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Exercise training improves functional recovery and motor nerve conduction velocity after sciatic nerve crush lesion in the rat.

OBJECTIVE: To observe the effects of exercise training on recuperation of sensorimotor function in the early phase of regeneration, and to monitor the long-term effects of exercise on electrophysiological aspects of the regenerating nerve. DESIGN: After sciatic nerve crush in 20 male Wistar rats, one random selected group was subjected to 24 days of exercise training, whereas the other group served as sedentary controls. INTERVENTIONS: Exercise training was induced for 24 days, starting the first postoperation day, by placing bottles of water at such a height that the exercising rats had to maximally erect on both hindpaws to drink. MAIN OUTCOME MEASURES: Recovery of motor and sensory function in the early phase was monitored by analysis of the free walking pattern and the foot reflex withdrawal test, respectively. Electrophysiological measurements on postoperation days 50, 75, 100, 125, and 150 were used to evaluate the late phase of recovery of nerve conduction velocity. RESULTS: During the early phase of the recovery period, exercise training enhanced functional recovery. The motor nerve conduction velocity (MNCV), as measured in the late phase of recovery, was significantly better in the trained group than in the control group (p < .01). CONCLUSIONS: We conclude that exercise training enhances the return of sensomotoric function in the early phase of recovery from peripheral nerve lesion. Furthermore, these results suggest that the beneficial effects of 24 days of exercise training after crush persist in the late phase of peripheral nerve recovery.

Animals↗

Membrane-associated phospholipase D activity in rat sciatic nerve.

Rat sciatic nerve contains a membrane-bound phospholipase D that catalyzes the hydrolysis of exogenous phosphatidylcholine (PC) to phosphatidic acid (PA) and choline. The enzyme is associated with a particulate fraction consisting primarily of microsomes and myelin. This fraction also contains phosphatidate phosphohydrolase activity leading to the production of diacylglycerols (DAG). The phosphohydrolase activity can be completely inhibited by NaF. Hydrolysis of exogenous PC requires detergent and is linear up to about 40 micrograms of protein at a pH optimum of 6.5. In the absence of NaF, the sum of PA and DAG increases linearly for 40 min, whereas in its presence, PA production is linear for only 15 min. At optimum conditions, PC hydrolysis proceeds at 15 nmol/h/mg of protein. Addition of increasing amounts of ethanol to the incubation system leads to the generation of increasing amounts of phosphatidylethanol, indicating transphosphatidylation activity. At an ethanol concentration of 0.4 M, phosphatidylethanol represents about one-half of the reaction products generated at approximately the same rate of enzymic activity observed in the absence of ethanol. Higher ethanol concentrations are inhibitory.

Animals↗

Controlled expansion of peripheral nerves: comparison of nerve grafting and nerve expansion/repair for canine sciatic nerve defects.

The inherent disadvantages of nerve grafting have made it necessary to find alternative techniques for treating segmental nerve loss. This study compares the techniques of nerve grafting and nerve expansion/repair for the management of nerve injuries with segmental nerve loss in an animal model. Bilateral segmental sciatic nerve defects were created in eight dogs. On one side a 2-cm segment was excised and replaced with a nerve graft; on the other side a 2-cm defect was created with ligatures and the nerve underwent preliminary expansion and then repair. Eighteen months later nerve conduction velocity (NCV), gastrocnemius contraction force (GCF), and muscle weight (GMW) were determined for the seven surviving animals. NCV for the expanded repair was 58.66 +/- 34.18 m/sec and 47.73 +/- 7.93 for the grafted repair (p = 0.4); GCF was 619.04 +/- 353.70 gm for the expanded repair and 726.80 +/- 415.78 gm (p = 0.2) for the grafted repair; and GMW was 82.80 +/- 5.68 gm for the expanded repair and 109.55 +/- 20.63 gm (p = 0.02) for the grafted repair. The data suggest that: 1) conventional tissue expansion techniques can be used successfully to repair segmental peripheral nerve defects; 2) NCV and GCF are comparable for grafting and expansion/repair techniques although GMW is significantly higher in the grafted group; and 3) nerve expansion/repair may prove to be a useful alternative to grafting.

Action Potentials↗

Post-operative analgesia following total knee replacement: an evaluation of the addition of an obturator nerve block to combined femoral and sciatic nerve block.

BACKGROUND: Femoral and sciatic nerve block may not provide complete post-operative analgesia following total knee replacement. This study was designed to evaluate whether the addition of an obturator nerve block to combined femoral and sciatic nerve block improves the quality of post-operative analgesia following primary total knee replacement. METHODS: Sixty patients were randomised into one of two groups: combined femoral and sciatic nerve block with 15 ml 0.75% ropivacaine to each nerve or combined femoral and sciatic nerve block with 15 ml 0.75% ropivacaine to each nerve and an obturator nerve block with 5 ml 0.75% ropivacaine. RESULTS: Peripheral nerve blocks were successful in 85% of patients. The group which received the obturator nerve block showed a significant increase in the time until their first request for analgesia (mean 257.0 vs. 433.6 min) and a significant reduction in the total requirements for morphine throughout the study period (mean 83.8 vs. 63.0 mg) (P<0.05). There were no systemic or neurological sequelae in any of the groups. CONCLUSIONS: The addition of an obturator nerve block to femoral and sciatic blockade improved post-operative analgesia following total knee replacement.

Aged↗

Catheter confocal fluorescence imaging and functional magnetic resonance imaging of local and systems level recovery in the regenerating rodent sciatic nerve.

The goal of the present work was to develop minimally invasive imaging techniques to monitor local regeneration of peripheral nerves and to determine the extent of return to function of brain cortical regions associated with that nerve. The sciatic nerve crush model was applied to Sprague-Dawley rats and conventional histological staining for myelin, axons and cell architecture was carried out, as well as traditional behavioral testing, to verify that nerve regeneration was occurring. The rate of sciatic nerve regeneration was measured by determining the distance a lipophilic, fluorescence probe (DiO) would move along the nerve's membrane following a direct injection into the sciatic nerve. This movement was monitored using a catheter based, confocal fluorescence microscope. Two to five days after the crush, the dye moved 1.4 + 0.6 mm/day, as compared to a distance of 5.3 + 0.5 mm/day in the normal nerve. Between 9 and 13 days following the crush, the distance the dye moved increases to 5.5 + 0.5 mm/day, similar to the control, and by 15 days following the crush, the distance increased to 6.5 + 0.9 mm/day. Functional Magnetic Resonance Imaging (fMRI) measurements were performed on alpha-chloralose anesthetized rats to monitor the return of somatosensory cortical functions, which were activated by the stimulation of the lesioned peripheral nerve. fMRI results showed the return of cortical activation around 15 days following the crush procedure. However, the somatosensory cortical region activated by stimulating the crushed hindpaw was significantly smaller in extent than the intact hindpaw stimulation. These findings demonstrate that fluorescence imaging and fMRI can integrate local and system level correlates of nerve regeneration in a non-destructive manner, thus enabling serial imaging of individual animals.

Animals↗

Increase of preprotachykinin mRNA and substance P immunoreactivity in spared dorsal root ganglion neurons following partial sciatic nerve injury.

Complete sciatic nerve injury reduces substance P (SP) expression in primary sensory neurons of the L4 and L5 dorsal root ganglia (DRG), due to loss of target-derived nerve growth factor (NGF). Partial nerve injury spares a proportion of DRG neurons, whose axons lie in the partially degenerating nerve, and are exposed to elevated NGF levels from Schwann and other endoneurial cells involved in Wallerian degeneration. To test the hypothesis that SP is elevated in spared DRG neurons following partial nerve injury, we compared the effects of complete sciatic nerve transection (CSNT) with those of two types of partial injury, partial sciatic nerve transection (PSNT) and chronic constriction injury (CCI). As expected, a CSNT profoundly decreased SP expression at 4 and 14 days postinjury, but after PSNT and CCI the levels of preprotachykinin (PPT) mRNA, assessed by in situ hybridization, and the SP immunoreactivity (SP-IR) of the L4 and L5 DRGs did not decrease, nor did dorsal horn SP-IR decrease. Using retrograde labelling with fluorogold to identify spared DRG neurons, we found that the proportion of these neurons expressing SP-IR 14 days after injury was much higher than in neurons of normal DRGs. Further, the highest levels of SP-IR in individual neurons were detected in ipsilateral L4 and L5 DRG neurons after PSNT and CCI. We conclude that partial sciatic nerve injury elevates SP levels in spared DRG neurons. This phenomenon might be involved in the development of neuropathic pain, which commonly follows partial nerve injury.

Animals↗

Aortic occlusion and reperfusion and conduction, blood flow, and the blood-nerve barrier of rat sciatic nerve.

We studied the effect of ischemia and reperfusion on blood flow, electrophysiology, and the blood-nerve barrier of the sciatic nerve of the rat. Ischemia for 10 to 60 min, with up to 3 h of reperfusion, was produced by closure and then release of a noose around the abdominal aorta. Nerve blood flow and function were measured serially using microelectrode-hydrogen polarography and electrophysiologic recordings, respectively. The integrity of the blood-nerve barrier was assessed using the permeability surface area product to [14C]sucrose. Ischemia of up to 30 min did not impair reperfusion. One hour of ischemia resulted in reperfusion abnormalities that affected about half of the nerves. The ischemic and reperfusion stresses did not disrupt the blood-nerve barrier to [14C]sucrose nor produce conduction block. Possible mechanisms for this resistance to ischemic and reperfusion injury are discussed.

Animals↗

Novel heparin/alginate gel combined with basic fibroblast growth factor promotes nerve regeneration in rat sciatic nerve.

We have developed an alginate gel crosslinked with covalent bonds for regeneration of dermis, nerve, and bone. Recently, a novel matrix (H/A gel) which consists of heparin and alginate covalently crosslinked with ethylenediamine, was designed. It can stabilize and release biologically active basic fibroblast growth factor (bFGF) for 1 month, which is one of the heparin-binding growth factors. In the present report, we examined the effect of this novel H/A gel on nerve regeneration in the rat sciatic nerve. In this study, regenerated axons in H/A gel with bFGF grew faster than in ordinary alginate gel with bFGF in the early stage. Myelinated fibers showed a tendency to increase in diameter toward the normal size in the later stage. Nerve bundles in the implantation exhibited minimal fibrosis and good vascularization. H/A gel with bFGF exhibited better-developed vascularization than ordinary alginate gel with bFGF. These findings suggested that H/A gel with bFGF could serve not only as an efficient cellular scaffold, but also as a stabilizing matrix for bFGF for peripheral nerve regeneration.

Alginates↗

Thrombospondin expression in nerve regeneration I. Comparison of sciatic nerve crush, transection, and long-term denervation.

Patterns of expression of the extracellular matrix molecule thrombospondin (TSP) were examined during peripheral nerve regeneration following sciatic nerve crush or transection. In noninjured nerve, was present in the axoplasm, Schwann cells, endoneurium, and perineurium of the adult mouse sciatic nerve. Following nerve crush or nerve transection, levels of TSP rapidly increased distal to the trauma site. Elevated levels of TSP were present distal to regenerating axons, while expression gradually returned to normal proximal to the regenerating axons. When reinnervation was blocked, TSP levels remained high in the endoneurium in excess of 30 days, but TSP was absent by 60 days. Following reanastomosis of the proximal and distal segments after 60 days of denervation, TSP was re-expressed in the distal nerve stump. These results indicate that TSP, which is involved in neuronal migrations in the embryo and neurite outgrowth in vitro, appears to play a role in axonal regeneration in the adult peripheral nervous system.

Animals↗

Endoscopic-assisted sciatic nerve exploration.

A sciatic nerve lesion is uncommon. We report the utility of the endoscope in an 18-year-old female with multiple lesions of her sciatic nerve. Somatosensory evoked potentials and MRI were indicative of a sciatic nerve lesion. We describe a simple technique of endoscopic exploration of the sciatic nerve to assist intraoperative decision making.

Adolescent↗

[Adipose tissue within peripheral nerves. Study of the human sciatic nerve].

AIM: To describe the distribution of intraneural adipose cells in relation to nerve fascicles in a portion of peripheral nerve usually involved in accomplishing an anesthetic blockade of a lower extremity. METHOD: Using a scanning electron microscope, we studied sciatic nerve samples from the point of amputation of a lower limb of three patients. The samples were obtained at the upper angle of the popliteal fossa, 10-15 cm cephalad to the knee joint line. RESULTS: During dissection of the sciatic nerve samples, we observed a solitary trunk, but examination of the cross-sections under the microscope revealed the components of two clearly separated branches joined by supporting tissue. The sciatic nerve had an oval form in the portion under study, measuring 6.5 to 7.5 mm by 3.6 to 3.9 mm. Between the fascicles, the adipose tissue varied in thickness from 0.5 mm in the central zones to 0.2 mm in the peripheral zones. The adipocytes, which were all similar in the size with diameters of 40 microns, were empty, as a result of elimination of the lipid vacuoles during fixation. The adipose tissue was distributed inside the epineurium to surround isolated fascicles or groups of fascicles. CONCLUSIONS: The adipose tissue inside a nerve surrounded the fascicles to form adipose sheaths that separated the fascicles from one another. The thicknesses of these adipose sheaths varied from one fascicle to another. Cells join to make it possible to create a compact adipose sheet that can delay the diffusion of local anesthetic injected near a nerve and that can therefore interfere with the characteristics of an anesthetic blockade.

Adipose Tissue↗

Controlled release of nerve growth factor enhances sciatic nerve regeneration.

Based on previous studies demonstrating the potential of growth factors to enhance peripheral nerve regeneration, we developed a novel growth factor delivery system to provide sustained delivery of nerve growth factor (NGF). This delivery system uses heparin to immobilize NGF and slow its diffusion from a fibrin matrix. This system has been previously shown to enhance neurite outgrowth in vitro, and in this study, we evaluated the ability of this delivery system to enhance nerve regeneration through conduits. We tested the effect of controlled NGF delivery on peripheral nerve regeneration in a 13-mm rat sciatic nerve defect. The heparin-containing delivery system was studied in combination with three doses of NGF (5, 20, or 50 ng/mL) and the results were compared with positive controls (isografts) and negative controls (fibrin alone, NGF alone, and empty conduits). Nerves were harvested at 6 weeks postoperatively for histomorphometric analysis. Axonal regeneration in the delivery system groups revealed a marked dose-dependent effect. The total number of nerve fibers at both the mid-conduit level and in the distal nerve showed no statistical difference for NGF doses at 20 and 50 ng/mL from the isograft (positive control). The results of this study demonstrate that the incorporation of a novel delivery system providing controlled release of growth factors enhances peripheral nerve regeneration and represents a significant contribution toward enhancing nerve regeneration across short nerve gaps.

Animals↗

Effect of ACTH4-10 on nerve fiber regeneration after sciatic nerve crush in rabbits: an electrophysiological and morphological study.

Crush of sciatic nerve in rabbits supported by morphologic and electrophysiologic data was used to evaluate the effects of ACTH4-10 on nerve fiber regeneration. Treated animals showed a statistically significant higher regeneration rate than did control rabbits. Fiber density and mean diameters of myelinated nerve fibers were measured in semithin nerve sections at 1 and 3 cm distal from the crushed point at three different time points. Nerve fiber density results were higher in ACTH4-10-than in vehicle-treated rabbits. This difference showed an unequivocal trend and attained a statistically significant level in the sections 3 cm distal from the crush. ACTH4-10 seemed therefore to have a beneficial effect on nerve fiber regeneration.

Adrenocorticotropic Hormone↗

[Effect of oxythiamine on rat peripheral nerve. --Morphological changes in sciatic nerve and plantar nerve of thiamine deficiency-- (author's transl)].

Morphological changes in rat sciatic nerve (SN) and plantar nerve (PN) induced by a thiamine deficient diet (TDD) and administration of oxythiamine (OT: 4 mg/100 g X 6 days) were observed, and thiamine (T) levels in rat nerve were simultaneously determined. Body weight gain ratio in rats which received OT fed a TDD (OTD group) was much reduced, and anorexia and ataxia were recognized in this group. Rats fed a regular diet, whose weights were restricted to be the same as those in the OTD group (EWC group), showed the symptoms of starvation. T levels of the SN and PN in the OT group, OTD group, and rats fed a TDD (TDD group) were reduced, but in the EWC group, T levels were the same as those in the control group (C group). There were myelin folds and myelin oboids in the EWC group, and these were recognized before axonal degeneration. In the TDD group, an increase in the number of mitochondria (Mit) was seen in the myelinated axon (MAx). In the TDD group, an increase in the number of mitochondria (Mit) was seen in the myelinated axon (MAx). In the OT and OTD groups, axonal degeneration (increase in the number of Mit, appearance of degenerated Mit, axonal shrinkage, and disappearance of neurofilament and neurotubule) was observed in the MAx. Degeneration of the MAx caused by TDD and OT was more severe in the PN than in the SN. Since these changes progressed from the peripheral nerve to the centripetal one, these changes in OTD group might be dying-back polyneuropathy.

Animals↗