Pathological Characterization of AAV2-Flex-taCaspa3-2A-TEVp-Induced Temporal Lobe Epilepsy in a Mice Model Open Access

Ijeh, Nwamaka (Spring 2021)

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Temporal lobe epilepsy (TLE) affects 6 out of 10 people with focal epilepsy. It is characterized by (i) severe hippocampal atrophy, (ii) limited extra hippocampal damage, (iii) latent period between beginning of spontaneous recurrent seizures and progressive epilepsy (iv) neuronal loss in the subiculum-CA1, CA3 and the dentate hilus, (v) localization of seizure foci in the amygdala. Mice models of epilepsy are used to better elucidate mechanisms of TLE and test treatment options. Most mice models using chemo convulsants, like Kainic acid or Pilocarpine, to create spontaneous recurrent seizures and mimic some of the damaged characteristics observed in human TLE. However, they provide results with lots of variability in neuropathology, and extensive damage to the hippocampus, and loss of subjects - up to 30% mortality. Since depletion of GABAergic neurons creates an imbalance of excitation and inhibition which increases occurrence of spontaneous recurrent seizures, this study aims to induce apoptosis of GABAergic neurons using AAV2-Flex-taCaspa3-2A-TEVp to model pathology of TLE. Injecting the dorsal and ventral hippocampi with rAAV2-Flex-taCaspa3-2A-TEVp at a rate of 200 nl/min caused significant loss of neurons in dentate gyrus hilus, CA1 and CA3 Stratum Oriens (SO) and Stratum Radiatum (SR) regions. Also, loss of GABAergic neurons in these regions of the hippocampus was also observed. The greatest loss of neurons was found closest to the site of injection, and a loss of volume was observed in the injected hemisphere. Furthermore, reactive gliosis was observed in the injected side of the brain. This model of TLE caused SRSs and had the key characteristics of TLE typically observed in human tissue.

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