Distal Stump Research Articles

Potential utility of aldose reductase-deficient Schwann cells IKARS1 for the study of axonal degeneration and regeneration.

Potential utility of aldose reductase-deficient Schwann cells IKARS1 for the study of axonal degeneration and regeneration.

Robotic Appendiceal Interposition With Right Lower Pole Calycostomy, Downward Nephropexy, and Psoas Hitch for the Management of an Iatrogenic Near-complete Ureteral Avulsion

Although iatrogenic ureteral injuries are rare, they have potentially devastating consequences for both patients and physicians, and their management remains challenging. We report a case of a 51-year-old morbidly obese (body mass index = 63) woman who suffered an iatrogenic 15-cm right ureteral avulsion during hysteroscopic biopsy. Preoperative antegrade and retrograde pyelograms demonstrated no true renal pelvis and a 3-cm blind-ending distal ureteral stump. The patient underwent a right robotic downward nephropexy, psoas hitch, lower pole calycostomy, and 11-cm appendiceal interposition. At 6 months postoperatively, renal scan demonstrated stable right renal function with no evidence of obstruction.

Morphofunctional evaluation of end-to-side neurorrhaphy through video system magnification

BackgroundThe surgical microscope is an essential tool for microsurgery. Nonetheless, several promising alternatives are being developed, including endoscopes and laparoscopes with video systems. However, these alternatives have only been used for arterial anastomoses so far. The aim of this study was to evaluate the use of a low-cost video-assisted magnification system in end-to-side neurorrhaphy in rats. Materials and methodsForty rats were randomly divided into four matched groups: (1) normality (sciatic nerve was exposed but was kept intact); (2) denervation (fibular nerve was sectioned, and the proximal and distal stumps were sutured—transection without repair); (3) microscope; and (4) video system (fibular nerve was sectioned; the proximal stump was buried inside the adjacent musculature, and the distal stump was sutured to the tibial nerve). Microsurgical procedures were performed with guidance from a microscope or video system. We analyzed weight, nerve caliber, number of stitches, times required to perform the neurorrhaphy, muscle mass, peroneal functional indices, latency and amplitude, and numbers of axons. ResultsThere were no significant differences in weight, nerve caliber, number of stitches, muscle mass, peroneal functional indices, or latency between microscope and video system groups. Neurorrhaphy took longer using the video system (P < 0.05). The amplitude was higher in the microscope group than in the video group. ConclusionsIt is possible to perform an end-to-side neurorrhaphy in rats through video system magnification. The success rate is satisfactory and comparable with that of procedures performed under surgical microscopes.

α6 and β1 Integrin Heterodimer Mediates Schwann Cell Interactions with Axons and Facilitates Axonal Regeneration after Peripheral Nerve Injury

Several isoforms of integrin subunits are expressed in Schwann cells and mediate Schwann cell interactions with axons. Here, we identify α6 and β1 integrins as heterodimeric proteins expressed in Schwann cells and define their functions in axonal regeneration. α6 and β1 integrins are induced in Schwann cells in the sciatic nerve after a crush injury, and the blocking of integrin activity by siRNA expression and by treatment with anti-integrin antibodies attenuates Schwann cell contact with cultured neurons and decreases neurite outgrowth. After nerve transection, the levels of α6 and β1 integrins in the distal nerve stump are lower than those in the corresponding nerve area after a crush injury. Schwann cells prepared from the distal nerves 7 days after transection are less supportive of neurite outgrowth in co-cultured neurons than those prepared from the nerves 7 days after a crush injury. When the transected nerves are reconnected after a delay of 1 to 2 weeks, the induced levels of α6 and β1 integrins in the reconnected distal nerves are significantly reduced compared to those in the nerves after a crush injury. These changes correlate with retarded axonal regeneration in animals that have experienced nerve transections and delayed coaptation, which implies an attenuated Schwann cell capacity to support axonal regeneration due to delayed Schwann cell contact with axons. The present data suggest that α6 and β1 integrins induced in Schwann cells after nerve injury may play a role in mediating Schwann cell interactions with axons and promote axonal regeneration.

Produit d’ingénierie tissulaire comme chambre de régénération nerveuse – vaisseau ombilical traité, déshydraté et stérile

Umbilical vein and arteries are located in the umbilical cord and surrounded by a dense extracellular matrix named Wharton's jelly. Due to their origin, these tissues are highly available. Nerve lesions or sections are common pathologies + healing can be accelerated by the use of a chamber sleeved or wrapped around the nerve. The goal is to develop from umbilical vessels a biologic conduit, secured and dehydrated to be used as nerve regeneration chamber. The umbilical cord is sampled according to directive 2006 17 CE (clinical and biological donor criteria). The vessels are extracted and inverted to expose to have an internal dense Wharton's jelly that takes part in the tissue holding. The vessels are treated with a disinfectant and virally inactivating chemical process. They are freeze-dried and finally gamma sterilized. Viral and microbiological security of the process are evaluated by spiking 10exp6 viruses strain in the Wharton's jelly and determining their destruction after process application. Biocompatibility tests are carried out according to ISO 10993 standard. Viability and attachment of mesenchymal stem cells (MSC) are conducted. Structural properties of the vessels are determined by staining the main proteins and components. Its physical characteristics are evaluated through its tensile mechanical resistance. In vivo implantation of the product on 1 cm sciatic nerve gap in a rat model evaluates its efficacy as a nerve regeneration chamber. The chemical treatment applied reduces the viral load of enveloped and non-enveloped viruses by more than 4 logs. No strain is recovered after the gamma sterilization. The product meets ISO 10993 requirements. MSC are viable and attached all along the product surface. The process applied enables the preservation of the product structure and the maintenance of the main components, collagen IV, elastin, laminin I and hyaluronic acid. The tensile mechanical resistance of the product is 100 kPa. The in vivo study shows effective nerve regeneration after 8 weeks with presence of early myelinated mature axons from the proximal to the distal stumps and a complete integration of the well-tolerated product. The process applied on the umbilical vessels is secured. The final product presents a physiologic structural integrity and an excellent biocompatibility. The tissue engineering product from inverted umbilical vessels is secured and dehydrated. Due to its physical and biological properties, it is an innovative alternative as nerve regeneration chamber, available in different sizes.

Reconstruction of bladder function and prevention of renal deterioration by means of end-to-side neurorrhaphy in rats with neurogenic bladder.

To investigate the feasibility of restoring bladder function and prevention of renal deterioration by neurorrhaphy in rats with neurogenic bladder (NB). Forty-two rats were assigned to the end-to-side nerve coaptation group (ECG, n = 16), no nerve coaptation group (NCG, n = 16), and control group (CG, n = 10). In the ECG, the left ventral root (VR) and dorsal root (DR) of L6 and S1 were transected, and the distal stump of L6VR was sutured to the lateral face of L4VR. In the NCG, the left VR and DR of L6 and S1 were transected, but coaptation was not performed. In the CG, no operation was performed. Nerve regeneration, bladder function, and renal function were evaluated by FluoroGold (FG) retrograde tract tracing, cystometry, electrical stimulation, MRI, histology and biochemical assays. In the ECG, FG-labeled neurons were observed in the left ventral horn of L4 spinal cord. There was a significant increase in intravesical pressure upon stimulation of the left L4VR proximal to the coaptation. Maximum cystometric capacity, post-void residual urine, bladder compliance and weight, serum creatinine, blood urea nitrogen, and fibrotic area of bladder and kidney were lower in the ECG than in the NCG, but higher than the CG. Hydronephrosis was noticed in ECG and NCG rats. Maximum detrusor voiding pressure was higher in the ECG and CG than in the NCG. End-to-side neurorrhaphy is a useful method for restoring bladder function and preventing renal injury in rats with NB.

The anatomy and clinical applications of flexor hallucis longus tendon transfer in treatment of chronic Achilles tendinopathy

Objective To evaluate the effectiveness of flexor hallucis longus tendon transfer in treatment of chronic Achilles tendinopathy using different technique. Methods Sixty-four embalmed feet of 32 cadavers were analyzed and classified anatomically with respect to the individual cross links in the Henry's knot. These three techniques were then combined to determine the total potential tendon graft length obtainable using single incision, double incision and minimally invasive incision. From January, 2012 to June, 2015, 10 patients (10 feet) with chronic Achilles tendinopathy were treated with double incision technique. The score was 63.04 ±7.75 according to American Orthopedic Foot and Ankle Society (AOFAS) ankle and hindfoot score system. Results Only two different configurations were found. Type 1, a tendinous slip branched from the FHLT to the FDLT was 96.9% (62 of 64 feet) . Type 2, a slip branched from the FHLT to the FDLT and another slip from the FDLT to FHLT was 3.1% (2 of 64) . The average length of the FHLT graft available from a single incision measured (5.08±1.09) cm, double incision technique measured (6.72 ± 1.02) cm, and minimally invasive incision measured (17.49 ± 1.80) cm. The difference between the lengths obtained from these three techniques was statistically significant. Ten patients were followed-up 12-36 months (mean, 13.7 months) . At 12 months after operation, the AOFAS ankle and hindfoot score was 93.28 ± 3.72, showing significant difference when compared with that before operation. The results were excellent in 6 cases, good in 3 cases, and fair in 1 case with an excellent and good rate of 90%. No sural nerve injury, posterior tibial nerve injury, medial plantar nerve injury, and lateral plantar nerve injury occurred. Conclusion In over 96% of the feet, a proximal to distal connection from the FHLT to the FDLT was found, which might contribute to the residual function of the lesser toes after FDLT transfer. The distal stump of the FHLT tendon should be sutured onto the FDLT tendon under tension to enable a co-activation of the great toe, preserved hallux plantar flexion. Chronic Achilles tendinopathy reconstruction with flexor hallucis longus tendon harvested using double incision technique offers a desirable outcome in operative recovery, tendon fixation, preserved hallux plantar flexion and less complications. Key words: Flexor hallucis longus; Flexor digitorum longus; Achilles tendon disorders; Tendon transfer

Lysophosphatidic acid propagates post-injury Schwann cell dedifferentiation through LPA1 signaling.

Lysophosphatidic acid (LPA) is a pleiotropic signaling lipid that acts as ligand for at least six specific G-protein coupled receptors. Schwann cells (SC) are known to mainly express the LPA1 receptor subtype. An emerging body of evidence has linked LPA with injury-induced peripheral nerve demyelination as well as neuropathic pain. However, the molecular mechanisms underlying its demyelinating effect have not been conclusively elucidated. We aimed to decipher the demyelinating effect in vitro as well as in vivo by studying markers of SC differentiation and dedifferentiation: Myelinated dorsal root ganglia (DRG) cultures were treated either with LPA, LPA plus AM095 (LPA1 antagonist) or vehicle. Myelin content was subsequently investigated by Sudan Black staining and immunocytochemistry. In vivo, we performed sciatic nerve crush in C57BL/6 mice treated with AM095 at 10mg/kg. In DRG cultures, LPA caused a significant reduction of myelin as demonstrated by both Sudan Black staining and immunocytochemical analysis of myelin basic protein. Demyelination was paralleled by an upregulation of TNF-alpha as well as downregulation of Sox10, a marker for SC differentiation. LPA mediated effects were largely blocked by the addition of the LPA1 receptor antagonist AM095. In the in vivo model, AM095 treatment prior to crush injury increased Sox10 expression in SCs in the distal nerve stump while reducing the number of cells expressing the SC dedifferentiation marker Sox2. Additionally, TNF-alpha immunofluorescence was reduced in CD11b-positive cells. These data indicate that LPA may be a critical factor that shifts SCs towards a post-injury phenotype and contributes to the onset of Wallerian degeneration.

Retroperitoneal and laparoscopic heminephrectomy in duplex kidney in infants and children.

Two main techniques are adopted to perform partial nephrectomy in children: laparoscopy and retroperitoneoscopy. The aim of this paper is to review the larger multicentric experience recently published by our group to review indications, techniques and results of both approaches. Data of 102 patients underwent partial nephrectomy in a 5-year period using minimally invasive surgery (MIS) procedures were analyzed. Fifty-two children underwent laparoscopic partial nephrectomy (LPN), and 50 children underwent retroperitoneoscopic partial nephrectomy (RPN). Median age at surgery was 4.2 years. Statistical analysis was performed using χ2 test and Student's t-test. The overall complications rate was significantly higher after RPN (15/50, 30%) than after LPN (10/52, 19%) (χ2 =0.05). In LPN group, complications [4 urinomas, 2 symptomatic refluxing distal ureteral stump (RDUS) and 4 urinary leakages] were conservatively managed. In RPN group, complications (6 urinomas, 8 RDUS, 1 opening of remaining calyxes) required a re-operation in 2 patients. In both groups no conversion to open surgery was reported. Operative time (LPN: 166.2 min vs. RPN: 255 min; P<0.001) and hospitalization (LPN: 3.5 days vs. RPN: 4.1 days; P<0.001) were significantly shorter in LPN group. No postoperative loss of renal function was reported in both groups. MIS now represents the gold standard technique to perform partial nephrectomy in children with duplex kidney. Our results demonstrate that RPN remains a technically demanding procedure with a significantly higher complications and re-operation rate compared to LPN. In addition, length of surgery and hospitalization were significantly shorter after LPN compared to RPN. LPN seems to be a faster, safer and technically easier procedure to perform in children compared to RPN due to a larger operative space and the possibility to perform a complete ureterectomy in refluxing systems.

Effects of FK1706 on nerve regeneration and bladder recovery after spinal cord injury

Objective To investigate the effects of FK1706 on nerve regeneration and bladder function recovery after spinal cord injury in rats. Methods Thirty adult male SD rats weighing 230-250 g were randomly divided into three groups for different treatments: FK1706 group, neurorrhaphy group and control group (10 rats each group). In FK1706 group, the spinal cords were transected in the level of L5 to make rat spinal injury model. Then the distal stump of L6VR was sutured to the lateral face of L4 ventral root (L4VR) in an end-to-side (ETS) fashion under microscope. FK1706 (0.3 mg/kg) was administrated subcutaneously for 5 consecutive days per week for a total of 8 weeks after neurorrhaphy. In neurorrhaphy group, the same operation as FK1706 group was performed but without FK1706 applied after surgery. In control group, left ventral and dorsal roots of L5, L6, S1 and S2 were transected but the left L6VR was preserved as normal control. After four months, FG and FB were injected into left major pelvic ganglion (MPG) and sciatic nerve (SN), respectively, for retrograde nerve tracing to ascertain whether neural pathway was established after surgery. The left L6VR distal to coaptation was harvested for semi-thin sectioning and toluidine blue staining to count the number of myelinated axons. Urodynamic parameters such as maximum detrusor pressure (MDP) and residual urine volume (RUV) were measured in rats through BL-420 biological experimental system. Results The neural pathways were successfully established between left L4VR and L6VR in FK1706 group and neurorrhaphy group through retrograde nerve tracing. The number of regenerated myelinated axons of left L6VR distal to coaptation in FK1706 group and neurorrhaphy group was 535.7±45.2 and 337.4±56.5, respectively, which had a significant difference (P=0.000). The MDP and RUV were (44.6±6.7) mmHg (1 mmHg=0.133 kPa) and (1.16±0.24) ml in FK1706 group, respectively, when the left L4VR proximal to coaptation was stimulated by BL-420 experimental system. The MDP and RUV were (32.5±5.4) mmHg and (2.36±0.34) ml in neurorrhaphy group, respectively. There were statistically significant differences in the MDP and RUV between the two groups (P=0.000). Conclusion The effects of nerve regeneration and bladder function recovery could be evidently enhanced by FK1706 after neurorrhaphy in rat spinal cord injury model. Key words: FK1706; Spinal cord injury; Nerve regeneration; Functional recovery

Arthroscopic Posterior Cruciate Ligament Reconstruction With Remnant Preservation Using a Posterior Trans-septal Portal

We describe a surgical technique for arthroscopic posterior cruciate ligament (PCL) reconstruction with remnant preservation of the original PCL fibers using a posterior trans-septal portal approach. Using the transtibial technique and the posterior trans-septal portal approach allows good visualization of the tibial tunnel preparation, easy access to the tibial tunnel without neurovascular injury, and preservation of remnant PCL fibers. In the preparation of the tibial tunnel, we expose the PCL tibial attachment site completely, detach the posterior capsule from the PCL, and preserve the distal stump of the PCL without neurovascular injury. PCL reconstruction is performed in a way that preserves the remnant PCL fibers. We report on our surgical technique for arthroscopic PCL reconstruction preserving the original PCL fibers.

Short and long gap peripheral nerve repair with magnesium metal filaments

A current clinical challenge is to replace autografts for repair of injury gaps in peripheral nerves, which can occur due to trauma or surgical interruption. Biodegradable metallic magnesium filaments, placed inside hollow nerve conduits, could support nerve repair by providing contact guidance support for axonal regeneration. This was tested by repairing sciatic nerves of adult rats with single magnesium filaments placed inside poly(caprolactone) nerve conduits. Controls were empty conduits, conduits containing titanium filaments and/or isografts from donor rats. With a nerve gap of 6 mm and 6 weeks post-repair, magnesium filaments had partially resorbed. Regenerating cells had attached to the filaments and axons were observed in distal stumps in all animals. Axon parameters were improved with magnesium compared to conduits alone or conduits with single titanium filaments. With a longer gap of 15 mm and 16 weeks post-repair, functional parameters were improved with isografts, but not with magnesium filaments or empty conduits. Magnesium filaments were completely resorbed and no evidence of scarring was seen. While axon outgrowth was not improved with the longer gap, histological measures of the tissues were improved with magnesium compared to empty conduits. Therefore, the use of magnesium filaments is promising because they are biocompatible and improve aspects of nerve regeneration. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 3148-3158, 2017.

Cauda equina repair in the rat: Part 3. Axonal regeneration across Schwann cell-Seeded collagen foam.

Treatments for patients with cauda equina injury are limited. In this study, we first used retrograde labeling to determine the relative contributions of cauda equina motor neurons to intrinsic and extrinsic rat tail muscles. Next, we transected cauda equina ventral roots and proceeded to bridge the proximal and distal stumps with either a type I collagen scaffold coated in laminin (CL) or a collagen-laminin scaffold that was also seeded with Schwann cells (CLSC). Regeneration was assessed by way of serial retrograde labeling. After accounting for the axonal contributions to intrinsic vs. extrinsic tail muscles, we noted a higher degree of double labeling in the CLSC group (58.0 ± 39.6%) as compared with the CL group (27.8 ± 16.0%; P = 0.02), but not the control group (33.5 ± 18.2%; P = 0.10). Our findings demonstrate the feasibility of using CLSCs in cauda equina injury repair. Muscle Nerve 57: E78-E84, 2018.

MicroRNA-352 regulates collateral vessel growth induced by elevated fluid shear stress in the rat hind limb

Although collateral vessel growth is distinctly enhanced by elevated fluid shear stress (FSS), the underlying regulatory mechanism of this process remains incompletely understood. Recent studies have shown that microRNAs (miRNAs) play a pivotal role in vascular development, homeostasis and a variety of diseases. Therefore, this study was designed to identify miRNAs involved in elevated FSS-induced collateral vessel growth in rat hind limbs. A side-to-side arteriovenous (AV) shunt was created between the distal stump of one of the bilaterally occluded femoral arteries and the accompanying vein. The miRNA array profile showed 94 differentially expressed miRNAs in FSS-stressed collaterals including miRNA-352 which was down-regulated. Infusion of antagomir-352 increased the number and proliferation of collateral vessels and promoted collateral flow restoration in a model of rat hind limb ligation. In cell culture studies, the miR-352 inhibitor increased endothelial proliferation, migration and tube formation. In addition, antagomir-352 up-regulated the expression of insulin-like growth factor II receptor (IGF2R), which may play a part in the complex pathway leading to arterial growth. We conclude that enhanced collateral vessel growth is controlled by miRNAs, among which miR-352 is a novel candidate that negatively regulates arteriogenesis, meriting additional studies to unravel the pathways leading to improved collateral circulation.

Tendon end separation with loading in an Achilles tendon repair model: comparison of non-absorbable vs. absorbable sutures

BackgroundRupture of the Achilles tendon often leads to long-term morbidity, particularly calf weakness associated with tendon elongation. Operative repair of Achilles tendon ruptures leads to reduced tendon elongation. Tendon lengthening is a key problem in the restoration of function following Achilles tendon rupture. A study was performed to determine differences in initial separation, strength and failure characteristics of differing sutures and numbers of core strands in a percutaneous Achilles tendon repair model in response to initial loading.MethodsNineteen bovine Achilles tendons were repaired using a percutaneous/minimally invasive technique with a combination of a modified Bunnell suture proximally and a Kessler suture distally, using non-absorbable 4-strand 6-strand repairs and absorbable 8-strand sutures. Specimens were then cyclically loaded using phases of 10 cycles of 100 N, 100 cycles of 100 N, 100 cycles of 190 N consistent with early range of motion training and weight-bearing, before being loaded to failure.ResultsPre-conditioning of 10 cycles of 100 N resulted in separations of 4 mm for 6-strand, 5.9 mm for 4-strand, but 11.5 mm in 8-strand repairs, this comprised 48.5, 68.6 and 72.7% of the separation that occurred after 100 cycles of 100 N. The tendon separation after the third phase of 100 cycles of 190 N was 17.4 mm for 4-strand repairs, 16.6 mm for 6-strand repairs and 26.6 mm for 8-strand repairs. There were significant differences between the groups (p < 0.0001). Four and six strand non-absorbable repairs had significantly less separation than 8-strand absorbable repairs (p = 0.017 and p = 0.04 respectively).The mean (SEM) ultimate tensile strengths were 4-strand 464.8 N (27.4), 6-strand 543.5 N (49.6) and 8-strand 422.1 N (80.5). Regression analysis reveals no significant difference between the overall strength of the 3 repair models (p = 0.32) (4 vs. 6: p = 0.30, 4 vs. 8: p = 0.87; 6 vs. 8: p = 0.39). The most common mode of failure was pull out of the Kessler suture from the distal stump in 41.7% of specimens.ConclusionThe use of a non-absorbable suture resulted in less end-to-end separation when compared to absorbable sutures when an Achilles tendon repair model was subject to cyclical loading. Ultimate failure occurred more commonly at the distal Kessler suture end although this occurred with separations in excess of clinical failure. The effect of early movement and loading on the Achilles tendon is not fully understood and requires more research.

Functional and Molecular Characterization of a Novel Traumatic Peripheral Nerve-Muscle Injury Model.

Traumatic injuries to human peripheral nerves are frequently associated with damage to nerve surrounding tissues including muscles and blood vessels. Currently, most rodent models of peripheral nerve injuries (e.g., facial or sciatic nerve) employ surgical nerve transection with scissors or scalpels. However, such an isolated surgical nerve injury only mildly damages neighboring tissues and weakly activates an immune response. In order to provide a rodent nerve injury model accounting for such nerve-associated tissue damage and immune cell activation, we developed a drop tower-based facial nerve trauma model in mice. We compare nerve regeneration in this novel peripheral nerve trauma model with the established surgical nerve injury along several parameters. These include gene expression, histological and functional facial motoneuron (FMN) regeneration, facial nerve degeneration, immune cell activation and muscle damage. Regeneration-associated genes (RAGs; e.g., Atf3) were strongly induced in FMNs subjected to traumatic and surgical injury. Regeneration of FMNs and functional recovery of whisker movement were faster in traumatic versus complete surgical injury, thus cutting down experimentation time. Wallerian degeneration of distal nerve stumps was readily observed in this novel trauma injury model. Importantly, drop tower-inflicted facial nerve injury resulted in muscle damage, activation of muscle satellite cell markers (PAX7) and pronounced infiltration of immune cells to the injury site only in this model but not upon surgical nerve transection. Thus, we provide a novel rodent PNS trauma model that can be easily adopted to other PNS nerves such as the sciatic nerve. Since this nerve trauma model replicates multiple tissue damage frequently encountered in clinical routine, it will be well suited to identify molecular and cellular mechanisms of PNS nerve repair in wild-type and genetically modified rodents.

Bridging the Gap

This study aims to compare engineered nerve conduits constructed from porcine-derived urinary bladder matrix (UBM) with the criterion-standard nerve autografts, for segmental loss peripheral nerve repairs. Forty-eight Sprague-Dawley rats were divided into 2 groups. All underwent a 10-mm sciatic nerve gap injury. This was repaired using either (1) reverse autograft-the 10-mm cut segment was oriented 180 degrees and used to coapt the proximal and distal stumps or (2) UBM conduit-the 10-mm nerve gap was bridged with UBM conduit. Behavior assessments such as sciatic function index and foot fault asymmetry scores were performed weekly. At 3- or 6-week time endpoints, the repaired nerves and bilateral gastrocnemius/soleus muscles were harvested from each animal. Nerves were evaluated using immunohistochemistry for motor and sensory axon staining and with diffusion tensor imaging. The net wet muscle weights were calculated to assess the degree of muscle atrophy. The UBM group demonstrated significantly improved foot fault asymmetry scores at 2 and 4 weeks, whereas there was no difference in sciatic function index. The net muscle weights were similar between both groups. Motor axon counts proximal/inside/distal to the conduit/graft were similar between UBM conduits and reverse autografts, whereas sensory axon counts within and distal to the conduit were significantly higher than those of the autograft at 6 weeks. Sensory axonal regeneration seemed to be adherent to the inner surface of the UBM conduit, whereas it had a scattered appearance in autografts. Diffusion tensor imaging parameters between groups were similar. Urinary bladder matrix conduits prove to be at least similar to nerve autografts for the repair of peripheral nerve injuries with a short gap. The matrix perhaps serves as a scaffold to augment sensory nerve growth. In a clinical setting, UBM may eliminate the donor site morbidity and increased operative time associated with nerve autografting.

Advantages of transanal approach in low rectal cancer resections

Laparoscopic surgery is proven equal technique to open rectal surgery. Despite advantages, some problems in case of low rectal surgery are existing: visualization of the pelvis, securing safe distal resection margin, preparing single stapled rectal stump with safe conjunction to the colorectal anastomosis. Approximately 500 procedures have been performed worldwide until today by applying Transanal Total Mesorectal Excision (TaTME) technique, which evolved from a combination of laparoscopy and transanal approach. TaTME presents a solution to the low and mid-level rectal cases. The transanal path provides a better opportunity for preparing safe distal resection margin, an easier way for making a secure distal stump closure, and also offers perfect visualization even in the most difficult area, supporting the aim of nerve-sparing. We present a case, where we performed a synchronous laparoscopic and transanal TaTME resection of a down-sized low rectal tumor at 5 cm, after neoadjuvant radio-chemotherapy. To the best of our knowledge, this was the first case in Hungary, when TaTME was administered in a synchronous way.

Improving the regenerative potential of olfactory ensheathing cells by overexpressing prostacyclin synthetase and its application in spinal cord repair

BackgroundOlfactory ensheathing cells (OEC), specialized glia that ensheathe bundles of olfactory nerves, have been reported as a favorable substrate for axonal regeneration. Grafting OEC to injured spinal cord appears to facilitate axonal regeneration although the functional recovery is limited. In an attempt to improve the growth-promoting properties of OEC, we transduced prostacyclin synthase (PGIS) to OEC via adenoviral (Ad) gene transfer and examined the effect of OEC with enhanced prostacyclin synthesis in co-culture and in vivo. Prostacyclin is a vasodilator, platelet anti-aggregatory and cytoprotective agent.ResultsCultured OEC expressed high level of cyclooxygneases, but not PGIS. Infection of AdPGIS to OEC could selectively augument prostacyclin synthesis. When cocultured with either OEC or AdPGIS-OEC, neuronal cells were resistant to OGD-induced damage. The resulted OEC were further transplanted to the transected cavity of thoracic spinal cord injured (SCI) rats. By 6 weeks post-surgery, significant functional recovery in hind limbs occurred in OEC or AdPGIS-OEC transplanted SCI rats compared with nontreated SCI rats. At 10–12 weeks postgraft, AdPGIS-OEC transplanted SCI rats showed significantly better motor restoration than OEC transplanted SCI rats. Futhermore, regenerating fiber tracts in the distal spinal cord stump were found in 40–60% of AdPGIS-OEC transplanted SCI rats.ConclusionsEnhanced synthesis of prostacyclin in grafted OEC improved fiber tract regeneration and functional restoration in spinal cord injured rats. These results suggest an important potential of prostacyclin in stimulating OEC therapeutic properties that are relevant for neural transplant therapies.

Deficiency of adaptive immunity does not interfere with Wallerian degeneration.

Following injury, distal axons undergo the process of Wallerian degeneration, and then cell debris is cleared to create a permissive environment for axon regeneration. The innate and adaptive immune systems are believed to be critical for facilitating the clearance of myelin and axonal debris during this process. However, immunodeficient animal models are regularly used in transplantation studies investigating cell therapies to modulate the degenerative/regenerative response. Given the importance of the immune system in preparing a permissive environment for regeneration by clearing debris, animals lacking, in part or in full, a functional immune system may have an impaired ability to regenerate due to poor myelin clearance, and may, thus, be poor hosts to study modulators of regeneration and degeneration. To study this hypothesis, three different mouse models with impaired adaptive immunity were compared to wild type animals in their ability to degenerate axons and clear myelin debris one week following sciatic nerve transection. Immunofluorescent staining for axons and quantitation of axon density with nerve histomorphometry of the distal stump showed no consistent discrepancy between immunodeficient and wild type animals, suggesting axons tended to degenerate equally between the two groups. Debris clearance was assessed by macrophage density and relative myelin basic protein expression within the denervated nerve stump, and no consistent impairment of debris clearance was found. These data suggested deficiency of the adaptive immune system does not have a substantial effect on axon degeneration one week following axonal injury.