Morphological and electrophysiological changes of peripheral nerve-muscle unit in the aged rat prevented by levocarnitine acetyl.

The effects of levocarnitine acetyl on structure and function of the sciatic nerve and neuromuscular junctions of the soleus and extensor digitorum longus muscles were studied in the aged rat. To that end, neuromuscular conduction velocity (NMCV) was measured in vivo and morphological and morphometric evaluations were performed. Treatment with levocarnitine acetyl, 150 mg/kg day for six months, restored NMCV values to the levels measured in the young rat; significantly reduced the number of degenerating elements; and increased the number of myelinated fibres having normal structural features. In the soleus and extensor digitorum longus muscles, levocarnitine acetyl increased the complexity of neuromuscular junctions. These experimental findings suggest a neurotrophic action of levocarnitine acetyl on the peripheral nervous system that might have therapeutical applications in age-related peripheral nerve changes.     

Levocarnitine acetyl promotes the regeneration of peripheral sensory axons and reduces the hypertrophy of axotomized spinal cord motoneurons in rats.

In previous studies, the neurotrophic action of levocarnitine acetyl on the regeneration of the sciatic nerve in rats has been demonstrated. The present study investigated the particular effect of levocarnitine acetyl on the initial stages of sciatic nerve regeneration. In the first 8 days after sciatic nerve lesion caused by crushing (Group A) or cutting (Group B), the rats of both groups were divided into 2 subgroups: treated rats received daily intraperitoneal levocarnitine acetyl (a megadose of 100 mg in saline solution); untreated rats only received saline solution. Treatment started on the day of operation. The regeneration growth rate of sensory fibres was studied using the pinch test. The size of the axotomized spinal motoneurons was studied using retrograde axonal tracers (horseradish peroxidase or Fast blue). The results showed that: (a) levocarnitine acetyl promoted the elongation of sensory fibres in the first 8 days following the crushing or sectioning of the sciatic nerve, but the data were only statistically significant (p less than 0.01) for the first 3 days after crushing; (b) levocarnitine acetyl accelerated the velocity of sensory fibre regeneration when compared to untreated rats by 16% in the first 3 days after nerve crushing, by 14% in the first 4 days after nerve section, and by 32% from the 5th to the 8th day after nerve section; (c) levocarnitine acetyl promoted a significant reduction in spinal motoneuron hypertrophy when compared to untreated rats at both 4 and 8 days after sciatic nerve section.(ABSTRACT TRUNCATED AT 250 WORDS)     

Protective effect of PNQX on motor units and muscle property after sciatic nerve crush in neonatal rats.

Sciatic nerve injury in neonatal rats results in significant reduction in the number of surviving motoneurons and impairs muscle development. We examined the possible neuroprotective effects of daily in vivo administration of 1,4,7,8,9,10-hexahydro-9-methyl-6-nitropyrido[3,4-f]quinoxaline-2,3-dione (PNQX), an AMPA/kainate receptor antagonist, on sciatic nerve injured rats, during the period of plasticity of the rat nervous system. Furthermore, we investigated the effect of PNQX on muscle properties impaired by nerve crush. At the second postnatal day, the sciatic nerve of the rat left hind limb was crushed. Twenty-four rats were subsequently treated with PNQX and an equal number of rats, as control group, were treated with saline. PNQX was injected subcutaneously once daily (14 mg kg(-1) body weight). Treatment continued until the rats were 14 days old. Measurements were then carried out to assess the contractile properties of the extensor digitorum longus (EDL), a fast-contracting muscle, and of the soleus muscle, a slow-contracting muscle, in four "age groups" of rats, each consisting of six PNQX-treated and six control animals: (a) postnatal day (P) 14, (b) postnatal day (P) 21, (c) postnatal day (P) 28 and (d) adult rats. The following parameters were recorded: number of motor units, muscle weight, maximal tetanic tension (TET 100), time to peak (TTP), half relaxation time (HRT), and fatigue index (FI). Improvement in motor unit survival after nerve injury was observed in all age groups administering PNQX. Also axotomy-induced impairment of muscle properties such as muscle weight, tension development, contraction and relaxation velocity was counteracted by injection of PNQX. The fatigue index was altered by axotomy and mostly normalized by treatment with this compound. AMPA/kainate receptor antagonists, with low toxicity, may serve in the future, as possible neuroprotective agents after acute neural injury or even as therapeutic agents in neurodegenerative diseases.     

Levocarnitine acetyl prevents cell death following long-term section of the vagus nerve in rats.

Levocarnitine acetyl has previously been found to significantly prevent axotomy-induced cell death in the spinal cord motor nucleus 9 and 12 months after section of the sciatic nerve in rats. In the present paper, the effects of levocarnitine acetyl on axotomy-induced cell death in the brain stem motor nuclei 90 days after section of the vagus nerve were studied. The right vagus nerve was cut at the neck. To prevent regeneration, a 5 mm-long segment of the vagus nerve was excised and the distal stump was displaced caudally. After surgery, a group of rats (n = 6) was treated with levocarnitine acetyl dissolved in the drinking water (75 mg/kg/day) (Group I). A second group of operated rats (n = 4) received drinking water alone. (Group II). Ninety days postoperatively, in the rats of both groups the proximal nerve stump of the vagus nerve was injected with horseradish peroxidase to label retrogradely the brain stem motoneurons of the dorsal motor vagal and the ambiguus nuclei. The brain stem nuclei were also labelled by horseradish peroxidase in three unoperated control rats (Group III). In the Group II rats, the number of horseradish peroxidase-labelled motoneurons of the dorsal motor vagal nucleus was found to be significantly smaller than in either the Group I (p < 0.01) or the Group III (p < 0.02) animals. In the Group I rats, the number of motoneurons of the dorsal motor vagal nucleus was not significantly smaller compared to the Group III rats.(ABSTRACT TRUNCATED AT 250 WORDS)     

Ganglioside treatment and nerve regeneration: a morphological study after nerve crush in rats

The left sciatic nerve of male Wistar rats was crushed by a standardized technique. From the day of the nerve crush onwards the rats were given a daily subcutaneous injection of 50 mg/kg of a ganglioside mixture. The controls were given an equal volume of phosphate buffer. Morphometric analysis of the sciatic nerve was carried out on days 11 and 15 after the nerve crush. The number of nerve fibres in the rats treated with gangliosides was larger than in the controls on both days and cross-sections through the regenerating fibres showed larger areas of axon and myelin. These differences were statistically significant (P less than 0.05) for most parameters.     

Regeneration of the sciatic nerve in mice and rats exposed to trichloroethylene

The effects of trichloroethylene (TCE) on regeneration of the sciatic nerve after a crush lesion was tested in mice and rats. A lesion was made on nerves in unexposed animals and in animals pre-exposed to TCE for 20 days. Experimental animals were then exposed to TCE for an additional 4 days. Exposures were continuous at 150 or 300 ppm. Regeneration was measured by pinching the outgrowing nerve fibers. Regeneration was retarded in the TCE-exposed animals compared to the air-exposed controls. Mice were more sensitive to TCE exposure than rats. Liver weight increased in TCE-exposed mice but there was no correlation between this effect and that on nerve regeneration.     

Studies on the trophic influence of nerve on skeletal muscle

Colchicine is a drug known to block axoplasmic transport in myelinated nerves. When injected under the perineurium of the sciatic nerve of the rat, the drug induced denervation-like changes in the extensor digitorum longus muscle. These changes, consisting of the appearance of extra-junctional cholinergic sensitivity and of action potentials resistant to the blocking effect of tetrodotoxin, developed despite the fact that nerve impulse conduction, transmitter release and neuromuscular transmission were intact. The results indicate that trophic substances, necessary for the prevention of denervation changes, are transported by axoplasmic flow.

β-Bungarotoxin, a purified neurotoxin from Bungarus multicinctus acts selectively on motor nerve terminals blocking the release of acetylcholine from the nerve. S.c. injection of the toxin into the hind leg of rats produced paralysis and complete blockade of spontaneous transmitter release in the extensor digitorum longus muscle. The toxin also induced the aforementioned denervation-like changes in the muscle membrane. It is suggested that β-bungarotoxin in addition to blocking transmitter release blocks the release of trophic substances from the nerve or alternatively that neuromuscular transmission and resulting muscle activity constitute trophic influences necessary for the prevention of the appearance of denervation changes.     

Enhancement of nerve fibre regeneration by nucleotides after peripheral nerve crush damage. Electrophysiologic and morphometric investigations.

The effect of nucleotide administration on the regeneration of myelinated nerve fibres following crush injury to the sciatic nerve of the rat was studied using both morphometric and electroneurophysiologic techniques. After a standardized localized crush lesion of the right sciatic nerve, rats were given nucleotides daily at a dosage of 3.0 mg/kg body wt uridine monophosphate (UMP), 2.5 mg/kg body wt cytidine monophosphate (CMP) or 3.0 plus 2.5 mg/kg body wt UMP plus CMP, respectively. Observations were made after 20, 40 and 60 days of nerve regeneration for comparison with age-matched crushed or nonoperated controls. Electroneurophysiologic studies of right sural nerves were performed as single fibre measurements. Morphometry was performed on semithin transverse sections of the right common peroneal nerve with a fully automatic interactive image analysis system. Forty days after crush injury the single fibre conduction velocity of all type II afferents in the UMP/CMP treated group was significantly accelerated. There was a trend (10% greater than or equal to p greater than or equal to 5%) to increase of mean efferent single nerve fibre function at this time. Morphometry of nerve fibres revealed a trend to enlargement of mean fibre area and mean fibre diameter related to increased myelin area and myelin thickness. After 60 days, there was a trend to increase of single fibre conduction velocity of all type II afferents in the UMP/CMP treated group. Automated morphometry revealed a significant increase for the following parameters: fibre area, fibre diameter, myelin area, myelin thickness and axon area.(ABSTRACT TRUNCATED AT 250 WORDS)     

Counteraction on experimentally induced diabetic neuropathy by levocarnitine acetyl.

The effect of levocarnitine acetyl on diabetic peripheral neuropathy induced by a single injection of streptozotocin or alloxan was studied. Levocarnitine acetyl was administered intraperitoneally one week after induction of diabetes at the dose of 50 mg/kg/day for five and ten weeks. At the end of treatment, neuromuscular conduction velocity (m/sec) was evaluated by stimulating the sciatic nerve and recording the soleus muscle potentials evoked, and the muscle contraction force (mm) by measuring the isometric muscular tension. Motor coordination was evaluated on the Rota-rod apparatus. Treatment with levocarnitine acetyl fully prevented the reduction (20%) in the neuromuscular conduction velocity observed in both experimental models of diabetes. The decrease (30-33%) in muscle contraction force was prevented partially in streptozotocin-induced diabetes and fully in alloxan-induced diabetes. Levocarnitine acetyl also improved the concomitantly reduced motor performance. The results of the present study suggest a beneficial effect of levocarnitine acetyl on peripheral neuropathy and muscle performance.     

Studies on the degenerative and regenerative phenomena occurring after transection and repair of the sciatic nerve in rats: effects of acetyl-L-carnitine

The effects of acetyl-L-carnitine on some degenerative and regenerative phenomena following sciatic nerve transection in rats, were studied. In Experiment 1, acetyl-L-carnitine was administered intraperitoneally at the dose of 50 mg/kg/day for 28 and 56 days following transection and microsurgical repair of the sciatic nerve. On day 56, the acetyl-L-carnitine-treated rats showed a significantly (p less than 0.05) better motor recovery ("clinical assessment") of the peroneal component of the sciatic nerve than the control rats. Twenty-eight days after nerve repair, the acetyl-L-carnitine-treated rats showed a significantly higher (p less than 0.05) number of myelinated axons in the postlesional nerve stump than control rats. Finally, the treated rats had a significantly lower (p less than 0.05) presence of atrophic fibres in the extensor digitorum longus muscle. In Experiment 2 the sciatic nerve was cut. To prevent spontaneous regeneration, a metallic clip was applied to the distal nerve stump and then the nerve stumps were positioned in different anatomical compartments. After surgery, a group of rats was treated with acetyl-L-carnitine dissolved in the drinking water (75 mg/kg/day). Another group of rats received normal water and served as the control group. Three, 6, 9, 12 and 18 months postoperatively, in the rats of both groups, the proximal sciatic nerve stump was injected with horseradish peroxidase to label the spinal cord neurons of the sciatic nerve nucleus. While in untreated rats the number of horseradish peroxidase-labelled neurons decreased with the increase in denervation time, in acetyl-L-carnitine-treated rats the number of horseradish peroxidase-labelled neurons remained stable for as long as 12 months of denervation and decreased only after 18 months of denervation. Furthermore, acetyl-L-carnitine-treated rats showed a significantly higher (p less than 0.05) number of horseradish peroxidase-labelled neurons with respect to untreated rats both after 9 and 12 months of denervation. In Experiment 3, the sciatic nerve was cut and then repaired after periods of 3, 6, 9, 12, and 18 months. Four months after nerve repair, the sciatic nerve was again cut and the proximal nerve stump was injected with horseradish peroxidase to label the spinal cord neurons of the sciatic nerve nucleus. Both acetyl-L-carnitine-treated and untreated rats showed a tendency to have an increased number of horseradish peroxidase-labelled neurons with respect to intact rats of correspondent ages.(ABSTRACT TRUNCATED AT 400 WORDS)     

Levocarnitine acetyl treatment promotes iris reinnervation following 6-hydroxydopamine-induced noradrenergic denervation in rats.

The effect of levocarnitine acetyl on neurite regeneration was evaluated following administration of 6-hydroxydopamine which caused a selective degeneration of peripheral catecholaminergic neurites in the irides of newborn and young rats. Levocarnitine acetyl 20 mg/kg body weight was administered either subcutaneously to newborn rats for 20 days or dissolved in drinking water to young rats for 90 days. Treatment with levocarnitine acetyl promoted neurite outgrowth following axotomy in both groups, thus demonstrating a stimulatory role of the substance in nerve regeneration of the peripheral nervous system. The results further confirm that levocarnitine acetyl is endowed with therapeutical efficacy in peripheral neuropathies.     

Fatigue and contractile responses of rat hindlimb muscles following excessive dexamethasone administration

Muscle weight, protein content and contractile performance (tetanic tension, fatigue and recovery) of extensor digitorum longus and soleus were investigated in rat following systemic administration of Dexamethasone (DX), 5 mg/kg/day for ten days. These animals showed marked reduction in food intake during the course of DX treatment. As a control, a group of food restricted (FR) rats receiving equal amount of food consumed by the DX treated rats was also studied along with the saline control group, to differentiate the effect of DX on muscle from that of dietary deficiency. There was a greater degree of atrophy (reduced muscle mass and protein content) of extensor digitorum longus in DX treated rats as compared to that of the FR rats. In-situ isometric tetanic tension per gram of muscle and per unit weight of protein was similar in both the muscles in the DX treated and the FR rats. There was increased fatiguability with reduced post fatigue recovery in both the muscles of DX treated rats as compared to the FR rats. The results indicate that besides atrophy of fast twitch muscles, DX increases the fatiguability and decreases the postfatigue recovery in both fast and slow muscles.     

小鼠2.5s神经生长因子对大鼠和小鼠受损坐骨神经再生的影响

目的：证实ＮＧＦ促进坐骨神经再生的作用，方法：夹断小鼠和大鼠坐骨神经轴索，测再生同索计数及分类，在比目鱼肌远（Ｄｉｓ），近（Ｐｒｏ）端测神经，肌肉电潜伏期（ＮＭＥＰＬ），结果：小鼠ＮＧＦｉｍ０．５－１ｋＢＵ．ｋｇ＾－１２０ｄ增加轴索再生率，２－４ｋＢＵ．ｋｇ＾－１减轻比目鱼肌萎缩，大鼠ＮＧＦｉｍ１（４０ｄ），２（３０和４０ｄ），４（２０，３０，４０ｄ）ｋＢＵ．ｋｇ＾－１均显著增加损伤神经的轴索再生     

Effect of soluble factors from nerve and muscle on alpha-bungarotoxin binding sites in isolated sarcolemmal membranes of the rat.

1. Sarcolemmal membranes were isolated from normal and from denervated muscles and the specific binding of [125I]-alpha-bungarotoxin to the membranes was determined. 2. Cytosol prepared from either slow (soleus) or fast (extensor digitorum longus) muscle increased the toxin binding. Similar effects were seen with cytosol from muscles which had been denervated 5 to 7 days previously and with cytosol from sciatic nerve. A purified preparation of a bacterial phospholipase C also produced this effect. 3. Bathing medium in which normal or denervated muscles had been incubated, increased the toxin binding to normal membranes, but the normal bathing medium decreased the binding to membranes prepared from denervated muscles. 4. The possibility that pre-existing latent acetylcholine receptors can be activated by intracellular factors released from muscles is discussed.     

吡咯喹啉醌对大鼠损伤坐骨神经的修复作用

目的探讨吡咯喹啉醌 (PQQ)对损伤的坐骨神经的修复作用。方法Wistar大鼠 30只 ,制备坐骨神经夹损模型 ,术后每日分别局部注射一定量的PQQ、神经生长因子 (NGF)和生埋盐水 14d ,检测大鼠趾间距和电生理指标 ,比较PQQ对损伤神经的修复作用。结果PQQ及NGF组的趾间距及电生理指标在前两周的恢复明显好于生理盐水组 ,且有显著性差异。结论PQQ能明显改善损伤的坐骨神经功能     

Taurine transport in chronically stimulated fast- and slow-twitch muscles of the rat

Indirect stimulation via the sciatic nerve, 10 or 100 Hz stimulus trains of 1 sec duration, applied every 3 sec, 8 hr/day for 1-4 weeks increased taurine concentration of the extensor digitorum longus (EDL, fast-twitch) muscle of the rat. The uptake of [3H]-taurine into the EDL and tibialis anterior (TA, fast-twitch) muscle was also increased by the stimulation. Concentration and uptake of taurine in the soleus muscle (SL, slow-twitch) did not change by chronic 10 Hz stimulation. Taurine concentration in the SL muscle was significantly reduced by chronic 100 Hz stimulation. This study shows that chronic nerve stimulation increases the uptake of taurine in the fast-twitch muscles, but not in the slow-twitch muscle.     

依达拉奉对大鼠坐骨神经损伤后脊髓脂质过氧化的影响

目的:探讨自由基清除剂依达拉奉对坐骨神经损伤后神经功能及脊髓脂质过氧化反应的影响.方法:Wistar大鼠48只,随机分为3组:坐骨神经挤压伤组、依达拉奉治疗组、假手术组.分别于7、14、21、28 d检测各组大鼠坐骨神经功能指数(SFI)、脊髓内过氧化物歧化酶(SOD)和丙二醛(MDA)的变化.结果:伤后各组大鼠SFI均降低,挤压伤组大鼠SFI较依达拉奉治疗组低(P<0.05),神经功能恢复较治疗组缓慢.伤后挤压伤组大鼠脊髓内SOD活性升高,依达拉奉治疗组大鼠脊髓内SOD活性与假手术组相比升高不明显(P>0.05).伤后挤压伤组大鼠脊髓内MDA含量上升明显,依达拉奉治疗组大鼠脊髓内MDA含量在各个时间点均显著低于挤压伤组大鼠脊髓内MDA含量(P相似文献   

医用三氧对慢性坐骨神经损伤大鼠神经生长因子水平的影响

目的 探讨不同浓度医用三氧(O3)对慢性坐骨神经损伤(chronic constriction injury,CCI)大鼠神经生长因子水平的影响,为临床治疗神经病理性疼痛提供基础科学依据.方法 60只SPF级健康成年雄性SD大鼠随机分为假手术组、CCI组和不同浓度O3(15、30和60μg/ml依序为O3-15组、O3...     

The effects of Anemonia sulcata toxin II on vertebrate skeletal muscle.

Some effects of the sea anemone toxin, ATX-II, on vertebrate skeletal muscle have been described. At a concentration of 1 X 10(-7)-1 X 10(-6)M, ATX-II caused a sodium-dependent depolarization of the muscle fibres of the rat soleus and extensor digitorum longus, of the mouse soleus and extensor digitorum longus and of the chicken posterior latissimus dorsi. The muscle fibres of the frog sartorius were insensitive to the toxin. Action potentials generated by direct stimulation were prolonged by ATX-II, but the degree of prolongation was variable. Chicken posterior latissimus dorsi muscle fibres were most sensitive in this regard, and mouse extensor digitorum longus were least sensitive. Both denervated and immature muscle fibres were more sensitive to ATX-II than mature innervated muscle fibres. The sensitivity to ATX-II declined rapidly as muscle fibres matured. In some muscles, the prolongation of the action potential was enhanced by repetitive stimulation, but not by the passive depolarization or hyperpolarization of the muscle fibres. The actions of ATX-II could be reversed by washing in all but the innervated soleus of the mature rat.     

SELECTIVE DEVELOPMENT OF TOLERANCE TO β-ADRENOCEPTOR AGONISTS IN SKELETAL MUSCLE AS COMPARED WITH AIRWAY SMOOTH MUSCLE FROM THE GUINEA-PIG

1. Guinea-pig were fed with a diet containing terbutaline or placebo for 4--5 days. The trachea, soleus muscle and the extensor digitorum longus (EDL) from these animals were prepared for recording of isometric contractions in vitro. 2. After treatment with terbutaline in vivo, the response of the pilocarpine-contracted trachea to terbutaline and isoprenaline was slightly suppressed with no change in maximum relaxation. 3. After treatment with terbutaline in vivo the maximum depression of the incomplete tetanic contractions of the soleus muscle brought about by terbutaline or isoprenaline was diminished by about 70%. The response of the EDL was also attenuated after previous treatment with terbutaline in vivo. 4. These data indicate a selective development of tolerance to the effects of beta-adrenoceptor agonists in skeletal muscle as compared with tracheal smooth muscle. 5. The present results provide an experimental analogue to the clinical observation that patients being treated with beta-adrenoceptor agonists become tolerant to the tremorogenic rather than to the bronchodilating effect.