The LTB4-BLT1 Axis Mediates Neutrophil Infiltration and Secondary Injury in Experimental Spinal Cord Injury

Saiwai, Hirokazu; Ohkawa, Yasuyuki; Yamada, Hisakata; Kumamaru, Hiromi; Harada, Akihito; Okano, Hideyuki; Yokomizo, Takehiko; Iwamoto, Yukihide; Okada, Seiji

doi:10.2353/ajpath.2010.090839

Cited by 153 publications

(161 citation statements)

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“…Adult female C57BL6 mice were anesthetized via an intraperitoneal injection of sodium pentobarbital (somnopentyl; 50 mg kg − 1 ). SCI was induced using Infinite Horizons Impactor at 70 kilodyne on 10th thoracic level 47 . A 25-µl Hamilton syringe (Hamilton) with a glass tip was inserted into the epicentre of the injured spinal cord and 2 µl of the cell suspension was injected at 0.5 µl min − 1 using a stereotaxic injector (KDS 310; Muromachi-kikai).…”

Section: Methodsmentioning

confidence: 99%

“…At the over-dose experiment, 4 µl of cell suspension or conditioned medium was injected into injured spinal cords of each group. Motor functions were evaluated with a locomotor open-field rating scale on the BBB score 13 and the Basso Mouse Scale 47 . Footprint analysis was performed only on mice scored as frequently or consistently plantar stepping at 42 days after SCI.…”

Section: Methodsmentioning

confidence: 99%

“…For analysis of the infiltrated inflammatory cells, the spinal cord samples (4-mm long) were dissociated in collagenase (Invitrogen) and stained with antibodies, as previously described 47 , followed by analysis using FACSAria II flow cytometer and FACSDiva software (BD Biosciences). Phycoerythrin-Cy7 (PE-Cy7)-conjugated CD45 (1:10), fluorescein isothiocyanateconjugated CD11b (1:10), PE-conjugated Gr-1 (1:50) and biotin-conjugated Nk1.1 (1:10) antibodies were used to examine myeloid cell infiltration.…”

Section: Methodsmentioning

confidence: 99%

“…After the mice were transcardially fixed with 4% paraformaldehyde, the spinal cord was removed, dehydrated and embedded in an OCT compound 47 . The frozen sections were cut in the sagittal plane at 14 µm or axial plane at 20 µm.…”

Section: Immunohistochemistry and Immunoblottingmentioning

confidence: 99%

“…The number of TUNEL + /GFP − cells was counted in axial sections at 500 µm intervals and the number of TUNEL + /GFP + cells was counted in sagittal sections at 280-µm intervals. Luxol Fast Blue staining was performed to calculate the area of spared myelin as described previously 47 . For immunoblotting, the following antibodies were used for: activated caspase 9, cleaved caspase 3, phospho-Akt, phospho-p65 (Ser536) and α-tubulin.…”

Section: Immunohistochemistry and Immunoblottingmentioning

confidence: 99%

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Direct isolation and RNA-seq reveal environment-dependent properties of engrafted neural stem/progenitor cells

et al. 2012

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neural stem/progenitor cell (nsPC) transplantation is a promising treatment for various neurodegenerative disorders including spinal cord injury, however, no direct analysis has ever been performed on their in vivo profile after transplantation. Here we combined bioimaging, flow-cytometric isolation and ultra-high-throughput RnA sequencing to evaluate the cellular properties of engrafted nsPCs. The acutely transplanted nsPCs had beneficial effects on spinal cord injury, particularly neuroprotection and neurohumoral secretion, whereas their in situ secretory activity differed significantly from that predicted in vitro. The RnA-sequencing of engrafted nsPCs revealed dynamic expression/splicing changes in various genes involved in cellular functions and tumour development depending on graft environments. notably, in the pathological environment, overall transcriptional activity, external signal transduction and neural differentiation of engrafted nsPCs were significantly suppressed. These results highlight the vulnerability of engrafted nsPCs to environmental force, while emphasizing the importance of in situ analysis in advancing the efficacy and safety of stem cell-based therapies.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Immunohistochemistry and Immunoblottingmentioning

confidence: 99%

Section: Immunohistochemistry and Immunoblottingmentioning

confidence: 99%

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Direct isolation and RNA-seq reveal environment-dependent properties of engrafted neural stem/progenitor cells

et al. 2012

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Clonidine, an alpha‐2 adrenoceptor agonist relieves mechanical allodynia in oxaliplatin‐induced neuropathic mice; potentiation by spinal p38 MAPK inhibition without motor dysfunction and hypotension

Yeo

Yoon

Kim

et al. 2016

Intl Journal of Cancer

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Cancer chemotherapy with platinum-based antineoplastic agents including oxaliplatin frequently results in a debilitating and painful peripheral neuropathy. We evaluated the antinociceptive effects of the alpha-2 adrenoceptor agonist, clonidine on oxaliplatin-induced neuropathic pain. Specifically, we determined if (i) the intraperitoneal (i.p.) injection of clonidine reduces mechanical allodynia in mice with an oxaliplatin-induced neuropathy and (ii) concurrent inhibition of p38 mitogen-activated protein kinase (MAPK) activity by the p38 MAPK inhibitor SB203580 enhances clonidine's antiallodynic effect. Clonidine (0.01-0.1 mg kg 21, i.p.), with or without SB203580(1-10 nmol, intrathecal) was administered two weeks after oxaliplatin injection(10 mg kg 21, i.p.) to mice. Mechanical withdrawal threshold, motor coordination and blood pressure were measured. Postmortem expression of p38 MAPK and ERK as well as their phosphorylated forms(p-p38 and p-ERK) were quantified 30 min or 4 hr after drug injection in the spinal cord dorsal horn of treated and control mice. Clonidine dose-dependently reduced oxaliplatininduced mechanical allodynia and spinal p-p38 MAPK expression, but not p-ERK. At 0.1 mg kg 21, clonidine also impaired motor coordination and decreased blood pressure. A 10 nmol dose of SB203580 alone significantly reduced mechanical allodynia and p-p38 MAPK expression, while a subeffective dose(3 nmol) potentiated the antiallodynic effect of 0.03 mg kg 21 clonidine and reduced the increased p-p38 MAPK. Coadministration of SB203580 and 0.03 mg kg 21 clonidine decreased allodynia similar to that of 0.10 mg kg 21 clonidine, but without significant motor or vascular effects. These findings demonstrate that clonidine treatment reduces oxaliplatin-induced mechanical allodynia. The concurrent administration of SB203580 reduces the dosage requirements for clonidine, thereby alleviating allodynia without producing undesirable motor or cardiovascular effects.Neuropathy is observed after application of various chemotherapy agents including paclitaxel, vincristine and cisplatin, 1,2 and presents as a mildly disrupting tingling sensation to an extremely painful paresthesia. 3 These dose-limiting side effects of chemotherapy treatments are much more disruptive and persistent, in comparison to other common side effects such as alopecia, emesis, diarrhea and fatigue. 4 Oxaliplatin is a third-generation platinum-based compound used as the primary therapy for metastatic colorectal cancer and other malignancies including lung, breast and ovarian cancer. 5-7Oxaliplatin can also induce prominent neuropathic pain that is characterized by pronounced cold and mechanical hypersensitivity and spontaneous pain. [8][9][10] Several types of analgesics, anticonvulsants and antioxidants that are approved for the treatment of other neuropathic pain states have shown little or no analgesic effect on chemotherapy-induced peripheral neuropathic pain in large randomized, placebo-controlled clinical trials. 11,12 Thus, it is of critical importance ...

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Photobiomodulation therapy in knee osteoarthritis reduces oxidative stress and inflammatory cytokines in rats

Yamada

Bobinski

Martins

et al. 2019

Journal of Biophotonics

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Knee osteoarthritis (OA) is a chronic disease that causes pain and gradual degeneration of the articular cartilage. In this study, MIA‐induced OA knee model was used in rats to test the effects of the photobiomodulation therapy (PBM). We analyzed the inflammatory process (pain and cytokine levels), and its influence on the oxidative stress and antioxidant capacity. Knee OA was induced by monosodium iodoacetate (MIA) intra‐articular injection (1.5 mg/50 μL) and the rats were treated with eight sessions of PBM 3 days/week (904 nm, 6 or 18 J/cm2). For each animal, mechanical and cold hyperalgesia and spontaneous pain were evaluated; biological analyses were performed in blood serum, intra‐articular lavage, knee structures, spinal cord and brainstem. Cytokine assays were performed in knee, spinal cord and brainstem samples. The effects of the 18 J/cm2 dose of PBM were promising in reducing pain and neutrophil activity in knee samples, together with reducing oxidative stress damage in blood serum and spinal cord samples. PBM improved the antioxidant capacity in blood serum and brainstem, and decreased the knee pro‐inflammatory cytokine levels. Our study demonstrated that PBM decreased oxidative damage, inflammation and pain. Therefore, this therapy could be an important tool in the treatment of knee OA.

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The LTB4-BLT1 Axis Mediates Neutrophil Infiltration and Secondary Injury in Experimental Spinal Cord Injury

Cited by 153 publications

References 57 publications

Direct isolation and RNA-seq reveal environment-dependent properties of engrafted neural stem/progenitor cells

Direct isolation and RNA-seq reveal environment-dependent properties of engrafted neural stem/progenitor cells

Clonidine, an alpha‐2 adrenoceptor agonist relieves mechanical allodynia in oxaliplatin‐induced neuropathic mice; potentiation by spinal p38 MAPK inhibition without motor dysfunction and hypotension

Photobiomodulation therapy in knee osteoarthritis reduces oxidative stress and inflammatory cytokines in rats

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