Abstracts

Rationale: Optical spectroscopic imaging of intrinsic signal currently offers the best resolution to visualize the spatio-temporal dynamics of perfusion and oximetry signal during neuronal activation. Acutely induced spontaneous epileptiform events in the rat neocortex cause an enormous increase in neuronal excitation and thus an increased metabolic demand. Recent evidence has shown that these increased demands are not adequately met by subsequent increased cerebral blood flow, and that this mismatch results in a transient, yet robust 'epileptic dip'. It is unclear whether chronically induced spontaneous epileptiform events are similarly associated with a transient mismatch in hemodynamics.Methods: We used a focal injection of tetanus toxin (TT) into the adult rat's neocortex to induce chronic epilepsy, which provides a more realistic insight into human epilepsy than acute models. Optical spectroscopic imaging at dual wavelengths was used to measure deoxyhemoglobin (Hbr), oxyhemoglobin (HbO2) and total hemoglobin (Hbt) during spontaneous epileptic events in chronic epileptic animals (n=3; average post-TT injection periods: 7.3±4.16 months). Optical data was collected every 33 msec for 400 seconds per session, and the local field potential (LFP) was recorded simultaneously.Results: Frequent poly-spike type epileptiform events (avg freq: 0.17±0.4 Hz; avg duration: 1.8±1.3 seconds; n=35 events) were observed in all animals under isoflurane anesthesia (~2-3 %). During these poly-spikes, there were small and transient increases in both Hbr (max changes: 0.3±0.2%) and Hbt (max changes: 0.1±0.05%). When the poly-spikes developed into a full-blown seizure (duration ~ 270 seconds), the epileptic dip (increase in Hbr) was prolonged for the entire seizure duration despite a consistent increase in Hbt. The map of Hbr and Hbt reveals that different epileptic events arose from a variety of locations surrounding the injection site, but only a full-blown seizure induced propagation of perfusion and oximetry signals across a large cortical area.Conclusions: This the first report of optical spectroscopic imaging of spontaneous epileptiform events in a chronic TT model of rodent neocortical epilepsy. The findings from this study confirm that the increase in metabolic demand associated with spontaneous epileptiform events is not adequately met by cerebrovascular perfusion, causing a robust tissue ischemia in chronically developed epileptic cortex. In addition, this study suggests that the topographical relationship between poly-spikes and ictal events may be highly variable when there is a permanent change in the neural circuit due to chronic epilepsy.