Early susceptibility for epileptiform activity in malformed cortex.

Area of Science:

• Neuroscience
• Developmental Neuroscience
• Epileptology

Background:

• Cortical malformations can disrupt brain development, leading to delayed hyperexcitability and epilepsy.
• In the freeze-lesion microgyria model, epileptiform activity is typically observed after postnatal day 12, despite earlier increases in excitatory input.

Purpose of the Study:

• To investigate the critical time window for assessing epileptogenic mechanisms in cortical malformations.
• To determine if increased susceptibility to seizures precedes the overt expression of epileptiform activity in a microgyria model.

Main Methods:

• Utilized a two-hit model combining neonatal freeze lesions with low-magnesium artificial cerebrospinal fluid (aCSF) to induce hyperexcitability.
• Assessed interictal activity using measures of incidence, time to the first epileptiform event, and magnitude of late activity across different postnatal survival groups (P7-9, P10-11, P12-15, P28-36).

Main Results:

• The two-hit model induced increased interictal activity in freeze-lesioned cortices compared to controls, evident even in the P7-9 group (before increased excitatory afferents).
• Susceptibility for interictal activity was observed across all tested age groups.
• While interictal activity did not differ in young adults (P28-36), only lesioned cortices exhibited ictal activity.

Conclusions:

• Epileptogenic processes in cortical malformations initiate early and extend beyond the manifestation of interictal activity.
• The susceptibility to interictal and ictal activity follows distinct developmental timelines.
• This highlights the importance of early assessment and understanding the protracted development of epilepsy in malformation contexts.