Magnetic Resonance Imaging in the Study of the Lithium–Pilocarpine Model of Temporal Lobe Epilepsy in Adult Rats

Abstract

Summary:Purpose: In temporal lobe epilepsy, it remains to be clarified whether hippocampal sclerosis is the cause or the consequence of epilepsy. We studied the temporal evolution of the lesions in the lithium-pilocarpine model of epilepsy in the rat with magnetic resonance imaging (MRI) to determine the progressive morphologic changes occurring before the appearance of chronic epilepsy.Methods: MRI was performed on an MR scanner operating at 4.7 T. We followed the evolution of lesions using T 2 -and T 1 -weighted sequences before and after the injection of gadolinium from 2 h to 9 weeks.Results: At 2 h after status epilepticus (SE), a blood-brain barrier breakdown could be observed only in the thalamus; it had disappeared by 6 h. At 24 h after SE, edema was present in the amygdala and the piriform and entorhinal cortices together with extensive neuronal loss; it disappeared progressively over a 5-day period. During the chronic phase, a cortical signal reappeared in all animals; this signal corresponded to gliosis, which appeared on glial fibrillary acidic protein (GFAP) immunohistochemically stained sections as hypertrophic astrocytes with thickened processes. In the hippocampus, the correlation between histopathology and T 2 -weighted signal underscored the progressive constitution of atrophy and sclerosis, starting 2 days after SE.Conclusions: These data show the reactivity of the cortex that characterizes the initial step leading to the development of epilepsy and the late gliosis that could result from the spontaneous seizures. Moreover, it appears that hippocampal sclerosis progressively worsened and could be both the cause and the consequence of epileptic activity.

Neuroimaging the Epileptogenic Process

“…Consistent with chemically-induced SE models, SE induced by electrical stimulation of the rat amygdala resulted in increased T 2 values in the amygdala beginning 2 days after SE [21], and increased T2W signal intensity in the hippocampus 2 weeks after kindling had ceased [22]. Taken together, these findings suggest temporal complexities in T 2 signal changes occurring in post-SE TLE models, likely representing the evolving pathophysiological processes in epileptogenesis [16,17] that must be clarified and considered when translating the use of T 2 -based biomarkers to the clinical setting.…”

“…These acute changes typically return to baseline within 48-72 h [15,20], and have been reported to predict the development of epilepsy at 4 months after SE [15]. However, in contrast to these findings, other studies have reported a global decrease in T 2 values in the acute stages after SE [17], and evidence of T2W hyperintensity for up to 9 weeks after SE [16]. Consistent with chemically-induced SE models, SE induced by electrical stimulation of the rat amygdala resulted in increased T 2 values in the amygdala beginning 2 days after SE [21], and increased T2W signal intensity in the hippocampus 2 weeks after kindling had ceased [22].…”

“…T 2 signal changes on MRI have been consistently reported at various phases of the epileptogenic process in numerous animal models, with the common underlying pathological changes being edema, gliosis, and cell loss (see Table 1) [15][16][17][18]. In chemoconvulsant SE models, increased T 2 values and T2W hyperintensity have been reported in several brain regions, including the cortex, hippocampus, thalamus, amygdala [19,20], and piriform and entorhinal cortices [15], beginning as early as 2 h after SE [20].…”

Metabolism is Normal in Astrocytes in Chronically Epileptic Rats: A 13C NMR Study of Neuronal—Glial Interactions in a Model of Temporal Lobe Epilepsy

“…This enzymatic downregulation does not seem to be the main underlying cause of the generation of spontaneous seizures in the Li-pilo model of TLE since glutamine synthesis appears normal in astrocytes. However, both cell bodies and astrocytic processes are hypertrophic in this model (Roch et al, 2002). If the larger volume occupied by this cell type is taken into account, a downregulation of GS may also take place in the present study.…”

“…In Li-pilotreated rats, changes in astrocytes were mainly characterized by hypertrophy of cell bodies and processes near the lesions rather than an increase in astrocyte number (Roch et al, 2002). Furthermore, in the pilocarpine model, only half of the chronically epileptic rats had reactive astrocytes in thalamic, hippocampal, amygdalar, and neocortical areas (Garzillo and Mello, 2002).…”