Neuroprotection by Nrf2 via modulating microglial phenotype and phagocytosis after intracerebral hemorrhage

Liang, Chuntian; Liu, Lirong; Bao, Shuangjin; Yao, Zhenjia; Bai, Qinqin; Fu, Pengcheng; Liu, Xiangyu; Zhang, Junyi; Wang, Gaiqing

doi:10.1016/j.heliyon.2023.e13777

Cited by 12 publications

(2 citation statements)

References 66 publications

(83 reference statements)

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“…First, our results have shown there is a reduction in the density of reactive microglia in sham-operated PCD mice, whose values were restored after IMC transplantation. Since activated microglia corresponds with those cells that can exert a neuroprotective effect [ 88 , 89 ], it is plausible to propose that a certain cell ratio of CD45 + would be necessary for protecting against neural damage, beyond the dichotomy of a pro- or anti-inflammatory phenotype [ 85 , 86 ]. This hypothesis is supported by the fact that the neuro-resistant lobe X [ 41 ] presents the highest ratio of CD45 + microglial cells in both untreated and transplanted PCD mice.…”

Section: Discussionmentioning

confidence: 99%

Intracerebellar injection of monocytic immature myeloid cells prevents the adverse effects caused by stereotactic surgery in a model of cerebellar neurodegeneration

del Pilar,

Garrido-Matilla,

del Pozo-Filíu

et al. 2024

J Neuroinflammation

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Background Myeloid-derived suppressor cells (MDSCs) constitute a recently discovered bone-marrow-derived cell type useful for dealing with neuroinflammatory disorders. However, these cells are only formed during inflammatory conditions from immature myeloid cells (IMCs) that acquire immunosuppressive activity, thus being commonly gathered from diseased animals. Then, to obtain a more clinically feasible source, we characterized IMCs directly derived from healthy bone marrow and proved their potential immunosuppressive activity under pathological conditions in vitro. We then explored their neuroprotective potential in a model of human cerebellar ataxia, the Purkinje Cell Degeneration (PCD) mouse, as it displays a well-defined neurodegenerative and neuroinflammatory process that can be also aggravated by invasive surgeries. Methods IMCs were obtained from healthy bone marrow and co-cultured with activated T cells. The proliferation and apoptotic rate of the later were analyzed with Tag-it Violet. For in vivo studies, IMCs were transplanted by stereotactic surgery into the cerebellum of PCD mice. We also used sham-operated animals as controls of the surgical effects, as well as their untreated counterparts. Motor behavior of mice was assessed by rotarod test. The Purkinje cell density was measured by immunohistochemistry and cell death assessed with the TUNEL technique. We also analyzed the microglial phenotype by immunofluorescence and the expression pattern of inflammation-related genes by qPCR. Parametric tests were applied depending on the specific experiment: one or two way ANOVA and Student’s T test. Results IMCs were proven to effectively acquire immunosuppressive activity under pathological conditions in vitro, thus acting as MDSCs. Concerning in vivo studios, sham-operated PCD mice suffered detrimental effects in motor coordination, Purkinje cell survival and microglial activation. After intracranial administration of IMCs into the cerebellum of PCD mice, no special benefits were detected in the transplanted animals when compared to untreated mice. Nonetheless, this transplant almost completely prevented the impairments caused by the surgery in PCD mice, probably by the modulation of the inflammatory patterns. Conclusions Our work comprise two main translational findings: (1) IMCs can be directly used as they behave as MDSCs under pathological conditions, thus avoiding their gathering from diseased subjects; (2) IMCs are promising adjuvants when performing neurosurgery.

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Section: Discussionmentioning

confidence: 99%

Intracerebellar injection of monocytic immature myeloid cells prevents the adverse effects caused by stereotactic surgery in a model of cerebellar neurodegeneration

del Pilar,

Garrido-Matilla,

del Pozo-Filíu

et al. 2024

J Neuroinflammation

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“…Balancing the beneficial and detrimental effects of inflammation in treating ICH remains challenging. ICH additionally triggers endogenous anti-inflammatory, anti-excitatory, antioxidant, and neurotrophic responses that are potentially neuroprotective 15 . Thus, ICH activates a cascade of events that involve a complex interplay of cellular responses, molecular signaling pathways, and dynamic microenvironmental changes 1 .…”

Section: Introductionmentioning

confidence: 99%

Spatiotemporal transcriptomic maps of mouse intracerebral hemorrhage at single-cell resolution

Xiang,

Wang,

Wang

et al. 2024

Preprint

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Intracerebral hemorrhage (ICH) is a severe and widespread disease that results in high mortality and morbidity. Despite significant advances made in clinical and preclinical research, the prognosis of ICH remains poor due to an incomplete understanding of the complex pathological responses. To address this challenge, we generated single-cell resolution spatiotemporal transcriptomic maps of mouse brain 1, 3, 7, 14, and 28 days after ICH. Our analysis revealed the cellular constituents and their dynamic responses following ICH. We found changes in gene expression that are indicative of active phagocytosis and lipid processing in the lesion core and identified genes associated with brain repair at the lesion border. Persistent lipid accumulation culminated in the phenotypic transition of macrophages into foam cells. Furthermore, our results demonstrate that ICH could stimulate neural stem cells in the subventricular zone, thereby enhancing neurogenesis in this niche. This study provides a spatiotemporal molecular atlas of mouse ICH that advances the understanding of both local and global responses of brain cells to ICH and offers a valuable resource that can aid the development of novel therapies for this devastating condition.

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Transcription Factor NRF2 in Shaping Myeloid Cell Differentiation and Function

Pfefferlé,

Vallelian

2024

Transcription Factors in Blood Cell Development

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Neuroprotection by Nrf2 via modulating microglial phenotype and phagocytosis after intracerebral hemorrhage

Cited by 12 publications

References 66 publications

Intracerebellar injection of monocytic immature myeloid cells prevents the adverse effects caused by stereotactic surgery in a model of cerebellar neurodegeneration

Intracerebellar injection of monocytic immature myeloid cells prevents the adverse effects caused by stereotactic surgery in a model of cerebellar neurodegeneration

Spatiotemporal transcriptomic maps of mouse intracerebral hemorrhage at single-cell resolution

Transcription Factor NRF2 in Shaping Myeloid Cell Differentiation and Function

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