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Reactive microglia in hippocampal sclerosis associated with human temporal lobe epilepsy
T G Beach1, W B Woodhurst, D B MacDonald
1Division of Neuropathology, University of British Columbia, Vancouver Hospital and Health Sciences Centre, Canada.
Abstract:
An immunoperoxidase method was used to demonstrate expression of HLA-DR (a Class II major histocompatibility antigen) as an indicator of microglial activation in cases of hippocampal sclerosis derived from temporal lobectomy for intractable seizures. HLA-DR-immunoreactive microglia were increased approximately 11-fold in CA1 and 3-fold in CA3, compared to control autopsy hippocampus. The numbers of HLA-DR-immunoreactive perivascular cells were also significantly increased in hippocampal sclerosis cases (9-, 7- and 6-fold increases in CA1, CA3 and CA2, respectively). Since animal studies have found microglial activation to be an acute or subacute response to injury, the results presented here suggest that, contrary to the classical conception of human hippocampal sclerosis as an inert scar, neuronal injury continues to occur as a result of ongoing seizure activity.
Insights
Microglial activation, indicated by HLA-DR expression, is significantly increased in hippocampal sclerosis. This suggests ongoing neuronal injury in this condition, challenging the view of it as an inert scar.
Area of Science:
- Neuroscience
- Immunology
- Pathology
Background:
- Hippocampal sclerosis is a common cause of intractable epilepsy.
- Microglial activation is a marker of central nervous system injury.
- The role of ongoing neuroinflammation in hippocampal sclerosis is not fully understood.
Purpose of the Study:
- To investigate microglial activation in hippocampal sclerosis using HLA-DR expression.
- To determine if ongoing neuronal injury occurs in hippocampal sclerosis.
Main Methods:
- Immunoperoxidase staining was used to detect HLA-DR expression.
- Quantification of HLA-DR-immunoreactive microglia and perivascular cells in hippocampal sclerosis and control autopsy samples.
- Comparison of cell counts between cases and controls.
Main Results:
- HLA-DR-immunoreactive microglia were significantly increased in hippocampal sclerosis (11-fold in CA1, 3-fold in CA3).
- HLA-DR-immunoreactive perivascular cells were also significantly increased in all hippocampal subfields (CA1, CA2, CA3).
- These findings indicate heightened microglial activation in hippocampal sclerosis.
Conclusions:
- Microglial activation is a prominent feature of human hippocampal sclerosis.
- The presence of activated microglia suggests ongoing neuronal injury, not an inert scar.
- These findings have implications for understanding the pathophysiology of intractable epilepsy associated with hippocampal sclerosis.