Epilepsy, Seizures, and Inflammation: Role of the C-C Motif Ligand 2 Chemokine

Bozzi, Yuri; Caleo, Matteo

doi:10.1089/dna.2016.3345

Cited by 45 publications

(46 citation statements)

References 30 publications

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“…Systemic inflammation implicates and disrupts the BBB, and the dysfunction of BBB is reported as a biomarker for epileptogenesis . Mounting evidence ascribes the precipitation and recurrence of seizures to the inflammation in the cerebral parenchyma . Differ from the traditional mechanisms that arouse epilepsy, which are known as imbalance between excitatory and inhibitory neurotransmiter systems as well as hormonal disturbance, inflammatory is supported to be a postulated important contributor to epilepsy .…”

Section: Introductionmentioning

confidence: 99%

Retracted: MicroRNA‐132 attenuates LPS‐induced inflammatory injury by targeting TRAF6 in neuronal cell line HT‐22

Wang

Liu

et al. 2018

J of Cellular Biochemistry

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Epilepsy is a common neurological disorder in the central nervous system. Inflammation disrupts the blood-brain barrier (BBB), which is responsible for maintaining brain homeostasis. This study was aimed to investigate the functional role of microRNA (miR)-132 in hippocampal HT-22 cells under lipopolysaccharide (LPS) stimulation. In vitro cell inflammatory model was constructed by LPS stimulation. Inflammatory cell injury was evaluated according to the alterations of cell viability, apoptosis, and expression of inflammatory cytokines. Then, miR-132 level after LPS treatment was assessed. Subsequently, miR-132 was abnormally expressed after cell transfection, and the effects of miR-132 on LPS-induced cell inflammatory injury as well as phosphorylated levels of key kinases in the NF-κB and MAPK kinase (MEK)/ERK pathways were determined. The target gene of miR-132 was virtually screened and verified, and whether miR-132 affected HT-22 cells under LPS stimulation through regulating the target gene was verified. The results showed that the level of miR-132 was down-regulated by LPS in HT-22 cells, and the LPS-induced inflammatory injury could be reduced by miR-132 overexpression. Then, the phosphorylated levels of kinases in the NF-κB and MEK/ERK pathways were decreased by miR-132 overexpression. Tumor necrosis factor receptor-associated factor 6 (TRAF6) was predicted and verified to be a target of miR-132. Moreover, the alterations induced by miR-132 overexpression in the LPS-treated HT-22 cells were abrogated by TRAF6 overexpression. Therefore, we drew the conclusion that LPS down-regulated miR-132 and miR-132 attenuated LPS-induced inflammatory cell injury by targeting TRAF6, along with the inhibition of the NF-κB and MEK/ERK pathways.

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Section: Introductionmentioning

confidence: 99%

Retracted: MicroRNA‐132 attenuates LPS‐induced inflammatory injury by targeting TRAF6 in neuronal cell line HT‐22

Wang

Liu

et al. 2018

J of Cellular Biochemistry

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“…In agreement with this, we detected a persistent increased expression of CCL2 in astrocytes of the epileptogenic human and rat brain. CCL2 is a potent chemoattractant for cells of the monocyte lineage (including macrophages, monocytes, and microglia), which may explain the increase of macrophages or monocytes that we observed in the epileptogenic human and rat brain. Increased expression of CCL2 has also been observed in mice and rats 1‐3 days after intrahippocampal–kainic acid injection, in mice in which pilocarpine was used to induce SE, and in the human epileptogenic brain .…”

Section: Discussionmentioning

confidence: 81%

“…CCL2 is a potent chemoattractant for cells of the monocyte lineage (including macrophages, monocytes, and microglia), which may explain the increase of macrophages or monocytes that we observed in the epileptogenic human and rat brain. Increased expression of CCL2 has also been observed in mice and rats 1‐3 days after intrahippocampal–kainic acid injection, in mice in which pilocarpine was used to induce SE, and in the human epileptogenic brain . CCL2 can induce the release of proinflammatory cytokines (eg, interleukin‐1β) and lead to neurodegeneration and BBB disruption .…”

Section: Discussionmentioning

confidence: 81%

Activation of the innate immune system is evident throughout epileptogenesis and is associated with blood‐brain barrier dysfunction and seizure progression

et al. 2018

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These data suggest a proepileptogenic role for monocytes/macrophages and other cells of the innate immune response, possibly via increased BBB leakage, and indicate that T cells and dendritic cells, which are closely associated with the adaptive immune response, are only sparsely infiltrated during epileptogenesis in the electrical post-status epilepticus rat model. Future studies should reveal the relative importance of these immune cells and whether specific manipulation can modify or prevent epileptogenesis.

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“…The chemokine CCL2 is elevated in brain tissue from patients with pharmacoresistant epilepsy . Caleo et al . showed a crucial role for CCL2 and its receptor CCR2 in seizure control.…”

Section: Chemokinesmentioning

confidence: 99%

Neuroinflammatory targets and treatments for epilepsy validated in experimental models

et al. 2017

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A large body of evidence that has accumulated over the past decade strongly supports the role of inflammation in the pathophysiology of human epilepsy. Specific inflammatory molecules and pathways have been identified that influence various pathologic outcomes in different experimental models of epilepsy. Most importantly, the same inflammatory pathways have also been found in surgically resected brain tissue from patients with treatment-resistant epilepsy. New anti-seizure therapies may be derived from these novel potential targets. An essential and crucial question is whether targeting these molecules and pathways may result in anti-ictogenesis, anti-epileptogenesis and/or disease-modification effects. Therefore, preclinical testing in models mimicking relevant aspects of epileptogenesis is needed to guide integrated experimental and clinical trial designs. We discuss the most recent preclinical proof-of-concept studies validating a number of therapeutic approaches against inflammatory mechanisms in animal models that could represent novel avenues for drug development in epilepsy. Finally, we suggest future directions to accelerate preclinical to clinical translation of these recent discoveries.

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Epilepsy, Seizures, and Inflammation: Role of the C-C Motif Ligand 2 Chemokine

Cited by 45 publications

References 30 publications

Retracted: MicroRNA‐132 attenuates LPS‐induced inflammatory injury by targeting TRAF6 in neuronal cell line HT‐22

Retracted: MicroRNA‐132 attenuates LPS‐induced inflammatory injury by targeting TRAF6 in neuronal cell line HT‐22

Activation of the innate immune system is evident throughout epileptogenesis and is associated with blood‐brain barrier dysfunction and seizure progression

Neuroinflammatory targets and treatments for epilepsy validated in experimental models

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