Abstracts

There is a long-standing hypothesis that status epilepticus (SE) can injure the hippocampus, with subsequent development of temporal lobe epilepsy (TLE). Identification of early pathophysiological changes may provide the framework for the development of neuroprotective and anti-epileptogenic strategies that ultimately reduce the incidence of TLE. MR imaging of patients has shown elevated T[sub]2[/sub] relaxation times in the hippocampus 2 days after SE but no differences from controls by 5 days. In addition, in patients following SE, an initial regional decrease in cerebral blood flow (CBF) followed by a subsequent increase has been reported. The aim of this study was to investigate the relationship between T[sub]2[/sub] relaxation times and CBF in the lithium-pilocarpine rat model of SE using MRI. Ten adult Sprague-Dawley rats were administered lithium chloride (3mEq/kg) intraperitoneally (i.p.) 18 to 20h prior to either pilocarpine (30mg/kg) (n=6) or saline (n=4). Methylscopolamine i.p. (1mg/kg) was given to reduce mortality. Diazepam (10mg/kg) was administered i.p. 90 min after the onset of SE. Imaging was performed before injections and immediately (day 0), 1 day and 2 days after SE. Animals were anaesthetised with 3% isoflurane and maintained on 1.5% isoflurane with 60/40% N[sub]2[/sub]O/O[sub]2[/sub].Coronal images were obtained approximately 3.3mm from bregma on a 2.35T horizontal bore SMIS system. 128 x 64pixels, 2mm slice thickness[italic] T[sub]2[/sub][/italic]: MASAGE-IEPI, FOV 40 x 40mm, 16 averages. [italic]Continuous Arterial Spin Labeling:[/italic] 88 averages and T1 fits using 8 different TI times with 22 averages. Regions were analysed in the hippocampus (HP), somatosensory cortex (SC), and the entorhinal and piriform cortices (EPC). No noticeable changes were observed in any of the saline-injected animals for CBF or T[sub]2[/sub] for any time points. In the pilocarpine animals, CBF in the SC decreased immediately after SE; by day 1 a considerable increase in CBF was observed, but CBF had returned to normal by day 2. In the HP, CBF increased on day 1 and remained high on day 2. No changes in CBF were observed on days 0 or 1 in the EPC, but by day 2 CBF was higher than normal.
No T[sub]2[/sub] changes were observed in the SC throughout the study. In the HP T[sub]2[/sub] increased only on day 2. On day 0, T[sub]2[/sub] in the EPC remained normal; however by day 1 a marked increase in T[sub]2[/sub] was observed and T[sub]2 [/sub]remained high on day 2. In conclusion, we have observed time-dependent regional changes in CBF following SE. Interestingly, CBF increases occurred prior to the T[sub]2[/sub] changes in the HC, an area known to present with pathological changes in a model of SE. Future studies are necessary to assess whether this is an epiphenomenon of the tissue damage or an underlying pathological mechanism. (Supported by the Epilepsy Research Foundation and the Wellcome Trust.)