Creative Biolabs offers a streptozotocin (STZ)-induced model of diabetic neuropathy, which exhibits similar manifestations as observed in human diabetic neuropathy, for the evaluation of painkillers and neuroprotective agents. With a full battery of assessment tools at our disposal, we can provide high-quality efficacy data to support your advancing proteins and small molecules to IND/NDA stage.
Diabetic Peripheral Neuropathy
Diabetic peripheral neuropathy (DPN) is one of the most common complications of diabetes mellitus and is associated with significant morbidity and mortality. DPN is characterized by progressive, distal-to-proximal degeneration of peripheral nerves that leads to pain, weakness, and eventual loss of sensation. To date, other than tight glycemic control, no effective treatments are available, stressing the importance for the development of novel therapeutic interventions. Animal rodent modeling of clinical DPN offers a powerful tool to understand diabetes-mediated peripheral nerve injury and to develop novel pharmacological strategies.
Introduction of STZ-Induced Diabetic Neuropathy Model
The STZ-induced rat model which reproduces metabolic lesional mechanisms of Type 1 Diabetes Mellitus (T1DM) is a commonly used model of DPN. STZ, an alkylating and antimicrobial agent, selectively destroys pancreatic β cells through DNA alkylation. Typically, diabetes can be induced by a single intraperitoneal or intravenous injection of STZ at a relatively high dose. This leads to prolonged hyperglycemia, hypoinsulinemia, and abnormal glucose metabolism, which cause the degeneration of neurons.
Decreases in neurotrophic factors occur in STZ-induced diabetic animals, as in patients with diabetic neuropathy, and this, in turn, exacerbates the degeneration of neurons. Slowing of nerve conduction velocity (NCV), a conventional electrophysiological parameter that reflects the severity of nerve dysfunction, also occurs in STZ-induced diabetic animals as in patients with diabetic neuropathy. In addition, STZ-induced diabetic rats show neuropathic pain, characterized by mechanical and thermal allodynia, one of the symptoms of diabetic neuropathy. Gabapentin, pregabalin, amitriptyline, mexiletine, and morphine, but not diclofenac, inhibit allodynia in a rodent model of STZ-induced diabetic neuropathy, suggesting that the STZ model is suitable for evaluating the clinical potential of compounds for treating painful diabetic neuropathy.
Fig. 1 Trends of the tail-flick test in diabetic group, STZ control group, and vehicle control group. (Gong et al. 2011)
Features of STZ-Induced Diabetic Neuropathy Model
Assessments
First, metabolic phenotypes such as body weight, fasting blood glucose, and impaired glucose tolerance (IGT) are measured longitudinally. The sensory function can be determined by assessing allodynia, hyperalgesia, and hypoalgesia through behavior response to thermal (e.g., tail-flick test, hind paw withdrawal test, Von Frey filaments) or mechanical stimuli. Moreover, oxidative and nitrosative stress, inflammatory infiltrates, and impaired angiogenesis within peripheral nerve tissue can be examined by immunohistochemistry. Briefly, Creative Biolabs provides assessments including but not limited to:
Meantime, Creative Biolabs offers other pain models to study different pain-related conditions and to evaluate the analgesic activity of novel drugs:
The comprehensive list of rodent neurological disease models is placed below for your review. Please click the links for more detailed description of each model:
Creative Biolabs has years of experience in helping our clients advance their innovations through preclinical efficacy stages. Our scientists will work with you to learn your specific preclinical study requirements and assist you from initial study design to final reporting of your data to provide you with dependable, reproducible results. Please contact us to start the conversation if you are interested in our services.
Reference
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