Figure 1
Schematic representation of epileptogenic features in main animal models of post-traumatic epilepsy (PTE). A, In classic models of status epilepticus (SE) (e.g., pilocarpine and kainic acid), after the initial sustained acute seizure, the development of spontaneous recurrent seizures occurs after a brief latent period in most animals. In contrast, the slow progression of evoked seizures in kindling models implies the need of massive repetition of the stimuli protocol in order for spontaneous seizures to develop, making this an extremely laborious protocol for that intention. Meanwhile, different parameters can be adjusted according to the desired lesion severity, and consequent occurrence or not of acute seizures, in different traumatic brain injury (TBI) models (e.g., lateral fluid percussion, controlled cortical impact, impact-acceleration, or weight drop). However, in TBI models, usually only a few animals, most of them requiring severe initial lesions, develop spontaneous recurrent seizures following a longer latent period. B, The lesion event may differently affect neurodegeneration occurrence. In general, chemically-induced SE causes severe and widespread neurodegeneration, while minor neuronal damage is detected in the kindling model. Importantly, by adjusting the mechanical force parameters, the neuronal damage can vary from cortical to subcortical regions, and from minor to severe neurodegeneration in TBI models. C, The neuroinflammatory response is rapidly initiated following the initial precipitating injury, characterized by the release of inflammatory cytokines, chemokines, and complement proteins. Astrocytes and microglial cells also became activated, proliferate, and, together with peripheral immune cells, are recruited to the lesion site. This response decreases over days, but residual neuroinflammation may chronically persist, supporting a pro-epileptogenic role. In general, the intensity of the neuroinflammation response can be considered quite similar between SE and TBI models, varying with the impact intensity in the latter. D, There is a transitory increase in newborn neurons in the subgranular zone of the dentate gyrus of the hippocampus and in the subventricular zone of lateral ventricles, in several animal models of PTE. After this initial increase, the number of newly generated cells returns to basal levels with the occurrence of spontaneous seizures. On the other hand, mossy fiber sprouting (MFS) increases after the initial insult and presents a permanent pattern together with spontaneous seizure occurrence.
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