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Expression of the pro-opiomelanocortin gene in dorsal root ganglia, spinal cord and sciatic nerve after sciatic nerve crush in the rat.

Neuropeptides related to alpha-melanocyte-stimulating hormone (alpha-MSH) stimulate nerve outgrowth following peripheral nerve injury and may play an important physiological role in peripheral nerve regeneration. The mechanism of action underlying the neurotrophic effect of pharmacologically administered alpha-MSH is unknown. Here we investigate the hypothesis that reexpression of the proopiomelanocortin (POMC) gene, the prohormone of alpha-MSH/adrenocorticotropic hormone (ACTH)-like peptides, is part of the endogenous repertoire of peripheral nerve responses following injury. The effect of sciatic nerve crush on the expression of POMC mRNA between 0.5 h and 14 days after crush was investigated using polymerase chain reaction (PCR) and Northern blot analysis. The presence of a POMC transcript in dorsal root ganglia (DRG), spinal cord and in the sciatic nerve at the crush site could be demonstrated in both control and lesioned animals by PCR using primers located in exon 1 and 3 of the POMC gene. Minute quantities of two POMC transcripts (1200 nt and 800 nt) could be detected by Northern blot analysis of total RNA prepared from DRG, spinal cord and the sciatic nerve of control animals and of animals subjected to nerve crush. POMC mRNA expression was, however, not increased following nerve crush. Probes specific for exons 1 and 2 or specific for exon 3 of the POMC gene were employed to demonstrate that the 800 nt transcript represents the truncated POMC mRNA previously shown to be present in extra-pituitary tissue. The larger 1200 nt transcript comigrates with the full length POMC mRNA expressed in the pituitary gland. The present results demonstrate the expression of small amounts of POMC mRNA in all compartments of the sciatic nerve. The absence of an induction of POMC expression in response to nerve crush suggests that the stimulating effect of exogenously applied alpha-MSH does not mimic a POMC derived neurotrophic peptide induced in the nerve following nerve injury.

Animals↗

[Block of the sciatic nerve].

Sciatic nerve blocks were seldom used until recently. They apply to most surgical procedures on the lower limb and are often combined with a "3 in 1" block. However they can be used alone for foot surgery or postoperative analgesia. Nerve stimulators make their realization easier and more reliable. Sciatic nerve block can be obtained by different techniques. The choice of which being helped by some guidelines according to the patients characteristics and the surgical site.

Anesthetics, Local↗

Effect of nerve growth factor on changes of myelin basic protein and functional repair of peripheral nerve following sciatic nerve injury in rats.

OBJECTIVE: To investigate the therapeutic effect of nerve growth factor (NGF) on changes of myelin basic protein (MBP) and functional repair of sensory and motor nerve following sciatic nerve injury. METHODS: The sciatic nerves of rats were injured by sectioning with shaver,and divided into 3 groups: NGF group (Group A), group of normal saline solution (Group B), untreated group (Group C). The time point of observation was at the 4th week after operation. Sensory evoked potential (SEP) and motor evoked potential (MEP) were detected by Model WD-4000 nerve potential working diagnosis system. Immunohistochemical analysis was used for identification of MBP. RESULTS: The latency of SEP in the Group A at the 4th week after operation was shorter than that in the Group B (P<0.05). The MEP was elicited in 76% of the Group A and was higher than that in the Group B. Results of immunohistochemistry showed that there were less MBP-positive cells in the Group A than in the Group B in one and four weeks respectively. CONCLUSIONS: NGF can improve the conductive function of injured peripheral nerve and facilitate regeneration of nerve.

Animals↗

Low volume, high concentration block of the sciatic nerve.

Sciatic nerve block was performed in two groups of patients using a low power peripheral nerve stimulator to aid nerve location. In group A 1% prilocaine with felypressin was used as the local anaesthetic agent in a volume of 0.25 ml/kg body weight. In group B 3% prilocaine with felypressin was used in a volume of 0.08 ml/kg body weight (i.e. equal total drug dosages). Use of the 3% solution resulted in highly significant reductions in the mean latency for analgesia of the nerve block and in the latency and degree of motor block achieved (p less than 0.005 in each case). The clinical value of high concentration, low volume nerve block is discussed.

Blood Pressure↗

Relative importance of basement membrane and soluble growth factors in delayed and immediate regeneration of rat sciatic nerve.

Sciatic nerve regeneration was studied in two groups of rats. In group I, nerves were transected and transplanted immediately to the contralateral side. In group II, nerves were transected and transplanted 30 days later to the contralateral side. At 4 weeks, group II had an average nerve action potential amplitude of 784 +/- 292 microV and 43.2% +/- 6.7% of myelinated fibers were > 4 microns in diameter. In comparison, the respective measurements were 94 +/- 35.6 microV (p = 0.05) and 29.5% +/- 1.9% (p = 0.04) in group I. At 8 weeks, there were no significant differences in these measurements between groups. These data suggest that the environment in the distal stump improves early regeneration of nerve fibers when that stump was transected 30 days earlier. These and previous findings suggest that soluble trophic factors may be important in initiation of axonal regeneration.

Animals↗

Hospitalization and discharge outcome of trauma patients sustaining sciatic nerve or sciatic branch injuries.

This study determined the number and severity of injuries, surgeries, and/or other complications and their impact on the acute hospital course of a series of 15 patients sustaining unilateral traumatic sciatic nerve or sciatic branch injuries. Outcome measures studied were length of stay, time to ambulate independently from admission, starting time for physical therapy, and number of physical therapy sessions. Median length of stay (LOS) and time to independent ambulation with assistive devices from admission were 12 and 8 days, respectively. Seven patients required fasciotomy, five required vascular repair, and five sustained fractures of the involved limb. Patients needing a fasciotomy had a significantly longer LOS (P < 0.002) and time to ambulate independently (P < 0.001), started physical therapy later (P < 0.006), and required more therapy sessions (P < 0.007) before independent ambulation was achieved. Patients with a vascular repair had a significantly longer LOS (P < 0.049) and time to ambulate independently (P < 0.012). These patients trended toward starting physical therapy later (P < 0.063) and requiring more therapy sessions (P < 0.109) before independent ambulation was achieved. The presence of a fracture in the involved limb did not affect outcome variables. The level and severity of nerve injuries were variable; therefore, their effects on LOS and ambulation could not be determined. These findings suggest that fasciotomies and vascular repairs but not fractures adversely affect the acute LOS, time to ambulate independently, start of physical therapy, and number of physical therapy sessions in trauma patients with sciatic nerve or sciatic branch injury. This information may be useful to the consulting physiatrist.

Accidents, Traffic↗

The internal structure of axons from rat sciatic nerve.

Sciatic nerves from rats were examined electron microscopically following fixation in 4% tannic acid in 2.5% glutaraldehyde, which allowed demonstration of a filamentous network between the usual intra-axonal organelles. The network appears to consist of longitudinal 10 nm in diameter filaments and cross-linking filaments of about 6 nm diameter. Exposure to cold caused disruption of microtubules, but not the filaments, and incubation at 37 degrees C following cold exposure resulted in reformation of the microtubules which again showed linking with the filaments. Exposure of the nerves to cold in the presence of D2O did not cause disruption of the microtubules but there did appear to be some loss of the fine filaments. These findings suggest that the finer cross-linking filaments are of a different nature than the longitudinal 10 nm filaments, and that there is a dynamic relationship between these filaments and microtubules since the cross-linkages reappear following microtubule disruption and reformation.

Animals↗

Regulation of opioid binding sites in the superficial dorsal horn of the rat spinal cord following loose ligation of the sciatic nerve: comparison with sciatic nerve section and lumbar dorsal rhizotomy.

The aim of the present study was to quantify time-related modifications in mu and delta opioid binding sites in the superficial layers (laminae I and II) of the L4 lumbar segment in a rat model of mononeuropathy induced by loose ligation of the sciatic nerve. We have shown a 28% (P < 0.01) and 24% (P < 0.01) decrease in ipsi/contralateral side binding ratios for tritiated (Tyr*-D-Ala-Gly-NMe-Phe-Gly-ol) ([3H]DAMGO) and tritiated (Tyr*-D-Thr-Gly-Phe-Leu-Thr) ([3H]DTLET) respectively, at two weeks postlesion which correspond to the delay of maximal hyperalgesia and of maximal alteration of fine diameter primary afferent fibers. In contrast, no change in [3H]U.69593 specific binding could be detected at this postlesion delay. For longer survival delays (four, eight and 15 weeks postlesion), mu and delta binding ratios return towards control values (approximately equal to 1), probably reflecting the occurrence of a long-term neuroplasticity (i.e. a new equilibrium in the metabolism of primary neurons, or collateral sprouting from intact primary afferents) following loose nerve ligation. In addition, a comparison of the results obtained in this model with those measured after sciatic nerve section and lumbar dorsal rhizotomy was performed in order to compare the degree of loss in opioid binding sites in these three types of lesion. The section of the sciatic nerve induced at eight days postlesion an 18% (P < 0.01) and 28% (P < 0.01) decrease in binding ratio for [3H]DAMGO and [3H]DTLET, respectively. At two weeks postlesion the loss was 24% (P < 0.01) for the two ligands, and at longer delays (four and 12 weeks), a progressive recovery in binding ratio was observed. Thus, it appears that both sciatic nerve lesions we have studied result in mu and delta binding modifications which have similar intensity and similar time course from two to 12-15 weeks postlesion. In contrast, the unilateral rhizotomy of nine consecutive dorsal roots (T13-S2), which is known to induce a massive degeneration of fine diameter primary afferent fibers, is followed by a dramatic decrease in binding ratios for [3H]DAMGO (53%, P < 0.001) and [3H]DTLET (45%, P < 0.001) at two weeks postlesion. These data suggest that the more deprived the dorsal horn is of fine diameter primary afferent fibers, the more dramatic is the opioid binding loss in the ipsilateral side as compared to the contralateral side.(ABSTRACT TRUNCATED AT 400 WORDS)

Analgesics↗

Differential effects of intravitreal optic nerve and sciatic nerve grafts on the survival of retinal ganglion cells and the regeneration of their axons.

We have investigated the effects of intravitreal sciatic nerve (SN) and/or optic nerve (ON) grafts on the survival and the axonal regeneration of retinal ganglion cells (RGCs). Following transection of the ON, approximately 40% RGCs survived at 7 days post-axotomy (dpa). Results showed that the intravitreal ON graft significantly promoted the survival of RGCs at 7 dpa (39,063 vs 28,246). Intravitreal SN graft, however, did not rescue axotomized RGCs at 5, 7 or 14 dpa. Axotomized RGCs could be induced to regenerate axons along a segment of SN graft attached to the proximal stump of ON. On average, 608 axotomized RGCs were induced to regenerate axons along the attached SN graft. The presence of intravitreal SN graft promoted about 100% increase in the number of regenerating RGCs (1,227) relative to the control groups. The intravitreal ON graft, surprisingly, also induced about 100% more regenerating RGCs (1220) than in the control group. When SN and ON grafts were co-transplanted into the vitreous, about 200% more regenerating RGCs (1916) were observed than in the control group. These findings illustrated that the intravitreal ON graft rescued axotomized RGCs and enhanced the regeneration of retinal axons. This is the first report to show that ON promotes RGC axonal regeneration. The intravitreal SN graft did not rescue RGCs but promoted axonal regeneration. The differential effects of intravitreal ON and SN grafts on the survival and the RGC regeneration suggest that these might be two independently operating events.

Animals↗

Sciatic nerve palsy following uneventful sciatic nerve block.

We describe the loss of function in the sciatic nerve after an uneventful sciatic nerve block using 25 ml of lignocaine 1% with adrenaline 1 in 200,000 in a patient receiving beta blocker drugs. Lack of pain on injection and complete regeneration of the nerve after 12 months in a patient with severe peripheral vascular disease led us to postulate ischaemic nerve damage as a mechanism of injury. Adrenaline-induced unopposed alpha-mediated vasoconstriction in a beta-blocked patient is suggested as a possible mechanism of peripheral nerve injury worthy of further investigation.

Female↗

[Effect of subcutaneous implant of peripheral nerve allograft on sciatic nerve regeneration in rats].

OBJECTIVE: To study the effect of subcutaneous implant of peripheral nerve allograft on sciatic nerve regeneration in rats. METHODS: Out of 30 male Wistar rats, 6 were donors and 24 were divided randomly into 2 groups. In experimental group (group A, n = 12), a 15 mm segment of sciatic nerve harvested from donors was separately inserted into subcutaneous compartment on the right thigh; two weeks later, the segment of sciatic nerve in subcutaneous compartment was removed and transplanted into a 10 mm sciatic nerve defect of left, which was made immediately. In the control group (group B, n = 12), a 10 mm sciatic nerve defect was made and immediately repaired in situ on the left thigh. The regeneration of sciatic nerve was examined histologically (after 2, 4, 8, and 14 weeks) and electrophysiologically (after 14 weeks of operation). RESULTS: After 2 weeks of operation, the inflammatory reaction was a little stronger in group A than in group B. After 4 weeks, the intensity of the inflammatory reaction was similar between two groups; some collagen fibers proliferated. After 8 weeks, the inflammatory reaction ended and the collagen fibers proliferated obviously. After 14 weeks of operation, the structure of epineurium was in integrity and there was no obvious difference in perineurium and endonurium between two groups. A large number of myelinated nerve fibers and a small number of unmyelinated nerve fibers regenerated. The structure of myelin sheath was in integrity. The number and size of regenerated axon had no significant difference between two groups(P > 0.05). The conduction velocity, the peak value and the latent period of motor nerve were no significant difference between two groups (P > 0.05). CONCLUSION: The allograft of sciatic nerve inserted into subcutaneous compartment can promote nerve regeneration.

Animals↗

Sciatic nerve block for children. Sciatic nerve block by the anterior approach for postoperative pain relief.

This study aimed to establish whether it was practical to perform sciatic nerve block by the anterior approach in a group of children of different ages and weights. A total of 82 blocks were performed of which 78 (95.2%) were judged to have been successful. The technique of the block differed slightly from that used in adult practice, in that great reliance was placed on the loss of resistance felt as the needle point passed through the thigh muscles into the sciatic neurovascular compartment. There were no immediate or late complications associated with this block in any of the patients. It is concluded that the block is easy to perform and can produce reliable postoperative analgesia for most common operations on the foot and ankle in paediatric practice.

Acetaminophen↗

The anatomic relationship of the sciatic nerve to the lesser trochanter: implications for anterior sciatic nerve block.

UNLABELLED: Classic descriptions of the anterior sciatic nerve block suggest needle placement at the level of the lesser trochanter of the femur. Recently, investigators have reported that the sciatic nerve is not accessible at this level. To define more accurately the anatomic relationship of the sciatic nerve to the lesser trochanter, we analyzed magnetic resonance scans performed on 20 patients in the supine position. After IRB approval, magnetic resonance scans of the hip and proximal femur were reviewed in 20 supine patients in the neutral position. Images from five axial levels were studied, specifically, at the level of the lesser trochanter and at 1-cm intervals inferior to the lesser trochanter for 4 cm. In each axial image, the medial or lateral distance was measured from the sciatic nerve to a sagittal plane at the medial border of the femur. If the sciatic nerve was lateral to this sagittal plane (inaccessible), the distance was assigned a negative value, and if the sciatic nerve was medial to the sagittal plane (accessible), the distance was assigned a positive value. The distance between the coronal plane at the anterior border of the femur and the coronal plane through the sciatic nerve was also recorded for each level. At the level of the lesser trochanter, the sciatic nerve was lateral to the femoral border (inaccessible) in 13 of 20 patients with a mean distance of -4.0 +/- 7.7 mm. At 4 cm below the lesser trochanter, the sciatic nerve was medial to the femoral border (accessible) in 19 of 20 patients with a mean distance 7.8 +/- 5.8 mm. The distance from the anterior border of the femur to the sciatic nerve was 42.9 +/- 5.8 mm at the level of the lesser trochanter and 45.7 +/- 9.5 mm at 4 cm below the lesser trochanter. The classic description of the anterior approach to the sciatic nerve suggests that the needle be walked off medially at the level of the lesser trochanter. Our data are consistent with recent reports suggesting that in the majority of subjects, the position of the sciatic nerve relative to lesser trochanter made it inaccessible from an anterior approach at this level. In contrast, at 4 cm below the lesser trochanter, the sciatic nerve was medial to the femur in 19 of 20 subjects. We conclude that needle insertion medial to the proximal femur, 4 cm below the lesser trochanter, is a more direct anatomical approach to the anterior sciatic nerve block. IMPLICATIONS: Magnetic resonance images suggest that in the majority of supine subjects, the sciatic nerve is lateral to the lesser trochanter of the femur and therefore not accessible using the classic anterior approach. By contrast, 4 cm below the lesser trochanter, the sciatic nerve is consistently medial to the femoral shaft and therefore may be more accessible using an anterior approach.

Adult↗

Presence and regulation of transforming growth factor beta mRNA and protein in the normal and lesioned rat sciatic nerve.

The transforming growth factors beta (TGF-beta), a family of regulatory polypeptides, are involved in numerous vital processes including inflammation and wound healing. Since repair of a peripheral nerve lesion includes a series of well-defined steps of cellular actions possibly controlled by TGF-beta s, and since TGF-beta mRNA and immunoreactivity have been found in the normal peripheral nerve, we have examined in the lesioned peripheral nerve. Sciatic nerves of adult rats were either crushed (allowing axonal regeneration) or transfected (to prevent axonal regeneration and to induce Wallerian degeneration in the distal stump). After intervals of 6 hours, 2 and 6 days post-lesion, the rats were sacrificed and each nerve was cut into four segments, two proximal and two distal to the lesion site. TGF-beta 1-3 mRNA were determined for each segment. We demonstrate that TGF-beta 1 mRNA levels are higher than those of TGF-beta 3; the amplitude of mRNA regulation depends on time, type of lesion and localization relative to the lesion site. TGF-beta 2 mRNA could not be detected. For TGF-beta 1-3 immunocytochemistry, animals were sacrificed 12, 24, 48, 72 hours and 7 and 14 days after surgery. TGF-beta immunoreactivity (IR) was observed for all isoforms in lesioned and unlesioned nerves. In the segment directly adjacent to the lesion at its proximal side, an increase of TGF-beta-IR became apparent as soon as 12 hours after surgery; it remained elevated during the whole period observed in both models. In the segment adjoining the distal side of the lesion, an increase of TGF-beta-IR was observed after 48 hours, which was still present after 14 days. At day 7 after crush or transection, an increase of TGF-beta-IR was detected in the most distal segments, which reached its highest levels at the end of our observation period. Our results suggest that the presence of axonal contact might induce an enhancement of TGF-beta expression by Schwann cells in the distal stump of a lesioned and regenerating peripheral nerve. Since we demonstrate an increase of TGF-beta mRNA and protein expression also in the distal stump of transected nerves where Schwann cells are not able to contact sprouting axons from the proximal part, other regulatory pathways must exist. The acquisition of a "reactive" Schwann cell phenotype after peripheral nerve lesion might involve an upregulation of TGF-beta expression.

Animals↗

Numbers of regenerated axons in tributary nerves following neonatal sciatic nerve crush in rat.

We determined numbers of regenerated axons in 5 tributary nerves 8 weeks after the complete axonal loss that follows crush of newborn rat sciatic nerve. The major findings are: (1) that proportionately many more axons are lost in cutaneous than in muscle nerves, (2) that myelinated axons are greatly increased over normal in two of the muscle nerves, and (3) that unmyelinated axons are normal or close to normal in muscle nerves. The major conclusions are: (1) there is a different pattern of regeneration in cutaneous as compared to muscle nerves after neonatal sciatic nerve crush, and (2) the responses after neonatal crushes are different than after adult nerve crushes.

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↗