Failure of thyroid hormone treatment to prevent inflammation-induced white matter injury in the immature brain

Schang, Anne-Laure; Steenwinckel, Juliette Van; Chevenne, Didier; Alkmark, Mårten; Hagberg, Henrik; Gressèns, Pierre; Fleiss, Bobbi

doi:10.1016/j.bbi.2013.11.005

Cited by 41 publications

(54 citation statements)

References 47 publications

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“…However, success with T4 supplementation in animal models as well as in preterm infants has been mixed. In animal models, T4 supplementation enhanced OPC maturation in WMI associated with intraventricular hemorrhage but not WMI caused by severe inflammation (Vose, Vinukonda et al 2013, Schang, Van Steenwinckel et al 2014). In humans, no evidence yet exists for specific rescue of diffuse WMI (Osborn and Hunt 2007, Osborn and Hunt 2007), although the ongoing TIPITS trial suggests that there may be a weak correlation between free T4 levels and DTI disturbances (Ng, Turner et al 2014).…”

Section: Key Factors Controlling Delayed Maturation and Recoverymentioning

confidence: 99%

Controversies in preterm brain injury

Penn

Gressèns

Fleiss

et al. 2016

Neurobiology of Disease

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Section: Key Factors Controlling Delayed Maturation and Recoverymentioning

confidence: 99%

Controversies in preterm brain injury

Penn

Gressèns

Fleiss

et al. 2016

Neurobiology of Disease

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“…These results have been confirmed by other labs in the cuprizone demyelination model in mouse (Harsan et al, ) and rat (Castelo‐Branco et al, ; Franco et al, ; Silvestroff et al, ). Contrasting results have been obtained by TH treatment in perinatal inflammation‐induced white matter injury, either positive (perinatal hypoxa‐ischemia, Hung et al, ; intraventricular hemorrhage, Vose et al, ), or no effects (white matter injury induced by interleukin‐1β, Schang et al, ). The substantial differences in adult vs. neonatal models, make quite difficult to compare these data sets, also considering the delicate balance between maternal‐derived TH and the perinatal development of fetal thyroid function (Moog et al, ).…”

Section: Introductionmentioning

confidence: 95%

Inflammation severely alters thyroid hormone signaling in the central nervous system during experimental allergic encephalomyelitis in rat: Direct impact on OPCs differentiation failure

Fernández

Baldassarro

Sivilia

et al. 2016

Glia

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Differentiation of oligodendrocyte precursor cells (OPCs) into myelinating oligodendrocytes is severely impaired by inflammatory cytokines and this could lead to remyelination failure in inflammatory/demyelinating diseases. Due to the role of thyroid hormone in the maturation of OPCs and developmental myelination, in this study we investigated (i) the possible occurrence of dysregulation of thyroid hormone signaling in the CNS tissue during experimental neuroinflammation; (ii) the possible impact of inflammatory cytokines on thyroid hormone signaling and OPCs differentiation in vitro. The disease model is the experimental allergic encephalomyelitis in female Dark-Agouti rats, whereas in vitro experiments were carried out in OPCs derived from neural stem cells. The main results are the following: (i) a strong upregulation of cytokine mRNA expression level was found in the spinal cord during experimental allergic encephalomyelitis; (ii) thyroid hormone signaling in the spinal cord (thyroid hormone receptors; deiodinase; thyroid hormone membrane transporter) is substantially downregulated, due to the upregulation of the thyroid hormone inactivating enzyme deiodinase 3 and the downregulation of thyroid hormone receptors, as investigated at mRNA expression level; (iii) when exposed to inflammatory cytokines, deiodinase 3 is upregulated in OPCs as well, and OPCs differentiation is blocked; (iv) deiodinase 3 inhibition by iopanoic acid recovers OPCs differentiation in the presence on inflammatory cytokines. These data suggest that cellular hypothyroidism occurs during experimental allergic encephalomyelitis, possibly impacting on thyroid hormone-dependent cellular processes, including maturation of OPCs into myelinating oligodendrocytes. GLIA 2016;64:1573-1589.

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“…In addition, injection of Ureaplasma parvum into pregnant mice induces myelin defects and loss of interneurons in the offspring [26]. Consequently, we developed a model where newborn mice received twicedaily intraperitoneal injections of IL-1β over 5 days and were studied for myelination, oligodendrogenesis, behaviour and MRI, in order to match this model with human data [23,43] (Figure 3). These latter studies provide the proof of concept that infection/inflammation can alter programmes of brain development.…”

Section: Role Of Inflammation In Perinatal Brain Damagementioning

confidence: 99%

Brain damage of the preterm infant: new insights into the role of inflammation

Steenwinckel

Schang

Sigaut

et al. 2014

Biochemical Society Transactions

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Epidemiological studies have shown a strong association between perinatal infection/inflammation and brain damage in preterm infants and/or neurological handicap in survivors. Experimental studies have shown a causal effect of infection/inflammation on perinatal brain damage. Infection including inflammatory factors can disrupt programmes of brain development and, in particular, induce death and/or blockade of oligodendrocyte maturation, leading to myelin defects. Alternatively, in the so-called multiple-hit hypothesis, infection/inflammation can act as predisposing factors, making the brain more susceptible to a second stress (sensitization process), such as hypoxic-ischaemic or excitotoxic insults. Epidemiological data also suggest that perinatal exposure to inflammatory factors could predispose to long-term diseases including psychiatric disorders.

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Failure of thyroid hormone treatment to prevent inflammation-induced white matter injury in the immature brain

Abstract: HighlightThyroid hormone treatment did not recover deficits in oligodendrocyte maturation and myelination in a mouse model of preterm inflammation-induced white matter damage.

Cited by 41 publications

References 47 publications

Controversies in preterm brain injury

Controversies in preterm brain injury

Inflammation severely alters thyroid hormone signaling in the central nervous system during experimental allergic encephalomyelitis in rat: Direct impact on OPCs differentiation failure

Brain damage of the preterm infant: new insights into the role of inflammation

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