Can we and should we use animal models to study neurobehavioral comorbidities of epilepsy?

Epilepsy and its neurobehavioral comorbidities: Insights gained from animal models

“…The role of seizures during development on subsequent epilepsy and its comorbidities is alluded to throughout this review and in several past reviews, only a few of which are cited here. 18,24,[139][140][141][142] In addition to the numerous experimental variables and potential confounders discussed in detail here, the variable of brain developmental stage is critical when considering outcomes and comorbidities. In general, although the developing brain can be less susceptible to overt neuronal damage and neurobehavioral comorbidities, there is no question that even early in development, seizures can be associated with impaired learning, memory, affective function, and behavior.…”

“…The role of seizures during development on subsequent epilepsy and its comorbidities is alluded to throughout this review and in several past reviews, only a few of which are cited here 18,24,139‐142 . In addition to the numerous experimental variables and potential confounders discussed in detail here, the variable of brain developmental stage is critical when considering outcomes and comorbidities.…”

Cognitive comorbidities in the rat pilocarpine model of epilepsy

“…Many scientific publications support the notion that an inadequate control of seizures may lead to changes in mood and cognition both in people with epilepsy and in laboratory animals ( 3 , 17 – 19 ). In general, animal models allow the study of comorbidities without the bias of drug treatments ( 20 – 27 ).…”

“…In clinical practice, this interdisciplinary issue is often underappreciated and in epilepsy preclinical research the situation is not better. However, there is a notable rise of the awareness for neuropsychiatric comorbidities of epilepsy and the number of clinical ( 1 , 2 ) and preclinical studies ( 3 , 4 ) of comorbidities in epilepsy seems to grow over the years. Many clinical reports indicate that mental disorders are more common in patients with epilepsy than in the general population ( 5 – 8 ).…”

“…Pilocarpine is a cholinergic agonist injected systemically or locally to induce status epilepticus (SE), which is followed by a latent period and the subsequently appearance of spontaneous recurrent seizures that mimics a focal epileptic condition similar to the human temporal lobe epilepsy ( 28 ). Besides the pilocarpine model, other animal models of acquired epilepsy like kainate, kindling, or traumatic brain injury are used to study comorbidities of epilepsy ( 3 , 29 ). Absence models, like genetic generalized epilepsy with absence seizures like Genetic Absence Epilepsy Rats from Strasbourg (GAERS) or WAG/Rij rats have been employed for the same reason ( 29 ).…”