 7 and 14 after sham surgery in a traumatic brain injury model. The anesthetic isoflurane activates GABA and inhibits NMDA receptor currents, both of which are known to decrease Brain-Derived Neurotrophic Factor (BDNF) mRNA in rat hippocampi. Hippocampal BDNF is necessary for normal cognitive function. Effects of isoflurane alone on hippocampal BDNF are not known. We hypothesized that, in D17 rat pups, isoflurane would decrease hippocampal mRNA/protein levels of BDNF and Synapsin I (a downstream target of BDNF important for cognitive function) and impair performance on the Novel Object Recognition Test (NOR). ISOF BDNF and Synapsin I mRNA decreased relative to Naive at day 1 and 8 after exposure, but not at day 14. Isoflurane exposure did not decrease hippocampal protein levels of BDNF or Synapsin I and did not impair NOR performance. In contrast to the neonatal rat pup, anesthetic exposure did not impair cognitive function. We speculate that adverse effects of anesthetics on rat pup cognitive function and BDNF expression are highly dependent on age at exposure.
Highlights
Sham surgery for traumatic brain injury decreased hippocampal Brain Derived Neurotrophic Factor (BDNF) mRNA in 17 day old (D17) male rats, relative to age and gender-matched Naïves, at days 1, 3, 7 and 14 after sham surgery [1]
Hippocampus-dependent learning was associated with selective induction of hippocampal BDNF mRNA [4] while inhibition of BDNF expression impaired learning and memory in rodents [5,6]
We have previously demonstrated that Sham rats maintain normal oxygenation and ventilation during isoflurane exposure [21]
Summary
Sham surgery for traumatic brain injury decreased hippocampal Brain Derived Neurotrophic Factor (BDNF) mRNA in 17 day old (D17) male rats, relative to age and gender-matched Naïves, at days 1, 3, 7 and 14 after sham surgery [1]. The effects of isoflurane alone on hippocampal BDNF expression are not known. Given the importance of BDNF in normal learning and memory, and the growing concern that anesthetic exposure during brain development may adversely affect cognitive function, we asked whether isoflurane exposure alone could decrease hippocampal BDNF expression and impair cognitive function in the D17 rat. Hippocampus-dependent learning was associated with selective induction of hippocampal BDNF mRNA [4] while inhibition of BDNF expression impaired learning and memory in rodents [5,6]. Interference with BDNF action impairs normal learning and memory, in part by disrupting synaptic plasticity [10,11]
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