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

Abstract

The atypical febrile seizure has important clinical implications because of its association with the mesial temporal lobe epilepsy syndrome, which is the most common of the intractable epilepsies. However, whether a causal relation exists between these conditions is currently unknown. We have previously shown that a focal cortical lesion induced in the neonatal rat predisposes to the development of atypical hyperthermic seizures. We show here that 86% of the lesion plus hyperthermia group experience development of spontaneous recurrent seizures recorded from the amygdala ipsilateral to the lesion. Control rats did not have spontaneous recurrent behavioral or electrographic seizures. Lesioned rats with hyperthermic seizures also showed an impaired performance on the Morris water maze when compared with naive control rats, suggesting mild deficits in learning and memory. These findings support a link between the atypical febrile seizure and mesial temporal lobe epilepsy, and at the same time establish a new model for this condition through which new preventative and therapeutic strategies can be tested.

Epileptogenesis Is Increased in Rats With Neonatal Isolation and Early-Life Seizure and Ameliorated by MK-801: A Long-Term MRI and Histological Study

“…Video monitoring has been demonstrated to detect behavioral seizures characterized by freezing, head nodding, and jaw myoclonus (9). The spontaneous behavioral seizures after pilocarpine-induced SE occurs in cyclicity, peaking every 5-8 d (34), and the seizure phenotype consists of freezing, automatisms, and even jumping (9,10,35,36). Thus, at the age of ϳ6 mo, the rat's behaviors were monitored using a video camera for 6 h per day for 10 consecutive days, excluding weekends to compare the incidence of behavioral seizures between groups.…”

“…Notwithstanding the higher susceptibility to seizures, the immature brain is less vulnerable to seizure-induced injuries than the mature brain (1)(2)(3)(4)(5), and diverse conditions, such as the seizure severity, causes of seizure, or precipitating injuries may affect the long-term neurologic outcome (6 -9). In this regard, the circumstances under which a seizure in immature brain can cause permanent brain damage is of great interest (9,10).…”

“…Stress or glucocorticoids (GCs) exposure potentiates the excitotoxic effect of concurrent neurologic insults (23), for example acceleration of kindling epileptogenesis (24), and change of seizure propensity (25). We have earlier demonstrated that rat pups subjected to repetitive neonatal isolation (NI) can exacerbate cognitive deficit and anxiety-like behaviors after recurrent seizures or status epilepticus (SE) (7,9,26). However, whether neonatal stress can precipitate the incidence of epileptogene sis in the context of early-life seizure is currently unknown.…”

Novel Animal Models of Pediatric Epilepsy

“…The same group examined the effects of focal lesions (induced with the same methods) in combination with hyperthermic seizures induced by a hair dryer. A 20-minute hyperthermic seizure was responsible for limbic seizures and memory deficits during adulthood in 86 % of the animals [93]. The mechanisms by which focal lesions lead to significant temporal lobe epileptogenesis are currently unknown [93].…”

“…A 20-minute hyperthermic seizure was responsible for limbic seizures and memory deficits during adulthood in 86 % of the animals [93]. The mechanisms by which focal lesions lead to significant temporal lobe epileptogenesis are currently unknown [93]. Once again, this model of focal lesions has allowed the clear establishment of the role of such lesions in epileptogenesis.…”