Local delivery of RhoA siRNA by PgP nanocarrier reduces inflammatory response and improves neuronal cell survival in a rat TBI model

Macks, Christian; Jeong, Daun; Lee, Jeoung Soo

doi:10.1016/j.nano.2020.102343

Cited by 12 publications

(5 citation statements)

References 56 publications

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“…Secondary injury, which typically manifests as severe inflammation and neuronal apoptosis [11, 46], is the principal pathogenic process that aggravates tissue damage and hampers recovery of motor function following SCI [4, 47]. Because secondary injury is a critical therapy window, several studies have focused on reducing inflammation and neuronal death following SCI to aid functional recovery [48, 49]. Microglia become over-activated if the central nervous system is injured, resulting in the release of a large number of inflammatory mediators [50, 51].…”

Section: Discussionmentioning

confidence: 99%

Aucubin promoted neuron functional recovery by suppressing inflammation and neuronal apoptosis in a spinal cord injury model

Xiao

Zhong

Yang

et al. 2022

Preprint

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Spinal cord injury (SCI) can cause severe motor impairment. Post-SCI treatment has focused primarily on secondary injury, with neuroinflammation and neuronal apoptosis as the primary therapeutic targets. Aucubin (Au), a Chinese herbal medicine, exerts anti-inflammatory and neuroprotective effects. The therapeutic effects of Au in SCI have not been reported. We showed that Au can promote functional recovery after SCI. Recovery may occur through the toll-like receptor 4 (TLR4)/nuclear factor kappa B (NF-κB) pathway to promote M2/M1 polarization in microglia and inhibit mitochondrial dysfunction to reduce neuronal apoptosis. These biochemical changes result in reduced secondary injury and facilitate axon regeneration. Therefore, Au may be a promising post-SCI therapeutic medication.

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Section: Discussionmentioning

confidence: 99%

Aucubin promoted neuron functional recovery by suppressing inflammation and neuronal apoptosis in a spinal cord injury model

Xiao

Zhong

Yang

et al. 2022

Preprint

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“…Rings were assembled fresh with one fluorescently labeled IRDye800 sequence per ring in order to visualize the biodistribution of the treatments over time. Rings were combined with the cationic amphiphilic copolymer poly(lactide-co-glycolide)-graftpolyethylenimine (here referred to as PgP [26,[38][39][40] ) as a delivery agent in a 30/1 N/P ratio (where N is number of nitrogen atoms in PgP and P is number of phosphorus atoms in NANPs) and allowed to incubate at room temperature for 30 min prior to loading and injection. Mice were anesthetized with 1-3% isoflurane and received 100 µL of 10 × 10 −6 m RNA ring with PgP via retro-orbital injection.…”

Section: Methodsmentioning

confidence: 99%

“…Several changes in the blood cytokine levels were observed in the presence of NANPs: i) MCP-1 levels were upregulated; ii) IL-1β, IFNγ, IL-2, MIP-1a, and KC levels were downregulated; iii) IL-6 and IL-10 showed bi-modal distribution in that IL-6 was upregulated in one-half of the treatment group whereas the second half of animals showed no change, and IL-10 was upregulated in one-half of animals and downregulated in the second half of the treatment group. Interestingly, changes in IL-1β and MCP-1 were seen with all rings acid carriers for central nervous system injury repair [38][39][40] some detectable amount of fluorescence and cytokine production in the brain demonstrated that NANPs were able to remain conjugated to the carrier to cross as well, which opens up possibilities for delivery to the central nervous system.…”

Section: Orientation Of Tnas Affects In Vivo Response To Nanpsmentioning

confidence: 99%

Expanding Structural Space for Immunomodulatory Nucleic Acid Nanoparticles via Spatial Arrangement of Their Therapeutic Moieties

Chandler

Rolband

Johnson

et al. 2022

Adv Funct Materials

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Different therapeutic nucleic acids (TNAs) can be unified in a single structure by their elongation with short oligonucleotides designed to self-assemble into nucleic acid nanoparticles (NANPs). With this approach, therapeutic cocktails with precisely controlled composition and stoichiometry of active ingredients can be delivered to the same diseased cells for enhancing pharmaceutical action. In this study, an additional nanotechnology-based therapeutic option that enlists a biocompatible NANP-encoded platform for their controlled patient-specific immunorecognition is explored. For this, a set of representative functional NANPs is extensively characterized in vitro, ex vivo, and in vivo and then further analyzed for immunostimulation of human peripheral blood mononuclear cells freshly collected from healthy donor volunteers. The results of the study present the advancement of the current TNA approach toward personalized medicine and offer a new strategy to potentially address top public health challenges related to drug overdose and safety through the biodegradable nature of the functional platform with immunostimulatory regulation.

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“…ESCs [222], iPSCs [43,223], NSCs/NPCs [224,225], MSCs [180,181], OPCs [226], DPSCs [216] and ADSCs [227] Olfactory ensheathing cells [228] and Schwann cells [229] Microglia [230] Directly reprogrammed NPCs (drNPCs) [231][232][233] Gene therapies Nucleic acid-based therapies Delivery methods Other siRNA to AQP-4 [234], nNOS [235], iNOS [236], IL-6 [237], claudin-5 [238], RhoA [239,240], PLK-4 [241], PTEN [242,243], Sema3A [244], CTGF [245], combinatorial [246] and in combination with MSCs [242] Nanoparticle-coated siRNA [247][248][249], polymer nanocarriers [239], exosome delivery [243,245] extracellular vesicles [250], intrathecal delivery [240], photomechanical wave [251] and intranasal delivery [242] Chemogenetic stimulation [252]…”

Section: Neural Cells Immune Cells Advanced Cell Therapiesmentioning

confidence: 99%

Neurotrauma—From Injury to Repair: Clinical Perspectives, Cellular Mechanisms and Promoting Regeneration of the Injured Brain and Spinal Cord

Stevens,

Belli,

Ahmed

2024

Biomedicines

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Traumatic injury to the brain and spinal cord (neurotrauma) is a common event across populations and often causes profound and irreversible disability. Pathophysiological responses to trauma exacerbate the damage of an index injury, propagating the loss of function that the central nervous system (CNS) cannot repair after the initial event is resolved. The way in which function is lost after injury is the consequence of a complex array of mechanisms that continue in the chronic phase post-injury to prevent effective neural repair. This review summarises the events after traumatic brain injury (TBI) and spinal cord injury (SCI), comprising a description of current clinical management strategies, a summary of known cellular and molecular mechanisms of secondary damage and their role in the prevention of repair. A discussion of current and emerging approaches to promote neuroregeneration after CNS injury is presented. The barriers to promoting repair after neurotrauma are across pathways and cell types and occur on a molecular and system level. This presents a challenge to traditional molecular pharmacological approaches to targeting single molecular pathways. It is suggested that novel approaches targeting multiple mechanisms or using combinatorial therapies may yield the sought-after recovery for future patients.

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Local delivery of RhoA siRNA by PgP nanocarrier reduces inflammatory response and improves neuronal cell survival in a rat TBI model

Cited by 12 publications

References 56 publications

Aucubin promoted neuron functional recovery by suppressing inflammation and neuronal apoptosis in a spinal cord injury model

Aucubin promoted neuron functional recovery by suppressing inflammation and neuronal apoptosis in a spinal cord injury model

Expanding Structural Space for Immunomodulatory Nucleic Acid Nanoparticles via Spatial Arrangement of Their Therapeutic Moieties

Neurotrauma—From Injury to Repair: Clinical Perspectives, Cellular Mechanisms and Promoting Regeneration of the Injured Brain and Spinal Cord

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