Abstracts

The susceptibility to damage from status epilepticus (SE) varies by brain region, and is greatest in the hippocampus. Two hypotheses compete to explain the mechanism of hippocampal injury following SE, namely apoptosis vs. metabolic cell death. To date, studies of hippocampal and cortical oxygen utilization have relied on invasive single point measurements. The availability of non-invasive magnetic resonance BOLD ([apos]blood oxygenation level detection) imaging allows simultaneous measurement of oxygen utilization in a large cross sectional area encompassing subregions in the hippocampus and cortex. We studied hippocampal and neocortical oxygenation and perfusion using BOLD imaging methods in anesthetized rats to measure regional variation of oxygenation in cortex and hippocampus during SE.
Adult Sprague-Dawley rats were anesthetized with urethane, intubated and mechanically ventilated for surgery to implant EEG electrodes, two intraperitoneal (IP) catheters and one intraarterial blood pressure (BP) catheter. In some cases, supplementary isoflurane anesthesia was also used. EEG recording contacts consisted of two ~3mm diameter region of thinned skull on either side of the midline anterior to bregma that were filled with conductive epoxy connected to silver wire leads. Rats were then placed in a 9.4T magnet with continuous monitoring of rectal temperature, BP, and EEG. Rats were next paralyzed with IP pancuronium and underwent baseline anatomic (T1) and BOLD imaging. Status epilepticus was induced by IP kainic acid. BOLD imaging centered on the dorsal hippocampus and overlying cortex was performed with continuous recording of EEG and electrographic seizures.
Variability in depth of anesthesia significantly affected the robustness of electrographic seizures and BOLD measurements. Electrographic seizures were obtained in some rats but not others, and ongoing seizures sometimes resulted in hemodynamic changes that could affect BOLD measurements. Preliminary BOLD data indicated that during status epilepticus venous oxygen levels increase or remain constant in the cortex and decline in the hippocampus. These results indicate a relative hypoxia in the hippocampus reflecting greater oxygen extraction in the hippocampus compared to cortex. Analysis of cortical and hippocampal subregions, and consistency of results across animals is ongoing.
We have evidence that oxygen extraction is greater in hippocampus than in neocortical regions, presumably because of markedly increased oxygen utilization in this region. We hypothesize that despite adequacy of circulation and ventilation, oxygen delivery to the hippocampus, in contrast to the neocortex, may be inadequate and increases the risk of metabolic or necrotic hippocampal damage. Additional studies evaluating regional perfusion and correlation with damage will help determine if metabolic insufficiency contributes to hippocampal damage.
[Supported by: NINDS K08-NS41340 (FAL), Heffer Family Medical Foundation (FAL)]