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| Animals models | References | Characterization of diabetic neuropathy/advantages | Limitations/disadvantages |
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| Streptozotocin-induced rat model (classic) | Jakobsen and Lundbeck [15]. | (i) Reduced sizes of nerve fiber, axon, and myelin sheath.
(ii) Impaired motor function.
| Not validated by antineuropathic drug. |
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| Streptozotocin-induced rat model (recent) | Filho and Fazan [22]. | (i) Significantly reduced right and left fascicular areas and myelination of phrenic nerves.
(ii) Validated by insulin (s.c.). | (i) Some major pathogenesis of diabetic neuropathy has not been characterized.
(ii) Although validated by insulin (s.c.), no antineuropathic drug has been used. |
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| C57BL/Ks (db/db) mice model (classic) | Sima and Robertson [16, 17];
Robertson and Sima [18]. | (i) Severely decreased motor nerve conduction velocity (MNCV).
(ii) Absence of large myelinated fibers.
(iii) Axonal atrophy.
(iv) Axonal dystrophy in myelinated and unmyelinated fibers.
(v) Loss, shrinkage, and breakdown of myeline sheath. | Not evaluated by any anti-diabetic or antineuropathic drug. |
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| Genetically modified C57BL/Ks (db/db) mice model (recent) | Hinder et al. [23]. | (i) Increased body weight, hyperglycemia, and hyperlipidemia.
(ii) Lower tail flick response to heat stimulus, sciatic motor nerve conduction velocity, and intraepididymal nerve fiber velocity. | (i) Mismatched results were observed for body weight, blood glucose, plasma lipids, and blood glycated hemoglobin.
(ii) Not validated by anti-diabetic or antineuropathic drugs. |
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| Streptozotocin-induced C57BL6/J mice model | Vareniuk et al. [24]. | (i) Peroxynitrite injury in peripheral nerve and dorsal root ganglion neurons.
(ii) Motor and sensory nerve conduction velocity deficits, thermal and mechanical hyperplasia, tactile allodynia, and loss of intraepidermal nerve fibers. | Not validated by using antineuropathic drug. |
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| Streptozotocin-induced diabetic sensory neuropathic ddY mice model | Murakami et al. [25]. | (i) Significantly lower sensory nerve conduction velocity, higher nociceptive threshold, hypoalgesia, and unmyelinated fiber atrophy.
(ii) Successfully evaluated by insulin treatment.
(iii) Can be a better model to study the human sensory polyneuropathy. | No significant change was found in the myelinated nerve fiber areas. |
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| Chinese hamster neuropathic model | Kennedy et al. [19]. | Reduced conduction velocity of both motor and sensory components of hind lamb nerves (16–22%). | (i) Peripheral diabetic neuropathy (PDN) was less severe than human diabetic neuropathy.
(ii) Further study needed for proper validation.
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| Rhesus monkey model of PDN | Cornblath et al. [20]. | (i) Significantly reduced motor conduction velocity.
(ii) Prolonged F-wave latencies.
(iii) Pathogeneses’ resembles to humans. | (i) No difference in motor-evoked amplitudes.
(ii) Prolonged nerve conduction induction time (2 years).
(iii) Not validated by antineuropathic drug. |
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| Spontaneously diabetic WBN/Kob rat model | Yagihashi et al. [26]. | (i) Slower motor nerve conduction and temporal dispersion of compound muscle action potential.
(ii) Structural de- and remyelination in the sciatic and tibial nerves at 12 month.
(iii) Axonal degeneration, dystrophy, and reduced myelinated fiber at 20 month.
(iv) Resembles human pathogenesis of PDN. | Not validated by antineuropathic drug. |
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| L-fucose induced neuropathic rat model | Sima et al. [27]. | (i) Reduced Na+-K+-ATPase activity.
(ii) Reduced nerve conduction velocity.
(iii) Axonal dystrophy.
(iv) Paranodal swelling and demyelination without increasing Walleran degeneration of nerve fiber loss. | Not validated by antineuropathic drug. |
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| Partial sciatic nerve ligated rat model | Fox et al. [28]. | (i) Produced long-lasting mechanical, but thermal hyperalgesia.
(ii) Evaluated by ant-diabetic neuropathic drugs. | Major pathogenesis was not characterized. |
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| Nonobese diabetic (NOD) mice model | Schmidt et al. [29];
Homs et al. [30]. | (i) Short induction period.
(ii) Markedly swollen axons and dendrites (neurotic dystrophy).
(iii) Consistent with the pathogenesis of other rodent models of PDN and human PDN.
(iv) Suggested as a better model than ICR mice particularly in terms of nerve regeneration. | Not validated by antineuropathic drug. |
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| Spontaneously induced Ins2 Akita mouse model | Choeiri et al. [31];
Schmidt et al. [32]. | (i) Spontaneously induced diabetic model.
(ii) Progressive and sustained chronic hyperglycemia.
(iii) Reduced sensory nerve conduction velocity.
(iv) Markedly swollen axons and dendrites (neurotic dystrophy).
(v) Consistent with the pathogenesis of other rodent models of PDN and human PDN. | Not validated by anti-diabetic or antineuropathic drug. |
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| Leptin-deficient (ob/ob) mice model | Drel et al. [6]. | (i) Clearly manifested thermal hypoalgesia. (ii) Relatively higher nonfasting blood glucose level (20 mmol/L).
(iii) Slow motor and sensory nerve conduction.
(iv) Significant reduction of intraepidermal nerve fiber.
(v) Validated by antiperipheral diabetic neuropathic drug. | May not be widely available for routine pharmacological screening of anti-diabetic or anti-neuropathic drugs. |
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| Otsuka Long-Evans Tokushima Fatty (OLETF) rats model | Kamenov et al. [33]. | (i) Significantly higher blood glucose and HbA1c levels.
(ii) Reduced motor nerve conduction velocity and thermal nociception. | (i) Some major pathogenesis of PDN has not been characterized.
(ii) Not validated by anti-diabetic neuropathic drugs. |
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| Rat insulin I promoter/human interferon-beta (RIP/IFNβ) transgenic ICR mice model | Serafín et al. [34]. | (i) Significantly hyperglycemia, slower tibial sensory nerve conduction velocity.
(ii) Reduced nerve fiber density and increased motor latencies. | (i) A sophisticated surgical approach has been used to develop the model.
(ii) Not validated by anti-diabetic or antineuropathic drugs. |
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| High-fat diet-fed female C57BL6/J mice model | Obrosova et al. [35]. | (i) Deficit of motor and sensory nerve conductions, tactile allodynia, and thermal hypoalgesia. (ii) Can be used as model for prediabetic or obesity related neuropathy. | (i) Intradermal nerve fiber loss, and axonal atrophy was absent.
(ii) Cannot be used for chronic diabetic neuropathy.
(iii) Not validated by antineuropathic drugs. |
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| Surgically-induced neuropathic model | Muthuraman et al. [36]. | (i) Thermal and mechanical hyperalgesia in paw and tail.
(ii) Reduced nerve fiber density and nerve conduction velocity.
(iii) Very short induction period. | (i) Not validated by using antineuropathic drug.
(ii) Not suitable to study the human diabetic neuropathy. |
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| Genetically modified SDT fatty rat model | Yamaguchi et al. [37]. | (i) Sustained hyperglycemia and dyslipidemia with delayed and reduced motor nerve conduction velocity.
(ii) Lower number of sural nerve fibers and thickened epinural arterioles.
(iii) Successfully validated by anti-diabetic drug such as pioglitazone. | Some pathogenesis was induced only after a long period of time such as 40 weeks. |
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