TRIF contributes to epileptogenesis in temporal lobe epilepsy during TLR4 activation

Wang, Faxiang; Yang, Xiaolin; Ma, Yuanshi; Wang, Yu; Yang, Meihua; Chen, Xin; Chen, Bing; He, Qian; Yang, Qingwu; Yang, Hui; Liu, Shiyong

doi:10.1016/j.bbi.2017.07.157

Cited by 21 publications

(21 citation statements)

References 60 publications

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“…We here extended these observations and showed that the TLR4 innate immunity receptor is expressed in resident microglia, reactive astrocytes and stressed neurons from hippocampus and piriform cortex during the latency period after the IPE. The innate immunity participation in epileptogenesis has been proposed [ 34 , 51 , 52 ] and specifically TLR4 receptor expression was directly linked to epilepsy development [ 7 , 10 , 53 , 54 , 55 ]. Various experimental approaches have shown that targeting IL1β/TLR4 signaling may prevent epileptogenesis, showing disease-modifying effects [ 7 , 56 ].…”

Section: Discussionmentioning

confidence: 99%

Early Gabapentin Treatment during the Latency Period Increases Convulsive Threshold, Reduces Microglial Activation and Macrophage Infiltration in the Lithium-Pilocarpine Model of Epilepsy

et al. 2017

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The lithium-pilocarpine model of epilepsy reproduces several features of temporal lobe epilepsy in humans, including the chronological timeline of an initial latency period followed by the development of spontaneous seizures. Epilepsy therapies in humans are implemented, as a rule, after the onset of the spontaneous seizures. We here studied the potential effect on epileptogenesis of starting an early treatment during the latency period, in order to prevent the development of spontaneous seizures. Adult male Wistar rats were treated with 3 mEq/kg LiCl, and 20 h later 30 mg/kg pilocarpine. Once status epilepticus (SE) was achieved, it was allowed to last for 20 min, and then motor seizures were controlled with the administration of 20 mg/kg diazepam. At 1DPSE (DPSE, days post-status epilepticus), animals started to receive 400 mg/kg/day gabapentin or saline for 4 days. At 5DPSE, we observed that SE induced an early profuse microglial and astroglial reactivity, increased synaptogenic trombospondin-1 expression and reduced AQP4 expression in astroglial ending feet. Blood brain barrier (BBB) integrity seemed to be compromised, as infiltrating NG2+ macrophages and facilitated access to the CNS was observed by transplanting eGFP+ blood cells and bone marrow-derived progenitors in the SE animals. The early 4-day gabapentin treatment successfully reduced microglial cell reactivity and blood-borne cell infiltration, without significantly altering the mRNA of proinflammatory cytokines IL-1β and TNFα immediately after the treatment. After 21DSPE, another group of animals that developed SE and received 4 days of gabapentin treatment, were re-exposed to subconvulsive accumulative doses of pilocarpine (10 mg/kg/30 min) and were followed by recording the Racine scale reached. Early 4-day gabapentin treatment reduced the Racine scale reached by the animals, reduced animal mortality, and reduced the number of animals that achieved SE (34% vs. 72%). We conclude that early gabapentin treatment following SE, during the latency period, is able to reduce neuroinflammation and produces a persistent effect that limits seizures and increases convulsive threshold, probably by restricting microglial reactivity and spurious synaptogenesis.

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Section: Discussionmentioning

confidence: 99%

Early Gabapentin Treatment during the Latency Period Increases Convulsive Threshold, Reduces Microglial Activation and Macrophage Infiltration in the Lithium-Pilocarpine Model of Epilepsy

et al. 2017

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“…We utilized the Fluoro-Jade B (FJB) stain to assess degenerative neurons according to our previous study [19]. Briefly, brain tissues were dehydrated in 15–30% sucrose solutions and cut into 25 µm thick sections.…”

Section: Methodsmentioning

confidence: 99%

Young plasma ameliorates aging-related acute brain injury after intracerebral hemorrhage

et al. 2019

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Aging has been shown to contribute to both the declined biofunctions of aging brain and aggravation of acute brain damage, and the former could be reversed by young plasma. These results suggest that young plasma treatment may also reduce the acute brain damage induced by intracerebral hemorrhage (ICH). In the present study, we first found that the administration of young plasma significantly reduced the mortality and neurological deficit score in aging ICH rodents, which might be due to the decreased brain water content, damaged neural cells, and increased survival neurons around the perihematomal brain tissues. Then, proteomics analysis was used to screen out the potential neuroprotective circulating factors and the results showed that many factors were changed in health human plasma among young, adult, and old population. Among these significantly changed factors, the plasma insulin-like growth factor 1 (IGF-1) level was significantly decreased with age, which was further confirmed both in human and rats detected by ELISA. Additionally, the brain IGF-1 protein level in aging ICH rats was markedly decreased when compared with young rats. Interestingly, the relative decreased brain IGF-1 level was reversed by the treatment of young plasma in aging ICH rats, while the mRNA level was non-significantly changed. Furthermore, the IGF-1 administration significantly ameliorated the acute brain injury in aging ICH rats. These results indicated that young circulating factors, like IGF-1, may enter brain tissues to exert neuroprotective effects, and young plasma may be considered as a novel therapeutic approach for the clinical treatment of aging-related acute brain injury.

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“…FJB staining was performed as described in our previous study [21]. Briefly, brain tissues were dehydrated in 30% sucrose solution and cut into 10-μm-thick sections.…”

Section: Fluoro-jade B (Fjb) Stainingmentioning

confidence: 99%

“…Nissl staining was performed according to our previously described method [21]. Briefly, brain tissue sections were stained with thionin (Sigma-Aldrich), dehydrated in alcohol, cleared in xylene, and then sealed with coverslips to allow the perihematomal brain tissues to be observed.…”

Section: Nissl Stainingmentioning

confidence: 99%

Age-related CCL12 Aggravates Intracerebral Hemorrhage-induced Brain Injury via Recruitment of Macrophages and T Lymphocytes

et al. 2020

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Circulating factors associated with aging have been shown to be involved in the development of age-related chronic and acute brain diseases. Here, we aimed to investigate the roles and mechanisms of CCL12, a circulating factor that is highly expressed in the plasma of aged rodents after intracerebral hemorrhage (ICH) using parabiosis and ICH models. Neurological deficit score (NDS), mortality rate, brain water content (BWC), and levels of inflammatory factors were determined to assess the degree of ICH-induced brain injury. Peripheral inflammatory cell infiltration was examined using immunofluorescence and flow cytometry. After confirming that acute brain injury after ICH was aggravated with age, we found that brain and plasma CCL12 levels were markedly higher in old mice than in young mice after ICH, and that plasma CCL12 was able to enter the brain. Using CCL12-/mice, we showed that the degree of damage in the brain-as determined by NDS, mortality rate, BWC, levels of inflammatory factors, and numbers of degenerative and apoptotic neural cells and surviving neurons was significantly attenuated compared to that observed in old wild-type (WT) mice. These effects were reversed in CCL12-treated old mice. The detrimental effects caused by CCL12 may involve its ability to recruit macrophages and T cells. Finally, the administration of an anti-CCL12 antibody markedly improved the outcomes of ICH mice. Our results are the first to indicate that elevated peripheral CCL12 levels in old mice aggravates ICH-induced brain injury by recruiting macrophages and T cells. Thus, CCL12 may be a new target for ICH treatment.

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TRIF contributes to epileptogenesis in temporal lobe epilepsy during TLR4 activation

Cited by 21 publications

References 60 publications

Early Gabapentin Treatment during the Latency Period Increases Convulsive Threshold, Reduces Microglial Activation and Macrophage Infiltration in the Lithium-Pilocarpine Model of Epilepsy

Early Gabapentin Treatment during the Latency Period Increases Convulsive Threshold, Reduces Microglial Activation and Macrophage Infiltration in the Lithium-Pilocarpine Model of Epilepsy

Young plasma ameliorates aging-related acute brain injury after intracerebral hemorrhage

Age-related CCL12 Aggravates Intracerebral Hemorrhage-induced Brain Injury via Recruitment of Macrophages and T Lymphocytes

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