Abstracts

Rationale: Epileptic events elicit an increase in neuronal metabolism and an increase in cerebral blood flow (CBF), bringing oxygenated hemoglobin to the activated neurons. Whether the systemic oxygen supply and blood pressure adequately meet metabolic demand in the seizure is unknown. Methods: We induced acute focal seizures in the rat neocortex by injection of 4-aminopyridine (4-AP, 15mM, 0.5 μl). The local field potential was recorded to identify the ictal discharge. The partial pressure of tissue oxygen (pO2) was measured with one Clark-style polarographic oxygen microelectrode located in the focus. Optical spectroscopic imaging was used to measure deoxyhemoglobin (Hbr), oxyhemoglobin (HbO2) and total hemoglobin (Hbt). The mean arterial blood pressure (MABP) and arterial oxygen saturation (SpO2) were also continuously recorded. Hypotension was induced by intravenous infusion of sodium nitroprusside and hypoxia was induced by reducing the oxygen concentration of inhaled isoflurane gas. Results: The duration of ictal discharge ranged from 10 to 150 sec (n=6 rats). The spontaneous ictal event induced an initial dip in oxygenation signal preceding the positive blood oxygenation-level dependent (BOLD) response. Sodium nitroprusside produced a 30~50% reduction in MABP. The duration of initial dip was enhanced from 3.7± 1.7 to 6.5± 1.4 sec during low arterial blood pressure conditions. Hypoxia increased the amplitude of initial dip from -30.8± 7.6 % to -46.3± 14.1 % and reduced the amplitude of positive BOLD signal from 162.8± 15.4 % to 121.7± 16.2 % in tissue oxygenation. The optical spectroscopic analysis also showed the hemoglobin oxygenation responses correlated with the pO2 changes under the condition of hypoxia and hypotension. Conclusions: These results demonstrated that epileptic changes in local oxygenation during ictal events were associated with the systemic supply of blood and oxygen. This suggests that consideration of global vascular condition is critical to analyzing the data of activity-related intrinsic signals from functional neuroimaging methods, including fMRI and intrinsic optical imaging.