Short-Term Environmental Enrichment Enhances Adult Neurogenesis, Vascular Network and Dendritic Complexity in the Hippocampus of Type 1 Diabetic Mice

Background: Several brain disturbances have been described in association to type 1 diabetes in humans. In animal models, hippocampal pathological changes were reported together with cognitive deficits. The exposure to a variety of environmental stimuli during a certain period of time is able to prevent brain alterations and to improve learning and memory in conditions like stress, aging and neurodegenerative processes. Methodology/Principal Findings: We explored the modulation of hippocampal alterations in streptozotocin-induced type 1 diabetic mice by environmental enrichment. In diabetic mice housed in standard conditions we found a reduction of adult neurogenesis in the dentate gyrus, decreased dendritic complexity in CA1 neurons and a smaller vascular fractional area in the dentate gyrus, compared with control animals in the same housing condition. A short exposure-10 days- to an enriched environment was able to enhance proliferation, survival and dendritic arborization of newborn neurons, to recover dendritic tree length and spine density of pyramidal CA1 neurons and to increase the vascular network of the dentate gyrus in diabetic animals. Conclusions/Significance: The environmental complexity seems to constitute a strong stimulator competent to rescue th

Need for pathogenetically oriented therapy of neuropathy in diabetes mellitus

Peripheral and/or autonomous neuropathy is associated with increased cardiovascular risk in diabetes patients. One of the common pathogenetic factors is increased production of free oxygen radicals and their derivatives; a hyperglycaemic metabolism impairs endoneural blood perfusion, leading to neuronal cell damage as typical in diabetic neuropathy. The aim of pathogenetically oriented treatment is to slow down, stop, or reverse the progression of neuropathic damage, and clear indications show that benfotiamine and alpha-lipoic acid along with blood glucose optimization and risk factor management may have a positive effect on the processes involved in neuropathy. Benfotiamine inhibits pathways involved in developing neuropathy while stimulating pathways that play a role in improving neuropathy, such as the pentose-phosphate shunt. Alpha-lipoic acid - an effective antioxidant - may partly inhibit pathogenetic processes caused by oxidative stress. Both of these substances have been shown better tolerance profiles than drugs aimed at controlling symptoms, and should play a role in treating patients with diabetic neuropathy

Need for pathogenetically oriented therapy of neuropathy in diabetes mellitus

Peripheral and/or autonomous neuropathy is associated with increased cardiovascular risk in diabetes patients. One of the common pathogenetic factors is increased production of free oxygen radicals and their derivatives; a hyperglycaemic metabolism impairs endoneural blood perfusion, leading to neuronal cell damage as typical in diabetic neuropathy. The aim of pathogenetically oriented treatment is to slow down, stop, or reverse the progression of neuropathic damage, and clear indications show that benfotiamine and alpha-lipoic acid along with blood glucose optimization and risk factor management may have a positive effect on the processes involved in neuropathy. Benfotiamine inhibits pathways involved in developing neuropathy while stimulating pathways that play a role in improving neuropathy, such as the pentose-phosphate shunt. Alpha-lipoic acid - an effective antioxidant - may partly inhibit pathogenetic processes caused by oxidative stress. Both of these substances have been shown better tolerance profiles than drugs aimed at controlling symptoms, and should play a role in treating patients with diabetic neuropathy

Benfotiamine: Commentary and update on recent studies

The thiamine prodrug benfotiamine (S-benzoylthiamine-O-monophosphate) has been shown to prevent the formation of advanced glycation endproducts (AGEs), thus decreasing hyperglycaemia-induced damage and neuropathic sensory symptoms. However, recent studies have yielded contradictory results. Other studies emphasize the need for further research on the potential of benfotiamine in the treatment of vascular and diabetes complications. Currently, benfotiamine is considered to be a pathogenetic treatment in counteracting oxidative stress and hyperglycaemia-induced metabolic changes that lead to neuropathy

Combination Therapy in Diabetic Neuropathy

A high percentage of diabetic patients develop peripheral neuropathy with more than 10 % suffering from severe symptoms. Therapeutic alternatives for diabetic sensorimotor polyneuropathy (DSPN) have so far involved pathogenesis oriented or symptomatic treatments. These two therapeutic approaches differ in their effects: the former aims to reverse, halt or delay progression of neuropathic damage, while the latter aims to relieve neuropathic pain and its associated secondary consequences without impact on the underlying neuropathic process. Most guidelines recommend symptomatic treatments to alleviate the complaints associated with DSPN. Tricyclic antidepressants, serotonin-noradrenaline reuptake inhibitors, and alpha(2)-delta ligands are frequently mentioned as first-line drugs for painful diabetic peripheral neuropathy. However, new evidence points to pathogenesis-oriented treatments based on alpha-lipoic acid or benfotiamine as promising therapeutic alternatives to classical purely symptomatic treatments. A few new trials have reported an advantage of combination therapies versus single-drug administration, but the limited extent of studies on specific combinations together with design flaws in these studies have caused reluctance in recommending combination therapy as a first treatment option in guidelines. However, combination therapy stands as a powerful instrument for DSPN treatment based on the positive evidence accumulated and the otherwise common use of multidrug treatments in clinical diabetic neuropathy

Neuropathy in chronic kidney disease

Chronic kidney disease (CKD) is characterised by an increasing prevalence, with the current prevalence of approximately 10 % in adults > 20 years in Western industrialized countries. In patients with CKD, frequently both the central nervous system (CNS) and the peripheral nervous system (PNS) are affected. Uremia, accumulation of AGE and oxidative stress, hyperkalemia, insulin resistance, adipocytokines, and erythropoietin deficiency and resistance have been identified as potential triggering factors. An impaired cerebral cognitive function in uremic patients is demonstrable even in clinically asymptomatic stages. Typical neurological sequelae include, among others, uremic encephalopathy, dialysis disequilibrium syndrome, and uremic polyneuropathy. In general, initiation of renal replacement treatment is suggested as the most promising therapeutic approach. Additionally, symptomatic treatment of neuropathic pain with first line drugs, such as gabapentin, pregabalin, tricyclic antidepressants or duloxetine, remains a reasonable approach. With respect to the important role of inflammation and oxidative stress in the further deterioration of renal function and nervous damage, additional treatment with benfotiamine may be considered as a pathogenesis-oriented approach