Modeling of post-traumatic epilepsy and experimental research aimed at its prevention

Animal Models of Epilepsy: A Phenotype-oriented Review

“…Fluid percussion injury (FPI) models are implemented by exposing the intact dura mater to a fluid pressure pulse through craniotomy and a closed hydraulic system [ 33 ], leading to neuronal injury and seizure attack [ 34 ]. FPI models are also widely used in the study of posttraumatic epilepsy (PTE) [ 35 ], dividing them into midline, parasagittal, and lateral models based on the position of the craniotomy away from the sagittal suture [ 36 ].…”

“…However, precise surgical progress is vital, given that a slight deviation can easily cause high variability. In addition, the model lacks translation to therapeutic predictive validity [ 33 - 38 ]. Nonetheless, other studies have indicated FPI models as potential candidates for drug-resistant epilepsy models, contributing to preclinical drug development [ 39 ].…”

“…The impact-acceleration model, which is also known as the weight drop model [ 33 ], refers to the specific weight dropping from a specific height above the naked dura mater [ 35 ]. This model can cause severe brain injury and induce generalized tonic-clonic seizures [ 35 ], which is widely used in the study of brain hyperexcitability after trauma [ 34 ], and may also cause early convulsions with a mild-to-moderate degree in the acute stage, and even late convulsions persisting up to 15 weeks after injury [ 33 ]. Morphologically, immediate white matter hemorrhage below the contused cortex in the first hour post-injury can be observed, which gradually evolves into a necrotic cavity after 24 h and expands over the next 2 weeks.…”

“…The iron ion model refers to the intracortical injection of iron ions into the sensorimotor cortex through stereotaxic surgery [ 42 , 43 ]. Ferrous chloride can promote lipid peroxidation, free radical formation, and abnormal glutamate transportation, mimicking TBI and recurrent PTE attacks [ 33 ]. Similarly, ferric chloride (FeCl 3 ) can also induce recurrent seizure attacks and epileptic discharges [ 44 ].…”

“…The iron ion model presents recurrent seizure attacks with high susceptibility to seizures and neurodegeneration restricted to the cortex. However, stereotaxic surgery is technologically demanding [ 33 , 42 - 45 ].…”