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Updated: Aug 23, 2026
The Pilocarpine Model of Temporal Lobe Epilepsy and EEG Monitoring Using Radiotelemetry System in Mice
Published on: February 27, 2018
Reciprocal changes of CD44 and GAP-43 expression in the dentate gyrus inner molecular layer after status epilepticus
Karin Borges1, Dayna L McDermott, Raymond Dingledine
1Department of Pharmacology, Emory University School of Medicine, Atlanta GA 30322, USA. kborges@pharm.emory.edu
Abstract:
Mossy fiber sprouting (MFS), a common feature of human temporal lobe epilepsy and many epilepsy animal models, contributes to hippocampal hyperexcitability. The molecular events responsible for MFS are not well understood, although the growth-associated protein GAP-43 has been implicated in rats. Here, we focus on the hyaluronan receptor CD44, which is involved in routing of retinal axons during development and is upregulated after injury in many tissues including brain. After pilocarpine-induced status epilepticus (SE) in mice most hilar neurons died and neuropeptide Y (NPY) immunoreactivity appeared in the dentate inner molecular layer (IML) after 10-31 days indicative of MFS. Strong CD44 immunoreactivity appeared in the IML 3 days after pilocarpine, then declined over the next 4 weeks. Conversely, GAP-43 immunoreactivity was decreased in the IML at 3-10 days after pilocarpine-induced SE. After SE induced by repeated kainate injections, mice did not show any hilar cell loss or changes in CD44 or GAP-43 expression in the IML, and MFS was absent at 20-35 days. Thus, after SE in mice, early loss of GAP-43 and strong CD44 induction in the IML correlated with hilar cell loss and subsequent MFS. CD44 is one of the earliest proteins upregulated in the IML and coincides with early sprouting of mossy fibers, although its function is still unknown. We hypothesize that CD44 is involved in the response to axon terminal degeneration and/or neuronal reorganization preceding MFS.
Insights
Mossy fiber sprouting (MFS) in epilepsy involves CD44 and GAP-43. Pilocarpine-induced seizures in mice showed CD44 upregulation and GAP-43 loss, correlating with MFS, suggesting CD44
Area of Science:
- Neuroscience
- Epilepsy Research
- Molecular Biology
Background:
- Mossy fiber sprouting (MFS) is a hallmark of temporal lobe epilepsy, contributing to hyperexcitability.
- The molecular mechanisms driving MFS are not fully understood, though GAP-43 is implicated.
- CD44, a hyaluronan receptor, is involved in axonal guidance and upregulated after brain injury.
Purpose of the Study:
- To investigate the role of CD44 in mossy fiber sprouting following status epilepticus (SE).
- To examine the relationship between CD44 expression, neuronal loss, and MFS in an epilepsy model.
Main Methods:
- Induced status epilepticus (SE) in mice using pilocarpine and kainate.
- Assessed hilar neuron survival using histology.
- Quantified CD44 and GAP-43 immunoreactivity in the dentate inner molecular layer (IML) via immunohistochemistry.
- Evaluated mossy fiber sprouting (MFS) by observing Neuropeptide Y (NPY) expression.
Main Results:
- Pilocarpine-induced SE caused hilar neuron loss, CD44 upregulation, and GAP-43 downregulation in the IML, preceding MFS.
- Kainate-induced SE, without hilar neuron loss, did not alter CD44 or GAP-43 levels and showed no MFS.
- Early CD44 induction in the IML correlated with hilar cell loss and subsequent MFS.
Conclusions:
- CD44 upregulation and GAP-43 downregulation in the IML are associated with hilar neuron loss and MFS after pilocarpine-induced SE.
- CD44 may play a role in the response to neuronal damage and reorganization preceding MFS.
- The findings highlight CD44 as a potential early marker and player in epilepsy-associated neuroplasticity.
