Animal models of epilepsy: use and limitations

Figures & data

Table 1 Summary of main models reviewed

Model	Induction	Manifestations	Human relevance	Use	Limitations
Chemoconvulsants
KA-SE	Systemic or intrahippocampal injection	Limbic SE and chronic seizures	TLE with hippocampal sclerosis	AED screening, mechanisms of epileptogenesis	High mortality; variable frequency and severity of spontaneous seizures; not all neural damage comes from seizures
Pilo-SE	Systemic or intrahippocampal injection	Limbic SE and chronic seizures	TLE with hippocampal sclerosis	AED screening, mechanisms of epileptogenesis, and cognitive/psychiatric comorbidities	High mortality; variable frequency and severity of spontaneous seizures; neocortical lesions
Acute chemical models	Systemic or intrahippocampal injection	Nonconvulsive absence or generalized tonic-clonic seizures, depending on the drug and dose	Acute and repetitive seizures	Rapid screening of AED, effect of repetitive seizures	Lack of spontaneous recurrent seizures and of neuronal loss or other neuropathological hallmarks
SE in immature rodents	Systemic injection of KA or Pilo	Tonic-clonic seizures	Prolonged seizures during development	Epileptogenesis and long-term consequences	KA and Pilo are not clinical causes of seizures; more extensive damage compared with other models
Repetitive seizures in immature rodents	Systemic injection of PTZ or flurothyl inhalation	Myoclonic and generalized tonic-clonic seizures	Repetitive brief seizures during development	AED screening and cognitive deficits	No spontaneous seizures in adulthood
Electrical stimulation
Electroshock-induced seizures	Corneal or auricular stimulation	Generalized tonic-clonic seizures	Tonic-clonic seizures	AED screening and molecular and physiological alterations related to epileptiform activities	Low predictive validity for some AEDs
Afterdischarges	Focal electrical stimulation	Complex partial seizures and myoclonic seizures	Focally generated seizure-like patterns that often spread to other regions	Electrophysiological and behavioral changes caused by focally generated seizure patterns	No specificity for groups of neurons; studying neuronal activity during stimulation is difficult
Kindling	Repeated afterdischarge induction	Partial seizures evolving into secondary generalization and, eventually, spontaneous seizures	Consequences of poorly controlled seizures and dynamics of epileptogenic processes	Prevention of epileptogenesis processes and treatment of pharmacoresistant epilepsies	Costly and time-consuming procedure
Brain pathology
Hyperthermic seizures	Increase of body temperature in immature rodents through stream of heated air	Immobility, facial automatism, myoclonic jerks	Febrile seizure	Epileptogenesis mechanisms and cognitive consequences	Subtle behavioral seizures, necessity of EEG recording, possible morbidity from heat exposure
Hypoxia model	Exposure to air with low O2 concentration in immature rodents	Brief and repetitive tonic-clonic seizures	Neonatal hypoxic encephalopathy	AED screening, long-term consequences, and epileptogenesis mechanisms	Susceptibility for seizures varies with the strain and age of rodents
Posttraumatic epilepsy	Rostral parasagittal fluid percussion injury	Generalized tonic-clonic seizures in the long term, with low frequency	Posttraumatic epilepsy	AED screening, mechanisms of epileptogenesis, and hippocampal sclerosis with dual pathology	Laborious induction, long latency periods, mild seizures during the first 4 months posttrauma
Genetic models
Audiogenic models	Acoustic stimulation in genetically prone rats	Wild running and tonic-clonic seizures	Reflex epilepsy and TLE studies	Epileptogenesis mechanisms and comorbidities associated with epilepsies	Necessity of a trigger to evoke seizures; lack of spontaneous recurrent seizures
GAERS, WAG/Rij, and mouse models of absence seizures	Spontaneous seizures	SWD generalization, behavioral arrest	Generalized idiopathic epilepsies	Electrographic and behavioral similarity to human absence seizures, response to AEDs	Diverse (and not fully known) genetic alterations

Abbreviations: KA, kainic acid; SE, status epilepticus; TLE, temporal lobe epilepsy; AED, antiepileptic drugs; Pilo, pilocarpine; PTZ, pentylenetetrazol; EEG, electroencephalography; GAERS, Genetic Absence Epilepsy in Rats from Strasbourg; WAG/Rij, Wistar Albino Glaxo/Rijswijk rats; SWD, spike-and-wave discharges.