Rosuvastatin positively changes nerve electrophysiology in diabetic rats.

OBJECTIVE: To examine the effect of rosuvastatin on peripheral nerve function in diabetic rats using electrophysiological measurements. BACKGROUND: Diabetes was induced in 5-day-old male Wistar rats by intraperitoneal (i.p.) injection of streptozotocin (STZ). As many as 45 diabetic rats were randomized to three groups: one treated with rosuvastatin (group R), another with rosuvastatin and mevalonate (group MR) and the other was untreated (group U). The data were compared with a group of normal age-matched rats i.e. control rats (group C). METHODS: Neurophysiological measurements were performed at the age of 3 months (T1) and again at the age of 8 months (T2), after 3 months of treatment. RESULTS: At T1, there was a trend to lower amplitude of compound motor action potential (CMAP) in the three diabetic groups as compared to controls, and no difference for motor nerve conduction velocity (MNCV), amplitude of sensory nerve action potential (SNAP), sensory nerve conduction velocity (SNCV) between diabetic groups and controls. At T2, the amplitude of CMAP was significantly lower in groups R and MR versus group U and control rats. MNCV was significantly and similarly decreased in the three diabetic groups; the latency of the first sensory peak (fastest sensory fibres) was significantly increased in group U but was normal in groups R and MR. CONCLUSIONS: This study shows that: 1.rosuvastatin exerts a beneficial effect on the conduction of the fastest sensory fibres;2.these effects are independent of blood pressure and lipid changes.

Nerve electrophysiological changes in rats with early induced diabetes.

In rats with diabetes induced at weaning, pathological examinations have shown that the reduction of myelin thickness occurs earlier than axon size reduction. The aim of this study was to provide a detailed description of neurophysiological changes during nerve growth and maturation in rats with streptozotocin-induced diabetes in prepubertal stage. Five-day male Wistar rats received an injection of streptozotocin. Motor and sensory conduction velocities increased until 6.5 months in diabetic and control rats and at this age it became lower in diabetic rats. In diabetic rats, the amplitudes of the compound motor action potentials (CMAP) were lower by the 3 months and did not increase later. The amplitudes and areas of sensory action potentials (SNAP) increased until 9 months in both groups. SNAP duration decreased with ageing. Sensory peak 1 and peak 2 latencies became longer from 6.5 to 9 months in diabetic rats, with a longer latency difference between the 2 sensory peaks by 4 months. At 3 and 4 months of age, peak 1 and peak 2 latencies correlated with SNAP amplitude and duration in control rats but not in diabetic rats. In conclusion, in rats with early induced diabetes, the earliest electrophysiological impairments consist of lower CMAP amplitudes, and longer difference between latencies of sensory peaks 1 and 2. These sequential neurophysiological changes should be considered when testing new therapeutic approaches in diabetic neuropathy.

Effect of cerivastatin on peripheral capillary permeability to albumin and peripheral nerve function in diabetic rats.

OBJECTIVE: To examine the effect of cerivastatin on capillary permeability to albumin and peripheral nerve function in diabetic rats. ANIMALS: Diabetes was induced in male Wistar rats by i.p. injection of streptozotocin (STZ) at the age of 5 days. Forty diabetic rats were randomized in two groups: one treated by cerivastatin (diabetic treated group, DT) and the other untreated (diabetic untreated group, DU). The data were compared to a group of normal rats. MEASUREMENTS: The peripheral capillary filtration of albumin (CFA) was studied on a limb by a non-invasive isotopic method, and nerve electrophysiological measurements were performed. Rats were followed-up until 6 months. In group DU albumin retention (AR) increased by 3 months and lymphatic uptake of interstitial albumin was impaired at 6 months. None of these disorders was observed in group DT. Motor and sensory nerve conduction velocities (MNCV and SNCV) were significantly slower at 6 months in group DU but not in group DT as compared to control rats. The duration of the sensory nerve action potential (SNAP) was significantly longer in group DU than in control rats at 6 months whereas it did not differ in group DT and in control animals. CONCLUSIONS: This study shows that cerivastatin may prevent the peripheral increase in CFA and lymphatic dysfunction induced by diabetes. These beneficial effects on microcirculation may be involved in the prevention of nerve function deterioration. The underlying mechanisms are likely to be independent of a lipid-lowering effect, but their clarification needs further investigations.

Motor and sensory conduction velocities and amplitude of nerve or muscle potentials in the normal rat according to age.

The relative changes in sensory and motor nerve conductions and SNAP and CMAP amplitudes were studied on the sural and tibial posterior nerves in anesthetized male rats, between the 1st and the 23rd month. Neural growth was controlled with the measure of the nerve path length on the skin, between stimulating and recording cathodes for the sural nerve and proximal and distal stimulating cathodes for the tibial posterior nerve. The sural SCV and SNAP amplitude are consistent with a more accurate method than the H-reflex one. Similar changes were observed in both parameters. During the maturation of the peripheral nervous system, between the 1st and the 5th month, parameters rapidly increased. Over 14 months old, parameters decrease: the diminution of SNAP and CMAP amplitudes is characteristic of aging. The results were analyzed through quadratic and linear regression and were similar to those in young and elderly human patients. Parabola curves fitted the best way to represent the evolution of parameters. Moreover, the linear regression permitted to divide the rat life in 3 parts and to distinguish a period between the 6th and 13th months during which studied parameters are considered as constant. SCV, MCV, SNAP and CMAP amplitudes from the 1st to the 5th, from 6th to 13th and over the 14th month, could be used as reference.

In vivo sequential study of skeletal muscle capillary permeability in diabetic rats: effect of anthocyanosides.

Alterations in the capillary filtration of macromolecules are well documented in diabetic patients and experimental diabetes. Various flavonoids including anthocyanosides and ginkgo biloba extracts have been shown to be effective against experimentally induced capillary hyperfiltration. The aim of the present study was to test the effects of anthocyanosides on capillary filtration in diabetic rats. For this purpose, we have validated the use of our previously described in vivo method for measurement of the capillary filtration of albumin (CFA) in rats. Male Wistar rats with streptozotocin (STZ)-induced diabetes were randomized in 3 groups to receive either ginkgo biloba (group A), Vaccinium myrtillus (group B), or no treatment (group C). The isotopic test of CFA consisted of intravenously injecting 99mtechnetium-labeled albumin, inducing venous compression on a hindquarter, and measuring radioactivity externally on the limb before, during, and after removal of venous compression. After removal of the tourniquet, the radioactivity curve decreased. Interstitial albumin retention (AR) and the ratio of the amplitudes of the low- and high-frequency peaks (LF/HF ratio), an index of lymphatic function obtained by the fast Fourier transform of the last part of the radioactivity curve, were calculated. In STZ-treated animals, the isotopic test was performed at a mean age of 97 days (time 1) and after 6 weeks (time 2) and 12 weeks (time 3) of treatment, ie, 6 and 12 weeks after time 1. At time 1, AR was significantly higher in the 3 diabetic groups than in the control rats, without a significant difference between these groups. In group B, AR decreased significantly (P = .015) at times 2 and 3. In group C, AR increased significantly (P < .0005) from time 1 to time 3. In group A, AR increased slightly (NS) between time 1 and time 3. In groups A and C, the LF/HF ratio significantly increased with time (P < .0005) and the levels at time 3 were significantly higher versus control rats (P < .0001). In group B, the LF/HF ratio remained unchanged from time 1 to time 3 and similar to the values found in the control rats. In conclusion, these data show that (1) this new in vivo noninvasive method can be used to study CFA in skeletal muscle in diabetic rats, (2) it is reproducible and may be repeated over several months to evaluate spontaneous microcirculatory changes, and (3) anthocyanosides appear to be effective in preventing the increase in CFA and the failure of lymphatic uptake of interstitial albumin in diabetic animals.

In vitro model of far-field stationary potentials: boundary effects on propagated potentials.

Far-field stationary potentials have been said to result from several factors such as changes in the anatomical orientation of the direction of a propagating nerve action potential (AP) or local modifications of the impedance in the external volume conductor by changes in its geometry or resistivity. In the case of an impedance variation due to the presence of boundaries in the geometry of the medium, the findings reported in this paper showed that it is possible to record simultaneously AP and stationary potentials which we have called boundary potentials (BPs). The BP amplitude depended on the number of active axons at the boundary, on the distance between the boundary and one of the recording electrodes, and on the local impedance variation. Its polarity depended only on the direction of the AP propagation relative to the sign of the local impedance modification, the recording electrodes being in the same relative positions with respect to the direction of the propagating impulse. Finally, the recording of a BP remained possible whatever the relative position of the boundary and of the recording electrodes. These findings are in accordance with some clinical observations not yet explained.