Traumatic Brain Injury: Ultrastructural Features in Neuronal Ferroptosis, Glial Cell Activation and Polarization, and Blood–Brain Barrier Breakdown

Qin, Delong; Wang, Junmin; Le, Anh; Wang, Tom J.; Wang, Jian

doi:10.3390/cells10051009

Cited by 38 publications

(33 citation statements)

References 183 publications

(301 reference statements)

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“… 97 Various iron chelators exhibit cerebral protection against acute traumatic and non-traumatic brain injuries. 12 , 89 , 98 For example, the brain-permeable iron chelator VK28 (5-[4-(2-hydroxyethyl) piperazine-1-ylmethyl]-quinoline-8-ol), the lipid-permeable iron chelator 2.2’-dipyridyl, and the iron chelator deferoxamine currently in clinical use decrease iron accumulation, ROS production, microglial activation, and neuronal death. Treatment with these iron chelators can protect the brain against iron toxicity and improve neurologic recovery after ICH.…”

Section: Ferroptosis and Its Underlying Mechanismmentioning

confidence: 99%

COVID-19-Related Brain Injury: The Potential Role of Ferroptosis

Zhang

Sun

Han

et al. 2022

JIR

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The COVID-19 pandemic has caused devastating loss of life and a healthcare crisis worldwide. SARS-CoV-2 is the causative pathogen of COVID-19 and is transmitted mainly through the respiratory tract, where the virus infects host cells by binding to the ACE2 receptor. SARS-CoV-2 infection is associated with acute pneumonia, but neuropsychiatric symptoms and different brain injuries are also present. The possible routes by which SARS-CoV-2 invades the brain are unclear, as are the mechanisms underlying brain injuries with the resultant neuropsychiatric symptoms in patients with COVID-19. Ferroptosis is a unique iron-dependent form of non-apoptotic cell death, characterized by lipid peroxidation with high levels of glutathione consumption. Ferroptosis plays a primary role in various acute and chronic brain diseases, but to date, ferroptosis in COVID-19-related brain injuries has not been explored. This review discusses the mechanisms of ferroptosis and recent evidence suggesting a potential pathogenic role for ferroptosis in COVID-19-related brain injury. Furthermore, the possible routes through which SARS-CoV-2 could invade the brain are also discussed. Discoveries in these areas will open possibilities for treatment strategies to prevent or reduce brain-related complications of COVID-19.

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Section: Ferroptosis and Its Underlying Mechanismmentioning

confidence: 99%

COVID-19-Related Brain Injury: The Potential Role of Ferroptosis

Zhang

Sun

Han

et al. 2022

JIR

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“…The up-regulation of 4-HNE was observed within some regions of the brain in patients with slightly impaired cognition indicates lipid peroxidation [ 50 ]. On the other hand, iron accumulation is associated with impaired cognition among mTBI patients [ 51 ]. Furthermore, GPx4 depletion aggravated impaired cognition [ 52 ].…”

Section: Discussionmentioning

confidence: 99%

Mesenchymal stromal cell treatment attenuates repetitive mild traumatic brain injury-induced persistent cognitive deficits via suppressing ferroptosis

Wang

Zhang

et al. 2022

J Neuroinflammation

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The incidence of repetitive mild traumatic brain injury (rmTBI), one of the main risk factors for predicting neurodegenerative disorders, is increasing; however, its underlying mechanism remains unclear. As suggested by several studies, ferroptosis is possibly related to TBI pathophysiology, but its effect on rmTBI is rarely studied. Mesenchymal stromal cells (MSCs), the most studied experimental cells in stem cell therapy, exert many beneficial effects on diseases of the central nervous system, yet evidence regarding the role of MSCs in ferroptosis and post-rmTBI neurodegeneration is unavailable. Our study showed that rmTBI resulted in time-dependent alterations in ferroptosis-related biomarker levels, such as abnormal iron metabolism, glutathione peroxidase (GPx) inactivation, decrease in GPx4 levels, and increase in lipid peroxidation. Furthermore, MSC treatment markedly decreased the aforementioned rmTBI-mediated alterations, neuronal damage, pathological protein deposition, and improved cognitive function compared with vehicle control. Similarly, liproxstatin-1, a ferroptosis inhibitor, showed similar effects. Collectively, based on the above observations, MSCs ameliorate cognitive impairment following rmTBI, partially via suppressing ferroptosis, which could be a therapeutic target for rmTBI.

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“…Published data show that overexpression of HDDC3 (also known as MESH1) sensitize cells to ferroptosis [ 24 ]. Another study links ferroptosis to neuronal cell death [ 46 ]. Taken together, deficiency of TGFβ signaling in retinal neurons and Müller cells might sensitize the retina towards ferroptosis associated neuronal cell death.…”

Section: Discussionmentioning

confidence: 99%

Deficiency in Retinal TGFβ Signaling Aggravates Neurodegeneration by Modulating Pro-Apoptotic and MAP Kinase Pathways

Bielmeier

Schmitt

Kleefeldt

et al. 2022

IJMS

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Transforming growth factor β (TGFβ) signaling has manifold functions such as regulation of cell growth, differentiation, migration, and apoptosis. Moreover, there is increasing evidence that it also acts in a neuroprotective manner. We recently showed that TGFβ receptor type 2 (Tgfbr2) is upregulated in retinal neurons and Müller cells during retinal degeneration. In this study we investigated if this upregulation of TGFβ signaling would have functional consequences in protecting retinal neurons. To this end, we analyzed the impact of TGFβ signaling on photoreceptor viability using mice with cell type-specific deletion of Tgfbr2 in retinal neurons and Müller cells (Tgfbr2ΔOC) in combination with a genetic model of photoreceptor degeneration (VPP). We examined retinal morphology and the degree of photoreceptor degeneration, as well as alterations of the retinal transcriptome. In summary, retinal morphology was not altered due to TGFβ signaling deficiency. In contrast, VPP-induced photoreceptor degeneration was drastically exacerbated in double mutant mice (Tgfbr2ΔOC; VPP) by induction of pro-apoptotic genes and dysregulation of the MAP kinase pathway. Therefore, TGFβ signaling in retinal neurons and Müller cells exhibits a neuroprotective effect and might pose promising therapeutic options to attenuate photoreceptor degeneration in humans.

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Traumatic Brain Injury: Ultrastructural Features in Neuronal Ferroptosis, Glial Cell Activation and Polarization, and Blood–Brain Barrier Breakdown

Cited by 38 publications

References 183 publications

COVID-19-Related Brain Injury: The Potential Role of Ferroptosis

COVID-19-Related Brain Injury: The Potential Role of Ferroptosis

Mesenchymal stromal cell treatment attenuates repetitive mild traumatic brain injury-induced persistent cognitive deficits via suppressing ferroptosis

Deficiency in Retinal TGFβ Signaling Aggravates Neurodegeneration by Modulating Pro-Apoptotic and MAP Kinase Pathways

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