Podcast
Questions and Answers
What is the primary measurement focus of nerve conduction studies according to the Neurodiab guidelines?
What is the primary measurement focus of nerve conduction studies according to the Neurodiab guidelines?
- Small fiber function
- Peripheral nerve structure
- Autonomic nerve function
- Large fiber function (correct)
Which aspect is emphasized in the assessment of nerve conduction velocity (NCV)?
Which aspect is emphasized in the assessment of nerve conduction velocity (NCV)?
- All nerve types regardless of temperature
- Blinding researchers during analysis (correct)
- Using only sensory nerves
- Ignoring core temperature changes
Why is assessing nerve conduction velocity in the caudal nerve not strongly recommended?
Why is assessing nerve conduction velocity in the caudal nerve not strongly recommended?
- It does not represent small fiber function
- It yields highly variable results
- It is not part of standard nerve conduction studies
- It lacks sufficient anatomical relevance in rodents (correct)
What is a critical factor for accurate nerve conduction velocity assessment?
What is a critical factor for accurate nerve conduction velocity assessment?
The Neurodiab guidelines suggest which of the following as endpoints for phenotyping?
The Neurodiab guidelines suggest which of the following as endpoints for phenotyping?
What is the role of reporting both positive and negative results in research according to the guidelines?
What is the role of reporting both positive and negative results in research according to the guidelines?
What is a reliable and sensitive marker of small sensory nerve fiber loss in diabetic rodents?
What is a reliable and sensitive marker of small sensory nerve fiber loss in diabetic rodents?
Which of these criteria is necessary for defining diabetic peripheral neuropathy (DPN) in rodent models?
Which of these criteria is necessary for defining diabetic peripheral neuropathy (DPN) in rodent models?
What is a commonly utilized behavioral test for assessing small fiber neuropathy in rodent models?
What is a commonly utilized behavioral test for assessing small fiber neuropathy in rodent models?
How have T2DM and T1DM demonstrated differences in DPN treatment effectiveness according to research?
How have T2DM and T1DM demonstrated differences in DPN treatment effectiveness according to research?
Which factor is NOT typically assessed when evaluating DPN in relation to the Neurodiab guidelines?
Which factor is NOT typically assessed when evaluating DPN in relation to the Neurodiab guidelines?
What recent advancements have been made in T2DM rat models for studying DPN?
What recent advancements have been made in T2DM rat models for studying DPN?
Which behavioral test primarily assesses large fiber dysfunction in neuropathy evaluation?
Which behavioral test primarily assesses large fiber dysfunction in neuropathy evaluation?
What primary metabolic comorbidity associated with T2DM is focused on in preclinical models of DPN?
What primary metabolic comorbidity associated with T2DM is focused on in preclinical models of DPN?
Which method has been criticized for having variability when assessing DPN in rodent models?
Which method has been criticized for having variability when assessing DPN in rodent models?
Which type of neuropathy assessment was excluded from the focus of the review on DPN?
Which type of neuropathy assessment was excluded from the focus of the review on DPN?
What is the predominant model used in studies of diet and chemically induced T2DM in rats?
What is the predominant model used in studies of diet and chemically induced T2DM in rats?
Which criteria were used to exclude studies from the review?
Which criteria were used to exclude studies from the review?
Which T2DM model was most frequently studied among the transgenic models?
Which T2DM model was most frequently studied among the transgenic models?
Which of the following DPN endpoints was assessed most frequently by diet and chemically induced T2DM models?
Which of the following DPN endpoints was assessed most frequently by diet and chemically induced T2DM models?
How many articles were ultimately included in the review after screening?
How many articles were ultimately included in the review after screening?
What percentage of diet and chemically induced T2DM studies assessed all three DPN endpoints?
What percentage of diet and chemically induced T2DM studies assessed all three DPN endpoints?
What was the primary focus of the scoping review conducted up to 3rd November 2020?
What was the primary focus of the scoping review conducted up to 3rd November 2020?
Which of the following terms was NOT part of the search terms used in the literature search?
Which of the following terms was NOT part of the search terms used in the literature search?
Flashcards
DPN Phenotyping
DPN Phenotyping
Using multiple methods (behaviour, nerve conduction, and nerve structure) to identify and characterize diabetic peripheral neuropathy in rodent models.
Neurodiab Guidelines
Neurodiab Guidelines
A set of consensus criteria for phenotyping diabetic peripheral neuropathy (DPN) in rodent models, aiming for standardized data reporting and collaboration.
Nerve Conduction Studies (NCS)
Nerve Conduction Studies (NCS)
Gold standard clinical tests for assessing large fiber function in rodent models of DPN.
Nerve Conduction Velocity (NCV)
Nerve Conduction Velocity (NCV)
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Intraepidermal Nerve Fiber Density (IENFD)
Intraepidermal Nerve Fiber Density (IENFD)
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Peripheral Nerve Structure
Peripheral Nerve Structure
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Experimental Design
Experimental Design
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Rodent Models
Rodent Models
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Scoping Review
Scoping Review
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T2DM
T2DM
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DPN
DPN
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Rat Models
Rat Models
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PubMed, Web of Science, Scopus
PubMed, Web of Science, Scopus
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High-Fat Diet (HFD)
High-Fat Diet (HFD)
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Study Selection Criteria
Study Selection Criteria
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Transgenic/Spontaneous Models
Transgenic/Spontaneous Models
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Distinct Pathophysiological Mechanisms of DPN in T1DM and T2DM
Distinct Pathophysiological Mechanisms of DPN in T1DM and T2DM
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Glycemic Control's Limited Effect on T2DM DPN
Glycemic Control's Limited Effect on T2DM DPN
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T2DM Preclinical Models
T2DM Preclinical Models
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Hargreaves Test
Hargreaves Test
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Von Frey Monofilaments
Von Frey Monofilaments
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DPN Phenotyping in Rodent Models
DPN Phenotyping in Rodent Models
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Study Notes
Peripheral Neuropathy in Rat Models of T2DM
- Diabetic peripheral neuropathy (DPN) affects over half of type 2 diabetes mellitus (T2DM) patients.
- Effective pharmacotherapies are urgently needed.
- Phenotyping DPN in rodent models has been challenging due to inconsistencies across laboratories.
- A consensus guideline ("Neurodiab") was published in 2014 to standardize preclinical DPN phenotyping.
- This review examines rat T2DM models' DPN phenotyping, evaluating guideline uptake and identifying future directions.
- 125 studies (diet/chemically induced & transgenic/spontaneous T2DM models) were reviewed, focusing mainly on diet-induced models (predominantly high-fat diet (HFD) + low-dose streptozotocin (STZ) in Sprague-Dawley (SD) rats).
- The use of HFD and chemically induced T2DM models surpassed transgenic models. The Neurodiab guidelines' introduction hasn't appreciably increased studies assessing all DPN endpoints.
Neurodiab Criteria for Rodent Models
- DPN is defined as statistically significant differences in at least two of three measures: behavioral assessment, nerve conduction, and peripheral nerve structure, between diabetic and age-matched control animals.
- Key behavioral tests include Hargreaves (for small fiber neuropathy), von Frey monofilaments (for large fiber dysfunction), and others.
- Nerve conduction studies (NCS) measure large-fiber function (motor and sensory nerve conduction velocity, NCV).
- Peripheral nerve structure is assessed by intraepidermal nerve fiber density (IENFD) in footpads, nerve trunk morphometry, and corneal nerve fiber analysis.
Study Methods and Results
- A literature search (PubMed, Scopus, Web of Science) identified 1,625 articles. 125 articles met inclusion criteria (rat T2DM model & assessment of at least one DPN endpoint).
- Studies using diet-induced T2DM models more frequently assessed all three DPN endpoints than transgenic models, although this difference wasn't statistically significant.
- Most commonly used diet+chemical model is HFD + low-dose STZ in SD rats, often with varied duration of HFD feeding and STZ doses.
- Many studies showed significant impairment in at least two DPN endpoints irrespective of whether the duration of diabetes was short (0-6 weeks) or long (> 6 weeks).
Influence of Sex and Duration of Diabetes
- Sex differences in DPN phenotypes are a limited area of research, with few studies using female rats and inconsistencies in results for differences in pain-related behaviors between genders.
- Diabetes duration affects DPN phenotypes in a dynamic manner. Hyperalgesia is more common in the initial phases, giving way to hypoalgesia in later stages of diabetes.
Discussion and Future Directions
- The review highlights the limitations of current rat models for DPN, emphasizing the need to better characterize models like HFHS/STZ and STZ/NA.
- Further studies need to incorporate more female rat models, explore DPN phenotypes across multiple time points, and systematically assess the relationship between metabolic measures and DPN severity.
- The development of more standardized and spontaneous T2DM models is essential to accelerate the development of effective treatments.
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