Pepino polyphenolic extract improved oxidative, inflammatory and glycative stress in the sciatic nerves of diabetic mice

2016 ◽  
Vol 7 (2) ◽  
pp. 1111-1121 ◽  
Author(s):  
Chin-Tsu Ma ◽  
Charng-Cherng Chyau ◽  
Cheng-Chin Hsu ◽  
Shyh-Ming Kuo ◽  
Chin-Wen Chuang ◽  
...  
Keyword(s):  
Diabetic Neuropathy ◽  
Diabetic Mice ◽  
Polyphenolic Extract ◽  
Sciatic Nerves

The effect of pepino polyphenolic extract (PPE) on diabetic neuropathy was examined.

Abstract 241: Direct Injection of Bone Marrow Mononuclear Cells Reversed Experimental Diabetic Neuropathy by Augmenting Neovascularization and Providing Angio-neurotrophic Cytokines

Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
Hyongbum Kim ◽  
Yong Jin Choi ◽  
Jong-seon Park ◽  
Masaaki Ii ◽  
Marcy Silver ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Diabetic Neuropathy ◽  
Neurotrophic Factors ◽  
Mononuclear Cells ◽  
Motor Nerve ◽  
Therapeutic Option ◽  
Direct Injection ◽  
Saline Group ◽  
Vasa Nervorum ◽  
Sciatic Nerves

Background: Bone marrow (BM)-derived mononuclear cells (MNCs) have been shown to effectively treat ischemic cardiovascular diseases. Recent evidence suggested that diabetic neuropathy (DN) is causally related to impaired angio-vasculogenesis in vasa nervorum and deficiency of angiogenic and neurotrophic factors. Accordingly, we sought to investigate whether DN can be ameliorated by local injection of BM-derived MNCs. Methods and Results: A severe peripheral neuropathy, characterized by significant slowing of motor nerve conduction velocities (MCV) developed 12 wks after the induction of diabetes with streptozotocin in Fisher rats (vs normal rats; 46.6±2.6 vs 32.0±2.5 m/s, P < 0.05). These rats were randomly assigned to MNC or saline injection groups (n = 9, each group) and received either 5x106 MNCs or saline intramuscularly around the sciatic nerves. In the MNC group, MCV were significantly improved within 4 wks after treatment (MNC vs Saline, 41.9±3.2 vs 32.7±2.8 m/s, P < 0.01). Microvascular circulation of sciatic nerve, measured by laser Doppler perfusion imaging was markedly increased only in the MNC group. Capillary density at 4 wks was significantly higher in the MNC group than in the saline group (68±5.9 vs 37±4.4 /cross section, P < 0.01). Robust engraftment of MNCs were observed in sciatic nerves, which sustained over 4 wks. A fraction of engrafted MNCs expressed endothelial markers suggestive of transdifferentiation into endothelial cells in the vasa nervorum. Intriguingly, a large number of the engrafted MNCs are following the course of vasa nervorum in close proximity. Real-time RT-PCR on sciatic nerves revealed that the expression of angio-neurotrophic factors were significantly increased in the MNC group compared to the saline group: VEGF (2.1 fold), FGF-2 (2.4), eNOS (18.1), Brain-derived neurotrophic factor (35.1), IGF-1 (25.5) (all P < 0.05). The protein levels were well correlated with mRNA expression levels. Conclusion: Local transplantation of BM-derived MNCs could improve experimental DN by augmenting neovascularization and increasing angiogenic and neurotrophic factors in peripheral nerves. These findings suggest that BM-MNC transplantation may represent a novel therapeutic option for treating DN.

scholarly journals Spinal Serotonin and 5HT6 Receptor Levels During Development of Neuropathy and Influence of Blockade of these Receptors on Thermal Hyperalgesia in Diabetic Mice

Drug Research ◽  
2019 ◽  
Vol 69 (08) ◽  
pp. 428-433 ◽  
Author(s):  
Cagda Celik Sari ◽  
Ozgur Gunduz ◽  
Ahmet Ulugol
Keyword(s):  
Diabetic Neuropathy ◽  
Single Injection ◽  
Thermal Hyperalgesia ◽  
Receptor Expression ◽  
Diabetic Mice ◽  
Hot Plate ◽  
Hot Plate Test ◽  
Plate Test ◽  
Diabetes Development

AbstractLittle is known about the role of 5-HT6 receptors in the pathophysiology of neuropathic pain. The aim of this study is firstly, to investigate the influence of spinal and systemic 5-HT6 receptors on thermal hyperalgesia, one of the most significant symptoms of neuropathy occurring in diabetes; and secondly to determine spinal lumbar serotonin and 5-HT6 receptor levels during development of diabetic neuropathy in mice. Diabetes was produced in Balb/c mice with a single injection of streptozocin (150 mg/kg, i.p.). Using the hot plate test, the 5-HT6 antagonist SB-258585 was given systemically (3, 10, 30 mg/kg) and intrathecally (0.01, 0.1, 1 nmol/mouse) to determine its effect on thermal hyperalgesia. Furthermore, on days 7 and 15 of diabetes, development of thermal hyperalgesia was evaluated in relation to changes in spinal serotonin and 5-HT6 receptor levels by using LC/MS/MS and Western blot analyses, respectively. Two-way analysis of variance and unpaired t-tests were used to evaluate data from hot-plate tests and 5-HT levels/ 5-HT6 receptor expression, respectively. Thermal hyperalgesia was observed in neuropathic mice, starting from day 5 after streptozocin administration. On day 15, systemic, but not intrathecal, SB-258585 attenuated thermal hyperalgesia in neuropathic mice. Spinal serotonin levels did not change during development of hyperalgesia after induction of diabetes, whereas spinal 5-HT6 receptor levels were significantly reduced on days 7 and 15. Our findings show that systemic, but not spinal, blockade of 5-HT6 receptors may exert antihyperalgesic effects in neuropathic mice and suggest that systemic 5-HT6 receptors contribute to the pathophysiology of diabetic neuropathy.

Transplantation of human mobilized mononuclear cells improved diabetic neuropathy

2018 ◽  
Vol 239 (3) ◽  
pp. 277-287
Author(s):  
Se Hee Min ◽  
Jung Hee Kim ◽  
Yu Mi Kang ◽  
Seung Hak Lee ◽  
Byung-Mo Oh ◽  
...  
Keyword(s):  
Stem Cells ◽  
Diabetic Neuropathy ◽  
Mononuclear Cells ◽  
Related Factor ◽  
Paracrine Effects ◽  
Muscle Perfusion ◽  
Hind Limbs ◽  
Compound Muscle Action Potentials ◽  
Sciatic Nerves

Rodent stem cells demonstrated regenerative effects in diabetic neuropathy via improvement in nerve perfusion. As a pre-clinical step, we explored if human mobilized mononuclear cells (hMNC) would have the same effects in rats. hMNC were injected into Rt. hind-limb muscles of streptozotocin-induced diabetic nude rats, and the grafts were monitored using with MRI. After 4 weeks, the effects were compared with those in the vehicle-injected Lt. hind limbs. Nerve conduction, muscle perfusion and gene expression of sciatic nerves were assessed. Induction of diabetes decreased nerve function and expression of Mpz and Met in the sciatic nerves, which are related with myelination. hMNC injection significantly improved the amplitude of compound muscle action potentials along with muscle perfusion and sciatic nerve Mpz expression. On MRI, hypointense signals were observed for 4 weeks at the graft site, but their correlation with the presence of hMNC was detectable for only 1 week. To evaluate paracrine effects of hMNC, IMS32 cells were tested with hepatocyte growth factor (HGF), which had been reported as a myelination-related factor from stem cells. We could observe that HGF enhanced Mpz expression in the IMS32 cells. Because hMNC secreted HGF, IMS32 cells were co-cultured with hMNC, and the expression of Mpz increased along with morphologic maturation. The hMNC-induced Mpz expression was abrogated by treatment of anti-HGF. These results suggest that hMNC could improve diabetic neuropathy, possibly through enhancement of myelination as well as perfusion. According to in vitro studies, HGF was involved in the hMNC-induced myelination activity, at least in part.

scholarly journals Contribution of Trem2 Signaling to the Development of Painful Diabetic Neuropathy by Mediating Microglial Polarization in Mice

2021 ◽  
Author(s):  
Xin Chen ◽  
Yue Le ◽  
Wan-you He ◽  
Jian He ◽  
Yun-hua Wang ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Diabetic Neuropathy ◽  
Mechanical Allodynia ◽  
Type I Diabetes ◽  
Intraperitoneal Administration ◽  
Thermal Hyperalgesia ◽  
Lumbar Spinal Cord ◽  
Type I ◽  
Painful Diabetic Neuropathy ◽  
Diabetic Mice

Abstract Background Painful diabetic neuropathy (PDN) is a common and intractable complication of diabetes mellitus, with little effective treatment. PDN has been associated with spinal neuroinflammation characterized by microglial activation. Recently, the triggering receptor expressed on myeloid cells 2 (TREM2), specifically localized on microglia, has been identified as a vital factor in modulating neuroinflammation and microglial phenotypes in neural diseases. Therefore, we hypothesized that spinal TREM2 might contribute to PDN and neuroinflammation by regulating microglial activity and phenotypes. Methods Type I diabetes mellitus was elicited by a single intraperitoneal administration of streptozotocin (STZ) in mice. The pain behaviors were reflected by paw mechanical withdrawal thresholds (PMWT) and thermal withdrawal latency (PTWL). Results We demonstrated that up-regulation of microglial TREM2 and amplification of both microglial M1 and M2 response was along with the presence of diabetes-related mechanical allodynia and thermal hypersensitivity. Moreover, we found that overexpression of TREM2 in microglia aggravated the symptom of PDN, amplified microglia M1 response, and suppressed microglia M2 polarization in the lumbar spinal cord of diabetic mice. However, inhibition of TREM2 with anti-TREM2 neutralizing antibodies attenuated mechanical allodynia and thermal hyperalgesia in diabetic mice. Besides, we identified Galectin-3 (GLT-3) as the potential ligand of the TREM2 receptor in facilitating the progression of PDN. Conclusions TREM2 could be a critical microglial membrane molecule that modulates microglial phenotypes pain hypersensitivity in PDN. GLT-3 might act as a specific ligand to trigger TREM2 signaling in PDN or other neuropathic pain.

scholarly journals Administration of CORM-2 inhibits diabetic neuropathy but does not reduce dyslipidemia in diabetic mice

PLoS ONE ◽  
2018 ◽  
Vol 13 (10) ◽  
pp. e0204841 ◽  
Author(s):  
Karen Alejandra Méndez-Lara ◽  
David Santos ◽  
Núria Farré ◽  
Sheila Ruiz-Nogales ◽  
Sergi Leánez ◽  
...  
Keyword(s):  
Diabetic Neuropathy ◽  
Diabetic Mice
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