Effects of Non-invasive, Targeted, Neuronal Lesions on Seizures in a Mouse Model of Temporal Lobe Epilepsy
| Autor: | Sara Natasha Ghobadi, Max Wintermark, Haibo Qu, Siqin Huang, Hong Jiang, Yanrong Zhang, Chengde Liao, Edward H. Bertram, Haiyan Zhou, Arsenii V. Telichko, Frezghi Habte, James Woznak, Kevin S. Lee, Timothy C. Doyle, Ningrui Li |
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| Rok vydání: | 2020 |
| Předmět: |
Male
0301 basic medicine Pathology medicine.medical_specialty Acoustics and Ultrasonics Biophysics Hippocampus Pilot Projects Status epilepticus Article Temporal lobe Mice 03 medical and health sciences chemistry.chemical_compound Epilepsy 0302 clinical medicine Ultrasonic Surgical Procedures Parenchyma Animals Medicine Neurotoxin Radiology Nuclear Medicine and imaging Epilepsy surgery Neurons Microbubbles Radiological and Ultrasound Technology business.industry Pilocarpine medicine.disease Magnetic Resonance Imaging Disease Models Animal 030104 developmental biology Epilepsy Temporal Lobe nervous system chemistry Blood-Brain Barrier Feasibility Studies medicine.symptom business 030217 neurology & neurosurgery Quinolinic acid |
| Zdroj: | Ultrasound Med Biol |
| ISSN: | 0301-5629 |
| DOI: | 10.1016/j.ultrasmedbio.2020.01.008 |
| Popis: | Surgery to treat drug-resistant epilepsy can be quite effective but remains substantially underutilized. A pilot study was undertaken to test the feasibility of using a non-invasive, non-ablative, approach to produce focal neuronal loss to treat seizures in a rodent model of temporal lobe epilepsy. In this study, spontaneous, recurrent seizures were established in a mouse model of pilocarpine-induced status epilepticus. After post-status epilepticus stabilization, baseline behavioral seizures were monitored for 30 d. Non-invasive opening of the blood–brain barrier targeting the hippocampus was then produced by using magnetic resonance-guided, low-intensity focused ultrasound, through which a neurotoxin (quinolinic acid) administered intraperitoneally gained access to the brain parenchyma to produce focal neuronal loss. Behavioral seizures were then monitored for 30 d after this procedure, and brains were subsequently prepared for histologic analysis of the sites of neuronal loss. The average frequency of behavioral seizures in all animals (n = 11) was reduced by 21.2%. Histologic analyses along the longitudinal axis of the hippocampus revealed that most of the animals (n = 8) exhibited neuronal loss located primarily in the intermediate aspect of the hippocampus, while sparing the septal aspect. Two other animals with damage to the intermediate hippocampus also exhibited prominent bilateral damage to the septal aspect of the hippocampus. A final animal had negligible neuronal loss overall. Notably, the site of neuronal loss along the longitudinal axis of the hippocampus influenced seizure outcomes. Animals that did not have bilateral damage to the septal hippocampus displayed a mean decrease in seizure frequency of 27.7%, while those with bilateral damage to the septal hippocampus actually increased seizure frequency by 18.7%. The animal without neuronal loss exhibited an increase in seizure frequency of 19.6%. The findings indicate an overall decrease in seizure frequency in treated animals. And, the site of neuronal loss along the longitudinal axis of the hippocampus appears to play a key role in reducing seizure activity. These pilot data are promising, and they encourage additional and more comprehensive studies examining the effects of targeted, non-invasive, neuronal lesions for the treatment of epilepsy. |
| Databáze: | OpenAIRE |
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