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At least 145 records · Page 8Linked to original sources
PubMed1994

Acetyl-L-carnitine prevents age-dependent structural alterations in rat peripheral nerves and promotes regeneration following sciatic nerve injury in young and senescent rats.

Morphologic and morphometric alterations of the sciatic nerve from old Sprague-Dawley rats and of lesioned tibial nerve from young and senescent Sprague-Dawley rats were studied. The possible therapeutical effects of treatment with acetyl-L-carnitine (ALCAR) were also investigated, ALCAR being a compound shown to exert a beneficial pharmacological action on diabetic neuropathies. Nerve sections from animals sacrificed under anesthesia were stained with toluidine blue. In old rats, a 6-month treatment with ALCAR markedly reduced the percentage of myelinated fibers (MF) characterized by age-dependent morphologic alterations (4% in treated rats versus 11% in untreated ones), such as myelin balloons, infolded loops of myelin, myelin reduplication, and ovoids. In the lesioned animals, ALCAR-treatment (15-60 days for young rats and 6-9 months for senescent rats) produced a significant increase versus controls in the density of regenerating myelinated fibers (RMF) at 15 days (young rats) and at 30 days (senescent rats) after crush, as well as an increase in the axon diameter in both young and senescent rats at 60 days after nerve crush. The MF diameter (sheath + axons) was significantly larger in treated senescent rats than in controls at 100 days after nerve crush. In ALCAR-treated rats, both young and senescent, the density of degenerative elements was lower and the RMF ratio (RMF density/RMF density + density of degenerative elements) was higher than that in controls at all detection times.

Acetylcarnitine↗
PubMed1988

Expansion of spinal cord primary sensory afferent projection following combined sciatic nerve resection and saphenous nerve crush: a horseradish peroxidase study in the adult rat.

Transganglionic transport of horseradish peroxidase was used to study the potential for collateral sprouting of saphenous nerve afferent fibers in the lumbar dorsal horn of the adult rat following (1) combined unilateral saphenous nerve crush and ipsilateral sciatic nerve resection, (2) unilateral saphenous nerve crush, and (3) unilateral sciatic nerve resection. The saphenous nerve on the nonlesioned contralateral side served as control. Eight weeks after the lesion(s) the animals were subjected to bilateral application of horseradish peroxidase to the saphenous nerves. The distribution of the ensuing labeling in the superficial dorsal horn was subsequently mapped. Combined saphenous nerve crush and sciatic nerve resection resulted in expansion of the saphenous nerve projection area in the dorsal horn when compared to the nonlesioned control side (mean = 13%, P less than 0.05). No expansion of the saphenous nerve projection was found following isolated saphenous nerve crush or sciatic nerve resection, respectively (P greater than 0.05). The findings indicate that in the adult rat, central processes of primary sensory neurons which are regenerating their peripheral processes can extend collateral sprouts into adjacent projection areas in the superficial dorsal horn subjected to previous deafferentation by peripheral nerve resection.

Animals↗
PubMed2004

[Role of transthyretin in posttraumatic regeneration of the sciatic nerve in mouse].

Although thyroid hormones are known to have a significant influence on the development of nervous system, the absence of changes in the brain of mice deficient in transthyretin--a protein providing thyroid hormone transport across the blood-brain and blood-nerve barrier--remains unexplained. Therefore, the aim of this study was to determine the effect of transthyretin on the formation of myelinated and unmyelinated nerve fibers in sciatic nerve of mice. The myelinated and unmyelinated nerve fibers were counted in sciatic nerve of 3-months-old normal and transthyretin-knockout (transthyretin(-/-)) mice 15 and 30 days after nerve crushing. No differences were detected in the number of myelinated and unmyelinated nerve fibers in intact control (wild-type) animals group vs. transthyretin(-/-) mice. By days 15 and 30 after nerve crushing the number of myelinated nerve fibers was diminished by 54.7 and 71.8%, respectively, in transthyretin(-/-) mice, as compared to that in control animals. The number of unmyelinated nerve fibers at day 15 after the injury was not different in transthyretin(-/-) and control mice, however, by day 30 the number of these fibers in control group was found to increase significantly, exceeding that one in transthyretin(-/-) mice by 27.9%. These results indicate the important contribution of transthyretin, as a thyroxin carrier protein, to the process of posttraumatic regeneration of sciatic nerve. The absence of changes in nerve fiber numbers in transthyretin-knockout mice in postembryonic period suggests the presence of transthyretin-independent mechanism of thyroxin transport into the peripheral nervous system.

Animals↗
PubMed1990

Remyelination of nerve fibers in the transected frog sciatic nerve.

This project tests an important aspect of the cellular events controlling the processes of recovery of function and remyelination that follow demyelination in the peripheral nervous system. Frog sciatic nerves have been shown to survive and remain functional for up to 10 days following transection. We have utilized this property in order to dissociate the recovery process from possible control by the neuronal soma. Xenopus sciatic nerves were demyelinated in one branch by an intraneural injection of lysolecithin. The nerve was cut proximally to the injection site either immediately before, or several days after the lysolecithin injection. Recovery of function and remyelination were then followed by electrophysiological, optical, and ultrastructural techniques applied both to whole branches and single fibers. Controls included the cut but uninjected branch, and injected but uncut nerves. The progression of events during both demyelination and recovery in cut axons was indistinguishable from that in uncut fibers. This suggests that this process may be under local control and can be initiated and carried out in the absence of constant communication with the nerve cell body.

Action Potentials↗
PubMed1993

Nerve growth factor facilitates regeneration across nerve gaps: morphological and behavioral studies in rat sciatic nerve.

The rat sciatic nerve does not possess a high potential for regeneration through silastic tubes when the interstump nerve gap is greater than 10 mm. In this study, the effect of NGF treatment on regeneration of the rat sciatic nerve in 10- and 15-mm silastic chambers was compared. In addition, regeneration in 15-mm silastic chambers was compared to regeneration in 15-mm semipermeable chambers. Sections of tubing were implanted and filled with NGF or a control solution of cytochrome C (Cyt. C). Tube implants were removed at various postoperative times and regeneration was assessed histologically and behaviorally. NGF treatment promoted regeneration success rate. It enhanced the initial outgrowth of nonneuronal cells and neuronal fibers into the chamber producing more cellular, organized regenerates. At 2 weeks, in 10-mm chambers, NGF-treated regenerates had fourfold more unmyelinated fibers than controls. At 3 weeks, NGF-treated regenerates possessed threefold more myelinated fibers than controls. After 4 weeks all regenerates had similar numbers of myelinated nerves at the chamber's midpoint. This initial "head start" was sustained peripherally as indicated by the earlier return of sensory function (response to a noxious temperature stimulus) in NGF-treated animals. Finally, regeneration success rate in 15-mm semipermeable tubes is greater than that in 15-mm silastic chambers (NGF and Cyt. C). However, regenerates in silastic chambers possessed twofold more myelinated fibers than regenerates in semipermeable chambers. The positive effects of NGF on neural regeneration and recovery of sensory function provide support for the potential use of NGF in treating peripheral nerve injuries.

Animals↗
PubMed1987

Numerical patterns of axon regeneration that follow sciatic nerve crush in the neonatal rat.

Different proportions of axons regenerate in cutaneous nerves compared with muscle nerves after sciatic nerve crush in the rat. The questions here are whether or not these differences reflect the proportions of axons that regenerate in the different nerves from which these nerves arise and do the differences persist. The findings indicate that the numbers of axons that regenerate in the muscle nerves do not reflect the numbers in the nerve from which the muscle nerves originate and that these differences persist. This leads to the conclusion that some factors determining numbers of axons in the muscle nerves must operate distal to the lesion. Thus when one is considering mechanisms that control regenerated axon numbers after neonatal nerve crush, one must consider not only the lesion site but also branching and axon diversion far distally, presumably at the origin of the muscle nerves.

Animals↗
PubMed2005

Extracts obtained from predegenerated nerves improve functional recovery after sciatic nerve transection.

Gap injuries of peripheral nerves, resulting from trauma or neurosurgical procedures, presage badly, for the presence of the distal stump of the nerve seems to be indispensable for regeneration. The standard grafting method requires a lesion of a healthy nerve, and therefore various substitutional materials are under consideration. The aim of the present work was to examine the recovery of rat sciatic nerves after supplying 10-mm-long gaps with an autologous connective-tissue chambers filled with fibrin only or fibrin and various neuroactive substances (brain-derived neurotrophic factor (BDNF), extracts from predegenerated or non-predegenerated nerves). The nerves were allowed to regenerate for 16 weeks. Recovery was measured functionally using the sciatic functional index, and by comparing the weight ratios of calf muscles. The histologic features of regeneration were assessed by counting the number of acetylcholinesterase-positive nerve fibers present inside implanted chambers. We found that chambers filled with fibrin and predegenerated peripheral nerve extracts or BDNF supported functional nerve regeneration much more strongly than chambers filled with fibrin only or fibrin and non-predegenerated peripheral nerve extracts. We conclude that autologous connective-tissue chambers filled with fibrin and predegenerated peripheral nerve extracts or BDNF seem to be a promising tool in peripheral nerve gap injury treatment, with likely clinical implications.

Animals↗
PubMed1985

Nerve growth factor counteracts the neurophysiological and neurochemical effects of chronic sciatic nerve section.

The sciatic nerve was sectioned unilaterally in rats and nerve growth factor (NGF) applied locally to the nerve stump for the following 10-14 days using an indwelling osmotic pump. The aim of the experiment was to test whether NGF had any effect on the previously reported neurophysiological and neurochemical events that occur central to a peripheral nerve lesion. The method of application allowed the sciatic nerve on the other side to be used as a control. Primary afferent depolarization fell, as expected, to 13% of its control value after chronic nerve section but if NGF was administered it fell to only 43.5% of control. Chronic nerve section is also known to result in expansion of the receptive fields of deafferented dorsal horn cells. NGF treatment reduced the number of such large receptive fields by 50%. The normal depletion of fluoride resistant acid phosphatase from the cut nerve terminals in the dorsal horn did not occur following NGF treatment. Radioimmunoassay of substance P revealed that the 30% reduction in dorsal horn levels that follows chronic sciatic nerve section did not occur when NGF was applied and that the accompanying 60% decrease in dorsal root ganglion levels was changed to a 64% increase by NGF. The results show that chronic NGF treatment of a cut sciatic nerve does partially reverse the central changes that normally follow deafferentation.

Acid Phosphatase↗
PubMed2004

Effects of repeated injection of local anesthetic on sciatic nerve blocks response.

In order to examine whether repeated sciatic nerve blocks showed tachyphylaxis and continuity of sciatic nerve with spinal cord affected development of tachyphylaxis when assayed in vivo by duration of depression compound action potentials (CAP), rats were anesthetized with halothane, ventilated, monitored and supported with stable hemodynamics and temperature. Posterior tibial nerve distally and sciatic nerve in thigh were exposed, placed on bipolar silver electrodes for stimulation and recording respectively. Three sequential sciatic nerve blocks were performed between these electrodes using 0.15 ml of 3% chloroprocaine. Nine rats were chosen to observe the effects of repeated sciatic nerve blocks on CAP. In another 18 rats, a second investigator exposed the sciatic nerve near its origin at spinal cord and randomly performed nerve cut and sham (n=9), and closed the incision blinding the electrophysiologic investigator. The results showed that electrical stimulated tibial nerve induced sciatic nerve Aalpha/beta, Adelta, C fiber mediated CAP waves. CAP amplitudes were remained stable during whole experimental procedure. CAP amplitudes were decreased completely with 3% chloroprocaine blocked sciatic nerve and recovered fully. The duration of CAP depression were reduced with repeated blocks. There were no selective blocked effects on Aalpha/beta, Adelta, C fiber mediated CAP. With sciatic nerve cut proximally, there was no statistical significant tachyphylaxis with 3% chloroprocaine repeated blocked sciatic nerve, and the duration of first and third blocked Adelta fiber mediated CAP was 108+/-20 and 92+/-14 min respectively (P>0.05). In normal rats the duration of first and third blocked Adelta fiber mediated CAP was 110+/-20 and 75+/-16 min respectively (P<0.05). It was suggested that tachyphylaxis to local anesthetics can occur in rats repeated blocked sciatic nerve when assayed in vivo by duration of depression CAP. The continuity of sciatic nerve with spinal cord is one of the important factors affecting the development of tachyphylaxis.

Anesthetics, Local↗
PubMed1991

Adrenergic nerve fibers in the human fetal sciatic nerve.

The adrenergic innervation was studied in the human sciatic nerve at the gestational age of 16, 17, 18 and 21 weeks. Formaldehyde-induced catecholamine fluorescence, tyrosine hydroxylase (TH) and neuropeptide Y (NPY) peroxidase-antiperoxidase immunohistochemistry methods were used. At the gestational age of 16, 17 and 18 weeks no adrenergic or NPY-positive nerve fibers were seen. At 21 weeks both fluorescence microscopy and TH immunohistochemistry showed adrenergic nerve fibers around arterioles in the epiperineurium and single nerve fibers in the endoneurium not related to blood vessels. The number of adrenergic nerve fibers appeared to be higher in the sciatic than in the tibial segment of the nerve. At this age, as at earlier stages of gestation, no NPY-positive nerve fibers were seen either in the epiperineurium or in the endoneurium. The results suggest that adrenergic nerve fibers may be associated with the epiperineurial blood vessels in the human sciatic nerve, and that the innervation starts to develop between 18 and 21 weeks of gestational age.

Female↗
PubMed1999

Efficacy of delayed or discontinuous FK506 administrations on nerve regeneration in the rat sciatic nerve crush model: lack of evidence for a conditioning lesion-like effect.

We examined whether the nerve regenerative property of FK506 exhibits a 'window-of-opportunity' corresponding to the time of injury for maximal efficacy in the sciatic nerve crush model. FK506 (5 mg/kg, s.c.) was administered over the 18-day period of study according to three dosage regiments: delayed (days 9-17), discontinuous (days 0-8) and continuous (days 0-17) administrations. Quantitation of axonal calibers and the extend of myelination in the soleus nerve at 18 days demonstrated that both delayed and discontinuous administrations were equally effective, arguing against a 'window-of-opportunity' for FK506 nerve regenerative effect. However, both protocols were less effective than continuous administration indicating that the compound needs to be given during the entire regenerative period to elicit maximal efficacy.

Animals↗
PubMed2001

Morphometric study of regeneration through vascularized nerve graft in a rabbit sciatic nerve model.

Adequate vascularization is essential for a successful nerve graft. Theoretically, immediate vascularization will minimize fibroblast infiltration and support axonal regeneration. In this study, histomorphologic and morphometric studies were carried out to determine whether vascularized grafts are beneficial, in terms of axonal regeneration. In a rabbit model, 4-cm segments of sciatic nerve were obtained and placed as a nonvascularized graft on one side, and as a pedicled vascularized graft fed by the inferior gluteal vessel on the contralateral side. Histomorphologically, the distribution of myelinated nerve fibers and Schwann cells was evaluated after toluidine blue staining, at 2-, 3-, and 4-month intervals. The following results were obtained. 1) Myelinated nerve fibers were more abundant in the proximal, middle, and distal segments of the vascularized nerve group at 2 and 3 months. 2) The average nerve-fiber diameter was greater in the vascularized nerve graft group at 2, 3, and 4 months (2 to 10 microm). 3) Schwann cells were more abundant in the proximal, middle, and distal segments of the vascularized nerve graft group at all time points. Based on the above findings, the immediate restoration of circulation in the vascularized nerve graft can be accountable for the increased number of surviving Schwann cells, the rapid clearing of axons, and myelin-sheath changes that occur during Wallerian degeneration, thus enabling "morphologically" optimal regeneration.

Animals↗
PubMed2006

Correlation between parameters of electrophysiological, histomorphometric and sciatic functional index evaluations after rat sciatic nerve repair.

The rat sciatic nerve is a well-established model for the study of recovery from peripheral nerve injuries. Traditional methods of assessing nerve regeneration after nerve injury and repair, such as electrophysiology and histomorphometry, despite widely used in neural regeneration experiments, do not necessarily correlate with return of motor and sensory functions. The aim of this experimental study is to investigate the possible correlation between several parameters of peripheral nerve regeneration after repair of sectioned sciatic nerve in Wistar rat. A two-stage approach was used to obtain 17 parameters after electrophysiological, morphometric and sciatic functional index evaluations. Pearson's correlation analysis was performed between these results. Only two positives correlations between different classes of peripheral nerve assessments were noted, between sciatic functional index and proximal nerve fiber diameter (r=0.56, p<0.01) and between sciatic functional index and distal fiber diameter (r=0.50, p<0.01). The data presented in our study demonstrates that there is a poor correlation between the sciatic functional index and outcome measures of electrophysiological and morphometric evaluations.

Animals↗
PubMed1963

ACETYLCHOLINE-LIKE ACTIVITY IN SCIATIC NERVE.

Extracts of sciatic nerve exhibit acetylcholine-like activity that is only partly attributable to acetylcholine. The extracts show relatively greater activity on the rectus abdominis muscle of the frog than on the ileum of the guinea pig. To prevent the action of the extract on the frog rectus abdominis muscle, a greater concentration of d-tubocurarine is required than is necessary to prevent the action of known acetylcholine.

Abdominal Wall↗
PubMed1993

Reduction of cyclic AMP in the sciatic nerve of rats made diabetic with streptozotocin and the mechanism involved.

We have investigated the relationship between cyclic nucleotides and nerve function in the sciatic nerve of rats made diabetic with streptozotocin. Cyclic AMP (cAMP) content in the sciatic nerves of diabetic rats was significantly (P < 0.05) lower than in those of normal rats, while cyclic GMP content did not differ between the two groups. Administration of the stable prostacyclin analogue iloprost or dibutyryl cyclic AMP (dbcAMP) significantly (P < 0.05) restored the cAMP content in the sciatic nerves and motor nerve conduction velocity, which reflects nerve function. There was a positive correlation between cAMP content in the sciatic nerves and motor nerve conduction velocity in both normal and diabetic rats. Endoneurial preparations of sciatic nerves obtained from normal rats were incubated in Krebs-Ringer bicarbonate buffer containing D-glucose (30 or 5.5 mmol/l). Cyclic AMP accumulation was significantly (P < 0.05) suppressed in the buffer containing 30 mmol D-glucose/l compared with that containing 5.5 mmol/l. Iloprost (P < 0.05) and dbcAMP (P < 0.01) increased cAMP accumulations in the tissues incubated in buffer containing both 5.5 and 30 mmol D-glucose/l. When non-metabolizing hexoses, such as L-glucose or 3-O-methylglucose instead of D-glucose were used, cAMP accumulations at 30 mmol hexose/l were not significantly different from those at 5.5 mmol/l. Cyclic AMP phosphodiesterase activity in the sciatic nerves of diabetic rats did not change compared with that in nerves from normal rats. Although not significant, mean ATP content in the sciatic nerves of diabetic rats was about 30% lower than that in nerves of normal rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenylyl Cyclases↗
PubMed1995

Increased levels of mitogen activated protein kinase (MAP-K) detected in the injured adult mouse sciatic nerve.

Adult mouse sciatic nerves (SNs) with attached dorsal root ganglia (DRG) were analysed for the presence of mitogen activated protein kinase (MAP-K) during normal and regenerative conditions. By immunohistochemistry, MAP-K was found to be present in the normal nerve at low levels in both Schwann cells and DRG nerve cell bodies, with a profoundly increased expression during regeneration. In axonal outgrowth assays, treatment with 2 mM 2-aminopurine (2-AP), a MAP-K antagonist, inhibited the regeneration of axons from the SN as well as from the cultured superior cervical ganglia. The reduced outgrowth was probably not due to toxic effects of the drug since the ganglionic protein synthesis was not inhibited. It is possible that 2-AP interferes with regeneration-related events by inhibition of MAP-K.

2-Aminopurine↗