T2 relaxation time post febrile status epilepticus predicts cognitive outcome

• We induced prolonged febrile seizures in an animal model of febrile status epilepticus (FSE).
• Animals were imaged with a high resolution MRI within 2 h of status epilepticus.
• Animals with low MRI T2 relaxation times were most likely to learn an active avoidance task.
• FSE animals that were unable to learn the avoidance task also had less precise place fields.
• Results suggest a systems level mechanism that may improve cognitive outcomes post FSE.

Evidence from animal models and patient data indicates that febrile status epilepticus (FSE) in early development can result in permanently diminished cognitive abilities. To understand the variability in cognitive outcome following FSE, we used MRI to measure dynamic brain metabolic responses to the induction of FSE in juvenile rats. We then compared these measurements to the ability to learn an active avoidance spatial task weeks later. T2 relaxation times were significantly lower in FSE rats that were task learners in comparison to FSE non-learners. While T2 time in whole brain held the greatest predictive power, T2 in hippocampus and basolateral amygdala were also excellent predictors. These signal differences in response to FSE indicate that rats that fail to meet metabolic and oxygen demand are more likely to develop spatial cognition deficits. Place cells from FSE non-learners had significantly larger firing fields and higher in-field firing rate than FSE learners and control animals and imply increased excitability in the pyramidal cells of FSE non-learners. These findings suggest a mechanistic cause for the spatial memory deficits in active avoidance and are relevant to other acute neurological insults in early development where cognitive outcome is a concern.

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