Handling iron in restorative neuroscience

Routhe, Lisa Juul; Moos, Torben

doi:10.4103/1673-5374.165316

Cited by 10 publications

(7 citation statements)

References 17 publications

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“…In the context of SCI, the initial injury triggers the rapid death of local neurons and glial cells at the injury site within min to h. Subsequently, the nervous system undergoes an inflammatory response that leads to secondary damage ( 3 ). Hypoxia, ischemia-reperfusion injury and microenvironmental imbalances following SCI contribute to the generation and release of a significant number of free radicals and reactive oxygen species, further disrupting the local microvascular system and causing dysfunction in nerve cells ( 4 , 5 ). Therefore, achieving a swift equilibrium between oxidative stress and the inflammatory response plays a critical role in safeguarding the spinal cord and preserving the functionality of spinal cord nerve cells.…”

Section: Discussionmentioning

confidence: 99%

“…Primary injury results in local necrosis and apoptosis of neurons and glial cells, while the subsequent inflammatory response of the nervous system leads to secondary damage. In the case of secondary injury, spinal cord ischemia and hypoxia trigger the generation and release of numerous free radicals and reactive oxygen species, further disrupting the microenvironment and impairing the functioning of the nervous system ( 4 , 5 ).…”

Section: Introductionmentioning

confidence: 99%

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Melatonin exerts neuroprotective effects in mice with spinal cord injury by activating the Nrf2/Keap1 signaling pathway via the MT2 receptor

Yan,

Han,

Zhang

et al. 2023

Exp Ther Med

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Spinal cord injury (SCI) is a devastating event that often leads to severe disability, and effective treatments for SCI are currently limited. The present study investigated the potential effects and specific mechanisms of melatonin treatment in SCI. Mice were divided into Sham (Sham), Vehicle (Veh), Melatonin (Mel), and Melatonin + 4-phenyl-2-propionamidotetralin (4P-PDOT) (Mel + 4PP) groups based on randomized allocation. The expression of MT2 and the nuclear factor-erythroid 2-related factor 2 (Nrf2)/Keap1 signaling pathways were examined, along with oxidative stress indicators, inflammatory factors and GFAP-positive cells near the injury site. The polarization of microglial cells in different inflammatory microenvironments was also observed. Cell survival, motor function recovery and spinal cord tissue morphology were assessed using staining and Basso Mouse Scale scores. On day 7 after SCI, the results revealed that melatonin treatment increased MT2 protein expression and activated the Nrf2/Keap1 signaling pathway. It also reduced GFAP-positive cells, mitigated oxidative stress, and suppressed inflammatory responses around the injury site. Furthermore, melatonin treatment promoted the polarization of microglia toward the M2 type, increased the number of neutrophil-positive cells, and modulated the transcription of Bax and Bcl2 in the injured spinal cord. Melatonin treatment alleviated the severity of spinal injuries and facilitated functional recovery in mice with SCI. Notably, blocking MT2 with 4P-PDOT partially reversed the neuroprotective effects of melatonin in SCI, indicating that the activation of the MT2/Nrf2/Keap1 signaling pathway contributes to the neuroprotective properties of melatonin in SCI. The therapeutic and translational potentials of melatonin in SCI warrant further investigation.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Melatonin exerts neuroprotective effects in mice with spinal cord injury by activating the Nrf2/Keap1 signaling pathway via the MT2 receptor

Yan,

Han,

Zhang

et al. 2023

Exp Ther Med

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“…For example, transferrin receptors and insulin receptors are two common targeted receptors that have been used to develop actively targeted nanoparticles. Studies have evidenced that neuroinflammatory conditions and disease progression influence the expression of these receptors 44 , 45 . The iron regulatory protein system (IRPs) regulates the expression of transferrin receptor.…”

Section: Current Strategies To Deliver Drugs Into the Brainmentioning

confidence: 99%

Current Strategies for Brain Drug Delivery

2018

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The blood-brain barrier (BBB) has been a great hurdle for brain drug delivery. The BBB in healthy brain is a diffusion barrier essential for protecting normal brain function by impeding most compounds from transiting from the blood to the brain; only small molecules can cross the BBB. Under certain pathological conditions of diseases such as stroke, diabetes, seizures, multiple sclerosis, Parkinson's disease and Alzheimer disease, the BBB is disrupted. The objective of this review is to provide a broad overview on current strategies for brain drug delivery and related subjects from the past five years. It is hoped that this review could inspire readers to discover possible approaches to deliver drugs into the brain. After an initial overview of the BBB structure and function in both healthy and pathological conditions, this review re-visits, according to recent publications, some questions that are controversial, such as whether nanoparticles by themselves could cross the BBB and whether drugs are specifically transferred to the brain by actively targeted nanoparticles. Current non-nanoparticle strategies are also reviewed, such as delivery of drugs through the permeable BBB under pathological conditions and using non-invasive techniques to enhance brain drug uptake. Finally, one particular area that is often neglected in brain drug delivery is the influence of aging on the BBB, which is captured in this review based on the limited studies in the literature.

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“…In addition, Liu et al demonstrated that iron was rapidly increased within 20 min 155 . Iron plays a significant role in glutamate excitotoxicity, the formation of ROSs and the production of free radicals 158 , 159 , which inhibit the regeneration of SCI. Our team utilized deferoxamine (DFO), an iron chelator, in the repair of SCI.…”

Section: Molecular Imbalancementioning

confidence: 99%

Microenvironment Imbalance of Spinal Cord Injury

et al. 2018

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Spinal cord injury (SCI), for which there currently is no cure, is a heavy burden on patient physiology and psychology. The microenvironment of the injured spinal cord is complicated. According to our previous work and the advancements in SCI research, ‘microenvironment imbalance’ is the main cause of the poor regeneration and recovery of SCI. Microenvironment imbalance is defined as an increase in inhibitory factors and decrease in promoting factors for tissues, cells and molecules at different times and spaces. There are imbalance of hemorrhage and ischemia, glial scar formation, demyelination and re-myelination at the tissue’s level. The cellular level imbalance involves an imbalance in the differentiation of endogenous stem cells and the transformation phenotypes of microglia and macrophages. The molecular level includes an imbalance of neurotrophic factors and their pro-peptides, cytokines, and chemokines. The imbalanced microenvironment of the spinal cord impairs regeneration and functional recovery. This review will aid in the understanding of the pathological processes involved in and the development of comprehensive treatments for SCI.

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Handling iron in restorative neuroscience

Cited by 10 publications

References 17 publications

Melatonin exerts neuroprotective effects in mice with spinal cord injury by activating the Nrf2/Keap1 signaling pathway via the MT2 receptor

Melatonin exerts neuroprotective effects in mice with spinal cord injury by activating the Nrf2/Keap1 signaling pathway via the MT2 receptor

Current Strategies for Brain Drug Delivery

Microenvironment Imbalance of Spinal Cord Injury

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