A review of the neuroprotective role of vitamin D in traumatic brain injury with implications for supplementation post-concussion

Lawrence, David Wyndham; Sharma, Bhanu

doi:10.3109/02699052.2016.1147081

Cited by 33 publications

(19 citation statements)

References 88 publications

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“…The effects may vary in different cells and under different conditions. Studies examining vitamin D‐dependent responses have, in some cases, indicated a protective role and, in others, a stimulation of apoptosis . However, the reported suppression on proliferation and survival in many cell types has led to an interest in vitamin D administration as a possible treatment to counteract tumour growth or reduce cancer risk …”

Section: Vitamin D and Inhibition Of Cellular Proliferation: A Role Imentioning

confidence: 99%

Effects of vitamin D in the nervous system: Special focus on interaction with steroid hormone signalling and a possible role in the treatment of brain cancer

Norlin

2019

J Neuroendocrinology

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The active vitamin D hormone, 1,25-dihydroxyvitamin D 3 , exerts many physiological actions in the body, including effects on the nervous system. Studies of steroidogenesis in cells of the nervous system and elsewhere not only indicate that 1,25-dihydroxyvitamin D 3 affects steroidogenic pathways but also suggest varying responses in different cell types. For example, 1,25-dihydroxyvitamin D 3 stimulates the expression of aromatase in human glioma but not in human neuroblastoma cells or rat astrocytes. However, in astrocytes, 1,25-dihydroxyvitamin D 3 suppresses 3β-hydroxysteroid dehydrogenase and steroid 17-hydroxylase/lyase. Other studies indicate cross-talk between vitamin D signalling and signalling of oestrogens, progesterone or glucocorticoids. Reported data indicate synergistic effects of combinations of 1,25-dihydroxyvitamin D 3 and other steroid hormones on neuroinflammation, neurite outgrowth and neuroprotection. Also, dysregulation of steroid pathways affecting brain cells is found in vitamin D deficiency. Thus, several studies suggest that active vitamin D may affect steroid hormone synthesis and/or signalling in the nervous system, although the potential mechanisms for these responses remain unclear.1,25-Dihydroxyvitamin D 3 suppresses proliferation in several cell types and is therefore of interest in cancer treatment. Also, epidemiological studies associate vitamin D levels with cancer risk or outcomes. Reported data on tumours of the nervous system are mainly on glioma, a common type of brain cancer. Expression of the vitamin D receptor in glioma tumours is associated with improved survival. Several studies show that 1,25-dihydroxyvitamin D 3 and vitamin D analogues (synthetic vitamin D-like compounds) suppress proliferation and migration in human vitamin D receptor-expressing glioma cell lines. Studies on mechanisms for actions of 1,25-dihydroxyvitamin D 3 or its analogues indicate regulation of cell cycle proteins and senescence markers. These compounds also show synergism in combination with other cancer therapies treating glioma. From the data available, vitamin D analogues emerge as interesting candidates for the future improved treatment of human glioma and possibly also other cancers of the nervous system. K E Y W O R D Sglioblastoma, growth, steroid hormone, steroidogenesis, vitamin D

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Section: Vitamin D and Inhibition Of Cellular Proliferation: A Role Imentioning

confidence: 99%

Effects of vitamin D in the nervous system: Special focus on interaction with steroid hormone signalling and a possible role in the treatment of brain cancer

Norlin

2019

J Neuroendocrinology

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“…Recently, VD supplementation and VD deficiency have been associated with neuronal injury and function recovery after TBI [10, 11]. However, the neuroprotective mechanisms of VD are complex and multidimensional [12] and have not been fully addressed.…”

Section: Introductionmentioning

confidence: 99%

Induction of the Vitamin D Receptor Attenuates Autophagy Dysfunction-Mediated Cell Death Following Traumatic Brain Injury

Chen

Feng

Cui

et al. 2017

Cell Physiol Biochem

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Background/Aims: Traumatic brain injury (TBI) is a major public health problem in the world and causes high rates of mortality and disability. Recent evidence suggests that vitamin D (VD) has neuroprotective actions and can promote function recovery after TBI. In vitro and in vivo studies have demonstrated that autophagy could be enhanced following supplementation with an active metabolite of VD (calcitriol). However, it is unclear whether autophagy participates in the protective effects of calcitriol after TBI. To test this hypothesis, we examined the protective effects of calcitriol on TBI-induced neurological impairment and further investigated whether calcitriol could modulate autophagy dysfunction-mediated cell death in the cortex region of rat brain. Methods: Eighty-five male rats (250-280 g) were randomly assigned to sham (n=15), TBI model (TBI, n=35) and calcitriol treatment (calcitriol, n=35) groups. Rats were injected intraperitoneally with calcitriol (1 µg/kg) at 30 min, 24 h and 48 h post-TBI in the calcitriol group. The lysosomal inhibitor, chloroquine (CQ), was used to evaluate autophagic flux in the TBI and calcitriol groups. Neurological functions were evaluated via the modified neurological severity score test at 1-7 days after TBI or sham operation, and the terminal deoxynucleotidyl transferase-mediated FITC-dUTP nick-end labeling method was used to evaluate the ability of calcitriol to inhibit apoptosis. The expression of VDR, LC3 and p62 proteins was measured by western blot analysis at 1, 3 and 7 days post-injury Results: Calcitriol treatment attenuated mNSS at 2-7 days post-TBI (P < 0.05 versus TBI group). Calcitriol dramatically increased VDR protein expression compared with the untreated counterparts at 1, 3 and 7 days post-TBI (P < 0.05). The rate of apoptotic cells in calcitriol-treated rats was significantly reduced compared to that observed in the TBI group (P < 0.05). The LC3II/LC3I ratio was decreased in the cortex region at 1, 3 and 7 days post-TBI in rats treated with calcitriol (p < 0.05 versus TBI group), and the p62 expression was also attenuated (p < 0.05 versus TBI group). The LC3II/LC3I ratio in the calcitriol group was significantly increased when pretreated with CQ (P < 0.05). Conclusion: Calcitriol treatment activated VDR protein expression and attenuated neurological deficits in this rat TBI model. The protective effects might be associated with the restoration of autophagy flux and the decrease in apoptosis in the cortex region of rat brain.

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“…More recently, it has been identified as a substance with substantial involvement in brain development, health and function. 83 The vitamin D receptor (VDR) protein is reportedly expressed broadly in the brain, including the neurons and glial cells. 84 Further, 1,25(OH)D appears to influence neuronal cell differentiation and exert neuroprotective actions against cytotoxicity.…”

Section: Vitamin Dmentioning

confidence: 99%

“…Vitamin D deficiency exacerbates inflammatory response and cell death. 83 The role of vitamin D supplementation post-TBI and/or investigation of the role of vitamin D deficiency on outcomes following TBI was recently reviewed. 83 A significant reduction in phosphorylation of nuclear factors, which in turn stimulate downstream genes involved in the inflammatory cascade, were shown to be reduced by vitamin D treatment post-TBI.…”

Section: Vitamin Dmentioning

confidence: 99%

“…83 The role of vitamin D supplementation post-TBI and/or investigation of the role of vitamin D deficiency on outcomes following TBI was recently reviewed. 83 A significant reduction in phosphorylation of nuclear factors, which in turn stimulate downstream genes involved in the inflammatory cascade, were shown to be reduced by vitamin D treatment post-TBI. 85 In separate studies, Tang et al 86 and Cekic et al 87 demonstrated that vitamin D deficiency was associated with more adverse pathophysiological outcomes following TBI.…”

Section: Vitamin Dmentioning

confidence: 99%

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Nutrition as Medicine to Improve Outcomes in Adolescents Sustaining a Sports-related Concussion

Casazza¹,

Swanson²

2017

Exploratory Research and Hypothesis in Medicine

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Recognition and diagnosis of sports-related concussion (SRC) among adolescents has significantly increased. In, fact, among high school adolescents, SRC incidence has more than doubled from 2007 to 2014, with recent estimates at approximately 2 per 100 athletes. SRC-related research has also increased; recognition of symptoms that may prolong recovery have been examined, potential biomarkers have been scrutinized, return-to-learn and return-to-play protocols have been developed and honed. However, to date, clinicians and researchers have struggled to find effective interventions to mitigate the significant symptoms after SRC and shorten recovery times. Despite the understood role of the brain as the primary regulator of metabolism, and the well-established metabolic impairments evoked after a concussion, nutrition is often ignored as a core complement to the recovery and rehabilitation process. In this article, we will identify deficiencies and/or inadequacies in nutrients post-concussion and provide support for potential exacerbation of injury and delayed recovery due to inadequate intake of nutrients prior to sustaining an SRC. Additionally, we will discuss the effect of derangement of the metabolic cascade post-concussion, and identify key nutrients, that if supplemented immediately post-injury, could increase neuroprotection, and improve recovery outcomes. Animal and cell culture studies have provided substantial evidence for not only the interrelationship of nutrient adequacy and the adaptation in the metabolic cascade post-concussion on neuroprotection, but also key nutrients that if supplemented immediately post-injury could enhance standard of care with minimal risk.

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A review of the neuroprotective role of vitamin D in traumatic brain injury with implications for supplementation post-concussion

Abstract: A protective role for VDH and a vitamin D sufficient status was identified for numerous outcomes following TBI. However, VDH supplementation cannot be recommended at this time to improve outcomes following TBI.

Cited by 33 publications

References 88 publications

Effects of vitamin D in the nervous system: Special focus on interaction with steroid hormone signalling and a possible role in the treatment of brain cancer

Effects of vitamin D in the nervous system: Special focus on interaction with steroid hormone signalling and a possible role in the treatment of brain cancer

Induction of the Vitamin D Receptor Attenuates Autophagy Dysfunction-Mediated Cell Death Following Traumatic Brain Injury

Nutrition as Medicine to Improve Outcomes in Adolescents Sustaining a Sports-related Concussion

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