The immunomodulatory properties of adult skin-derived precursor Schwann cells: implications for peripheral nerve injury therapy.

Skin-derived precursor Schwann cell (SKPSC) therapy has been identified as a potentially beneficial treatment for peripheral nerve injuries. One hypothesised mechanism by which SKPSCs enhance recovery is via the modulation of macrophages. In the present study, we investigated the immunomodulatory properties of adult rat SKPSCs, and demonstrated that these cells expressed a battery of cytokines, including interferon-γ (IFN-γ), interleukin (IL)-1ß, and, most abundantly, IL-6. Whereas macrophages exposed to depleted or fibroblast-conditioned medium secreted minimal amounts of tumor necrosis factor-α (TNF-α), in the presence of SKPSC-conditioned medium, macrophages secreted > 500 pg/mL TNF-α. Following the transplantation of SKPSCs into injured rat sciatic nerves, we observed an SKPSC density-dependent increase in the number of macrophages (Pearson's r = 0.66) and an SKPSC density-dependent decrease in myelin debris (Pearson's r = -0.68). To determine the effect of IL-6 in a proinflammatory context, macrophage cultures were primed with either lipopolysaccharide (LPS)/IFN-γ/IL-1ß or LPS/IFN-γ/IL-1ß + IL-6, and this showed a 212% and 301% increase in the number of inducible nitric oxide synthase (iNOS)-positive proinflammatory macrophages respectively. In contrast to neurons exposed to conditioned medium from unprimed macrophages, neurons treated with conditioned medium from proinflammatory-primed macrophages showed a 13-26% reduction in neurite outgrowth. Anti-IL-6 antibody combined with SKPSC transplant therapy following nerve injury did not alter macrophage numbers or debris clearance, but instead reduced iNOS expression as compared with SKPSC + IgG-treated rats. SKPSC + anti-IL-6 treatment also resulted in a two-fold increase in gastrocnemius compound muscle action potential amplitudes as compared with SKPSC + IgG treatment. Understanding the mechanisms underlying immunomodulatory aspects of SKPSC therapy and developing approaches to manipulate these responses are important for advancing Schwann cell-based therapies.

Comparison of results between chitosan hollow tube and autologous nerve graft in reconstruction of peripheral nerve defect: An experimental study.

OBJECT: This study evaluated a chitosan tube for regeneration of the injured peripheral nerve in a rodent transected sciatic nerve model in comparison to autologous nerve graft repair. METHODS: Chitosan hollow tube was used to bridge a 10-mm gap between the proximal and distal ends in 11 rats. In the control group, an end-to-end coaptation of 10-mm long autologous nerve graft was performed in 10 rats for nerve reconstruction. RESULTS: SFI showed an insignificant advantage to the autologous group both at 30 days (P = 0.177) and at 90 days post procedure (P = 0.486). Somato-sensory evoked potentials (SSEP) and compound muscle action potentials (CMAP) tests showed similar results between chitosan tube (group 1) and autologous (group 2) groups with no statistically significant differences. Both groups presented the same pattern of recovery with 45% in group 1 and 44% in group 2 (P = 0.96) showing SSEP activity at 30 days. At 90 days most rats showed SSEP activity (91% vs.80% respectively, P = 0.46). The CMAP also demonstrated no statistically significant differences in latency (1.39 ms in group 1 vs. 1.63 ms in group 2; P = 0.48) and amplitude (6.28 mv vs. 6.43 mv respectively; P = 0.8). Ultrasonography demonstrated tissue growth inside the chitosan tube. Gastrocnemius muscle weight showed no statistically significant difference. Histomorphometry of the distal sciatic nerve, 90 days post reconstructive procedure, showed similar number of myelinated fibers and size parameters in both groups (P ≥ 0.05). CONCLUSIONS: Chitosan hollow tube used for peripheral nerve reconstruction of rat sciatic nerve showed similar results in comparison to autologous nerve grafting. © 2015 Wiley Periodicals, Inc. Microsurgery 36:664-671, 2016.

The ventricular system and choroid plexus as a primary site for renal cell carcinoma metastasis.

BACKGROUND: Brain metastases (BM) are the most common intracranial tumours amongst adults. Ten to 40 % of patients with cancer will develop BM. In this study, we observed a high affinity of renal cell carcinoma (RCC) to the ventricular system, with close association to the choroid plexus. METHODS: This is a retrospective study evaluating data of our prospectively maintained brain tumour database, focusing on consecutive BM patients, who were treated at our center between March 2003 and December 2011. Data collected included primary pathologies, anatomical distribution of the brain metastasis according to neuroimaging, and treatment modalities. RESULTS: We identified 614 patients with BM, of whom 24 (3.9 %) were diagnosed with RCC, harboring 33 lesions. Nine of the 24 patients (37.5 %) presented with an intraventricular location (10 of 33 RCC BM lesions). Of the remaining 590 patients with non-RCC pathologies, five patients (0.8 %) were diagnosed with intraventricular lesions (p < 0.0001). CONCLUSION: In this unselected, consecutive treated BM patient cohort we observed a high affinity of RCC BM to the ventricular system with close association to the choroid plexus. The reason for this affinity is unknown. Surgical approaches for resection of these lesions should be planned to include early control on the vascular supply from the choroidal vessels.

Core outcomes in nerve surgery: development of a core outcome set for ulnar neuropathy at the elbow.

OBJECTIVE: Ulnar neuropathy at the elbow (UNE) is common, affecting 1%-6% of the population. Despite this, there remains a lack of consensus regarding optimal treatment. This is primarily due to the difficulty one encounters when trying to assess the literature. Outcomes are inconsistently reported, which makes comparing studies or developing meta-analyses difficult or even impossible. Thus, there is a need for a core outcome set (COS) for UNE (COS-UNE) to help address this problem. The objective of this study was to utilize a modified Delphi method to develop COS-UNE. METHODS: A 5-stage approach was utilized to develop COS-UNE: stage 1, consortium development; 2, literature review to identify potential outcome measures; 3, Delphi survey to develop consensus on outcomes for inclusion; 4, Delphi survey to develop definitions; and 5, consensus meeting to finalize the COS and definitions. The study followed the Core Outcome Set-STAndards for Development (COS-STAD) recommendations. RESULTS: The Core Outcomes in Nerve Surgery (COINS) Consortium comprised 21 participants, all neurological surgeons representing 11 countries. The final COS-UNE consisted of 22 data points/outcomes covering the domains of demographic characteristics, diagnostics, patient-reported outcomes, motor/sensory outcomes, and complications. Appropriate instruments, methods of testing, and definitions were set. The consensus minimum duration of follow-up was 6 months, with the consensus optimal timepoints for assessment identified as preoperatively and 3, 6, and 12 months postoperatively. CONCLUSIONS: The authors identified consensus data points/outcomes and also provided definitions and specific scales to be utilized to help ensure that clinicians are consistent in their reporting across studies on UNE. This COS should serve as a minimum set of data to be collected in all future neurosurgical studies on UNE. The authors hope that clinicians evaluating ulnar neuropathy will incorporate this COS into routine practice and that future studies will consider this COS in the design phase.

Core outcomes in nerve surgery: development of a core outcome set for brachial plexus and upper extremity nerve injuries.

OBJECTIVE: When considering traumatic brachial plexus and upper extremity nerve injuries, iatrogenic nerve injuries, and nontraumatic nerve injuries, brachial plexus and upper extremity nerve injuries are commonly encountered in clinical practice. Despite this, data synthesis and comparison of available studies are difficult. This is at least in part due to the lack of standardization in reporting and a lack of a core outcome set (COS). Thus, there is a need for a COS for adult brachial plexus and upper extremity nerve injuries (COS-BPUE). The objective of this study was to develop a COS-BPUE using a modified Delphi approach. METHODS: A 5-stage approach was used to develop the COS-BPUE: 1) consortium development, 2) literature review to identify potential outcome measures, 3) Delphi survey to develop consensus on outcomes for inclusion, 4) Delphi survey to develop definitions, and 5) consensus meeting to finalize the COS and definitions. The study followed the Core Outcome Set-STAndards for Development (COS-STAD) recommendations. RESULTS: The Core Outcomes in Nerve Surgery (COINS) Consortium comprised 23 participants, all neurological surgeons, representing 13 countries. The final COS-BPUE consisted of 36 data points/outcomes covering demographic, diagnostic, patient-reported outcome, motor/sensory outcome, and complication domains. Appropriate instruments, methods of testing, and definitions were set. The consensus minimum duration of follow-up was 24 months, with the consensus optimal time points for assessment being preoperatively and 3, 6, 12, and 24 months postoperatively. CONCLUSIONS: The COINS Consortium developed a consensus COS and provided definitions, methods of implementation, and time points for assessment. The COS-BPUE should serve as a minimum set of data that should be collected in all future neurosurgical studies on adult brachial plexus and upper extremity nerve injuries. Incorporation of this COS should help improve consistency in reporting, data synthesis, and comparability, and should minimize outcome reporting bias.

Peroneal and tibial intraneural ganglion cysts in children.

BACKGROUND/AIMS: Intraneural ganglion cyst is a rare and underrecognized clinical entity in the pediatric population, which may cause pain as well as motor and sensory neurological deficits. This study presents 4 pediatric patients harboring ganglion cysts involving the peroneal and tibial nerves. METHODS: Data encompassing pre- and postoperative analyses of 4 pediatric patients with intraneural ganglion cyst was evaluated. RESULTS: Out of these 4 patients, 3 had an intraneural ganglion cyst involving the peroneal nerve, and 1 patient had his tibial nerve involved. Two patients were operated for recurrent ganglion cysts with severe postoperative neurological deficits, after preceding operations in other institutions. The other 2 patients had no history of previous surgery, and they had their initial surgical treatment in our institute for primarily diagnosed ganglion cysts. With a mean follow-up of 24 months, all patients experienced pain relief. Significant improvement of motor deficits was achieved in 3 patients. No recurrences were encountered during the 24-month follow-up. CONCLUSION: Intraneural ganglion cysts in children can be treated with excellent outcome in experienced and dedicated centers, which specialize in peripheral nerve microsurgery.

Corynebacterium bovis surgical site infection and brain abscess: The first case report and literature review.

Corynebacterium bovis is a mainly zoonotic pathogen, a common cause of bovine mastitis. It is however rarely pathogenic in humans, with only few cases reported in the literature. We present the first reported case of neurosurgical site infection due to c.bovis, resulting in a brain abscess. A 75-year-old female presented with dysphasia resulting from lung metastases. She underwent surgical resection, and four months later presented with swelling, tenderness and crusted exudate over the surgical site. Mri revealed surgical site infection and brain abscess, therefore the patient underwent urgent surgery. C.bovis was isolated from all specimens sent from different locations. The patient received appropriate antibiotic treatment without sequela. C. Bovis is being increasingly reported as a cause of various human infections, and should not automatically be considered to be a mere contaminant. It is imperative to be certain, prior to the antibiotics treatment, that this particular isolate is likely to be the pathogen, as it can be evident when there are multiple positive cultures of this pathogen from several locations.

Functional outcome following intracapsular resection of head and neck peripheral nerve sheath tumors: a retrospective cohort.

BACKGROUND: Intracapsular resection of head and neck peripheral nerve sheath tumors (PNST) has emerged as a nerve-preserving technique compared to en bloc resection. The aim of this study was to evaluate and compare the functional outcome of both surgical techniques performed at a single tertiary referral center. METHODS: This is a retrospective cohort of patients with head and neck PNST undergoing surgical resection from 2011 to 2021 at the Tel Aviv Sourasky Medical Center. Demographic data, the nerve of origin and surgical technique, including the use of intraoperative nerve monitoring were recorded and analyzed in association with postoperative functional outcomes. RESULTS: Overall, 25 patients who had a cervical or parapharyngeal PNST resected were included. Nerve function was preserved in 11 of 18 patients (61%) who underwent intracapsular resection, while all those who underwent en bloc resections inevitably suffered from neurologic deficits (100%, N = 7). Sympathetic chain origin and an apparent neurologic deficit pre-operatively were associated with postoperative neural compromise. CONCLUSION: Improved functional outcome can be anticipated following intracapsular resection of extracranial head and neck PNST compared to complete resection, particularly in asymptomatic patients.

Self-similar amplification in fiber Bragg gratings written in fiber amplifiers.

We show, by using numerical simulations, that self-similar pulses with a duration on the order of few nanoseconds and an energy on the order of 10 µJ can be obtained at the output of a fiber Bragg grating (FBG) written in a fiber amplifier. The evolution of the amplified pulses is determined by the combined effect of Kerr nonlinearity, normal-dispersion, gain, and gain saturation, which limit the pulse energy. The output pulse mainly depends on the initial pulse energy rather than on the initial pulse profile. The reduced group velocity in FBGs can significantly increase the total gain for a given amplifier length. Hence we find that the proposed amplification scheme can be highly advantageous for amplification of nanosecond-scale pulses in fiber amplifiers.

A Rabbit Model for Peripheral Nerve Reconstruction Studies Avoiding Automutilation Behavior.

Background The rabbit sciatic nerve injury model may represent a valuable alternative for critical gap distance seen in humans but often leads to automutilation. In this study, we modified the complete sciatic nerve injury model for avoiding autophagy. Materials and Methods In 20 adult female New Zealand White rabbits, instead of transecting the complete sciatic nerve, we unilaterally transected the tibial portion and preserved the peroneal portion. Thereby loss of sensation in the dorsal aspect of the paw was avoided. The tibial portion was repaired in a reversed autograft approach in a length of 2.6 cm. In an alternative repair approach, a gap of 2.6 cm in length was repaired with a chitosan-based nerve guide. Results During the 6-month follow-up period, there were no incidents of autotomy. Nerve regeneration of the tibial portion of the sciatic nerve was evaluated histologically and morphometrically. A clear difference between the distal segments of the healthy contralateral and the repaired tibial portion of the sciatic nerve was detectable, validating the model. Conclusion By transecting the isolated tibial portion of the rabbit sciatic nerve and leaving the peroneal portion intact, it was possible to eliminate automutilation behavior.

Outside the box-Surgery for aggressive plasmacytoma in scar.

This report introduces the concept of large-scale surgery and reconstruction when all other medical means of treatment have failed. In select cases, this may act as a mode of buying time and allowing the patient to receive second- or third-line treatments.

Pulse propagation in a fiber Bragg grating written in a slow saturable fiber amplifier.

We have developed a model to study nonlinear pulse propagation in a fiber Bragg grating written in an erbium-doped fiber amplifier. The saturation effect in such amplifiers depends on the accumulated energy along the pulse rather than on the pulse instantaneous power. We have shown that the gain saturation effect cannot be neglected when Bragg solitons are amplified by erbium-doped fiber amplifiers. The slow saturation of the amplifier limits the output pulse power, and it tends to split the amplified pulse into several pulses. We have shown that when the propagation velocity of the amplified pulses decreases, the amplifier gain per unit length increases.

Brief Electrical Stimulation Promotes Nerve Regeneration Following Experimental In-Continuity Nerve Injury.

BACKGROUND: Brief electrical stimulation (ES) therapy to the nerve may improve outcome in lacerated, repaired nerves. However, most human nerve injuries leave the nerve in continuity with variable and often poor functional recovery from incomplete axon regeneration and reinnervation. OBJECTIVE: To evaluate the effect of brief ES in an experimental model for neuroma-in-continuity (NIC) injuries in rodents. METHODS: Lewis rats were randomly assigned to 1 of 4 groups: NIC injury immediately followed by brief (1 h) ES; NIC injury without ES; sham-operated controls; sciatic nerve transection without repair. Outcome measures included serial behavioral evaluation and electrophysiology together with terminal retrograde spinal cord motor neuron labeling and histomorphological analysis for axonal regeneration. RESULTS: Applying brief ES immediately after in-continuity nerve injury resulted in earlier recovery and significantly improved locomotion function at 4 and 6 wk. At 8 wk, brief ES resulted in higher compound action potential amplitude. By 12 wk there was no significant difference between the 2 groups in behavior or electrophysiology. Histomorphological analysis demonstrated a significantly higher percentage of neural tissue in the brief ES group. Spinal cord motor neuron pool cell counts revealed a preference for regeneration into a motor over a sensory nerve, for the group receiving ES. CONCLUSION: The application of brief ES for in-continuity nerve injury promotes faster recovery, although in a rat model where regeneration distances are short the control group ultimately recovers to a similar degree. Brief EF requires further evaluation as a promising therapy for in-continuity nerve injuries in humans.

Plasminogen-induced aggregation of PANC-1 cells requires conversion to plasmin and is inhibited by endogenous plasminogen activator inhibitor-1.

PANC-1 cells express proteinase-activated receptors (PARs)-1, -2, and respond to their activation by transient elevation of cytosolic [Ca(2+)] and accelerated aggregation (Wei et al., 2006, J Cell Physiol 206:322-328). We studied the effect of plasminogen (PGN), an inactive precursor of the PAR-1-activating protease, plasmin (PN) on aggregation of pancreatic adenocarcinoma (PDAC) cells. A single dose of PGN time- and dose-dependently promoted PANC-1 cells aggregation in serum-free medium, while PN did not. PANC-1 cells express urokinase plasminogen activator (uPA), which continuously converted PGN to PN. This activity and PGN-induced aggregation were inhibited by the uPA inhibitor amiloride. PGN-induced aggregation was also inhibited by alpha-antiplasmin and by the PN inhibitor epsilon-aminocaproic acid (EACA). Direct assay of uPA activity revealed very low rate, markedly enhanced in the presence of PGN. Moreover, in PGN activator inhibitor 1-deficient PANC-1 cells, uPA activity and PGN-induced aggregation were markedly potentiated. Two additional human PDAC cell lines, MiaPaCa and Colo347, were assayed for PGN-induced aggregation. Both cell lines responded by aggregation and exhibited PGN-enhanced uPA activity. We hypothesized that the continuous conversion of PGN to PN by endogenous uPA is limited by PN's degradation and negatively controlled by endogenously produced PAI-1. Indeed, we found that PANC-1 cells inactivate PN with t1/2 of approximately 7 h, while the continuous addition of PN promoted aggregation. Our data suggest that PANC-1 cells possess intrinsic, PAI-1-sensitive mechanism for promotion of aggregation and differentiation by prolonged exposure to PGN and, possibly, additional precursors of PARs agonists.

Purification and Characterization of Schwann Cells from Adult Human Skin and Nerve.

Despite its modest capacity for regeneration, peripheral nervous system injury often results in significant long-term disability. Supplementing peripheral nervous system injury with autologous Schwann cells (SCs) may serve to rejuvenate the postinjury environment to enhance regeneration and ultimately improve functional outcomes. However, human nerve-derived SC (hN-SC) collection procedures require invasive surgical resection. Here, we describe the characterization of SCs from adult human skin (hSk-SCs) of four male donors ranging between 27 and 46 years old. Within five weeks of isolating and culturing adherent mixed skin cells, we were able to obtain 3-5 million purified SCs. We found that hSk-SCs appeared transcriptionally indistinguishable from hN-SCs with both populations exhibiting expression of SC genes including: SOX10, SOX9, AP2A1, CDH19, EGR1, ETV5, PAX3, SOX2, CX32, DHH, NECL4, NFATC4, POU3F1, S100B, and YY1. Phenotypic analysis of hSk-SCs and hN-SCs cultures revealed highly enriched populations of SCs indicated by the high percentage of NES+ve, SOX10+ve, s100+ve and p75+ve cells, as well as the expression of a battery of other SC-associated proteins (PAX3, CDH19, ETV5, SOX2, POU3F1, S100B, EGR2, and YY1). We further show that both hSk-SCs and hN-SCs are capable of promoting axonal growth to similar degrees and that a subset of both associate with regenerating axons and form myelin following transplantation into the injured mouse sciatic nerve. Interestingly, although the majority of both hSk-SCs and hN-SCs maintained SOX10 immunoreactivity following transplant, only a subset of each activated the promyelinating factor, POU3F1, and were able to myelinate. Taken together, we demonstrate that adult hSk-SCs are genetically and phenotypically indistinguishable to hN-SCs.

Photobiomodulation Triple Treatment in Peripheral Nerve Injury: Nerve and Muscle Response.

BACKGROUND: Muscle preservation or decrease in muscle degeneration and progressive atrophy are major challenges in patients with severe peripheral nerve injury (PNI). Considerable interest exists in the potential therapeutic value of laser phototherapy (photobiomodulation) for restoring denervated muscle atrophy and for enhancing regeneration of severely injured peripheral nerves. As previously published, the laser phototherapy has a protective and immediate effect in PNI. Laser phototherapy in the early stages of muscle atrophy may preserve the denervated muscle by maintaining creatinine kinase (CK) activity and the amount of acetylcholine receptor (AChR). OBJECTIVE AND METHODS: In the present study, the effectiveness of triple treatment laser phototherapy, namely, applied simultaneously at three areas: injured area of the peripheral nerve, corresponding segments of the spinal cord, and corresponding denervated muscle (triple treatment), was evaluated for the treatment of incomplete PNI in rats with the ultimate goal of achieving improved limb function. RESULTS: Forty-five days after the sciatic nerve insult, all rats regained normal walking (functional sciatic index values returned to baseline); however, the long laser irradiation (7 min) group presented the fastest recovery as opposed to short laser irradiation (3 min). A histological evaluation of the nerves revealed that long laser irradiation led to a higher amount of neuronal fibers that were larger than 4 µm (543 ± 76.8, p < 0.01) than short irradiation (283 ± 35.36). A histological evaluation of muscular atrophy showed that long laser irradiation evolved with significantly less muscle atrophy (8.06% ± 1.23%, p < 0.05) than short irradiation (24.44% ± 7.26%). CONCLUSIONS: The present study and our previous investigations showed that the laser phototherapy increases biochemical activity and improves morphological recovery in muscle and, thus, could have direct therapeutic applications on muscle, especially during progressive atrophy resulting from PNI.

Craniectomy Versus Craniotomy for Posterior Fossa Metastases: Complication Profile.

OBJECTIVE: Surgical resection of posterior fossa metastases (PFM) includes either suboccipital craniotomy or suboccipital craniectomy. The optimal surgical technique is yet to be defined. We examined the association between the chosen surgical approach and the occurrence of postoperative complications. METHODS: We retrospectively evaluated medical records and imaging characteristics of patients who underwent resection of newly diagnosed PFM between 2003 and 2014 in our medical center to identify covariates that significantly affected postoperative complications. RESULTS: Of 917 patients with brain metastases, 88 patients underwent surgery for PFM and were included in the study. Craniectomy was performed in 54 cases (61%). Urgent postoperative posterior fossa decompression or cerebrospinal fluid diversion was performed in 4 patients (4.5%). Postoperative complications included postoperative central nervous system infection (n = 10 [12%]), cerebrospinal fluid leak (n = 3 [4%]), wound dehiscence (n = 6 [7%]), and long-term pseudomeningocele (n = 12 [14%]). The perioperative mortality rate was 2.3% (n = 2). Multivariate analysis that included patient baseline characteristics, imaging study parameters, and surgical approaches demonstrated that suboccipital craniectomy was associated with more postoperative complications (P = 0.03, odds ratio = 4.48, 95% confidence interval = 1.14-17.6). There was no correlation between patient baseline characteristics or surgical technique with the need for urgent postoperative posterior fossa decompression or cerebrospinal fluid diversion. CONCLUSIONS: Suboccipital craniotomy may be associated with a lower incidence of postoperative morbidity compared with suboccipital craniectomy and should be considered as the preferred approach for the resection of PFM.

Improved method to track and precisely count Schwann cells post-transplantation in a peripheral nerve injury model.

BACKGROUND: To optimize survival evaluation of Schwann cells (SCs) in vivo, we tested fluorescent labeling of the nucleus as an improved method of tracking and counting the transplanted SCs at sciatic nerve injury sites in rodents. We also investigated if co-administering cells with the glial growth factor Neuregulin-1 ß (NRG1ß) improves in vivo survival. NEW METHOD: We transduced SCs using a Lentiviral vector with a nuclear localization signal (NLS) fused with mCherry and transplanted them in the sciatic nerve of rat post-crush injury (bilateral) either in the presence or absence of NRG1ß in the injectate media. For comparison, in a separate group of similar injury, GFP-labeled cells were transplanted. After 10 days, nerves were harvested and sections (14µm) were counterstained with Hoechst and imaged. Cells showing co-localization with Hoechst and GFP or mCherry were exhaustively counted and data analyzed. RESULTS: Percentage cells counted in with- and without-NRG condition in both the groups were 0.83±0.13% and 0.06±0.04% (Group 1) & 2.83*±1.95% and 0.23*±0.29% (Group 2). COMPARISON TO EXISTING METHOD: We are introducing fluorescent labeling of the nucleus as a reliable and efficient technique to perform survival assessments in Schwann cell based treatment studies in animal model. This method can overcome the challenges and limitations of the existing method that could result in underestimation of the therapeutic outcome. CONCLUSIONS: Nucleus-restricted fluorescent labeling technique offer improved method of tracking as well as accurately counting transplanted SCs in vivo while NRG1ß in the injectate media can improve survival.

Shocking therapy: Brief electrical stimulation for delayed nerve repair.

This commentary provides perspective on a recent paper published in Experimental Neurology by Elzinga et al. where the authors investigated the effect of brief electrical stimulation (ES) on nerve regeneration after delayed nerve repair in a rodent model. Their results from a well controlled series of experiments indicated that brief ES promoted axonal outgrowth after chronic axotomy as well after chronic Schwann cell and muscle denervation. ES also increased chronically axotomized neurons regenerating into chronically denervated stumps, which represent a true delayed repair. The authors conclude that brief ES promotion of nerve regeneration after delayed nerve repair is as effective as after immediate repair. Given the prior experimental evidence, and the prior clinical data from patients with carpal tunnel syndrome and digital nerve repair, the implication of this new work is to consider a well designed clinical trial for use of brief ES in nerve graft and nerve transfer repairs.

Conflicting pathology reports: a diagnostic dilemma.

The differential diagnosis of a brain lesion with two discordant pathology reports includes the presence of collision tumor, metaplastic changes, and labeling errors that occurred during the processing of the specimen. The authors present a case in which the first brain biopsy from a 47-year-old patient with a history of heavy smoking was compatible with metastatic small cell carcinoma, and the second biopsy taken during decompression craniotomy 3 weeks later was compatible with WHO Grade IV glioblastoma. Using short tandem repeat (STR) analysis of the two specimens and nontumor-derived patient DNA, the authors found that the two specimens did not belong to the same individual. The authors conclude that allele imbalance or loss of heterozygosity detected by STR analysis is a reliable and valuable diagnostic tool for clarifying discrepancies in discordant pathology reports.