Chemokine CCL2 and its receptor CCR2 are increased in the hippocampus following pilocarpine-induced status epilepticus.
BACKGROUND
Neuroinflammation occurs after seizures and is implicated in epileptogenesis. CCR2 is a chemokine receptor for CCL2 and their interaction mediates monocyte infiltration in the neuroinflammatory cascade triggered in different brain pathologies. In this work CCR2 and CCL2 expression were examined following status epilepticus (SE) induced by pilocarpine injection.


METHODS
SE was induced by pilocarpine injection. Control rats were injected with saline instead of pilocarpine. Five days after SE, CCR2 staining in neurons and glial cells was examined using imunohistochemical analyses. The number of CCR2 positive cells was determined using stereology probes in the hippocampus. CCL2 expression in the hippocampus was examined by molecular assay.


RESULTS
Increased CCR2 was observed in the hippocampus after SE. Seizures also resulted in alterations to the cell types expressing CCR2. Increased numbers of neurons that expressed CCR2 was observed following SE. Microglial cells were more closely apposed to the CCR2-labeled cells in SE rats. In addition, rats that experienced SE exhibited CCR2-labeling in populations of hypertrophied astrocytes, especially in CA1 and dentate gyrus. These CCR2+ astroctytes were not observed in control rats. Examination of CCL2 expression showed that it was elevated in the hippocampus following SE.


CONCLUSIONS
The data show that CCR2 and CCL2 are up-regulated in the hippocampus after pilocarpine-induced SE. Seizures also result in changes to CCR2 receptor expression in neurons and astrocytes. These changes might be involved in detrimental neuroplasticity and neuroinflammatory changes that occur following seizures.
Foresti
Maira L
ML
Department of Neurosurgery, Scott and White Hospital, Temple, TX 76503, USA. mforesti@swmail.sw.org
Arisi
Gabriel M
GM
Katki
Khurshed
K
Montañez
Andres
A
Sanchez
Russell M
RM
Shapiro
Lee A
LA
D000818:Animals; D001253:Astrocytes / Q000378:metabolism; D056547:CA1 Region, Hippocampal / Q000098:blood supply / Q000378:metabolism; D002452:Cell Count; D018932:Chemokine CCL2 / Q000378:metabolism*; D018891:Dentate Gyrus / Q000098:blood supply / Q000378:metabolism; D042783:Endothelial Cells / Q000378:metabolism; D006624:Hippocampus / Q000098:blood supply / Q000378:metabolism*; D007150:Immunohistochemistry; D017628:Microglia / Q000378:metabolism; D018613:Microscopy, Confocal; D009457:Neuroglia / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism*; D010862:Pilocarpine; D051381:Rats; D017207:Rats, Sprague-Dawley; D054390:Receptors, CCR2 / Q000378:metabolism*; D012640:Seizures / Q000378:metabolism; D013226:Status Epilepticus / Q000139:chemically induced / Q000378:metabolism*
C491766:Ccl2 protein, rat; C515336:Ccr2 protein, rat; D018932:Chemokine CCL2; D054390:Receptors, CCR2; D010862:Pilocarpine