Neuro-Immune Crosstalk in CNS Diseases

Kerschensteiner, Martin; Meinl, Edgar; Hohlfeld, Reinhard

doi:10.1007/400_2009_6

Cited by 55 publications

(69 citation statements)

References 115 publications

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“…With respect to the role played by central IL-6 in regulating epileptic activity, prior studies demonstrate that IL-6 can stimulate the synthesis of corticotrophin and glucocorticoids, and initiate an anti-inflammatory feedback loop, suggesting a neuroprotective role played by IL-6 [29,30]. Consistent with the findings of prior studies [31][32][33], we have observed increases in the levels of IL-1β, IL-6 and TNF-α in the parietal cortex, hippocampus and amygdala 3 days after KA-induced SE.…”

Section: Discussionsupporting

confidence: 81%

Inhibiting HIF-1α Decreases Expression of TNF-α and Caspase-3 in Specific Brain Regions Exposed Kainic Acid-Induced Status Epilepticus

Yang

He²,

Meng³

et al. 2016

Cell Physiol Biochem

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Background/Aims: A recent study demonstrates that pro-inflammatory cytokines (PICs, i.e., IL-1β, IL-6 and TNF-α) in specific brain regions of rats play a role in regulating kainic acid (KA)-induced status epilepticus (SE) via a GABAergic mechanism. The purposes of this report were to examine contributions of hypoxia inducible factor subtype 1α (HIF-1α) to expression of PICs in these specific brain regions in epileptic rats. Particularly, we investigated the parietal cortex, hippocampus and amygdala. In addition, we further examined expression of Caspase-3 indicating cell apoptosis in those brain regions of epileptic rats after infusing 2-methoxyestradiol (2-MET, inhibitor of HIF-1α) and etanercept (TNF-α receptor antagonist). Methods: ELISA was used to determine the levels of HIF-1α and PICs and western blot analysis was used to examine Caspase-3 expression. Results: Our data show that HIF-1α was significantly increased in the parietal cortex, hippocampus and amygdala 1, 3 and 7 days after induction of SE (P<0.05 vs. control rats). Our results also show that inhibiting HIF-1α by central infusion of 2-MET significantly decreased the amplified TNF-α expression in these brain regions evoked by SE (P<0.05 vs. vehicle control), but did not modify IL-1β and IL-6. Our results demonstrate that 2-MET and etanercept attenuated an increase in Caspase-3 evoked by SE. Conclusion: Overall, we suggest that HIF-1α activated by SE is likely to contribute to epileptic activity via a TNF-α pathway, which has pharmacological implications to target specific HIF-1α and TNF-α pathways for neuronal dysfunction and vulnerability related to epilepsy.

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Section: Discussionsupporting

confidence: 81%

Inhibiting HIF-1α Decreases Expression of TNF-α and Caspase-3 in Specific Brain Regions Exposed Kainic Acid-Induced Status Epilepticus

Yang

He²,

Meng³

et al. 2016

Cell Physiol Biochem

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“…These processes may be kept in check for the restoration of homeostasis in the CNS. Neurons may inactivate immunocompetent cells by several mechanisms dependent on cell-cell contact or the secretion of soluble factors such as neurotrophins and neurotransmitters [3,16,31]. The balance between the induction and inhibition of several types of cells allows brain parenchyma remodelling and rebuilding following brain injury.…”

Section: Resultsmentioning

confidence: 99%

Morphological evidence of the beneficial role of immune system cells in a rat model of surgical brain injury

Frontczak-Baniewicz

Sulejczak

Andrychowski³

et al. 2013

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“…It is assumed that this discrepancy is likely due to intracellular signaling mechanisms for PICs to play a role. A great deal of evidence has demonstrated that IL-1β and TNF-α play a role mainly via p38 MAPK, ERK and JNK signaling transduction pathways, but IL-6 plays a role via JAK-STAT pathways [27][28][29]. After activation of those signaling pathways, gene transcription occurs [30][31][32].…”

Section: Discussionmentioning

confidence: 99%

Nefiracetam Attenuates Pro-Inflammatory Cytokines and GABA Transporter in Specific Brain Regions of Rats with Post-Ischemic Seizures

Fu¹,

He²,

Li³

et al. 2015

Cell Physiol Biochem

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Background/Aims: Prior studies demonstrated that pro-inflammatory cytokines (PICs) including IL-1β, IL-6 and TNF-α contribute to regulation of epilepsy-associated pathophysiological processes in the specific brain regions, namely the parietal cortex, hippocampus and amygdala. Moreover, GABA transporter type 1 and 3 (GAT-1 and GAT-3) modulating extracellular GABA levels are engaged in the role played by PICs in epileptogenesis. Note that brain ischemic injury also elevates cerebral PICs. Thus, in this report we examined the effects of nefiracetam (NEF), a pyrrolidone derivative, on the levels of IL-1β, IL-6 and TNF-α, and expression of GAT-1 and GAT-3 in the parietal cortex, hippocampus and amygdala using a rat model of post-ischemic nonconvulsive seizure (NCS). Methods: NCS was evoked by the middle cerebral artery occlusion (MCAO). ELISA and Western Blot analysis were employed to determine the levels of PICs and GAT-1/GAT-3, respectively. Results: MCAO significantly increased IL-1β, IL-6 and TNF-α in the parietal cortex, hippocampus and amygdala as compared with sham control animals (P<0.05 vs. control rats). Also, in these specific brain regions expression of GAT-1 and GAT-3 was amplified; and the levels of GABA were decreased in rats following MCAO (P<0.05 vs. control rats). Systemic administration of NEF significantly attenuated the elevated PICs, amplified GAT-1 and GAT-3 as well as impaired GABA. NEF also attenuated the number of NCS events following MCAO. Conclusion: our data demonstrate that NEF improves post-ischemia evoked-NCS by altering PICs, GABA transporters thereby alleviating GABA in the parietal cortex, hippocampus and amygdala. This support a role for PICs and GABA in engagement of the adaptive responses associated with epileptic activity, but also suggests that NEF has anti-epileptic effects via PICs-GABA mechanisms, having pharmacological implications to target the specific PICs for neuronal dysfunction and vulnerability related to post-ischemic seizures and cognitive impairment.

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Neuro-Immune Crosstalk in CNS Diseases

Cited by 55 publications

References 115 publications

Inhibiting HIF-1α Decreases Expression of TNF-α and Caspase-3 in Specific Brain Regions Exposed Kainic Acid-Induced Status Epilepticus

Inhibiting HIF-1α Decreases Expression of TNF-α and Caspase-3 in Specific Brain Regions Exposed Kainic Acid-Induced Status Epilepticus

Morphological evidence of the beneficial role of immune system cells in a rat model of surgical brain injury

Nefiracetam Attenuates Pro-Inflammatory Cytokines and GABA Transporter in Specific Brain Regions of Rats with Post-Ischemic Seizures

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