Parallel pathways of seizure generalization

Abstract

Generalized convulsive status epilepticus is a life-threatening emergency, because recurrent convulsions can cause death or injury. A common form of generalized convulsive status epilepticus is of focal onset. The neuronal circuits activated during seizure spread from the hippocampus, a frequent site of seizure origin, to the bilateral motor cortex, which mediates convulsive seizures, have not been delineated. Status epilepticus was initiated by electrical stimulation of the hippocampus. Neurons transiently activated during seizures were labelled with tdTomato and then imaged following brain slice clearing. Hippocampus was active throughout the episode of status epilepticus. Neuronal activation was observed in hippocampus parahippocampal structures: subiculum, entorhinal cortex and perirhinal cortex, septum, and olfactory system in the initial phase status epilepticus. The tdTomato-labelled neurons occupied larger volumes of the brain as seizures progressed and at the peak of status epilepticus, motor and somatosensory cortex, retrosplenial cortex, and insular cortex also contained tdTomato-labelled neurons. In addition, motor thalamic nuclei such as anterior and ventromedial, midline, reticular, and posterior thalamic nuclei were also activated. Furthermore, circuits proposed to be crucial for systems consolidation of memory: entorhinal cortex, retrosplenial cortex, cingulate gyrus, midline thalamic nuclei and prefrontal cortex were intensely active during periods of generalized tonic-clonic seizures. As the episode of status epilepticus waned, smaller volume of brain was activated. These studies suggested that seizure spread could have occurred via canonical thalamocortical pathway and many cortical structures involved in memory consolidation. These studies may help explain retrograde amnesia following seizures.

Neuronal Circuit Activity during Neonatal Hypoxic–Ischemic Seizures in Mice

“…Though this is a limitation of this technique, the TRAP technique offers superior signal-to-noise ratio and time specificity compared to traditional cfos IHC, which has been shown in our work (Fig 8) and in previous work. 21,26 Also, it is important to point out that the absence of tdTomato expression does not necessarily mean the cell is not active. Induction of cfos response varies based on the frequency and strength of stimulus.…”

“…21 Previous studies examined cfos immunohistochemistry (IHC) versus tdTomato-tagged cfos expression in the TRAP model, and found that TRAP has a superior signal-tonoise ratio and time specificity. 21,26 Validation in this experiment used cfos IHC 2 hours after HI. As a negative control, mice that did not receive 4-OHT were found to have no tdTomato expression.…”

α‐Amino‐3‐Hydroxy‐5‐Methyl‐4‐Isoxazolepropionic Acid Receptor Plasticity Sustains Severe, Fatal Status Epilepticus

“…Neuronal plasticity mechanisms that facilitate the spread of seizures from the hippocampus to the motor cortex during generalized convulsive SE are not understood. Generalized convulsive seizures likely arise from the activation of neurons in the motor cortex . The hippocampus is a common site of origin of focal seizures, and it is injured during generalized convulsive SE in patients with complex febrile SE …”

“…Generalized convulsive seizures likely arise from the activation of neurons in the motor cortex. 8,9 The hippocampus is a common site of origin of focal seizures, and it is injured during generalized convulsive SE in patients with complex febrile SE. 10,11 We hypothesized that α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor plasticity mediated by the GluA1 subunit is critical for secondary generalization of seizures and thus death during SE.…”

Estado epiléptico: Innovaciones ante este constante reto neurológico

“…Aún no se entienden bien los mecanismos que inician crisis anormalmente prolongadas (Sánchez Fernández, Goodkin, & Scott, 2019). Dabrowska y et al sugieren que la transmisión sostenida mediada por AMPAR (Receptor Alfa amino 3 hidroxil 5 metil 4 isoxacolepropiónico) y que las neuronas piramidales hipocampales tienen mayor reactivada durante crisis y EE (Dabrowska et al, 2019).…”