Experimental diabetic neuropathy: an update

Abstract

Diabetic neuropathy consists of several clinical syndromes affecting motor, sensory and autonomic nerves. Of these the most common is distal symmetric sensory polyneuropathy usually referred to as diabetic neuropathy. Animal studies, mainly in diabetic rodents, have contributed tremendously to our understanding of this disease. From these it is clear that the pathogenesis of diabetic neuropathy is multifactorial involving sequentially occurring and often closely interrelated metabolic aberrations. Major pathogenetic mechanisms include increased activity of the polyol pathway, abnormalities in vasoactive substances, non-enzymatic glycation, increased presence of free radicals, and perturbed neurotrophism. Traditionally the neuropathies accompanying Type I (insulin-dependent) and Type II (non-insulin-dependent) diabetes mellitus have been regarded as identical. Recent investigations have, however, clearly delineated distinct differences in the functional and structural expressions of the neuropathies in the two types of diabetes. Major future challenges are the identification of the differences in underlying pathogenetic mechanisms in the two types of neuropathy and in gaining a better understanding of the hierarchy of the multifactorial mechanisms underlying the disease. This will be important for designing meaningful therapies which to date have failed miserably in diabetic neuropathy.

Degeneration of the Golgi and neuronal loss in dorsal root ganglia in diabetic BioBreeding/Worcester rats

“…Previous studies examining 12-month STZ-D rats failed to demonstrate DRG neuronal loss [13,14], which is consistent with a retained number of peripheral myelinated fibre number in the STZ-D rat [12,13]. Differences in insulin and C-peptide deficiencies may account for these discrepancies between the STZ and BB/Wor models [7,16,20]. Some studies have suggested that neuronal loss of DRG in STZ-D rats is due to apoptotic cell death induced by mitochondrial dysfunction secondarily to oxidative stress [9][10][11].…”

Advanced Diabetic Neuropathy: A Point of no Return?

“…STZ-induced diabetic rats) may not exhibit the advanced structural changes and fiber loss seen in human neuropathy [11]. Moreover, despite similar hyperglycemic levels, differences exist between models of type 1 and type 2 DM in their expression of morphologic changes [17].…”

“…In this respect, the impairment of essential fatty acid synthesis and compromised vasoactive prostanoid production in diabetes may be a contributing factor [11]. Early changes in vascular function evolve into the progressive chronic endoneurial vascular damage seen in parallel to neurodegeneration in biopsy samples from diabetic patients [12].…”

Anthocephalus cadamba (Roxb.) Miq., Rubiaceae, extract shows hypoglycemic effect and eases oxidative stress in alloxan-induced diabetic rats

“…Excessive production of free radicals is believed to be involved in many diabetic complications including diabetic neuropathy in diabetes mellitus (Sima & Sugimoto, 1999). The neurological consequences of diabetes mellitus in the central nervous system (CNS) are now receiving greater attention.…”