The Role of the Inflammatory and the Vascular Pathogenesis in a Model of Streptozotocin Induced Diabetic Neuropathy in Rats

Background Peripheral diabetic neuropathy (DN) is one of the major health problems facing the whole world. There is no treatment that could completely reverse or prevent progression of DN except for good glycemic control. The inflammatory and vascular pathways are two main domains that are incorporated in the pathogenesis of diabetic neuropathic pain (DNP) and DN. Thus, targeting both of them could be an appropriate way to delay progression of DN. Aim To investigate the role of the inflammatory and the vascular pathogenesis in diabetic mechanical allodynia. Method Twenty male Wistar rats were divided randomly into naïve and diabetic groups (n = 10). Diabetes was induced through i.p injection of single dose of streptozotocin (STZ) (50mg/kg), then 8 weeks after induction of diabetes, the sciatic content of tumor necrosis factor alpha (TNFα) and vascular endothelial growth factor (VEGF) was assessed using ELISA technique. Additionally, the number of intercellular adhesion molecule-1 (ICAM-1) as well as CD31, the most specific vascular marker, positively stained vessels was counted manually in sciatic nerves cross sections. Whereas, DNP was assessed weekly throughout the experiment using 60%mechanical threshold of paw withdrawal test. Results There was a significant increase in the sciatic content of TNFα, VEGF and ICAM-1 positively stained vessels and a significant decrease in CD31 positively stained vessels in the diabetic group as compared to the naïve group. There was a correlation between TNFα, VEGF, ICAM-1, CD31 positively stained vessels in one side and the 60% mechanical threshold on the other side (r=-0.8, -0.9, -0.8 and 0.7 respectively). Conclusion The diabetic mechanical allodynia is negatively correlated to the sciatic nerve content TNFα, VEGF, ICAM-1 and positively correlated to the CD31.

The Network Analysis of Peripheral Diabetic Neuropathy Involved Genes

Aim: Screening of candidate genes related to sural nerve diabetic neuropathy to find the critical ones is the aim of this study. Back Ground: Diabetes mellitus is a chronic disease causes by insulin uptake or deficiency. Side effects of diabetes are numerous according to severity of disease. Diabetes could harm the peripheral nerves with chronic pain, lead to nerve damage entitled diabetic neuropathy (DN). Signs and symptoms of DN are sharp pains, numbness, and tangling. Many patterns of nerve injuries could happen during DN but distal symmetric polyneuropathy (DSP) is most common. On the other hand, network analysis is a useful tool to assess incidences and progression of diseases. Methods: Expression of different genes in diabetic patients with and without progressive neuropathy of surreal nerve (GSE24290) is considered as including data. GEO2R was applied to first step analysis to find the significant differentially expressed genes (DEGs). The queried significant DEGs plus 100 first neighbors were included in a network by Cytoscape software. The network was analyzed by Network analyzed application of Cytoscape and the central nodes were determined. Results: The total 26 significant DEGs plus 100 first neighbors were interacted to form the network. INS, ALB, AKT1, APP, SNAP25, NEFL, GFAP, IL6, NEFM, TNF, MAPT, GAP43, and MBP were identified as 13 hubs of the network. NEFL and NEFM were highlighted as the queried hub genes. Insulin as the top hub node was determined among all interacted genes (the queried and added genes). Conclusions: INS, NEFL, and NEFM are key genes in DN which are involve in metabolism regulation and intra cellular transportation into axons and denderites respectively.

Biomechanical Profile of People with Diabetic Neuropathy Attended in Primary Care In East Paulista, Brazil

Diabetic neuropathy is one of the main complications of Diabetes Mellitus, which can lead to loss of protective sensation, motor alteration, in plantar pressure, generating deformities, abnormal gait and mechanical trauma to the feet. OBJECTIVEto evaluate the distribution of plantar pressure, sensory, motor changes and balance in people with peripheral diabetic neuropathy. METHODCross-sectional study conducted with individuals registered in the municipal public health network of a city in the east of São Paulo - Brazil, with Diabetes Mellitus and Peripheral Neuropathy identified by the Michigan Screening Instrument, sensory-motor changes by the International Consensus, static and dynamic assessments of plantar pressure using Baropodometry with BaroScan and balance using the Berg scale. RESULTSOf the 200 individuals evaluated, 52.55% had no plantar protective sensitivity, the static evaluation did not identify changes in the peak of plantar pressure, however in the dynamics the average in the right foot was 6.08 (± 2) kgf / cm2 and 6 , 7 (± 1.62) kgf / cm2 on the left foot, the center of static pressure on the right foot was lower (10.55 ± 3.82) than on the left foot (11.97 ± 3.90), pointing hyper plantar pressure. The risk of falling was high, ranging from 8 to 56 points, with an average of 40.96 (± 10.77). CONCLUSIONThe absence of protective plantar sensitivity, increased pressure, biomechanical changes lead to loss of balance and are predictive of complications in the feet due to diabetic neuropathy.