Dataset Information

Identification of TIMP1 as an inflammatory biomarker associated with temporal lobe epilepsy based on integrated bioinformatics and experimental analyses.

ABSTRACT:

Background

Epilepsy is the second most prevalent neurological disease. Although there are many antiseizure drugs, approximately 30% of cases are refractory to treatment. Temporal lobe epilepsy (TLE) is the most common epilepsy subtype, and previous studies have reported that hippocampal inflammation is an important mechanism associated with the occurrence and development of TLE. However, the inflammatory biomarkers associated with TLE are not well defined.

Methods

In our study, we merged human hippocampus datasets (GSE48350 and GSE63808) through batch correction and generally verified the diagnostic roles of inflammation-related genes (IRGs) and subtype classification according to IRGs in epilepsy through differential expression, random forest, support vector machine, nomogram, subtype classification, enrichment, protein‒protein interaction, immune cell infiltration, and immune function analyses. Finally, we detected the location and expression of inhibitor of metalloproteinase-1 (TIMP1) in epileptic patients and kainic acid-induced epileptic mice.

Results

According to the bioinformatics analysis, we identified TIMP1 as the most significant IRG associated with TLE, and we found that TIMP1 was mainly located in cortical neurons and scantly expressed in cortical gliocytes by immunofluorescence staining. We detected decreased expression of TIMP1 by quantitative real-time polymerase chain reaction and western blotting.

Conclusion

TIMP1, the most significant IRG associated with TLE, might be a novel and promising biomarker to study the mechanism of epilepsy and guide the discovery of new drugs for its treatment.

SUBMITTER: He Y

PROVIDER: S-EPMC10294353 | biostudies-literature | 2023 Jun

REPOSITORIES: biostudies-literature

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Publications

Identification of TIMP1 as an inflammatory biomarker associated with temporal lobe epilepsy based on integrated bioinformatics and experimental analyses.

He Ya Y Zhang Hongxia H Ma Limin L Li Jingang J Wang Fei F Zhou Hui H Zhang Guangliang G Wen Yuetao Y

Journal of neuroinflammation 20230626 1

<h4>Background</h4>Epilepsy is the second most prevalent neurological disease. Although there are many antiseizure drugs, approximately 30% of cases are refractory to treatment. Temporal lobe epilepsy (TLE) is the most common epilepsy subtype, and previous studies have reported that hippocampal inflammation is an important mechanism associated with the occurrence and development of TLE. However, the inflammatory biomarkers associated with TLE are not well defined.<h4>Methods</h4>In our study, we ...[more]

PMID: 37365625

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Project description:Drug-resistant mesial-temporal lobe epilepsy is a devastating disease with seizure onset in the hippocampal formation. A fraction of hippocampi samples from epilepsy-surgical procedures reveals a peculiar histological pattern referred to as 'gliosis only' with unresolved pathogenesis and enigmatic sequelae. Here, we hypothesize that 'gliosis only' represents a particular syndrome defined by distinct clinical and molecular characteristics. We curated an in-depth multiparameter integration of systematic clinical, neuropsychological as well as neuropathological analysis from a consecutive cohort of 627 patients, who underwent hippocampectomy for drug-resistant temporal lobe epilepsy. All patients underwent either classic anterior temporal lobectomy or selective amygdalohippocampectomy. On the basis of their neuropathological exam, patients with hippocampus sclerosis and 'gliosis only' were characterized and compared within the whole cohort and within a subset of matched pairs. Integrated transcriptional analysis was performed to address molecular differences between both groups. 'Gliosis only' revealed demographics, clinical and neuropsychological outcome fundamentally different from hippocampus sclerosis. 'Gliosis only' patients had a significantly later seizure onset (16.3 versus 12.2 years, P = 0.005) and worse neuropsychological outcome after surgery compared to patients with hippocampus sclerosis. Epilepsy was less amendable by surgery in 'gliosis only' patients, resulting in a significantly worse rate of seizure freedom after surgery in this subgroup (43% versus 68%, P = 0.0001, odds ratio = 2.8, confidence interval 1.7-4.7). This finding remained significant after multivariate and matched-pairs analysis. The 'gliosis only' group demonstrated pronounced astrogliosis and lack of significant neuronal degeneration in contrast to characteristic segmental neuron loss and fibrillary astrogliosis in hippocampus sclerosis. RNA-sequencing of gliosis only patients deciphered a distinct transcriptional programme that resembles an innate inflammatory response of reactive astrocytes. Our data indicate a new temporal lobe epilepsy syndrome for which we suggest the term 'Innate inflammatory gliosis only'. 'Innate inflammatory gliosis only' is characterized by a diffuse gliosis pattern lacking restricted hippocampal focality and is poorly controllable by surgery. Thus, 'innate inflammatory gliosis only' patients need to be clearly identified by presurgical examination paradigms of pharmacoresistant temporal lobe epilepsy patients; surgical treatment of this subgroup should be considered with great precaution. 'Innate inflammatory gliosis only' requires innovative pharmacotreatment strategies.

Dataset Information

Identification of TIMP1 as an inflammatory biomarker associated with temporal lobe epilepsy based on integrated bioinformatics and experimental analyses.

Background

Methods

Results

Conclusion

Publications

Identification of TIMP1 as an inflammatory biomarker associated with temporal lobe epilepsy based on integrated bioinformatics and experimental analyses.

Similar Datasets

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