Partial Transection Research Articles

Fibrin biopolymer sealant and aquatic exercise association for calcaneal tendon repair.

ABSTRACTPurposeThe aim of this work was to analyze the effect of fibrin biopolymer sealant (FS) associated or not to aquatic exercise (AE) on the calcaneal tendon repair.MethodsForty-four female Wistar rats were randomly divided into four experimental groups: Lesion control (L), Lesion and FS (LS), Lesion and AE (LE) and Lesion and FS associated to AE (LSE). The edema volume (EV), collagen ratio, and histopathological analysis were evaluated after 7, 14, and 21 days of partial tendon transection.ResultsThe EV was statistically reduced for all treatment groups after 7 and 21 days when compared to L group. The LS and LSE had the highest EV reduction after 21 days of treatment. The FS group didn’t induce tissue necrosis or infections on the histopathological analysis. It was observed tenocytes proliferation, granulation tissue and collagen formation in the tendon partial transection area in the FS group. The LSE demonstrated higher amount of granulation tissue and increased the collagen deposition at the injury site.ConclusionsOur data suggests that the therapeutic potential of the association of heterologous fibrin biopolymer sealant with aquatic exercise program should be further explored as it may stimulate the regeneration phase and optimize calcaneal tendon recovery.

G protein-coupled receptor GPR151 is involved in trigeminal neuropathic pain through the induction of Gβγ/extracellular signal-regulated kinase-mediated neuroinflammation in the trigeminal ganglion.

Trigeminal nerve injury-induced neuropathic pain is a debilitating chronic orofacial pain syndrome but lacks effective treatment. G protein-coupled receptors (GPCRs), especially orphan GPCRs (oGPCRs) are important therapeutic targets in pain medicine. Here, we screened upregulated oGPCRs in the trigeminal ganglion (TG) after partial infraorbital nerve transection (pIONT) and found that Gpr151 was the most significantly upregulated oGPCRs. Gpr151 mRNA was increased from pIONT day 3 and maintained for more than 21 days. Furthermore, GPR151 was expressed in the neurons of the TG after pIONT. Global mutation or knockdown of Gpr151 in the TG attenuated pIONT-induced mechanical allodynia. In addition, the excitability of TG neurons was increased after pIONT in wild-type (WT) mice, but not in Gpr151-/- mice. Notably, GPR151 bound to Gαi protein, but not Gαq, Gα12, or Gα13, and activated the extracellular signal-regulated kinase (ERK) through Gβγ. Extracellular signal-regulated kinase was also activated by pIONT in the TG of WT mice, but not in Gpr151-/- mice. Gene microarray showed that Gpr151 mutation reduced the expression of a large number of neuroinflammation-related genes that were upregulated in WT mice after pIONT, including chemokines CCL5, CCL7, CXCL9, and CXCL10. The mitogen-activated protein kinase inhibitor (PD98059) attenuated mechanical allodynia and reduced the upregulation of these chemokines after pIONT. Collectively, this study not only revealed the involvement of GPR151 in the maintenance of trigeminal neuropathic pain but also identified GPR151 as a Gαi-coupled receptor to induce ERK-dependent neuroinflammation. Thus, GPR151 may be a potential drug target for the treatment of trigeminal neuropathic pain.

Correlation of damage score in PTOA with changes in stress on cartilage in an ovine model

There is a high risk of developing osteoarthritis (OA) following traumatic injury to the knee. Severe ligament injuries can disrupt the integrity of the multicomponent knee at both biological and biomechanical levels. We hypothesize changes in cartilages stresses could lead to tissue damage and development of OA. The in-vivo gait kinematics of the stifle (knee) joint of four adult female ovine subjects were recorded prior to and at ten-and-twenty weeks following partial ACL-MCL transection. The subjects were sacrificed and the experimental joint from each subject was mounted on a parallel robotic system programmed with the kinematic findings. Ten custom-built Fibre Bragg Grating optic sensors were arranged to measure contact stresses on the surface of the tibial plateau articular cartilage. These sensors provide the first accurate stress measurements in a joint during gait replication using the previously recorded in-vivo kinematics. The relationship between the results obtained and observed focal damage was assessed. The locations on the tibial plateaus that experienced the greatest change in contact stresses corresponded with the locations of focal damage development. No direct link was detected between individual animal differences in kinematics and variations in stress magnitudes or the development of focal cartilage damage. The findings highlight the importance of mechanical stress determinants in the integrated set point for the knee (with individual variation), and how injury-related stress changes correlate with development of PTOA.

Connexin 36 Mediates Orofacial Pain Hypersensitivity Through GluK2 and TRPA1.

Trigeminal neuralgia is a debilitating condition, and the pain easily spreads to other parts of the face. Here, we established a mouse model of partial transection of the infraorbital nerve (pT-ION) and found that the Connexin 36 (Cx36) inhibitor mefloquine caused greater alleviation of pT-ION-induced cold allodynia compared to the reduction of mechanical allodynia. Mefloquine reversed the pT-ION-induced upregulation of Cx36, glutamate receptor ionotropic kainate 2 (GluK2), transient receptor potential ankyrin 1 (TRPA1), and phosphorylated extracellular signal regulated kinase (p-ERK) in the trigeminal ganglion. Cold allodynia but not mechanical allodynia induced by pT-ION or by virus-mediated overexpression of Cx36 in the trigeminal ganglion was reversed by the GluK2 antagonist NS102, and knocking down Cx36 expression in Nav1.8-expressing nociceptors by injecting virus into the orofacial skin area of Nav1.8-Cre mice attenuated cold allodynia but not mechanical allodynia. In conclusion, we show that Cx36 contributes greatly to the development of orofacial pain hypersensitivity through GluK2, TRPA1, and p-ERK signaling.

Histological Assessment of Wallerian Degeneration of the Rat Tibial Nerve Following Crush and Transection Injuries.

Wallerian degeneration (WD) following peripheral nerve injury (PNI) is an area of growing focus for pharmacological developments. Clinically, WD presents challenges in achieving full functional recovery following PNI, as prolonged denervation of distal tissues for an extended period of time can irreversibly destabilize sensory and motor targets with secondary tissue atrophy. Our objective is to improve upon histological assessments of WD. Conventional methods utilize a qualitative system simply describing the presence or absence of WD in nerve fibers. We propose a three-category assessment that allows more quantification: A fibers appear normal, B fibers have moderate WD (altered axoplasm), and C fibers have extensive WD (myelin figures). Analysis was by light microscopy (LM) on semithin sections stained with toluidine blue in three rat tibial nerve lesion models (crush, partial transection, and complete transection) at 5 days postop and 5 mm distal to the injury site. The LM criteria were verified at the ultrastructural level. This early outcome measure was compared with the loss of extensor postural thrust and the absence of muscle atrophy. The results showed good to excellent internal consistency among counters, demonstrating a significant difference between the crush and transection lesion models. A significant decrease in fiber density in the injured nerves due to inflammation/edema was observed. The growth cones of regenerating axons were evident in the crush lesion group. The ABC method of histological assessment is a consistent and reliable method that will be useful to quantify the effects of different interventions on the WD process.

Shaved FUE vs Long Hair FUE: A Comparative Study During Excision, Extraction, and Placement

<b><i>Introduction:</i></b> Long hair follicular unit excision (FUE) is a challenging technique that requires advanced surgical skill. As this procedure becomes more well known, patients frequently ask for it and surgeons offer it more. Still, we have little information on the effects of this technique on the grafts and the overall result of the procedure. The objective of this study was to compare the surgical and graft quality in shaved and long hair FUE by evaluating different parameters during excision, extraction, and placement. <b><i>Methods:</i></b> Excision, extraction, and placement processes were compared between long hair and shaved hair FUE. For the excision comparison, two parallel boxes were marked and measured on each patient at the level of the center of the occipital area within the safe donor area. One box was shaved and the other was left with long hair. Grafts excised and extracted were counted under a microscope and inspected for partial or total transections; the time elapsed for the excision and extraction was also noted. For the placing comparison of long hair versus shaved hair FUE, two parallel boxes of 1 square centimeter were measured and marked on each patient at the level of the frontal hairline on either side. One box was for dense packing with 50 shaved follicular units (FUs) and the other box was for placement of long hair grafts in a great enough density to achieve desirable coverage. Time was also calculated during all placement processes. <b><i>Results:</i></b> A total of 10 male patients (n=10) were recruited (mean age of 44) and classified with the Norwood Scale between 3 and 5 (with an average of 4.2) regardless of location whether it was anterior, central, or vertex. During the excision and extraction phase of the procedure, we observed that in the long hair box, we could extract an average of 20% more grafts compared to the maximum calculated by the Hair Density Index (HDI) for that specific area t(18)=12.5, p&lt;0.001. We did not see a significant difference in the total transection rate (TTR) between the two boxes (t(18)= 2.277, p&lt;0.017), but we did see a significant difference in the partial transection rate (PTR), with an 8% higher partial transection rate in long hair excision and extractions compared to shaved excisions and extractions t(18)=−4.11, p&lt;0.001. Additionally, excision and extraction of long hair FUs takes almost twice the time to perform than shaved ones. When placing grafts, we observed that an average of 24% fewer grafts from the long hair batch were needed to achieve the ideal coverage t(18)=−22.13, p&lt;0.001. <b><i>Discussion:</i></b> Long hair FUE is a slow process that can cause a slight increase in partial transections, but stretches the boundaries in regards of maximum donor availability and minimum density needed for recipient area coverage.

Open tendoachilles injuries due to squatting type of toilet seats: Five-year prospective observational study from a tertiary care center in India

BackgroundOpen traumatic tendoachilles injuries due to toilet seats are least reported. The exact mechanism of such injuries is debatable. None of the studies have reported associated neurovascular injuries and the need for microvascular tissue transfer. MethodsIt is a 5-year prospective observational study from Sep 2013 – Aug 2018 at a tertiary care center on 26 patients who had sustained foot injuries due to squatting type toilet seats. All the patients were managed by thorough wound irrigation and debridement followed by repair of cut tendoachilles, other tendons and neurovascular structures. All the complications and secondary procedures required were recorded. Functional outcome was assessed by Boyden clinical outcome score. Follow up ranged from 1 to 5 years. ResultsAll the 26 patients reported a particular mechanism of injury. Complete transection of tendoachilles was seen in 23 (88.5%) patients and partial transection in three (11.5%) patients. Microvascular repair of cut posterior tibial artery was undertaken in three and posterior tibial nerve in two cases and microvascular parascapular flap in one case for soft tissue reconstruction. Twenty-three (88.5%) patients had good to excellent Boyden score while three patients (11.5%) had fair to poor score at 1 year. Such severe injuries due to toilet seats have never been reported in literature. ConclusionsSquatting toilet seats can cause devastating foot injuries involving tendons and neurovascular structures and may require microvascular tissue transfer for definitive wound management. The risk of such injuries will continue unless some modifications are undertaken in the design of the seat.

A crucial role of HMGB1 in orofacial and widespread pain sensitization following partial infraorbital nerve transection

• HMGB1 is upregulated both in the medulla and spinal cord after p-IONX. • HMGB1 is released mainly by neurons and astrocytes after p-IONX. • HMGB1 is sufficient and necessary for orofacial and widespread hypersensitivity. • HMGB1 mAb may serve as an effective therapeutic approach.

Lateral internal sphincterotomy (LIS)—still top gun in chronic anal fissure treatment?

Anal fissure is one of the most common proctological complaints. If the fissure persists for more than 6–8 weeks, it is termed a chronic fissure and will most likely need surgical intervention. Surgical partial transection of the internal sphincter muscle, lateral internal sphincterotomy (LIS), is still seen as the gold standard procedure for chronic anal fissure in many parts of the world, especially in the Anglo-American community. In contrast, the German-speaking surgical community favors fissurectomy ± application of Botox, as some studies report high postoperative incontinence rates after LIS. This paper aims to give an overview of the literature on LIS and its outcomes and answer the question, “Is LIS still the gold standard surgical approach for chronic anal fissure?” A literature search for “sphincterotomy,” “internal sphincter,” and “anal fissure” was performed in PubMed. For the purpose of this overview article, randomized controlled trials (RCTs), meta-analyses, up-to-date guidelines, and retrospective cohort studies were taken into account. LIS produces excellent rates of fissure healing (~95%), quick symptom relief, and high patient satisfaction. Incontinence after LIS is mostly described as mild and transient. In the authors’ view, open LIS is therefore rightfully still the gold standard procedure for treatment of chronic anal fissure in the majority of patients. A conservative approach with limited division of internal sphincter muscle is preferred. For patients with preexisting sphincter weakness and an increased risk of incontinence, further preoperative diagnostic assessment (anal manometry, endoanal ultrasound) is recommended. In this high-risk group, alternative surgical options might be preferred.

Tacr3 in the lateral habenula differentially regulates orofacial allodynia and anxiety-like behaviors in a mouse model of trigeminal neuralgia

Trigeminal neuralgia (TN) is debilitating and is usually accompanied by mood disorders. The lateral habenula (LHb) is considered to be involved in the modulation of pain and mood disorders, and the present study aimed to determine if and how the LHb participates in the development of pain and anxiety in TN. To address this issue, a mouse model of partial transection of the infraorbital nerve (pT-ION) was established. pT-ION induced stable and long-lasting primary and secondary orofacial allodynia and anxiety-like behaviors that correlated with the increased excitability of LHb neurons. Adeno-associated virus (AAV)-mediated expression of hM4D(Gi) in glutamatergic neurons of the unilateral LHb followed by clozapine-N-oxide application relieved pT-ION-induced anxiety-like behaviors but not allodynia. Immunofluorescence validated the successful infection of AAV in the LHb, and microarray analysis showed changes in gene expression in the LHb of mice showing allodynia and anxiety-like behaviors after pT-ION. Among these differentially expressed genes was Tacr3, the downregulation of which was validated by RT-qPCR. Rescuing the downregulation of Tacr3 by AAV-mediated Tacr3 overexpression in the unilateral LHb significantly reversed pT-ION-induced anxiety-like behaviors but not allodynia. Whole-cell patch clamp recording showed that Tacr3 overexpression suppressed nerve injury-induced hyperexcitation of LHb neurons, and western blotting showed that the pT-ION-induced upregulation of p-CaMKII was reversed by AAV-mediated Tacr3 overexpression or chemicogenetic inhibition of glutamatergic neurons in the LHb. Moreover, not only anxiety-like behaviors, but also allodynia after pT-ION were significantly alleviated by chemicogenetic inhibition of bilateral LHb neurons or by bilateral Tacr3 overexpression in the LHb. In conclusion, Tacr3 in the LHb plays a protective role in treating trigeminal nerve injury-induced allodynia and anxiety-like behaviors by suppressing the hyperexcitability of LHb neurons. These findings provide a rationale for suppressing unilateral or bilateral LHb activity by targeting Tacr3 in treating the anxiety and pain associated with TN.

Platelet-rich fibrin membrane nerve guidance conduit: a potentially promising method for peripheral nerve injuries.

Platelet-rich fibrin membrane nerve guidance conduit: a potentially promising method for peripheral nerve injuries.

Comparison of functional and volumetric increase of the future remnant liver and postoperative outcomes after portal vein embolization and complete or partial associating liver partition and portal vein ligation for staged hepatectomy (ALPPS)

BackgroundPortal vein embolization (PVE) is performed to induce hypertrophy of an insufficient future remnant liver (FRL) before major liver resection. Associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) aims to offer a more rapid and increased hypertrophy response. The first stage can be performed with complete or partial (laparoscopic) transection of the liver parenchyma. This study aimed to investigate the increase in FRL volume and function, as well as postoperative outcomes after PVE or complete- or partial-ALPPS1.MethodsPatients with insufficient FRL undergoing either PVE or ALPPS underwent CT-volumetry and functional assessment using 99mTc-mebrofenin hepatobiliary scintigraphy (HBS). Severe complications and 90-day mortality were evaluated after liver resection.ResultsSeventy-two patients were included; 51 underwent PVE, 12 complete-ALPPS1 and 9 partial-ALPPS1 of which 7 laparoscopic. The median increase in FRL function was 1.5-, 1.7- and 1.3-fold higher, respectively, than the increase in volume; (P<0.01, P<0.01 and P=0.44). The target hypertrophy response did not differ between the groups, but was reached earlier in both ALPPS1 groups (8 and 10 days) compared to the PVE group (23 days). Of the resected patients, 18%, 30% and 17% had severe postoperative complications and the 90-day mortality was 2%, 25% and 0%, respectively.ConclusionsIncrease of FRL function exceeded increase of volume after both PVE and ALPPS1. The target hypertrophy response was reached earlier in ALPPS. Complete and partial-ALPPS1 showed comparable functional and volumetric hypertrophy responses. A (laparoscopic) partial-ALPPS1 is preferred considering lower morbidity and mortality rates after resection.

Partial Infraspinatus Tendon Transection as a Means for the Development of a Translational Ovine Chronic Rotator Cuff Disease Model.

Rotator cuff tendon tears are the most common soft tissue injuries in the shoulder joint. Various animal models have been described for this condition, but all current translational animal models have inherent weaknesses in their ability to generate chronically degenerated rotator cuff tendons. The objective of this study was to evaluate a partial infraspinatus tendon transection model as a means of creating a chronically degenerated rotator cuff tendon in an ovine model and compare the injury characteristics of this model to those observed in human patients with severe chronic rotator cuff tendon injuries. The infraspinatus tendons of six sheep were partially detached followed by capping of the detached medial section of the tendon with Gore-Tex. Human tissue samples of the supraspinatus tendon were harvested from patients undergoing primary reverse shoulder arthroplasty and served as positive controls of chronic rotator cuff tendinopathy. Transected sheep tendons were characterized predominantly by an acute reactive and reparative pathological process as compared with the chronic degenerative changes observed in the human tendons. In contrast, the non-transected portion of the ovine tendon showed histological changes, which were more chronic and degenerative in nature when compared with the transected tendon. Overall, histological features of the non-transected portion of ovine tendon were more similar to those observed in the chronic degenerated human tendon.

Thoracic adverse events following spinal manipulative therapy: a systematic review and narrative synthesis

ABSTRACT Objectives: Spinal manipulative therapy (SMT) is widely used by manual therapists to manage spinal complaints. Notwithstanding the perceived relative safety of SMT, instances of severe thoracic adverse events (AE) have been documented. An evidence synthesis is required to understand the nature, severity and characteristics of thoracic AE following all SMT. The primary objective of this study was to report thoracic AE following SMT and secondly to report patient characteristics to inform further research for safe practice. Methods: A systematic review and data synthesis were conducted according to a registered protocol (PROSPERO CRD42019123140). A sensitive topic-based search strategy for key databases, gray literature and registers used study population terms and keywords, to search to 12/6/19. Two reviewers were involved at each stage. Using the Oxford Center for Evidence-based Medicine (CEBM) the level evidence was evaluated with grade presented for each AE. Results were reported in the context of overall quality. Results: From 1013 studies identified from searches, 19 studies (15 single case studies and 4 case series) reporting 21 unique thoracic AE involving the spinal cord tissues [nonvascular (n = 7), vascular (n = 6)], pneumothorax or hemothorax (n = 3), fracture (n = 3), esophageal rupture (n = 1), rupture of thoracic aorta (n = 1), partial pancreatic transection (n = 1). Reported outcomes included fully recovery (n = 8), permanent neurological deficit (n = 5), and death (n = 4). Conclusion: Although causality cannot be confirmed, serious thoracic AE to include permanent neurological deficit and death have been reported following SMT. Findings highlight the importance of clinical reasoning, including pre-thrust examination, as part of best and safe practice for SMT.

Topical recombinant human Nerve growth factor (rh-NGF) is neuroprotective to retinal ganglion cells by targeting secondary degeneration

Optic neuropathy is a major cause of irreversible blindness worldwide, and no effective treatment is currently available. Secondary degeneration is believed to be the major contributor to retinal ganglion cell (RGC) death, the endpoint of optic neuropathy. Partial optic nerve transection (pONT) is an established model of optic neuropathy. Although the mechanisms of primary and secondary degeneration have been delineated in this model, until now how this is influenced by therapy is not well-understood. In this article, we describe a clinically translatable topical, neuroprotective treatment (recombinant human nerve growth factor, rh-NGF) predominantly targeting secondary degeneration in a pONT rat model. Topical application of rh-NGF twice daily for 3 weeks significantly improves RGC survival as shown by reduced RGC apoptosis in vivo and increased RGC population in the inferior retina, which is predominantly affected in this model by secondary degeneration. Topical rh-NGF also promotes greater axonal survival and inhibits astrocyte activity in the optic nerve. Collectively, these results suggest that topical rh-NGF exhibits neuroprotective effects on retinal neurons via influencing secondary degeneration process. As topical rh-NGF is already involved in early clinical trials, this highlights its potential in multiple indications in patients, including those affected by glaucomatous optic neuropathy.

Anisotropic Alginate Hydrogels Promote Axonal Growth across Chronic Spinal Cord Transections after Scar Removal

We have previously reported that cell-seeded alginate hydrogels (AHs) with anisotropic capillaries can restore the continuity of the spinal cord and support axonal regeneration in a rat model of acute partial spinal cord transection. Whether similar effects can be found after transplantation into sites of complete chronic spinal cord transections without additional growth-promoting stimuli has not been investigated. We therefore implanted AHs into the cavity of a chronic thoracic transection following scar resection (SR) 4 weeks postinjury and examined electrophysiological and functional recovery as well as regeneration of descending and ascending projections within and beyond the AH scaffold up to 3 months after engraftment. Our results indicate that both electrophysiological conductivity and locomotor function are significantly improved after AH engraftment. SR transiently impairs locomotor function immediately after surgery but does not affect long-term outcomes. Histological analysis shows numerous host cells migrating into the scaffold channels and a reduction of fibroglial scaring around the lesion by AH grafts. In contrast to corticospinal axons, raphaespinal and propriospinal descending axons and ascending sensory axons regenerate throughout the scaffolds and extend into the distal host parenchyma. These results further support the pro-regenerative properties of AHs and their therapeutic potential for chronic SCI in combination with other strategies to improve functional outcomes after spinal cord injury.

Characteristics of orofacial operant test for orofacial pain sensitivity caused by occlusal interference in rats

To compare the orofacial pain sensitivity with operant test and mechanical hyperalgesia with von Frey filaments of two orofacial pain models (EOI: experimental occlusal interference; pIONX: partial infraorbital nerve transection). To investigate the operant and evoked characteristics of EOI-rats. The orofacial operant behaviors were tested by Ugo Basile Orofacial Stimulation Test System. The mechanical thresholds of vibrissal pads were tested by von Frey filaments. Male Sprague-Dawley rats were randomly divided into eight groups: von Frey group: sham-EOI, EOI, sham-pIONX, pIONX (sham: sham-operated group); operant test group: sham-EOI, EOI, sham-pIONX, pIONX (sham: sham-operated group). The mechanical thresholds and orofacial operant behaviors were tested on pre-operation and post-operation days l, 3, 7, 10, 14 and 21. In pIONX of von Frey group, the mechanical withdrawal threshold decreased from days 1 to 21 (P<0.05), peaking from days 7 to 10, and lasted until the end of the experiment. There was no significant difference between the bilateral sides. In pIONX of operant test group, the total contact time decreased from days 10 to 21 (P<0.05), peaking from days 10 to 14, and lasted until the end of the experiment. In EOI of von Frey group, the mechanical withdrawal threshold decreased from days 3 to 21 (P<0.05), peaking on day 7, and lasted until the end of the experiment. There was no significant difference between the bilateral sides. In EOI of operant test group, the total contact time decreased from days 1 to 21 (P<0.05), peaking from days 7 to 10, and lasting until the end of experiment. Orofacial operant test is a stable method to evaluate orofacial pain behaviors, which could discriminate the feature of neuropathic and EOI orofacial pain. In these two animal models, both of the operant behaviors and the mechanical hyperalgesia exhibited different time courses. Orofacial operant test provides a novel method for evaluating the orofacial pain sensitivity and studying the orofacial pain mechanism thoroughly.

Diffusion Tensor Tractrography Visualizes Partial Nerve Laceration Severity as Early as 1 Week After Surgical Repair in a Rat Model Ex Vivo.

Previous studies in our laboratory have demonstrated that a magnetic resonance imaging method called diffusion tensor imaging (DTI) can differentiate between crush and complete transection peripheral nerve injuries in a rat model ex vivo. DTI measures the directionally dependent effect of tissue barriers on the random diffusion of water molecules. In ordered tissues such as nerves, this information can be used to reconstruct the primary direction of diffusion along fiber tracts, which may provide information on fiber tract continuity after nerve injury and surgical repair. Sprague-Dawley rats were treated with different degrees of partial transection of the sciatic nerve followed by immediate repair and euthanized after 1 week of recovery. Nerves were then harvested, fixed, and scanned with a 7 Tesla magnetic resonance imaging to obtain DTIand fiber tractography in each sample. Additional behavioral (sciatic function index, foot fault asymmetry) and histological (Toluidine blue staining) assessments were performed for validation. Tractography yielded a visual representation of the degree of injury that correlated with behavioral and histological evaluations. DTI tractography is a noninvasive tool that can yield a visual representation of a partial nerve transection as early as 1 week after surgical repair.

Intravitreal application of AAV-BDNF or mutant AAV-CRMP2 protects retinal ganglion cells and stabilizes axons and myelin after partial optic nerve injury

Secondary degeneration following an initial injury to the central nervous system (CNS) results in increased tissue loss and is associated with increasing functional impairment. Unilateral partial dorsal transection of the adult rat optic nerve (ON) has proved to be a useful experimental model in which to study factors that contribute to secondary degenerative events. Using this injury model, we here quantified the protective effects of intravitreally administered bi-cistronic adeno-associated viral (AAV2) vectors encoding either brain derived neurotrophic factor (BDNF) or a mutant, phospho-resistant, version of collapsin response mediator protein 2 (CRMP2T555A) on retinal ganglion cells (RGCs), their axons, and associated myelin. To test for potential synergistic interactions, some animals received combined injections of both vectors. Three months post-injury, all treatments maintained RGC numbers in central retina, but only AAV2-BDNF significantly protected ventrally located RGCs exclusively vulnerable to secondary degeneration. Behaviourally, treatments that involved AAV2-BDNF significantly restored the number of smooth-pursuit phases of optokinetic nystagmus. While all therapeutic regimens preserved axonal density and proportions of typical complexes, including heminodes and single nodes, BDNF treatments were generally more effective in maintaining the length of the node of Ranvier in myelin surrounding ventral ON axons after injury. Both AAV2-BDNF and AAV2-CRMP2T555A prevented injury-induced changes in G-ratio and overall myelin thickness, but only AAV2-BDNF administration protected against large-scale myelin decompaction in ventral ON. In summary, in a model of secondary CNS degeneration, both BDNF and CRMP2T555A vectors were neuroprotective, however different efficacies were observed for these overexpressed proteins in the retina and ON, suggesting disparate cellular and molecular targets driving responses for neural repair. The potential use of these vectors to treat other CNS injuries and pathologies is discussed.

Hypertrophy responses after portal vein embolization, complete and partial ALPPS in patients undergoing major liver resection

Background: Portal vein embolization (PVE) is the standard technique to induce hypertrophy of a small future remnant liver (FRL). ALPPS offers a more rapid hypertrophy response. The first stage (ALPPS1) can be performed with complete or partial (laparoscopic) transection of the liver parenchyma. The aim of this study was to investigate the increases in volume, function and postoperative outcomes among these procedures. Material & Methods: 72 patients with insufficient FRL were included in this retrospective analysis and were divided into three groups: 51 underwent PVE, 12 complete-ALPPS1 (open) and 9 partial-ALLPS1. All patients underwent CT-volumetry and functional assessment using 99mTc-mebrofenin hepatobiliary scintigraphy before and after VPE or ALPPS1. The increase in FRL function and volume were compared between the groups. Severe complications (Clavien-Dindo=3A) and 90-day mortality were evaluated after final liver resection. Results: The median increase in FRL function in the PVE, complete-ALPPS1 and partial-ALPPS1 group was 1.5, 1.7 and 1.3 fold higher, respectively, than the increase in volume; this was however not significant in the partial-ALPPS1 group (P<0.01, P<0.01 and P=0.44). The volumetric hypertrophy response did not differ between the three groups, but was reached earlier in both ALPPS1 groups (8 and 10 days, respectively) compared to the PVE group (23 days). Of all groups, 37 (73%), 10 (83%) and 6 (67%), respectively, proceeded with liver resection. All resected patients after partial-ALPPS1 had laparoscopic stage 1 in combination with percutaneous PVE. Of the resected patients, 18%, 30% and 17% had severe postoperative complications and the 90-day mortality was 2%, 25% and 0%, respectively. Conclusion: Increase of FRL function exceeded increase of volume after both PVE and ALPPS1. The target hypertrophy response was reached earlier in ALPPS. Complete and partial-ALPPS1 showed comparable functional and volumetric hypertrophy responses. Laparoscopic partial-ALPPS1 is preferred considering lower morbidity and mortality rates after resection.