Diabetic Peripheral Neuropathy

A hallmark of degeneration is the blebbing of neurites, which is when neurites begin disassembly and degeneration. The neurodegeneration index (NI) compares the relative area of neurites and the number of neurites.

The Diabetes Neurodegeneration in vitro screening assay utilizes primary neurons from immature mice or rats. Following the conditioning phase with high concentrations of glucose, cultures are treated with compounds and evaluated for their neurodegeneration index. 

The assays are ideal for screening compounds prior to efficacy in in vivo studies. 

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STZ is used to induce type I diabetes and diabetes-related complications, including diabetic peripheral neuropathy. There are multiple theories on the mechanism that involves peripheral neuropathy following STZ. Some of the mechanisms suggested are related to the hyperglycemic state of the rats suggesting that following the hyperglycemia, nerve endings are damaged either through an inflammatory process or interfering with blood supply. However, vast studies are also suggesting a mechanism of neuronal damage that occurs following STZ but it is unrelated to the hyperglycemic state of the animals.

These studies suggest direct damage to the nerves. For example, reactive oxygen species (ROS) mediate elevation of TRPV1 in neurons and the DRG is exposed to STZ in vitro. Therefore, the STZ model involves direct changes in the nerves that are not related to the inflammatory process. 

Assessments

• Blood glucose measurements, tactile/mechanical allodynia
• Histology and biomarker analysis (protein or mRNA) of sciatic nerve or paw skin)

The high fat diet induced diabetic model is used to study peripheral neuropathy from  diabetes types II. Food intake and body weight are measured along with blood glucose levels to determine the onset of type II diabetes. 

Measures:

• Body weight
• Food intake
• Glucose tolerance (GTT)
• Blood glucose level (BGL)
• Von Frey
• Electrophysiology: nSEP-induced withdrawal reflex