Cognitive dysfunction after experimental febrile seizures

Abstract

While the majority of children with febrile seizures have an excellent prognosis, a small percentage are latter discovered to have cognitive impairment. Whether the febrile seizures produce the cognitive deficits or the febrile seizures are a marker or the result of underlying brain pathology is not clear from the clinical literature. We evaluated hippocampal and prefrontal cortex function in adult rats with a prior history of experimental febrile seizures as rat pups. All of the rat pups had MRI brain scans following the seizures. Rats subjected to experimental febrile seizures were found to have moderate deficits in working and reference memory and strategy shifting in the Morris water maze test. A possible basis for these hippocampal deficits involved abnormal firing rate and poor stability of hippocampal CA1 place cells, neurons involved in encoding and retrieval of spatial information. Additional derangements of interneuron firing in the CA1 hippocampal circuit suggested a complex network dysfunction in the rats. MRI T2 values in the hippocampus were significantly elevated in 50% of seizure-experiencing rats. Learning and memory functions of these T2-positive rats were significantly worse than those of T2-negative cohorts and of controls. We conclude that cognitive dysfunction involving the hippocampus and prefrontal cortex networks occur following experimental febrile seizures and that the MRI provides a potential biomarker for hippocampal deficits in a model of prolonged human febrile seizures.

Loss of dendritic inhibition in the hippocampus after repeated early-life hyperthermic seizures in rats

“…In particular, a loss of distal dendritic inhibition in seizure rats may affect spatial coding by a direct entorhinal to CA1 distal-dendritic excitation (Brun et al, 2008;Leung, 2011). Abnormal place cell activity was found in animals with early-life seizures (Dube et al, 2009(Dube et al, , 2010. Attenuation in GABA B R function may be a critical component of epilepsy, and it may participate in a role of ''seizures beget seizures'' (Tsai et al, 2008).…”

“…As a model of febrile seizures, hyperthermia-induced seizures in immature rats (Baram et al, 1997) were found to increase longterm seizure susceptibility and induce spontaneous seizures (Dube et al, 2010), without significant cell loss or sustained brain damage (Dube et al, 2000). Additionally, long-term behavioral changes have been reported after hyperthermic seizures (Chang et al, 2003;Dube et al, 2000Dube et al, , 2009Dube et al, , 2010. Long-term physiological changes after febrile seizure models include alteration of intrinsic membrane currents and an increased in GABA A receptor-mediated transmission in hippocampal slices in vitro (Chen et al, 1999).…”

The Brain, Seizures and Epilepsy Throughout Life: Understanding a Moving Target

“…In humans, it is more difficult to discern the relationship of the epilepsy and the cognitive defects (122). Temporal lobe or limbic seizures propagate through the same neuronal pathways that are engaged in learning and memory processes (111). Thus, seizures might directly cause such problems; alternatively, the abnormalities that result in the seizures might independently provoke cognitive dysfunction.…”

Novel Etiological and Therapeutic Strategies for Neurodiseases: Mechanisms and Consequences of Febrile Seizures: Lessons From Animal Models

“…The repeated-FS also caused long-lasting deficits in synaptic plasticity in CA1 pyramidal cells and reduced tyrosine phosphorylation of the NMDA-receptor subunit NR2A (96). Recently, an abnormal firing rate and poor stability of hippocampal CA1 place cells have been suggested as a basis for the deficits in eFS-induced hippocampal-dependent memory (97).…”

“…Furthermore, the development of noninvasive methods such as MRI (97) to detect the future effects of FS on hippocampal malfunction is required.…”