Evidence map›Paper›PMID 30075790›Full record

ArticleJournal of neuroinflammation2018

Metalloprotease Adam10 suppresses epilepsy through repression of hippocampal neuroinflammation.

Xinjian Zhu, Xiaolin Li, Mengyi Zhu, Kangni Xu, Li Yang, Bing Han, Rongrong Huang, Aifeng Zhang, Honghong Yao

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Journal of neuroinflammation, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.

0numbers the graph read from it
0cells of the map it votes in
16citing papers in PubMed
0.8field-weighted citation impact, top 27% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

16 citing papers in PubMed, 26 citations in OpenAlex.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

9 authors at 2 institutions in 1 country.

Xinjian ZhuDepartment of Pharmacology, Medical School of Southeast University, Dingjiaqiao 87th, Nanjing, 210009, China. xinjianzhu@seu.edu.cn.
Xiaolin LiDepartment of Geriatrics, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
Mengyi ZhuDepartment of Pharmacology, Medical School of Southeast University, Dingjiaqiao 87th, Nanjing, 210009, China.
Kangni XuDepartment of Pharmacology, Medical School of Southeast University, Dingjiaqiao 87th, Nanjing, 210009, China.
Li YangDepartment of Pharmacology, Medical School of Southeast University, Dingjiaqiao 87th, Nanjing, 210009, China.
Bing HanDepartment of Pharmacology, Medical School of Southeast University, Dingjiaqiao 87th, Nanjing, 210009, China.
Rongrong HuangDepartment of Pharmacology, Medical School of Southeast University, Dingjiaqiao 87th, Nanjing, 210009, China.
Aifeng ZhangDepartment of Pathology, Medical School of Southeast University, Nanjing, China.
Honghong YaoDepartment of Pharmacology, Medical School of Southeast University, Dingjiaqiao 87th, Nanjing, 210009, China.
Southeast University · CNJiangsu Province Hospital · CN

Funding

National Natural Science Foundation of China 81673413Natural Science Foundation of Jiangsu Province BK20141335the Fundamental Research Funds for the Central Universities 2242017K3DN33the Fundamental Research Funds for the Central Universities 2242017K40095the Scientific Research Foundation of State Education Ministry for the Returned Overseas Chinese Scholars No.311, 2015the Specialized Research Fund for the Doctoral Program of Higher Education 20130092120043
6 · The paper itself

Abstract

backgroundMice with pilocarpine-induced temporal lobe epilepsy (TLE) are characterized by intense hippocampal neuroinflammation, a prominent pathological hallmark of TLE that is known to contribute to neuronal hyperexcitability. Recent studies indicate that Adam10, a member of a disintegrin and metalloproteinase domain-containing protein (Adam) family, has been involved in the neuroinflammation response. However, it remains unclear whether and how Adam10 modulates neuroinflammation responses in the context of an epileptic brain or whether Adam10 affects epileptogenesis via the neuroinflammation pathway.

methodsAdult male C57BL/6J mice were subjected to intraperitoneal injection of pilocarpine to induce TLE. Adeno-associated viral (AAV) vectors carrying Adam10 (AAV-Adam10) or lentiviral vectors carrying short hairpin RNA, which is specific to the mouse Adam10 mRNA (shRNA-Adam10), were bilaterally injected into the hippocampus to induce overexpression or knockdown of Adam10, respectively. The specific anti-inflammatory agent minocycline was administered following status epilepticus (SE) to block hippocampal neuroinflammation. Continuous video EEG recording was performed to analyze epileptic behavior. Western blot, immunofluorescence staining, and ELISA were performed to determine Adam10 expression as well as hippocampal neuroinflammation.

resultsIn this study, we demonstrate that overexpression of Adam10 in the hippocampus suppresses neuroinflammation and reduces seizure activity in TLE mice, whereas knockdown of Adam10 exacerbates hippocampal neuroinflammation and increases seizure activity. Furthermore, increased seizure activity in Adam10 knockdown TLE mice is dependent on hippocampal neuroinflammation.

conclusionThese results suggest that Adam10 suppresses epilepsy through repression of hippocampal neuroinflammation. Our findings provide new insights into the Adam10 regulation of development of epilepsy via the neuroinflammation pathway and identify a potential therapeutic target for epilepsy.

Indexed as

Status EpilepticusADAM10 ProteinAmyloid Precursor Protein SecretasesAnimalsCalcium-Binding ProteinsCyclooxygenase 2Disease Models, AnimalEncephalitisGene Expression RegulationGlial Fibrillary Acidic ProteinHippocampusMaleMembrane ProteinsMiceMice, Inbred C57BLMice, TransgenicADAM10 ProteinAdam10 protein, mouseAif1 protein, mouseAmyloid Precursor Protein SecretasesCalcium-Binding ProteinsCyclooxygenase 2Glial Fibrillary Acidic ProteinMembrane ProteinsMicrofilament ProteinsMuscarinic AgonistsNF-kappa BNitric Oxide Synthase Type IIPilocarpineRNA, MessengerRNA, Small InterferingAdam10HippocampusMetalloproteaseNeuroinflammationTemporal lobe epilepsy

Identifiers

PMID30075790
PMCPMC6091106
OpenAlexW2885917397

What OpenQuestion holds

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LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.