Reducing age-dependent monocyte-derived macrophage activation contributes to the therapeutic efficacy of NADPH oxidase inhibition in spinal cord injury

Zhang, Bei; Bailey, William M.; McVicar, Anna Leigh; Stewart, Andrew N.; Veldhorst, Amy K.; Gensel, John C.

doi:10.1016/j.bbi.2018.11.013

Cited by 29 publications

(51 citation statements)

References 61 publications

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“…In contrast, on average females tend to receive SCI at an older age ( 8 , 9 ). Older age at time of SCI can exacerbate injuries ( 10 – 12 ) and mechanisms of primary trauma at older ages are often caused by less forceful events such as slip and fall accidents compared to vehicular and sporting accidents or acts of violence ( 13 ). However, even when age is controlled, in the clinical setting, females recover better than males ( 6 ).…”

Section: Resultsmentioning

confidence: 99%

“…Net effects of decreased estrogens and testosterone with age could reciprocally influence recovery, however this remains to be determined. Increased age at the time of injury is known to impair functional recovery following SCI in female rodents (10)(11)(12)(123)(124)(125)(126)(127)(128), however, no pre-clinical work has been done to evaluate if aging changes or exacerbates sex-dependent differences after SCI. Current ongoing projects in our lab are seeking to address this literature gap and have compiled mortality and weight loss data from several ongoing studies.…”

Section: Sex Dependent Effects Of Sci Change With Agementioning

confidence: 99%

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Considerations for Studying Sex as a Biological Variable in Spinal Cord Injury

et al. 2020

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In response to NIH initiatives to investigate sex as a biological variable in preclinical animal studies, researchers have increased their focus on male and female differences in neurotrauma. Inclusion of both sexes when modeling neurotrauma is leading to the identification of novel areas for therapeutic and scientific exploitation. Here, we review the organizational and activational effects of sex hormones on recovery from injury and how these changes impact the long-term health of spinal cord injury (SCI) patients. When determining how sex affects SCI it remains imperative to expand outcomes beyond locomotor recovery and consider other complications plaguing the quality of life of patients with SCI. Interestingly, the SCI field predominately utilizes female rodents for basic science research which contrasts most other male-biased research fields. We discuss the unique caveats this creates to the translatability of preclinical research in the SCI field. We also review current clinical and preclinical data examining sex as biological variable in SCI. Further, we report how technical considerations such as housing, size, care management, and age, confound the interpretation of sex-specific effects in animal studies of SCI. We have uncovered novel findings regarding how age differentially affects mortality and injury-induced anemia in males and females after SCI, and further identified estrus cycle dysfunction in mice after injury. Emerging concepts underlying sexually dimorphic responses to therapy are also discussed. Through a combination of literature review and primary research observations we present a practical guide for considering and incorporating sex as biological variable in preclinical neurotrauma studies.

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Section: Resultsmentioning

confidence: 99%

Section: Sex Dependent Effects Of Sci Change With Agementioning

confidence: 99%

Considerations for Studying Sex as a Biological Variable in Spinal Cord Injury

et al. 2020

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“…57,58 After TBI, macrophage specific nitrous oxide (NOX) activity (NOX2) is increased in microglia and macrophages responding to injury. 57,[59][60][61][62][63][64][65] Increased NOX activity is accompanied by increased production of ROS in microglia and macrophages and NOX inhibition improves outcome following TBI and spinal cord injury. 57,[60][61][62][63][64][65] In TBI, NOX2 inhibition reduces proinflammatory macrophage/microglial activation in vivo.…”

Section: Cns Immune Responsementioning

confidence: 99%

“…57,[59][60][61][62][63][64][65] Increased NOX activity is accompanied by increased production of ROS in microglia and macrophages and NOX inhibition improves outcome following TBI and spinal cord injury. 57,[60][61][62][63][64][65] In TBI, NOX2 inhibition reduces proinflammatory macrophage/microglial activation in vivo. 60,63,66,67 The observed changes in polarization associated with NOX2 inhibition implicate altered metabolism and the oxidative phase of the PPP in proinflammatory macrophage/microglial activation following neurotrauma.…”

Section: Cns Immune Responsementioning

confidence: 99%

“…Anti‐inflammatory macrophages use the nonoxidative phase of the PPP to provide redox support glutathione and other cellular antioxidants 57,58 . After TBI, macrophage specific nitrous oxide (NOX) activity (NOX2) is increased in microglia and macrophages responding to injury 57,59‐65 . Increased NOX activity is accompanied by increased production of ROS in microglia and macrophages and NOX inhibition improves outcome following TBI and spinal cord injury 57,60‐65 .…”

Section: Introductionmentioning

confidence: 99%

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Progenitor cell therapy for acquired pediatric nervous system injury: Traumatic brain injury and acquired sensorineural hearing loss

Baumgartner

et al. 2020

Stem Cells Translational Medicine

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While cell therapies hold remarkable promise for replacing injured cells and repairing damaged tissues, cell replacement is not the only means by which these therapies can achieve therapeutic effect. For example, recent publications show that treatment with varieties of adult, multipotent stem cells can improve outcomes in patients with neurological conditions such as traumatic brain injury and hearing loss without directly replacing damaged or lost cells. As the immune system plays a central role in injury response and tissue repair, we here suggest that multipotent stem cell therapies achieve therapeutic effect by altering the immune response to injury, thereby limiting damage due to inflammation and possibly promoting repair. These findings argue for a broader understanding of the mechanisms by which cell therapies can benefit patients. K E Y W O R D S autologous stem cell transplantation, bone marrow, clinical translation, progenitor cells, umbilical cord blood 1 | INTRODUCTION This review will first consider two neurological conditions with unappreciated similarities: traumatic brain injury (TBI) and sensorineural hearing loss (SNHL), paying particular attention to the role of the immune system in each. Next, it will review laboratory and clinical findings showing improved outcomes for TBI and SNHL upon treatment with allogenic or autologous stem cells, including mesenchymal progenitor cells (MPCs)-a range of nonhematopoietic, mesodermal lineage, multipotent stem cells. 1 Finally, it will evaluate the possible mechanisms of action, concentrating on the immune modulatory properties of MPCs.

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Advances in Biomaterial‐Based Spinal Cord Injury Repair

Shen

Fan

You

et al. 2021

Adv Funct Materials

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Spinal cord injury (SCI) often leads to the loss of motor and sensory functions and is a major challenge in neurological clinical practice. Understanding the pathophysiological changes and the inhibitory microenvironment is crucial to enable the identification of potential mechanisms for functional restoration and to provide guidance for the development of efficient treatment and repair strategies. To date, the implantation of specifically functionalized biomaterials in the lesion area has been shown to help promote axon regeneration and facilitate neuronal circuit generation by remolding SCI microenvironments. Moreover, structural and functional restoration of the spinal cord through the transplantation of naive spinal cord tissue grafts from adult donors, artificial spinal cord-like tissue developed from tissue engineering, and 3D printing will open up new avenues for SCI treatment. This review focuses on the dynamic pathophysiological changes in SCI microenvironments, biomaterials for SCI repairs, strategies for restoring spinal cord structure and function, experimental animal models, regenerative mechanisms, and clinical studies for SCI repair. The current status, recent advances, challenges, and prospects of scaffold-based SCI repair from basic to clinical settings are summarized and discussed, to provide a reference that will help to guide the future exploration and development of spinal cord regeneration strategies.

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Reducing age-dependent monocyte-derived macrophage activation contributes to the therapeutic efficacy of NADPH oxidase inhibition in spinal cord injury

Cited by 29 publications

References 61 publications

Considerations for Studying Sex as a Biological Variable in Spinal Cord Injury

Considerations for Studying Sex as a Biological Variable in Spinal Cord Injury

Progenitor cell therapy for acquired pediatric nervous system injury: Traumatic brain injury and acquired sensorineural hearing loss

Advances in Biomaterial‐Based Spinal Cord Injury Repair

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