Safety and Efficacy of Corticosteroid Use in Neurologic Trauma

Han, Zhe; Lat, Ishaq; Pollard, Sacha

doi:10.1177/0897190013516500

Cited by 5 publications

(3 citation statements)

References 47 publications

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“…Such therapeutic treatment of TBI, however, has received considerable attention in recent years. [9][10][11][12] For example, a thera-peutic strategy for modulating this neuroinflammatory response may be at the level of the epigenome. One class of promising drugs is histone deacetylase inhibitors (HDACI).…”

Section: Introductionmentioning

confidence: 99%

Resuscitation with Valproic Acid Alters Inflammatory Genes in a Porcine Model of Combined Traumatic Brain Injury and Hemorrhagic Shock

Bambakidis

Dekker

Sillesen

et al. 2016

Journal of Neurotrauma

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Traumatic brain injury and hemorrhagic shock (TBI+HS) elicit a complex inflammatory response that contributes to secondary brain injury. There is currently no proven pharmacologic treatment for TBI+HS, but modulation of the epigenome has been shown to be a promising strategy. The aim of this study was to investigate whether valproic acid (VPA), a histone deacetylase inhibitor, modulates the expression of cerebral inflammatory gene profiles in a large animal model of TBI+HS. Ten Yorkshire swine were subjected to computer-controlled TBI+HS (40% blood volume). After 2 h of shock, animals were resuscitated with Hextend (HEX) or HEX+VPA (300 mg/kg, n = 5/group). Six hours after resuscitation, brains were harvested, RNA was isolated, and gene expression profiles were measured using a porcine microarray. Ingenuity Pathway Analysis® (IPA), gene ontology (GO), Parametric Gene Set Enrichment Analysis (PGSEA), and DAVID (Database for Annotation, Visualization, and Integrated Discovery) were used for pathway analysis. Key microarray findings were verified using real-time polymerase chain reaction (PCR). IPA analysis revealed that VPA significantly down-regulated the complement system (p< 0.001), natural killer cell communication (p < 0.001), and dendritic cell maturation (p < 0.001). DAVID analysis indicated that a cluster of inflammatory pathways held the highest rank and gene enrichment score. Real-time PCR data confirmed that VPA significantly down-expressed genes that ultimately regulate nuclear factor-kB (NF-kB)-mediated production of cytokines, such as TYROBP, TREM2, CCR1, and IL-1β. This high-throughput analysis of cerebral gene expression shows that addition of VPA to the resuscitation protocol significantly modulates the expression of inflammatory pathways in a clinically realistic model of TBI+HS.

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Section: Introductionmentioning

confidence: 99%

Resuscitation with Valproic Acid Alters Inflammatory Genes in a Porcine Model of Combined Traumatic Brain Injury and Hemorrhagic Shock

Bambakidis

Dekker

Sillesen

et al. 2016

Journal of Neurotrauma

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“…In the physiology of traumatic brain injury (TBI), for example, the neurological damage can worsen due to the effects of the secondary injury (Sande & West 2010;Difazio & Fletcher 2013;Kuo et al, 2018). Despite the established benefits of corticosteroids in controlling the secondary injury (i.e., inhibiting lipid peroxidation) (Hanz et al, 2014), some studies have shown that their administration can potentiate neuronal damage by making neurons more vulnerable to metabolic insults and inhibiting the remyelination of injured neurons (Payne et al, 2003). The Corticosteroid Randomization After Significant Head Injury (CRASH) study demonstrated that the use of high doses of methylprednisolone in humans with severe TBI were associated with increased mortality, and did not show any clinical benefit (Roberts et al, 2004;Edwards et al, 2005); furthermore, steroidal therapy is not recommended for humans with TBI (Hoshide et al, 2016;Carney et al, 2017).…”

Section: Discussionmentioning

confidence: 99%

Corticosteroid use in neurology: how dogs are referrals to a neurology service?

et al. 2020

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Corticosteroids are drugs widely used in veterinary neurology due to their recognized anti-inflammatory, immunosuppressive and analgesic effects. However, their use in high doses and for long term may result in undesirable side effects. This study describes the prevalence of dogs with neurologic diseases referred to a veterinary neurology service with previous prescriptions for corticosteroids. In this retrospective study 284 medical records of dogs were evaluated in the period between August 2017 and April 2019. Of these, 194 (68%) dogs had already received medical care from a clinician and 100 (52%) had previously been prescribed corticosteroids. After diagnosis at the reference service, the corticosteroid dose was suspended in 28% of the cases, adjusted in 41% and maintained in 31%. Dogs receiving immunosuppressive doses were the most affected and in 71% and 21% of the cases, their medication was adjusted or suspended, respectively. In conclusion, the therapy for neurological diseases is still strongly associated with the indiscriminate use of corticosteroids, without the dosage correlated to the desired effect.

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“…The synthetic CS, MPRED is one of the main drugs used in the treatment of neurological trauma (acute SCI and traumatic brain injury) because of its ability to reduce brain edema, improve neurological recovery and reduce the inflammatory reaction after SCI (Han et al, 2014). This drug was therefore selected for use in…”

Section: Preparation Of Mpred Solutionmentioning

confidence: 99%

A proteomic investigation into mechanisms underpinning corticosteroid effects on neural stem cells

Al-Mayyahi

Sterio

Connolly

et al. 2018

Molecular and Cellular Neuroscience

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Corticosteroids (CSs) are widely used clinically, for example in pediatric respiratory distress syndrome, and immunosuppression to prevent rejection of stem cell transplant populations in neural cell therapy. However, such treatment can be associated with adverse effects such as impaired neurogenesis and myelination, and increased risk of cerebral palsy. There is increasing evidence that CSs can adversely influence key biological properties of neural stem cells (NSCs) but the molecular mechanisms underpinning such effects are largely unknown. This is an important issue to address given the key roles NSCs play during brain development and as transplant cells for regenerative neurology. Here, we describe the use of label-free quantitative proteomics in conjunction with histological analyses to study CS effects on NSCs at the cellular and molecular levels, following treatment with methylprednisolone (MPRED). Immunocytochemical staining showed that both parent NSCs and newly generated daughter cells expressed the glucocorticoid receptor, with nuclear localisation of the receptor induced by MPRED treatment. MPRED markedly decreased NSC proliferation and neuronal differentiation while accelerating the maturation of oligodendrocytes, without concomitant effects on cell viability and apoptosis. Parallel proteomic analysis revealed that MPRED induced downregulation of growth associated protein 43 and matrix metallopeptidase 16 with upregulation of the cytochrome P450 family 51 subfamily A member 1. Our findings support the hypothesis that some neurological deficits associated with CS use may be mediated via effects on NSCs, and highlight putative target mechanisms underpinning such effects.

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Safety and Efficacy of Corticosteroid Use in Neurologic Trauma

Cited by 5 publications

References 47 publications

Resuscitation with Valproic Acid Alters Inflammatory Genes in a Porcine Model of Combined Traumatic Brain Injury and Hemorrhagic Shock

Resuscitation with Valproic Acid Alters Inflammatory Genes in a Porcine Model of Combined Traumatic Brain Injury and Hemorrhagic Shock

Corticosteroid use in neurology: how dogs are referrals to a neurology service?

A proteomic investigation into mechanisms underpinning corticosteroid effects on neural stem cells

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