Consequences of Cortical Dysplasia During Development in Rats

Abstract

To determine whether focal cortical dysity in regions distant to the region of the dysplasia. Methods;We studied the physiological consequences of cortical dysplasia induced by either m e or three freeze lesions at birth. Seizure sis-c:fix.Cerebral dysgenesis has long been recognized as an important cause of epilepsy ( I ) . Cerebral dysgenesis is a heterogeneous disorder from very severe widespread disorders such as lissencephaly to more subtle abnormalities such as microdysgenesis (2). Although the severe malformations are relatively rare, dysplasia is not uncommon (2-5).Recently there has been an increased interest in treating intractable epilepsy in selected patients with resection of the dysplasia (2,4,6,7). However, there is some evidence that the altered cerebral excitation associated with these lesions may be widespread, extending beyond the actual region of dysplasia, raising concerns about whether patients with cerebral cortical dysplasia will remain at risk for seizures after the resection. For example, il number of authors reported the coexistence of dysplasia with mesial temporal sclerosis (6-1 I). Whether the hippocampal changes are the result of recurrent seizures arising from the cerebral dysgenesis is controversial (5). To investigate the effects of focal dysplasia on distant brain regions, we created microgyri in rats by using freeze lesions, a well-described model of cortical dysplasia (12-17). In this model, a freeze lesion is applied through the intact skull in newborn rats. This results in a focal region of cortical dysplasia resembling human four-layered microgyri (15,16). The dysplasia is a discrete lesion, surrounded by normal-appearing cortex. To determine whether this limited area of dysplasia results in changes in hippocampal excitability, we evaluated kindling in prepubescent rats and assessed c_fbs expression after kainic acid.

Does the region of epileptogenicity influence the pattern of change in cortical excitability?

“…Another explanation is that the more extensive inter-hemispheric synaptic connections between extra-temporal lobe regions facilitate the spread or propagation of epileptic activity between these hemispheres when the focus is in these regions. This is supported by evidence from EEG-fMRI studies (Yu et al, 2009;Kobayashi et al, 2006) (Tyvaert et al, 2008) as well as human and animal data (Keller and Roberts, 2008;Blumenfeld et al, 2007); (Holmes et al, 1999;Zilles et al, 1998;Silva-Barrat et al, 1986) which show regional as well as distant cortical and subcortical changes associated with focal interictal spikes, being more so in patients with extra-temporal foci. It also would correlate well with the described increased incidence of bilateral features in extra-temporal lobe seizure semiologies (Luders et al, 1998;Gastaut, 1970) and of bilateral interictal and ictal discharges seen in patients with extra-TLE (Bautista et al, 1998;Taylor et al, 2003;Gibbs and Gibbs, 1955) as opposed to TLE where most reports show that even if bilateral interictal discharges are recorded, they are predominant over the side with seizure onset in 60-70% of patients (Hirsch et al, 1991;Williamson et al, 1993).…”

Febrile seizures in the predisposed brain: A new model of temporal lobe epilepsy

“…19,23 The clinical significance of these changes remains unclear, because freeze lesions have not been shown to result in spontaneous recurrent seizures or to affect kindling thresholds in adult rats. 24 However, in the immature rat, some or all of these changes may account for the atypical (prolonged) HSs our group reported previously in lesioned rats after HSs. 11 We propose here that it is the atypical HSs that resulted in the development of chronic epilepsy in lesioned rats with HSs.…”

Multiple Pilocarpine‐Induced Status Epilepticus in Developing Rats: A Long‐Term Behavioral and Electrophysiological Study

“…Despite its seizure-prone condition, the immature brain is less vulnerable to seizure-triggered brain injury and synaptic reorganization (19,20). Indeed, a previous study from our group demonstrated that PILO-induced SE led to adulttype neuropathology and behavioral and EEG features only when animals were injected after P15 to P21 (7).…”