Nanoparticle-Based Estrogen Delivery to Spinal Cord Injury Site Reduces Local Parenchymal Destruction and Improves Functional Recovery

Cox, April; Capone, Mollie; Matzelle, Denise; Vertegel, Alexey; Bredikhin, Mikhail; Varma, Abhay K.; Haque, Azizul; Shields, Donald C.; Banik, Naren L.

doi:10.1089/neu.2020.7047

Cited by 19 publications

(9 citation statements)

References 55 publications

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“…The inhibitive pathological microenvironment post-SCI is the key adverse factor affecting neurofunctional recovery after injury ( Zhao et al, 2017 ; Cox et al, 2021 ). Following SCI, death of oligodendrocytes and profound demyelination results in the release of myelin-associated inhibitors, including myelin-associated glycoprotein, Nogo, and oligodendrocyte myelin glycoprotein, etc., which suppress axon regeneration ( Boghdadi et al, 2018 ; Wang et al, 2020 ).…”

Section: Discussionmentioning

confidence: 99%

Neural Stem Cells Overexpressing Nerve Growth Factor Improve Functional Recovery in Rats Following Spinal Cord Injury via Modulating Microenvironment and Enhancing Endogenous Neurogenesis

Wang

Gan

et al. 2021

Front. Cell. Neurosci.

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Spinal cord injury (SCI) is a devastating event characterized by severe motor, sensory, and autonomic dysfunction. Currently, there is no effective treatment. Previous studies showed neural growth factor (NGF) administration was a potential treatment for SCI. However, its targeted delivery is still challenging. In this study, neural stem cells (NSCs) were genetically modified to overexpress NGF, and we evaluated its therapeutic value following SCI. Four weeks after transplantation, we observed that NGF-NSCs significantly enhanced the motor function of hindlimbs after SCI and alleviated histopathological damage at the lesion epicenter. Notably, the survival NGF-NSCs at lesion core maintained high levels of NGF. Further immunochemical assays demonstrated the graft of NGF-NSCs modulated the microenvironment around lesion core via reduction of oligodendrocyte loss, attenuation of astrocytosis and demyelination, preservation of neurons, and increasing expression of multiple growth factors. More importantly, NGF-NSCs seemed to crosstalk with and activate resident NSCs, and high levels of NGF activated TrkA, upregulated cAMP-response element binding protein (CREB) and microRNA-132 around the lesion center. Taken together, the transplantation of NGF-NSCs in the subacute stage of traumatic SCI can facilitate functional recovery by modulating the microenvironment and enhancing endogenous neurogenesis in rats. And its neuroprotective effect may be mediated by activating TrkA, up-regulation of CREB, and microRNA-132.

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Section: Discussionmentioning

confidence: 99%

Neural Stem Cells Overexpressing Nerve Growth Factor Improve Functional Recovery in Rats Following Spinal Cord Injury via Modulating Microenvironment and Enhancing Endogenous Neurogenesis

Wang

Gan

et al. 2021

Front. Cell. Neurosci.

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“…These dosages also demonstrated decreased expression of calpain/caspases, while preventing the astrogliosis and invasion of peripheral monocytes/neutrophils in both white and gray matter [19,40,64]. Our recent study indicates that nanoparticle-mediated delivery of E2 (5.0 µg) successfully improved locomotor function by attenuating inflammation and other secondary injury factors [72,74]. Thus, low doses of intravenous estrogen can provide multiple neuroprotective effects following SCI [19,60,64].…”

Section: Estrogen Effectsmentioning

confidence: 84%

Pathophysiology, Biomarkers, and Therapeutic Modalities Associated with Skeletal Muscle Loss Following Spinal Cord Injury

et al. 2020

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A spinal cord injury (SCI) may lead to loss of strength, sensation, locomotion and other body functions distal to the lesion site. Individuals with SCI also develop secondary conditions due to the lack of skeletal muscle activity. As SCI case numbers increase, recent studies have attempted to determine the best options to salvage affected musculature before it is lost. These approaches include pharmacotherapeutic options, immunosuppressants, physical activity or a combination thereof. Associated biomarkers are increasingly used to determine if these treatments aid in the protection and reconstruction of affected musculature.

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“…After use, the E2 concentration at the injury site was twice as high as that of plasma because of its local release characteristics. Luxol fast blue staining showed that the level of CSPG in the lesion area was significantly lower than that of the control group, which is more conducive to the regeneration of the injured and adjacent axons (Cox et al, 2020). Another study found that the transplantation of linear ordered collagen scaffolds (LOCS) and human placentalderived MSCs into completely transected beagle dogs promoted hind limb motor function recovery.…”

Section: Biomaterials Reverse the Poor Immune Microenvironment By Red...mentioning

confidence: 99%

Reverse Adverse Immune Microenvironments by Biomaterials Enhance the Repair of Spinal Cord Injury

Wang

Xia

et al. 2022

Front. Bioeng. Biotechnol.

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Spinal cord injury (SCI) is a severe and traumatic disorder that ultimately results in the loss of motor, sensory, and autonomic nervous function. After SCI, local immune inflammatory response persists and does not weaken or disappear. The interference of local adverse immune factors after SCI brings great challenges to the repair of SCI. Among them, microglia, macrophages, neutrophils, lymphocytes, astrocytes, and the release of various cytokines, as well as the destruction of the extracellular matrix are mainly involved in the imbalance of the immune microenvironment. Studies have shown that immune remodeling after SCI significantly affects the survival and differentiation of stem cells after transplantation and the prognosis of SCI. Recently, immunological reconstruction strategies based on biomaterials have been widely explored and achieved good results. In this review, we discuss the important factors leading to immune dysfunction after SCI, such as immune cells, cytokines, and the destruction of the extracellular matrix. Additionally, the immunomodulatory strategies based on biomaterials are summarized, and the clinical application prospects of these immune reconstructs are evaluated.

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Nanoparticle-Based Estrogen Delivery to Spinal Cord Injury Site Reduces Local Parenchymal Destruction and Improves Functional Recovery

Cited by 19 publications

References 55 publications

Neural Stem Cells Overexpressing Nerve Growth Factor Improve Functional Recovery in Rats Following Spinal Cord Injury via Modulating Microenvironment and Enhancing Endogenous Neurogenesis

Neural Stem Cells Overexpressing Nerve Growth Factor Improve Functional Recovery in Rats Following Spinal Cord Injury via Modulating Microenvironment and Enhancing Endogenous Neurogenesis

Pathophysiology, Biomarkers, and Therapeutic Modalities Associated with Skeletal Muscle Loss Following Spinal Cord Injury

Reverse Adverse Immune Microenvironments by Biomaterials Enhance the Repair of Spinal Cord Injury

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