Neural Connections between the Nervus Intermedius and the Facial and Vestibulocochlear Nerves in the Cerebellopontine Angle: An Anatomic Study

Purpose Unexpected clinical outcomes following transection of single nerves of the internal acoustic meatus have been reported. Therefore, this study aimed to investigate interneural connections between the nervus intermedius and the adjacent nerves in the cerebellopontine angle. Methods On 100 cadaveric sides, dissections were made of the facial/vestibulocochlear complex in the cerebellopontine angle with special attention to the nervus intermedius and potential connections between this nerve and the adjacent facial or vestibulocochlear nerves. Results A nervus intermedius was identified on all but ten sides. Histologically confirmed neural connections were found between the nervus intermedius and either the facial or vestibulocochlear nerves on 34 % of sides. The mean diameter of these small interconnecting nerves was 0.1 mm. The fiber orientation of these nerves was usually oblique (anteromedial or posterolateral) in nature, but 13 connections traveled anteroposteriorly. Connecting fibers were single on 81 % of sides, doubled on 16 %, and tripled on 3 %, six sides had connections both with the facial nerve anteriorly and the vestibular nerves posteriorly. On 6.5 % of sides, a connection was between the nervus intermedius and cochlear nerve. For vestibular nerve connections with the nervus intermedius, 76 % were with the superior vestibular nerve and 24 % with the inferior vestibular nerve. Conclusions Knowledge of the possible neural interconnections found between the nervus intermedius and surrounding nerves may prove useful to surgeons who operate in these regions so that inadvertent traction or transection is avoided. Additionally, unanticipated clinical presentations and exams following surgery may be due to such neural interconnections

Engraftment of neural stem cells in the treatment of spinal cord injury

AbstractSpinal cord injury is one of the main causes of disability in the young population. Based on the underlying pathological changes, many modalities of treatments have been trialed. However, the most promising so far, has been the replacement of lost cellular elements, using stem cells and non-stem cells transplantation. The route of cellular administration and engraftment into the site of injury is an important determining factor for functional outcome, and should be chosen to be safe and efficacious in human patients. Herein, we will review the underlying changes following spinal cord injury, and the possible routes of cellular transplantation

Revisiting the physiological effects of methylene blue as a treatment of cyanide intoxication

International audienceBACKGROUND:Although methylene blue (MB) had long been proposed to counteract the effects of cyanide (CN) intoxication, research on its mechanisms of action and efficacy has been abandoned for decades. Recent studies on the benefits of MB in post-anoxic injuries have prompted us to reexamine the relevance of this historical observation.METHODS:Our study was performed in adult male Sprague-Dawley rats and on HEK293T epithelial cells. First, the effects and toxicity of MB (0-80 mg/kg) on circulation and metabolism were established in four urethane-anesthetized rats. Then nine rats received a lethal infusion of a solution of KCN (0.75 mg/kg/min) and were treated by either saline or MB, at 20 mg/kg, a dose that we found to be innocuous in rat and to correspond to a dose of about 4 mg/kg in humans. MB was also administered 5 min after the end of a sub-lethal exposure to CN in a separate group of 10 rats. In addition, ATP/ADP ratio, ROS production, mitochondrial membrane potential (Δψm) and cellular O2 consumption rate (OCR) were determined in HEK293T cells exposed to toxic levels of CN (200 µM for 10 min) before and after applying a solution containing MB (1-100 µM for 10 min).RESULTS:Methylene blue was found to be innocuous up to 50 mg/kg. KCN infusion (0.75 mg/kg/min) killed all animals within 7-8 min. MB (20 mg/kg) administered at the same time restored blood pressure, cardiac contractility and limited O2 deficit, allowing all the animals to survive, without any significant methemoglobinemia. When administered 5 min after a non-lethal CN intoxication, MB sped up the recovery of lactate and O2 deficit. Finally, MB was able to decrease the production of ROS and restore the ATP/ADP ratio, Δψm as well as OCR of epithelial cells intoxicated by CN.CONCLUSIONS:The present observations should make us consider the potential interest of MB in the treatment of CN intoxication. The mechanisms of the antidotal properties of MB cannot be accounted for by the creation of a cyanomethemoglobinemia, rather its protective effects appears to be related to the unique properties of this redox dye, which, depending on the dose, could directly oppose some of the consequences of the metabolic depression produced by CN at the cellular level

Treatment of life-threatening H2S intoxication: Lessons from the trapping agent tetranitrocobinamide

We sought to evaluate the efficacy of trapping free hydrogen sulfide (H2S) following severe H2S intoxication. Sodium hydrosulfide solution (NaHS, 20 mg/kg) was administered intraperitoneally in 69 freely moving rats. In a first group (protocol 1), 40 rats were randomly assigned to receive saline (n = 20) or the cobalt compound tetranitrocobinamide (TNCbi) (n = 20, 75 mg/kg iv), one minute into coma, when free H2S was still present in the blood. A second group of 27 rats received TNCbi or saline, following epinephrine, 5 min into coma, when the concentration of free H2S has drastically decreased in the blood. In protocol 1, TNCbi significantly increased immediate survival (65 vs 20 %, p < 0.01) while in protocol 2, administration of TNCbi led to the same outcome as untreated animals. We hypothesize that the decreased efficacy of TNCbi with time likely reflects the rapid spontaneous disappearance of the pool of free H2S in the blood following H2S exposure

Stem cell therapy for spinal cord injury: The use of oligodendrocytes and motor neurons derived from human embryonic stem cells

Over the past few years, the understanding of stem cells as a potential therapeutic source has significantly evolved, and the previous concept of irreparable neural injury is being reconsidered. Stem cells are pluripotent cells with high differentiation potential. Induced proliferation and differentiation of these cells under optimal in vitro conditions has been used to generate different transplantable cells of various types and stages of development. For spinal cord injury recovery, the human embryonic stem cells and, recently, the human induced pluripotent stem cells are used as a main source, and two major types of cells are the target: the oligodendrocytes and motor neurons. The extensive experimental research efforts have focused on translating in vitro cellular regeneration of these cells to in vivo transplantation and survival of the transplants, in order to improve clinical outcomes. In this review, we will discuss the progressive development of the cellular generation protocols and the locomotor outcome of their transplantation at sites on spinal cord injury. Keywords: Stem cells, Spinal cord injury, Oligodendrocytes, Motor neurons, Embryonic stem cells, Induced pluripotent stem cell

Mouse models of spinal cord injury and stem cell transplantation

AbstractSpinal cord injury is one of the most devastating neurologic conditions that mostly affects young, and otherwise healthy, patients. Following the primary phase of injury, deleterious secondary inflammation and vascular disruption lead to a more sustained and permanent damage. Over the years, various animal models of spinal cord injury have been developed to help understand the mechanism and the pathophysiology of injury, and to develop reliable treatment strategies. These animal models, especially for the mouse, have also become the target of stem cell therapy, which aims to replace the lost cellular element at the site of injury. In this review, we will discuss the different types of mouse models of spinal cord injury, and elaborate on the therapeutic use of stem cells transplantation

Estimating indirect parental genetic effects on offspring phenotypes using virtual parental genotypes derived from sibling and half sibling pairs

Indirect parental genetic effects may be defined as the influence of parental genotypes on offspring phenotypes over and above that which results from the transmission of genes from parents to their children. However, given the relative paucity of large-scale family-based cohorts around the world, it is difficult to demonstrate parental genetic effects on human traits, particularly at individual loci. In this manuscript, we illustrate how parental genetic effects on offspring phenotypes, including late onset conditions, can be estimated at individual loci in principle using large-scale genome-wide association study (GWAS) data, even in the absence of parental genotypes. Our strategy involves creating "virtual" mothers and fathers by estimating the genotypic dosages of parental genotypes using physically genotyped data from relative pairs. We then utilize the expected dosages of the parents, and the actual genotypes of the offspring relative pairs, to perform conditional genetic association analyses to obtain asymptotically unbiased estimates of maternal, paternal and offspring genetic effects. We apply our approach to 19066 sibling pairs from the UK Biobank and show that a polygenic score consisting of imputed parental educational attainment SNP dosages is strongly related to offspring educational attainment even after correcting for offspring genotype at the same loci. We develop a freely available web application that quantifies the power of our approach using closed form asymptotic solutions. We implement our methods in a user-friendly software package IMPISH (IMputing Parental genotypes In Siblings and Half Siblings) which allows users to quickly and efficiently impute parental genotypes across the genome in large genome-wide datasets, and then use these estimated dosages in downstream linear mixed model association analyses. We conclude that imputing parental genotypes from relative pairs may provide a useful adjunct to existing large-scale genetic studies of parents and their offspring

Estimating indirect parental genetic effects on offspring phenotypes using virtual parental genotypes derived from sibling and half sibling pairs

Indirect parental genetic effects may be defined as the influence of parental genotypes on offspring phenotypes over and above that which results from the transmission of genes from parents to their children. However, given the relative paucity of large-scale family-based cohorts around the world, it is difficult to demonstrate parental genetic effects on human traits, particularly at individual loci. In this manuscript, we illustrate how parental genetic effects on offspring phenotypes, including late onset conditions, can be estimated at individual loci in principle using large-scale genome-wide association study (GWAS) data, even in the absence of parental genotypes. Our strategy involves creating “virtual” mothers and fathers by estimating the genotypic dosages of parental genotypes using physically genotyped data from relative pairs. We then utilize the expected dosages of the parents, and the actual genotypes of the offspring relative pairs, to perform conditional genetic association analyses to obtain asymptotically unbiased estimates of maternal, paternal and offspring genetic effects. We apply our approach to 19066 sibling pairs from the UK Biobank and show that a polygenic score consisting of imputed parental educational attainment SNP dosages is strongly related to offspring educational attainment even after correcting for offspring genotype at the same loci. We develop a freely available web application that quantifies the power of our approach using closed form asymptotic solutions. We implement our methods in a user-friendly software package IMPISH (IMputing Parental genotypes In Siblings and Half Siblings) which allows users to quickly and efficiently impute parental genotypes across the genome in large genome-wide datasets, and then use these estimated dosages in downstream linear mixed model association analyses. We conclude that imputing parental genotypes from relative pairs may provide a useful adjunct to existing large-scale genetic studies of parents and their offspring