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Immediate epileptogenesis: Impact on brain in C57BL/6J mouse kainate model
Sreekanth Puttachary1, Shaunik Sharma1, Achala Thippeswamy1
1Department of Biomedical Sciences, College of Veterinary Medicine, Iowa State University, Ames IA 50011-1250, USA.
Abstract:
We have recently demonstrated immediate epileptogenesis in the C57BL/6J mouse, the strain that is resistant to kainate-induced neurotoxicity. By using a repeated low dose of kainate, we produced mild and severe status epilepticus (SE) models. In the present study, we demonstrate the impact of mild and severe SE, and spontaneous convulsive/nonconvulsive seizures (CS/NCS) on structure and function of the hippocampus, entorhinal cortex, and amygdala at 7, 14 and 28 day post-SE. Immunohistochemistry (IHC) of brain sections confirmed reactive astrogliosis and microgliosis, neurodegeneration, and increased neurogenesis in both groups. The epileptiform spike rate was higher in the severe group during first 12 days, but they decreased thereafter. Morris water maze test confirmed cognitive deficit in both mild and severe groups at 12d post-SE. However, MRI and IHC at 18 weeks did not reveal any changes in the hippocampus. These findings suggest that in C57BL/6J mice, immediate spontaneous CS could be responsible for early brain pathology or vice versa, however, the persistent spontaneous NCS for a long-term had no impact on the brain structure in both groups.
Insights
Mild and severe seizures in C57BL/6J mice cause early brain changes and cognitive deficits. However, long-term nonconvulsive seizures (NCS) did not impact brain structure.
Area of Science:
- Neuroscience
- Epilepsy Research
- Mouse Models
Background:
- C57BL/6J mice are typically resistant to kainate-induced neurotoxicity.
- Previous work established immediate epileptogenesis in this strain.
- Mild and severe status epilepticus (SE) models were created using repeated low-dose kainate.
Purpose of the Study:
- To investigate the impact of mild and severe SE on brain structure and function.
- To assess the effects of spontaneous convulsive seizures (CS) and nonconvulsive seizures (NCS) post-SE.
- To examine changes in the hippocampus, entorhinal cortex, and amygdala at different time points.
Main Methods:
- Immunohistochemistry (IHC) to detect reactive astrogliosis, microgliosis, neurodegeneration, and neurogenesis.
- Morris water maze test for cognitive function assessment.
- Magnetic resonance imaging (MRI) and IHC at 18 weeks for long-term structural analysis.
Main Results:
- IHC confirmed reactive gliosis, neurodegeneration, and increased neurogenesis in both SE groups.
- Higher epileptiform spike rates were observed in the severe group initially, decreasing over time.
- Cognitive deficits were evident in both groups at 12 days post-SE.
- No significant changes in hippocampal structure were detected by MRI and IHC at 18 weeks.
Conclusions:
- Immediate spontaneous CS may contribute to early brain pathology in C57BL/6J mice, or vice versa.
- Persistent spontaneous NCS over the long term did not affect brain structure in either mild or severe SE models.
