Abstracts

Rationale: Cerebral edema commonly occurs after brain injury including status epilepticus (SE), but the acute and long-term neuronal damage caused by cerebral edema and its role in epileptogenesis are unclear. This study aims to elucidate the relationship between SE-induced cerebral edema and post-SE epilepsy.Methods: The lithium-pilocarpine protocol was used to induce SE in adult Sprague-Dawley rats. Rats were pretreated with LiCl (127 mg/kg, i.p.); within 24 h, pilocarpine hydrochloride was administered (50 mg/kg, i.p.) preceded by scopolamine methyl bromide (2 mg/kg, i.p.) 30 min earlier. SE was terminated by phenobarbital (50 mg/kg, i.p.) after 90 min. Two days later, rats were anesthetized and underwent T2-weighted MRI scans for cerebral edema. Rat brain was scanned along the rostral-caudal axis, using a rapid acquisition with relaxation enhancement (RARE) sequence with an in-plane resolution of 100 µm x 100 µm and slice thickness = 500 µm (56 coronal slices with no gap, echo time = 12.5 ms, pulse repetition time = 6300 ms, 2 signal averages with rare-factor = 8). At day 4 after SE, a subset of rats was sacrificed for immunohistochemistry to examine SE-induced neuronal death using Dead End Fluorometric TUNEL system and its complementary cleaved caspase-3 specific immunostaining to identify degenerating neurons after SE. The remaining rats were MRI-scanned again 4-5 weeks after SE for chronic neuronal damage associated with cerebral edema.Results: The majority (~90%) of rats that received Li-pilocarpine injections developed SE and survived. Robust cerebral edema was detected by MRI in all SE-experiencing rats at day 2 or 3 after SE, particularly in the piriform cortex, across most of the cortex (12-14 sections) along the anterior-posterior axis. Immunohistochemistry revealed severe neuronal death in the piriform cortex and to a lesser extent, the hippocampus. Four to five weeks after SE, MRI revealed atrophy in piriform cortex and marked enlargement of the lateral ventricles.Conclusions: Our preliminary data suggest that SE causes consistent and severe cerebral edema, neuronal death and chronic damage in the piriform cortex, a brain area that is important yet under-appreciated in both human epilepsy (Vaughan and Jackson, 2014) and animal models (Loscher and Ebert, 1996). Understanding the roles of cerebral edema in piriform cortex and other brain areas in epileptogenesis may extend our knowledge of the mechanisms of acquired epilepsy and help to develop novel approaches for epilepsy treatment and prevention.