2017
DOI: 10.1523/jneurosci.0315-17.2017
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Chemokine CCL2–CCR2 Signaling Induces Neuronal Cell Death via STAT3 Activation and IL-1β Production after Status Epilepticus

Abstract: Elevated levels of chemokine C-C motif ligand 2 (CCL2) and its receptor CCR2 have been reported in patients with temporal lobe epilepsy and in experimental seizures. However, the functional significance and molecular mechanism underlying CCL2-CCR2 signaling in epileptic brain remains largely unknown. In this study, we found that the upregulated CCL2 was mainly expressed in hippocampal neurons and activated microglia from mice 1 d after kainic acid (KA)-induced seizures. Taking advantage of double-transgenic mi… Show more

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Cited by 145 publications
(167 citation statements)
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“…Here, using a transgenic mouse model, we show that the observed seizure‐induced expansion of microglial population is actually comprised of both local microglial proliferation and monocytes infiltration. This is in line with our recent study as well as another study showing the infiltration of monocytes following chemically‐induced epilepsy pathogenesis (Tian et al, ; Varvel et al, ; Zattoni et al, ). The infiltration of monocytes was shown to be dependent on the CCL2‐CCR2 chemokine signaling pathway and reduced infiltration in CCR2 knockout mice corresponded to reduced neuronal loss, reduced neuroinflammation, and better functional recovery (Tian et al, ; Varvel et al, ).…”
Section: Discussionsupporting
confidence: 93%
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“…Here, using a transgenic mouse model, we show that the observed seizure‐induced expansion of microglial population is actually comprised of both local microglial proliferation and monocytes infiltration. This is in line with our recent study as well as another study showing the infiltration of monocytes following chemically‐induced epilepsy pathogenesis (Tian et al, ; Varvel et al, ; Zattoni et al, ). The infiltration of monocytes was shown to be dependent on the CCL2‐CCR2 chemokine signaling pathway and reduced infiltration in CCR2 knockout mice corresponded to reduced neuronal loss, reduced neuroinflammation, and better functional recovery (Tian et al, ; Varvel et al, ).…”
Section: Discussionsupporting
confidence: 93%
“…This is in line with our recent study as well as another study showing the infiltration of monocytes following chemically‐induced epilepsy pathogenesis (Tian et al, ; Varvel et al, ; Zattoni et al, ). The infiltration of monocytes was shown to be dependent on the CCL2‐CCR2 chemokine signaling pathway and reduced infiltration in CCR2 knockout mice corresponded to reduced neuronal loss, reduced neuroinflammation, and better functional recovery (Tian et al, ; Varvel et al, ). This suggests that in addition to activating resident microglia, infiltrated monocytes also could contribute significantly to pathological progression of epilepsy.…”
Section: Discussionsupporting
confidence: 93%
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