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Faster nerve regeneration after sciatic nerve injury in mice over-expressing basic fibroblast growth factor.

Basic fibroblast growth factor (FGF-2) is expressed in the peripheral nervous system and is up-regulated after nerve lesion. It has been demonstrated that administration of FGF-2 protects neurons from injury-induced cell death and promotes axonal regrowth. Using transgenic mice over-expressing FGF-2 (TgFGF-2), we addressed the importance of endogenously generated FGF-2 on sensory neuron loss and sciatic nerve regeneration. After sciatic nerve transection, wild-type and transgenic mice showed the same degree of cell death in L5 spinal ganglia. Also, the number of chromatolytic, eccentric, and pyknotic sensory neurons was not changed under elevated levels of FGF-2. Morphometric evaluation of intact nerves from TgFGF-2 mice revealed no difference in number and size of myelinated fibers compared to wild-type mice. One week after crush injury, the number of regenerated axons was doubled and the myelin thickness was significantly smaller in transgenic mice. After 2 and 4 weeks, morphometric analysis and functional tests revealed no differences in recovery of sensory and motor nerve fibers. To study the role of FGF-2 over-expression on Schwann cell proliferation during the early regeneration process, we used BrdU-labeling to mark dividing cells. In transgenic mice, the number of proliferating cells was significantly increased distal to the crush site compared to wild-types. We propose that endogenously synthesized FGF-2 influences early peripheral nerve regeneration by regulating Schwann cell proliferation, axonal regrowth, and remyelination.

Animals↗

Immunohistochemical localization of cell adhesion molecules and cell-cell contact proteins during regeneration of the rat optic nerve induced by sciatic nerve autotransplantation.

BACKGROUND: The central nervous system neurons of adult mammals are known to regenerate into peripheral nerve autograft. The localization of cell adhesion molecules and cell-cell contact proteins were studied during axonal regeneration induced by sciatic nerve autotransplantation. METHODS: A sciatic nerve autograft was anastomosed to the proximal stump of the transected rat optic nerve. Immunofluorescence microscopy, thin sectioning, and immunoelectron microscopy with the preembedding method and ultrathin cryosections were used to localize cell adhesion molecules (L1; neural cell adhesion molecule, NCAM; myelin-associated glycoprotein, MAG) and cell-cell contact proteins (connexins 32, 43, ZO-1) at 3 days to 4 weeks postoperation. RESULTS: Most regenerating axons contacted astrocytes in the optic nerve and Schwann cells in the graft. Immunoreactivity of NCAM was widely distributed along the surface of axons, astrocytes, Schwann cells, and perineurial cells. The L1 immunoreactivity was confined to the interface of axon-astrocyte and of axon-Schwann cell. MAG immunoreactivity was seen at the interface of axon and myelin within the graft. Connexins 32, 43, and ZO-1 immunoreactivities were observed at contact sites between axons and Schwann cells within the graft. CONCLUSIONS: Cell adhesion molecules (L1, NCAM, MAG) are localized at the cell surface of regenerating axons, astrocytes, and Schwann cells during optic nerve regeneration elicited by peripheral nerve graft. Cell-cell contact proteins (connexins 32, 43, ZO-1) are present at the interface between axons and Schwann cells in the graft. Our results suggest that these molecules are involved in cell adhesion events during optic nerve regeneration.

Animals↗

Four PGE2 EP receptors are up-regulated in injured nerve following partial sciatic nerve ligation.

We previously reported that cyclooxygenase 2 (COX2) is up-regulated in macrophages in injured nerve of rats with partial sciatic nerve ligation (PSNL) and that local injection of the COX inhibitor ketorolac reversed tactile allodynia (Eur. J. Neurosci. 15: 1037-1047, 2002). These findings suggest that prostaglandins (PGs) are overproduced in injured nerve and are involved in the pathogenesis of neuropathic pain. In this study, we examined whether overproduced PGs alter the expression of PGE2 receptors, EP1-EP4, in injured nerve of PSNL rats. We found that cell profiles immunoreactive (IR) for four EP receptors, EP1, EP2, EP3, and EP4, are dramatically increased in injured nerve 2 and 4 weeks after PSNL. EP4-IR cells were the most abundant among these receptor-expressing cells. Immunoreactivities of all four EP receptors were localized to the cell nucleus. These EP-IR cells were never found in uninjured nerve. More than 80% EP1- and about 30% EP4-IR cells were identified as infiltrating macrophages since they coexpressed ED1. Only 3% EP2- and 6% EP3-IR cells coexpressed ED1. These findings suggest that majority of EP2-, EP3-, and EP4-IR cells are other types of inflammatory cells than macrophages. About 48% of macrophages expressed EP1 and 45% expressed EP4. Only 3 and 6% of macrophages, respectively, expressed EP2 and EP3. Perineural injection of ketorolac reversed tactile allodynia and suppressed the up-regulation of EP1 and EP4, but not the recruitment of ED1-IR marcrophages, in injured nerve. Our data suggest that following PSNL, PGE2 is one of the possible PGs overproduced in injured nerve and PG overproduction is involved in the up-regulation of EP receptors in injured nerve.

Animals↗

Induction of the plasminogen activator system accompanies peripheral nerve regeneration after sciatic nerve crush.

Peripheral nerve regeneration is dependent on the ability of regenerating neurites to migrate through cellular debris and altered extracellular matrix at the injury site, grow along the residual distal nerve sheath conduit, and reinnervate synaptic targets. In cell culture, growth cones of regenerating axons secrete proteases, specifically plasminogen activators (PAs), which are believed to facilitate growth cone movement by digesting extracellular matrices and cell adhesions. In this study, the PA system was shown to be specifically activated in sensory neurons after sciatic nerve crush in adult mice. The number of sensory neurons expressing urokinase PA receptor (uPAR) mRNA levels increased above sham levels by 8 hr after crush, whereas the number of sensory neurons expressing uPA and tissue PA (tPA) mRNAs was significantly increased by 3 d after crush. PA mRNA levels were also increased at the crush site, with uPA mRNA elevated by 8 hr after crush and tPA and uPAR mRNA levels markedly increased by 7 d. PA-dependent enzymatic activity was significantly increased from 1 to 7 d after crush in nerves that had been crushed compared with uncrushed nerves. Immunohistochemistry showed that tPA was localized within regenerating axons of the sciatic nerve. There were no significant changes in plasminogen activator inhibitor 1 activity between crush and sham after the injury. These results clearly demonstrated that after injury the PA system was rapidly induced in sensory neurons, where it may play an important role in nerve regeneration in vivo.

Animals↗

Posttraumatic osseous tunnel formation causing sciatic nerve entrapment.

Sciatic nerve entrapment in an osseous tunnel has only been reported twice previously. We describe a 19-year-old man evaluated for left lower limb pain and weakness that began one and one half years after sustaining stab wounds to the left buttock and midline back near the T11 vertebrae. The patient had sciatica and demonstrated motor and sensory deficits on physical exam. Electrodiagnostic studies demonstrated a localized injury to the sciatic nerve in the proximal thigh. Radiographic studies of the left pelvis and femur showed an 8 to 10cm linear opacification overshadowing the left femoral head and anatomic neck. An arteriogram of the left leg demonstrated a 3 x 4cm lobulated aneurysm arising from the distal portion of the inferior gluteal artery. Surgical exploration revealed the sciatic nerve to be encased in cylindrical bone. The ectopic bone was removed and the sciatic nerve released. The patient had gradual improvement with a nearly complete neurological recovery by three months after surgery.

Adult↗

Use of a low-power nerve stimulator during sciatic nerve block.

The use of a low-power nerve stimulator to aid nerve location during the performance of sciatic nerve block was compared with a conventional anatomically based technique. The success rate, both in terms of the production of an effective block and the duration of postoperative analgesia, was significantly higher in the stimulator groups than in the non-stimulator groups. The implications of the study for both clinical and teaching practice are discussed.

Anesthesia, General↗

Injection injury of the sciatic nerve: unusual anatomic distribution of nerve damage.

Sciatic nerve damage by intragluteal injections tends to injure the peroneal nerve trunk more severely than the other components of the sciatic nerve. 2 patients with predominant or sole damage to the posterior tibial nerve trunk were observed. This distribution was documented electrophysiologically. Our cases are unusual and point to a wider spectrum of such injuries. It is also suggested that internal fibrosis of the nerve is of greatest importance as a pathogenetic mechanism in these injuries.

Adult↗

Motoneurons of the rat sciatic nerve.

The sciatic nerve of the rat is a commonly used model for studies on nerve injury, regeneration, and recovery of function. To interpret the changes that occur in a neuron population subsequent to peripheral nerve injury, and to compare different repair procedures, it is essential to have a complete and accurate understanding of the population's normal cellular constituents and their locations. This study reports on the numbers, sizes, and topographic distributions of the motoneuron populations of individual branches of the rat sciatic nerve (peroneal, tibial, sural, and the medial and lateral gastrocnemius nerves), as determined by retrograde transport of HRP (or WGA-HRP) from cut proximal nerve ends isolated in wax to prevent spread of the tracer substance. Optimal labeling of motoneurons was evident between 42 and 73 h of survival. Reconstructions were made from 40-micron serial sections of spinal segments L6 through L2, usually in the coronal plane. Accurate motoneuron counts were obtained by detailed reconstructions in which an accounting of all "split cell" fragments was made to avoid double cell counts. The sciatic nerve of the albino rat contains a total population of about 2005 +/- 89 motoneurons. The tibial nerve contained 982 +/- 36 cells or 49% of the total. The common peroneal nerve contained 31% or 632 +/- 27 motoneurons. The medial and lateral gastrocnemius nerve branches contained collectively 322 +/- 16 (16%). The sural nerve accounted for only 68 +/- 10 motoneurons (3%). The sciatic motoneurons form a continuous, compact cell column in the dorsolateral quadrant of the ventral horn extending from rostral L6 into the caudal third of L3 over a longitudinal distance of about 6.3 to 7.5 mm. This fusiform column shows its greatest width, 0.5 mm, in mid-L4. Within this compartment motoneurons of each branch of the sciatic occupy spatially distinct subcompartments. Their relative positions are described in detail.

Animals↗

Polyglycolic acid suture in peripheral nerve II: sutured sciatic nerve.

This experiment investigates the holding property of polyglycolic acid suture in repair of divided dog sciatic nerves and the influence of absorption of this synthetic material on regeneration. The conclusion is that PGA maintains its tensile strength sufficently long to allow both physical union and good regeneration of the divided nerve. The suture absorption does not influence regeneration.

Absorption↗

The role of the saphenous nerve in experimental sciatic nerve mononeuropathy produced by loose ligatures: a behavioural study.

Four loose ligatures were tied round the sciatic nerve of rats to produce the model of altered pain sensation first described by Bennett and Xie (1988). Hyperalgesia and hyperaesthesia were detected from 4 days after tying ligatures, becoming maximal after 14 days; normal behaviour returned by 8 weeks post-operation. Using thermal tests involving immersion of the whole foot, it was found that section of the saphenous nerve at the time of, or within a week of, placing ligatures had the effect of abolishing the hyperaesthetic behaviour and instead caused hypoaesthesia from the 4th to 10-12th days. There was then a change to hyperaesthetic behaviour. The findings are interpreted as indicating that the early hyperaesthesia is possibly due to collateral sprouting, spreading nociceptor sensitivity of saphenous nerve fibres or both of these.

Animals↗

Skin-derived stem cells transplanted into resorbable guides provide functional nerve regeneration after sciatic nerve resection.

The regeneration in the peripheral nervous system is often incomplete and the treatment of severe lesions with nerve tissue loss is primarily aimed at recreating nerve continuity. Guide tubes of various types, filled with Schwann cells, stem cells, or nerve growth factors are attractive as an alternative therapy to nerve grafts. In this study, we evaluated whether skin-derived stem cells (SDSCs) can improve peripheral nerve regeneration after transplantation into nerve guides. We compared peripheral nerve regeneration in adult rats with sciatic nerve gaps of 16 mm after autologous transplantation of GFP-labeled SDSCs into two different types of guides: a synthetic guide, obtained by dip coating with a L-lactide and trimethylene carbonate (PLA-TMC) copolymer and a collagen-based guide. The sciatic function index and the recovery rates of the compound muscle action potential were significantly higher in the animals that received SDSCs transplantation, in particular, into the collagen guide, compared to the control guides filled only with PBS. For these guides the morphological and immunohistochemical analysis demonstrated an increased number of myelinated axons expressing S100 and Neurofilament 70, suggesting the presence of regenerating nerve fibers along the gap. GFP positive cells were found around regenerating nerve fibers and few of them were positive for the expression of glial markers as S-100 and glial fibrillary acidic protein. RT-PCR analysis confirmed the expression of S100 and myelin basic protein in the animals treated with the collagen guide filled with SDSCs. These data support the hypothesis that SDSCs could represent a tool for future cell therapy applications in peripheral nerve regeneration.

Action Potentials↗

[Sciatic nerves block].

Sciatic nerve block is considered difficult to perform, but very useful for lower limb anaesthesia and analgesia. The use of a nerve stimulator makes the technique easier. Functionally, it is better to consider that there are three independent sciatic nerves, namely, the posterior cutaneous nerve, the tibial nerve and the common peroneal nerve. Searching for blocking these three nerves and especially the latter two, specifically improve the reliability and quality of blockade.

Anesthetics, Local↗

Lateral popliteal sciatic nerve block: a single injection targeting the tibial branch of the sciatic nerve is as effective as a double-injection technique.

BACKGROUND: Evidence indicating that single- and double-injection techniques for inducing a sciatic nerve block via a posterior subgluteal approach yield a similar success rate prompted us to investigate whether the two anesthetic techniques yield a similar success rate via a lateral approach. We also hypothesized that, owing to the peculiar anatomic features of the sciatic nerve at the popliteal level, a single injection via the lateral approach might induce effective anesthesia by targeting the tibial nerve only. METHODS: Ninety-six patients undergoing popliteal sciatic nerve block via a lateral popliteal approach for foot surgery were randomized to receive a single 30-ml injection of ropivacaine 7.5 mg/ml to block the tibial nerve (TN group, n= 32) or the common peroneal nerve (CPN group, n= 32), or two separate 15-ml injections (TN + CPN group, n= 32), after stimulation to evoke motor responses from the target nerves. RESULTS: The mean time to obtain a complete sensory blockade (surgical anesthesia) was shorter in the TN group than in the CPN and TN + CPN groups (14 +/- 7 min vs. 23 +/- 17 and 21 +/- 14 min, respectively; P < 0.05). The success rate was similar in the TN and TN + CPN groups (94%) and, 25 min after the initial injection, was already better in these groups than in the CPN group (94% vs. 75%; P < 0.05). CONCLUSIONS: A lateral popliteal sciatic nerve block obtained with a single 30-ml injection of ropivacaine 7.5 mg/ml after electrostimulation to locate the tibial nerve is as effective as multiple TN + CPN stimulation and injection, and local anesthesia has a significantly shorter onset time.

Amides↗

Measurement of motor nerve conduction velocity of the sciatic nerve in patients with piriformis syndrome: a magnetic stimulation study.

OBJECTIVE: To assess the motor nerve conduction of the sciatic nerve by a magnetic stimulation method in patients with piriformis syndrome. DESIGN: Prospective study. SETTING: An electrodiagnostic laboratory in a university hospital. PARTICIPANTS: Twenty-three patients with piriformis syndrome and 15 healthy persons for control. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Motor nerve conduction velocity (MNCV) of the sciatic nerve was measured at the gluteal segment by magnetic stimulation proximally at L5 and S1 roots and distally at sciatic nerve at gluteal fold and recording at the corresponding muscles. Diagnostic sensitivities were measured in the magnetic stimulation method and the conventional nerve conduction, long latency reflex, and needle electromyography studies. RESULTS: The mean MNCV of the sciatic nerve +/- standard deviation at the gluteal segment in L5 component was 55.4+/-7.8 m/s in patients with piriformis syndrome, which was slower than the mean value of 68.1+/-10.3 m/s obtained in healthy controls (P=.014). The MNCV of the sciatic nerve in S1 component showed no significant difference between the patients and controls (P=.062). A negative relation was found between the disease duration and the MNCV values of sciatic nerves in patients with piriformis syndrome (r=-.68, P<.01). The diagnostic sensitivity by magnetic stimulation is .467. CONCLUSIONS: Magnetic nerve stimulation provides a painless, noninvasive, and objective method for evaluation of sciatic nerve function in patients with piriformis syndrome.

Aged↗

Proximal and segmental motor nerve conduction in the sciatic nerve produced by percutaneous high voltage electrical stimulation.

Percutaneous high voltage electrical stimulation was applied to the proximal sciatic nerve at the hip in 18 normal subjects to evaluate motor conduction in the proximal sciatic nerve, and short-segment stimulation of the sciatic and posterior tibial nerves was given in 6 normal subjects. Compound muscle action potentials (CMAPs) were recorded from the abductor hallucis (AH) and extensor digitorum brevis (EDB) muscles. Supramaximal stimulation was easily obtained at the proximal sciatic nerve and all the sites in the short-segment stimulation. The motor nerve conduction velocity of the sciatic nerve between the hip and the popliteal fossa was 49.2 +/- 4.24 m/sec in the tibial division and 54.1 +/- 6.48 m/sec in the peroneal division. The respective peak-to-peak amplitude and negative-peak areas of the CMAPs at the hip were reduced to 86.8 +/- 5.65% and 97.3 +/- 5.36% for the tibial division, and 93.4 +/- 7.06% and 96.8 +/- 5.09% for the peroneal division as compared to the values for the popliteal fossa. The negative-peak duration of the CMAPs at the hip point were increased to 109.2 +/- 7.2% for the tibial nerve and 107.1 +/- 5.68% for the peroneal nerve as compared with the duration at the popliteal fossa. This method is non-invasive and useful for evaluating motor nerve conduction in the lower limb.

Adult↗

Effect of crush lesion on ganglioside radiolabelling patterns in rat sciatic nerve.

Left sciatic nerves in rats were crushed and allowed to regenerate for variable periods of time up to 14 days; uncrushed right nerves from the same animals were used as controls. Two days before killing the rats, both L-5 dorsal root ganglia (DRG) were injected with 100 microcuries [3H]glucosamine. Gangliosides were purified separately from sciatic nerve (SN) distal to the crush site, lumbosacral trunk (LST) proximal to the crush site, and the injected DRG. Changes in major glycoconjugate classes were previously reported; in this study total gangliosides were separated by high performance thin layer chromatography, located by autofluorography and radioactivity was measured by liquid scintillography. In control DRG, major radiolabelled gangliosides were GM3 and LM1; in control LST and SN, GD1b and GT1b were the major ones. During day two and four following crush, GM3 and LM1 decreased in DRG, but at one and two weeks were at normal and elevated levels, respectively; there were inverse changes in GD3, GT1b and GQ1b. GD1b, GT1b and GQ1b were lower in crushed than in control LST and SN between days zero and four. In LST, GM3 and LM1 remained constant for four days, but were elevated at one and two weeks, whereas GD1a was elevated at all times. Indeed, GD1a is the major recently synthesized ganglioside that is transported into LST and SN two to four days after trauma, suggesting that it may play an important role in regeneration. Indices of oligosaccharide complexity and degree of sialylation indicated that between two and four days following crush, gangliosides in DRG had more complex oligosaccharides and more sialic acid residues than in either controls or in DRG of crushed nerves at one and two weeks post-crush. The degrees of ganglioside sialylation and oligosaccharide complexity in crushed LST and SN were lower than in control specimens between one and seven days after crush. Changes in the ganglioside composition of peripheral nerve following trauma may be important for axonal regeneration.

Animals↗

Computed tomography of the sacral plexus and sciatic nerve in the greater sciatic foramen.

The sacral plexus forms the sciatic nerve, which leaves the pelvis through the greater sciatic foramen. The anatomic boundaries of the greater sciatic foramen and the relation of the sacral plexus and sciatic nerve to the structures within are identified and described on axial computed tomography (CT). The piriform muscle, which passes through the center of the greater sciatic foramen, is a recognizable landmark that is extremely helpful in locating the sacral plexus and sciatic nerve on CT. The pelvic CT images of 25 patients studied for unrelated reasons and two patients studied for complaints related to the greater sciatic foramen were reviewed. CT was very useful in demonstrating the anatomy of this region and for the investigation of sciatic pain due to lesions outside the neural canal.

Humans↗