Reverse triiodothyronine (rT3) attenuates ischemia-reperfusion injury
Open accessAbstract
Hypothyroidism has been associated with better recovery from cerebral ischemia-reperfusion (IR) injury in humans. However, any therapeutic advantage of inducing hypothyroidism for mitigating IR injury without invoking the adverse effect of whole body hypothyroidism remains a challenge. We hypothesize that a deiodinase II (D2) inhibitor reverse triiodothyronine (rT3) may render brain specific hypometabolic state to ensue reduced damage during an acute phase of cerebral ischemia without affecting circulating thyroid hormone levels. Preclinical efficacy of rT3 as a neuroprotective agent was determined in rat model of middle cerebral artery occlusion (MCAO) induced cerebral IR and in oxygen glucose deprivation/reoxygenation (OGD/R) model in vitro. rT3 administration in rats significantly reduced neuronal injury markers, infarct size and neurological deficit upon ischemic insult. Similarly, rT3 increased cellular survival in primary cerebral neurons under OGD/R stress. Based on our results from both in vivo as well as in vitro models of ischemia reperfusion injury we propose rT3 as a novel therapeutic agent in reducing neuronal damage and improving stroke outcome.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
T3 has an effect on glial morphology and hence on glial function in the adult brain; therefore, it also has an effect on neuron-glia interactions.
“T3 has an effect on glial morphology and hence on glial function in the adult brain; therefore, it also has an effect on neuron-glia interactions. 115 , 116”
From Major depressive disorder: hypothesis, mechanism, prevention and treatment (2024) · cites this paper as [116]
The Results section on deiodinase expression reports that rT3 reduced glial D2 and increased neuronal D3, but does not address glial morphology or neuron–glia interactions. Searches for glial morphology, glial function, and neuron–glia interactions found no passage supporting the claim about T3 in the adult brain. Page numbers were not available in our copy. (LLM, conf=0.75)
Experimental — accuracy not yet measured
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Bederson, J. B., Pitts, L. H., Tsuji, M., Nishimura, M. C., Davis, R. L., & Bartkowski, H. (1986) · Stroke · doi:10.1161/01.str.17.3.472 · Cited by 2,681 · see citing works
Mitochondria, oxidative metabolism and cell death in stroke
Sims, N. R., & Muyderman, H. (2009) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2009.09.003 · Cited by 675 · see citing works
Simonides, W. S., Mulcahey, M. A., Redout, E. M., Muller, A., Zuidwijk, M. J., Visser, T. J., Wassen, F. W. J. S., Crescenzi, A., da‐Silva, W. S., Harney, J. W., et al. (2008) · Journal of Clinical Investigation · doi:10.1172/jci32824 · Cited by 270 · see citing works
The Role of Thyroid Hormones as Inductors of Oxidative Stress and Neurodegeneration
Villanueva, I., Alva-Sánchez, C., & Pacheco-Rosado, J. (2013) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2013/218145 · Cited by 204 · see citing works
Low triiodothyronine: a strong predictor of outcome in acute stroke patients
Alevizaki, M. K., Synetou, M., Xynos, K., Παππά, Θ., & Vemmos, K. N. (2007) · European Journal of Clinical Investigation · doi:10.1111/j.1365-2362.2007.01839.x · Cited by 115 · see citing works
Steinsapir, J., Bianco, A. C., Buettner, C., Harney, J., & Larsen, P. R. (2000) · Endocrinology · doi:10.1210/endo.141.3.7355 · Cited by 109 · see citing works
Koibuchi, N., Fukuda, H., & Chin, W. W. (1999) · Endocrinology · doi:10.1210/endo.140.9.6997 · Cited by 87 · see citing works
Rastogi, L., Godbole, M. M., Ray, M., et al. (2006) · Experimental Neurology · doi:10.1016/j.expneurol.2006.02.013 · Cited by 72 · see citing works
Self-citationType 2 Deiodinase Disruption in Astrocytes Results in Anxiety-Depressive-Like Behavior in Male Mice
Bocco, B. M. L. C., Werneck‐de‐Castro, J. P., Oliveira, K. C., Fernandes, G. W., Fonseca, T. L., do Nascimento, B. P. P., McAninch, E. A., Ricci, E. L., Kvárta-Papp, Z., Fekete, C., et al. (2016) · Endocrinology · doi:10.1210/en.2016-1272 · Cited by 63 · see citing works
Prognostic value of thyroid hormones in acute ischemic stroke – a meta analysis
Jiang, X., Xing, H., Wu, J., Du, R., Liu, H., Chen, J., Wang, J., Wang, C., & Wu, Y. (2017) · Scientific Reports · doi:10.1038/s41598-017-16564-2 · Cited by 57 · see citing works
Thyroid Hormone Deiodinases in the Central and Peripheral Nervous System
Courtin, F., Zrouri, H., Lamirand, A., Li, W. W., MERCIER, G., Schumacher, M., Goascogne, C. L., & Pierre, M. (2005) · Thyroid · doi:10.1089/thy.2005.15.931 · Cited by 56 · see citing works
Subclinical Hyperthyroidism Is a Risk Factor for Poor Functional Outcome After Ischemic Stroke
Wollenweber, F. A., Zietemann, V., Gschwendtner, A., Opherk, C., & Dichgans, M. (2013) · Stroke · doi:10.1161/strokeaha.113.000833 · Cited by 55 · see citing works
Decreased Glutamate Release during Hypothyroidism May Contribute to Protection in Cerebral Ischemia
Shuaib, A. M., Ijaz, S., Hemmings, S. J., et al. (1994) · Experimental Neurology · doi:10.1006/exnr.1994.1135 · Cited by 54 · see citing works
Hypothyroidism as a protective factor in acute stroke patients
Alevizaki, M. K., Synetou, M., Xynos, K., Alevizaki, C. C., & Vemmos, K. N. (2006) · Clinical Endocrinology · doi:10.1111/j.1365-2265.2006.02606.x · Cited by 53 · see citing works
Favorable functional outcomes in acute ischemic stroke patients with subclinical hypothyroidism
Akhoundi, F. H., Ghorbani, A., Soltani, A., & Meysamie, A. (2011) · Neurology · doi:10.1212/wnl.0b013e3182267ba0 · Cited by 52 · see citing works
Thyroid hormones and functional outcomes after ischemic stroke
O’Keefe, L. M., Conway, S. E., Czap, A. L., et al. (2015) · Thyroid Research · doi:10.1186/s13044-015-0021-7 · Cited by 52 · see citing works
Low free triiodothyronine predicts poor functional outcome after acute ischemic stroke
Suda, S., Muraga, K., Kanamaru, T., Okubo, S., Abe, A., Aoki, J., Suzuki, K., Sakamoto, Y., Shimoyama, T., Nito, C., et al. (2016) · Journal of the Neurological Sciences · doi:10.1016/j.jns.2016.06.063 · Cited by 44 · see citing works
Favorable Influence of Subclinical Hypothyroidism on the Functional Outcomes in Stroke Patients
Baek, J., Chung, P., Kim, Y. B., et al. (2010) · Endocrine Journal · doi:10.1507/endocrj.k09e-206 · Cited by 39 · see citing works
Obregón, M.-J., Larsen, P. R., & Silva, J. E. (1986) · Endocrinology · doi:10.1210/endo-119-5-2186 · Cited by 38 · see citing works
Thyroid Hormone Regulation of Adult Neurogenesis
Fanibunda, S. E., Desouza, L. A., Kapoor, R., Vaidya, R. A., & Vaidya, V. A. (2017) · Vitamins and hormones · doi:10.1016/bs.vh.2017.04.006 · Cited by 38 · see citing works
Differences in sensitivity of cultured rat brain neuronal and glial cytochrome P450 2E1 to ethanol
Kapoor, N., Pant, A. B., Dhawan, A., Dwievedi, U. N., Gupta, Y. K., Seth, P. K., & Parmar, D. (2006) · Life Sciences · doi:10.1016/j.lfs.2006.04.023 · Cited by 37 · see citing works
Margaill, I., Royer, J., Lerouet, D., Ramaugé, M., Goascogne, C. L., Li, W. W., Plotkine, M., Pierre, M., & Courtin, F. (2005) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1038/sj.jcbfm.9600041 · Cited by 36 · see citing works
Liu, J., Wang, D., Xiong, Y., Yuan, R., Tao, W., & Liu, M. (2016) · Neurological Research · doi:10.1080/01616412.2016.1178480 · Cited by 17 · see citing works
Rastogi, L., Gupta, S. K., & Godbole, M. M. (2007) · Journal of Endocrinology · doi:10.1677/joe-07-0483 · Cited by 16 · see citing works
Self-citationTavakoli‐Far, B., Rahbar‐Roshandel, N., Rahimi‐Moghaddam, P., et al. (2009) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2009.03.017 · Cited by 16 · see citing works
Domingues, J. T., Cattani, D., Cesconetto, P. A., de Almeida, B. A. N., Pierozan, P., dos Santos, K., Razzera, G., Silva, F. R. M. B., Pessoa‐Pureur, R., & Zamoner, A. (2017) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2017.11.013 · Cited by 16 · see citing works
Cettour-Rose, P., Visser, T. J., Burger, A. G., & Rohner-Jeanrenaud, F. (2005) · European Journal of Endocrinology · doi:10.1530/eje.1.01984 · Cited by 14 · see citing works
Effect of sub-clinical hypothyroidism on clinical severity in first-ever acute ischemic stroke.
Oshinaike, O. O., Ogbera, A. O., Azenabor, A., et al. (2016) · PubMed · Cited by 7 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Major depressive disorder: hypothesis, mechanism, prevention and treatment
Cui, L., Li, S., Wang, S., Wu, X., Liu, Y., Yu, W., Wang, Y., Tang, Y., Xia, M., & Li, B. (2024) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-024-01738-y · Cited by 1,061 · see citing works
“115,116 It has been shown that T3 induces astrocyte proliferation by autocrine production of growth factors such as epidermal growth factor (EGF) and FGF-2.”
BackgroundParadigms of dynamic control of thyroid hormone signaling
Bianco, A. C., Dumitrescu, A., Gereben, B., Ribeiro, M. O., Fonseca, T. L., Fernandes, G. W., & Bocco, B. M. L. C. (2019) · Endocrine Reviews · doi:10.1210/er.2018-00275 · Cited by 293 · see citing works
Intrathyroidal feedforward and feedback network regulating thyroid hormone synthesis and secretion
Jing, L., & Zhang, Q. (2022) · Frontiers in Endocrinology · doi:10.3389/fendo.2022.992883 · Cited by 61 · see citing works
Binding Characteristics of Thyroid Hormone Distributor Proteins to Thyroid Hormone Metabolites
Jongejan, R. M. S., Meima, M. E., Visser, W. E., Korevaar, T. I. M., van den Berg, S. A. A., Peeters, R. P., & de Rijke, Y. B. (2022) · Thyroid® · doi:10.1089/thy.2021.0588 · Cited by 20 · see citing works
- Authors
- Rastogi, L., Godbole, M. M., Sinha, R. A., & Pradhan, S.
- Affiliations
- Babasaheb Bhimrao Ambedkar University (IN)
- Sanjay Gandhi Post Graduate Institute of Medical Sciences (IN)
- Corresponding author
- Godbole, Madan M.
- Venue
- Biochemical and Biophysical Research Communications
- Publisher
- Elsevier BV
- Published
- 2018-11
- Volume
- 506
- Issue
- 3
- Pages
- 597-603
- ISSN
- 0006-291X (ISSN-L)
- PMC
- PMC7212030
- OpenAlex
- W2896889098
- Cited by
- 22
- References
- 29
- Citations by year
- 2025: 4 · 2024: 2 · 2023: 1 · 2022: 6 · 2021: 2 · 2020: 4 · 2019: 3
- FWCI
- 1.01
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- Locations
- Biochemical and Biophysical Research Communications (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- The Wellcome Trust DBT India Alliance (IA/I/16/2/502691)
- Rochester Academy of Science (1592/DEL/2015)
- Department of Science and Technology, Government of West Bengal (SR/WOS-A/LS-204/2007)
- Topics
- Life Sciences › Neuroscience › Neurology › Neurological Disorders and Treatments
- Health Sciences › Medicine › Epidemiology › Acute Ischemic Stroke Management
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Thyroid Disorders and Treatments
- Keywords
- ischemia-reperfusion injury, cerebral ischemia, stroke, neuroprotection, hypothyroidism, middle cerebral artery occlusion, oxygen-glucose deprivation/reoxygenation, neuronal injury, infarct size, neurological deficit, thyroid hormone metabolism
- MeSH terms
- Animals, Blood Pressure, Cells, Cultured, Glucose, Heart Rate, Iodide Peroxidase, Male, Neurons, Triiodothyronine, Reverse, Reperfusion Injury, Rats, Sprague-Dawley, Oxidative Stress, Protective Agents
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
