Stimulation of neurotrophic factors and inhibition of proinflammatory cytokines by exogenous application of triiodothyronine in the rat model of ischemic stroke

Sabbaghziarani, Fatemeh; Mortezaee, Keywan; Akbari, Mohammad; Kashani, Iraj Ragerdi; Soleimani, Mansooreh; Hassanzadeh, Gholamreza; Zendedel, Adib

doi:10.1002/cbf.3244

Cited by 16 publications

(19 citation statements)

References 18 publications

(46 reference statements)

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“…Two studies reported evident reductions of tissue infarction and edema in a transient middle cerebral artery occlusion (t-MCAO) model of male mice injected with T3, and attributed this anti-edema effect to suppression of the expression of aquaporin-4 (AQP4) water channels by T3 36 , 37 . Studies also found that T3 and T4 could inhibit apoptosis, resist excitability-related amino acid toxicity, suppress inflammatory reactions and increase ATP production by stimulation of astrocyte fatty acid oxidation in animal models of brain ischemia 34 , 35 , 38 , 39 . However, other experiments reported contradictory discoveries.…”

Section: Discussionmentioning

confidence: 97%

Prognostic value of thyroid hormones in acute ischemic stroke – a meta analysis

Jiang

Xing

et al. 2017

Sci Rep

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Previous studies on the association between thyroid hormones and prognosis of acute ischemic stroke (AIS) reported conflicting results. We conducted a meta-analysis to assess the prognostic value of thyroid hormones in AIS. The PubMed, EMBASE, and Cochrane library databases were searched through May 12, 2017 to identify eligible studies on this subject. Out of 2,181 studies retrieved, 11 studies were finally included with a total number of 3,936 acute stroke patients for analysis. Odds ratio (OR) for predicting poor outcome or standardized mean difference (SMD) of thyroid hormone levels with 95% confidence intervals (95% CI) obtained from the studies were pooled using Review Manager 5.3. From the results, in AIS, patients with a poor outcome had lower levels of triiodothyronine (T3) and higher thyroxine (T4). Pooled OR confirmed the same association. Our study provides statistical evidence supporting the utility of thyroid hormone levels in prognosis of acute stroke.

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Section: Discussionmentioning

confidence: 97%

Prognostic value of thyroid hormones in acute ischemic stroke – a meta analysis

Jiang

Xing

et al. 2017

Sci Rep

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“…Thyroid hormones (THs), including triiodothyronine (T3) and thyroxine (T4), are essential for brain development, morphogenesis and maturation processes [11]. Studies in animal stroke model have shown that T3 has therapeutic effects on cerebral ischemic stroke by increasing the neurotrophic factors and in vitro reduction of inflammation and restoration of neurotrophin expression, which lead to better neurological function [12, 13]. Despite the mechanisms depicted by the above studies, the detailed signaling pathways by which T3 affects functional outcome of stroke patients remain to be elucidated.…”

Section: Introductionmentioning

confidence: 99%

Low free triiodothyronineis predicts worsen neurological outcome of patients with acute ischemic stroke: a retrospective study with bioinformatics analysis

Zhang

Zhao

et al. 2019

BMC Neurol

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BackgroudPatients with acute ischemic stroke (AIS) often experience low serum free triiodothyronine (FT3), but the association of low FT3 with stroke severity, subtype and prognosis has not yet been thoroughly studied, and the molecular events underlying these clinical observation were also unclear.MethodsWe retrospectively collected 221 cases of AIS and 182 non-AIS cases with detailed clinical data from our department. FT3 concentrations were measured on admission to predict functional outcome within 3 months using multivariable models adjusted for other risk factors. Receiver operating characteristic (ROC) curves were calculated to define the best cutoff value of FT3 of stroke severity, subtypes and neurological outcome. Gene set enrichment, pathway mapping and network analyses of deferentially expressed genes (DEGs) were performed.ResultsFT3 was significantly decreased in AIS patients with National Institutes of Health Stroke Scale (NIHSS) > 3 and 3-months modified Rankin Scale (mRS) > 2. The cut-off value of FT3 for NIHSS on admission was 4.30 pmol/L. Also, FT3 level was significantly lower in large artery atherosclerosis (LAA) group and cardioembolism (CE) group than that in small vessel occlusion (SVO). FT3 value served as an independent predictor for neurological outcomes for which the cut-off value of FT3 was 4.38 pmol/l. Gene ontology (GO) analysis showed that the biological function of DEGs was mainly enriched in multicellur organism, neuron differentiation and cellular response to hypoxia. The cellular components were involved in extracelluar region, exosome and matrix, and the molecular functions were transcriptional activator activity, DNA binding and nuclear hormone receptor binding. Signal pathways analysis was indicative of neuroactive ligand-receptor interaction, thyroid hormone signaling pathway, and protein digestion and absorption these DEGs were involved in. Six related gene were identified as hubs from the protein-protein interaction (PPI) networks. Three modules were selected from PPI, of which MMP4, ADRA2C and EIF3E were recognized as the seed genes.ConclusionsLow FT3 value on admission was associated with stroke severity, subtype and prognosis. In addition, DEGs identified from bioinformatics analysis are likely to be candidates for elucidating clinical outcomes with low FT3, and provide us with therapeutic targets for improving stroke prognosis.

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“…- Sabbaghziarani et al 2017: similar to previous study from Mokhtari et al (2017), here cerebral ischemia was induced by MCAo in male Wistar rats; a group of rats was also injected with T3 (25 μg/kg, IV injection) at 24 hours after ischemia. BDNF gene and protein levels (along with nestin and Sox2) were increased upon T3 treatment vs ischemic group.…”

Section: Empirical Evidencementioning

confidence: 71%

Adverse Outcome Pathway on inhibition of Na+/I- symporter (NIS) leads to learning and memory impairment

Rolaki

Pistollato

Munn

et al. 2019

OECD Series on Adverse Outcome Pathways

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This Adverse Outcome Pathway (AOP) on Inhibition of Na+/I-symporter (NIS) leads to learning and memory impairment, has been developed under the auspices of the OECD AOP Development Programme, overseen by the Extended Advisory Group on Molecular Screening and Toxicogenomics (EAGMST), which is an advisory group under the Working Group of the National Coordinators for the Test Guidelines Programme (WNT). The AOP has been reviewed internally by the EAGMST, externally by experts nominated by the WNT, and has been endorsed by the WNT and the Working Party on Hazard Assessment (WPHA) in May 2019. Through endorsement of this AOP, the WNT and the WPHA express confidence in the scientific review process that the AOP has undergone and accept the recommendation of the EAGMST that the AOP be disseminated publicly. Endorsement does not necessarily indicate that the AOP is now considered a tool for direct regulatory application. The Joint Meeting of the Chemicals Committee and the Working Party on Chemicals, Pesticides and Biotechnology agreed to declassification of this AOP on 26 June 2019. This document is being published under the responsibility of the Joint Meeting of the Chemicals Committee and the Working Party on Chemicals, Pesticides and Biotechnology. The outcome of the internal and external reviews are publicly available respectively in the AOP Wiki and the eAOP Portal of the AOP Knowledge Base at the following links: [internal review] [external review].

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Stimulation of neurotrophic factors and inhibition of proinflammatory cytokines by exogenous application of triiodothyronine in the rat model of ischemic stroke

Cited by 16 publications

References 18 publications

Prognostic value of thyroid hormones in acute ischemic stroke – a meta analysis

Prognostic value of thyroid hormones in acute ischemic stroke – a meta analysis

Low free triiodothyronineis predicts worsen neurological outcome of patients with acute ischemic stroke: a retrospective study with bioinformatics analysis

Adverse Outcome Pathway on inhibition of Na+/I- symporter (NIS) leads to learning and memory impairment

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