Nerve Connections Research Articles

A Living 3D In Vitro Neuronal Network Cultured inside Hollow Electrospun Microfibers.

Micro/nanofiber-based scaffolds are widely used as a physical graft for axon growth in vitro for nerve tissue engineering. In this study, the fabrication of hollow coaxial microfibers with a 3D structure for directional neuronal cell culture is reported. The coaxial microfibers with poly-ε-caprolactone (PCL) sheath and polyvinyl alcohol (PVA) mixed with PC 12 cells as core are prepared using a coaxial double cylinder based on the liquid-liquid coflowing electrospinning method. By optimizing the electrospinning conditions, uniform microfibers with an average diameter of 54.6 µm are obtained using a PCL concentration of 20% and a tip-to-collector distance of 6 cm with a voltage of 6 kV. After selectively dissolving the PVA core, pheochromocytoma 12 (PC12) cells are successfully cultured inside these fibers. It is experimentally confirmed that such 3D hollow fibers can support and guide PC12 cells to grow, proliferate, and differentiate inside the hollow fibers and form 3D-connected neuronal networks with axons extended along the hollow fibers. This implies that complex nerve connection could be constructed using the low cost and powerful liquid-liquid coflowing electrospinning method, which open the door to culture well-controlled nerve connections as in vitro models for neural tissue regeneration, brain disease models, and so on.

Ephexin1 Is Required for Eph-Mediated Limb Trajectory of Spinal Motor Axons.

The precise assembly of a functional nervous system relies on the guided migration of axonal growth cones, which is made possible by signals transmitted to the cytoskeleton by cell surface-expressed guidance receptors. We investigated the function of ephexin1, a Rho guanine nucleotide exchange factor, as an essential growth-cone guidance intermediary in the context of spinal lateral motor column (LMC) motor axon trajectory selection in the limb mesenchyme. Using in situ mRNA detection, we first show that ephexin1 is expressed in LMC neurons of chick and mouse embryos at the time of spinal motor axon extension into the limb. Ephexin1 loss of function and gain of function using in ovo electroporation in chick LMC neurons, of either sex, perturbed LMC axon trajectory selection, demonstrating an essential role of ephexin1 in motor axon guidance. In addition, ephexin1 loss in mice of either sex led to LMC axon trajectory selection errors. We also show that ephexin1 knockdown attenuates the growth preference of LMC neurites against ephrins in vitro and Eph receptor-mediated retargeting of LMC axons in vivo, suggesting that ephexin1 is required in Eph-mediated LMC motor axon guidance. Finally, both ephexin1 knockdown and ectopic expression of nonphosphorylatable ephexin1 mutant attenuated the retargeting of LMC axons caused by Src overexpression, implicating ephexin1 as an Src target in Eph signal relay in this context. In summary, our findings demonstrate that ephexin1 is essential for motor axon guidance and suggest an important role in relaying ephrin:Eph signals that mediate motor axon trajectory selection.SIGNIFICANCE STATEMENT The proper development of functioning neural circuits requires precise nerve connections among neurons or between neurons and their muscle targets. The Eph tyrosine kinase receptors expressed in neurons are important in many contexts during neural-circuit formation, such as axon outgrowth, axon guidance, and synaptic formation, and have been suggested to be involved in neurodegenerative disorders, including amyotrophic lateral sclerosis and Alzheimer's disease. To dissect the mechanism of Eph signal relay, we studied ephexin1 gain of function and loss of function and found ephexin1 essential for the development of limb nerves toward their muscle targets, concluding that it functions as an intermediary to relay Eph signaling in this context. Our work could thus shed new light on the molecular mechanisms controlling neuromuscular connectivity during embryonic development.

Nerve terminals at the human corneoscleral limbus

AimsTo demonstrate and characterise distinct subepithelial compact nerve endings (CNE) at the human corneoscleral limbus.MethodsTen fresh human donor corneoscleral discs (mean age, 67 years) and 26 organ-cultured corneoscleral rims (mean...

Skin Stem Cell Resource Potential for Peripheral Nerve Repair Due to trauma of post regional anasthesia

This study is undertaken to investigate the utilization of rabbit skin to be used as a source of stem cell, especially stem cells that is derived from the skin, to provide the healing and connection of damaged peripheral nerves. Based on the existing studies, there are many failures in the healing and connection of nerve due to trauma after regional anesthesia, and there is an opportunity that stem cells from the skin is potential to help the process of healing and even improvement in the failure of nerve grafting. 24 rabbits is used as experimental animals in this research. The 24 rabbit devided into 2 groups, the first group is a control group without suplementary therapy of rabbit skin stem cells, and the second group is the treated group that given rabbit skin stem cell as a supplementary therapy to treat the peripheral nerve damage post ansthesia. The result of this study shows that there is a significant differences between control and treated group. Statistical analysis was performed by using reliability test - intraclass correlation coefficient to assess interobserver variation and investigate the correlation. Keywords : Stem Cell, Skin, Peripheral Nerve, Nerve Repair.

Dr Strange meets Dr Frankenstein

Fleming details neurosurgeon Sergio Canavero's motives and scientific credibility in performing a human head transplant. Unperturbed, two years ago Canavero agreed to help set up a team to carry out the procedure in China, working with Xiao-Ping Ren, an orthopaedic surgeon at Harbin Medical University who helped with one of the first hand transplants, in 1999. At the time of writing, Canavero claims several papers supporting the feasibility of human head transplantation will soon be published, that an operation could go ahead by the end of this year and that a game-changing announcement is imminent in China. Canavero calls his proposed procedure the head anastomosis venture, or HEAVEN. He says it would begin by cooling the donor body and recipient's head to delay tissue death. The heads would be detached and the donor body attached to the recipient's head. Polyethylene glycol would help fuse the cords by encouraging the fat in adjoining cells to mesh together. Stimulation from implanted electrodes would help to strengthen nerve connections.

Facial nerve: Essential aspects from the biomedical sciences

This article is a review of the anatomical literature about of the facial nerve. It has historical aspects, functional components, periphery route inside and outside of the petrous portion of the temporal bone. It describes the nerve branches and territories of innervation. It also describes its nervous connections to the brain`s stem, specifically to the pons, which is the cerebral center, where facial nerves’ motor and vegetative nucleus is located. The information presented here could be useful to students of medicine, dentistry and others health programs at level of undergraduate and postgraduate. In this article have been used known books of anatomy and neuroanatomy. It has been also used articles of the last five years written by professional in neurosurgery, otorhinolaryngology and morphology. This article presents a correlation among the facial nerve anatomy and its implications in pathology, trauma and surgery of head and neck region.

Marcus Gunn Syndrome and implications for Oral and Maxillofacial surgery (OMFS)

Introduction Marcus Gunn Syndrome, also known as Jaw Wink Syndrome or trigemino-oculomotor synkinesis, was first reported in 1883. It typically presents at birth with unilateral ptosis and eyelid elevation on jaw opening. Pathophysiology is explained by an oculofacial synkinesis. There is an aberrant connection of the oculomotor nerve and the mandibular branch of the trigeminal nerve resulting in eyelid elevation on mouth opening. The typically congenital syndrome is exceptionally rare. It is often diagnosed in infancy with complete ophthalmic examination and ptosis evaluation. This syndrome does not often require surgical intervention but it may still have an impact in clinical management. Case description A 32-year-old male presented in the OMFS outpatient clinic in Countess of Chester Hospital for extraction of his lower third molars. His past medical history included a known diagnosis of Marcus Gunn Syndrome but he was otherwise fit and well. He had resting ptosis of the left and elevation of the left eyelid on jaw protrusion. Results and conclusions Third molars were removed uneventfully under local anesthesia and no further treatment was required. Literature suggests that patients with Marcus Gunn Syndrome may have an atypical oculocardiac reflex during their surgical procedure and patients are at increased risk of malignant hypothermia. In this case, the procedure was performed under local anesthesia but this condition may impact on surgical planning if general anesthesia was to be considered.

Spinal Accessory Nerve to Triceps Transfer for Recovery of Elbow Extension in Traumatic Brachial Plexus Injuries

There is no financial information to disclose. To facilitate stabilization of the elbow after brachial plexus injury, reconstruction of not only elbow flexion but also elbow extension is desired. The aim of this study was to evaluate prevalence and quality of restored elbow extension in brachial plexus injury patients, who underwent spinal accessory nerve (SAN) to the radial nerve branch to the long head of the triceps (BLHT) transfer with an autologous nerve graft interposition and to identify patient and injury related factors that influence functional triceps outcome. In this retrospective cohort study, 42 patients with brachial plexus injury were included and evaluated. As a part of their reconstructive plan, all patients underwent SAN transfer to the BLHT using long autologous nerve grafts to achieve tension free nerve connections. The primary outcome measurement was elbow extension strength (MRC score). Furthermore, EMG recordings were used to measure triceps reinnervation. Various statistical tests were used for group comparisons as appropriate (e.g. Mann-Whitney U and Fisher’s exact tests). The effect of individual clinical and demographic factors was evaluated using univariate logistic regression analysis. Evaluating the total cohort (n = 42) with a follow-up between 12 and 45 months (mean 24.3 months), we found clinically meaningful recovery in 52.4% of patients. Triceps muscle strength of M0 and M1 was accomplished by 45.2%; 19.1% achieved M2 and 35.7% reached a muscle strength of M3 or more. A negative correlation was found between the existence of concomitant vascular injury and the functional outcomes of the triceps muscle. A subgroup with a minimum of 20 months follow up (n = 26) showed a clinically meaningful recovery of 69.5%. In the same group, 7.7% had no muscle function recovery (M0), 19.2% reached M1 and 23.1% achieved M2. In this cohort, 50% of the patients obtained a functional recovery of M3 or better, with 34.5% reaching M4 elbow extension. •Transfer of the SAN to the BLHT is an adequate option for restoration of elbow extension after brachial plexus injury, despite the relatively long time to reinnervation•Concomitant vascular injury impairs the functional recovery of the triceps muscle•Use of shorter nerve grafts is recommended when possible

Spatio-temporal pattern of neuronal differentiation in the Drosophila visual system: A user’s guide to the dynamic morphology of the developing optic lobe

Visual information processing in animals with large image forming eyes is carried out in highly structured retinotopically ordered neuropils. Visual neuropils in Drosophila form the optic lobe, which consists of four serially arranged major subdivisions; the lamina, medulla, lobula and lobula plate; the latter three of these are further subdivided into multiple layers. The visual neuropils are formed by more than 100 different cell types, distributed and interconnected in an invariant highly regular pattern. This pattern relies on a protracted sequence of developmental steps, whereby different cell types are born at specific time points and nerve connections are formed in a tightly controlled sequence that has to be coordinated among the different visual neuropils. The developing fly visual system has become a highly regarded and widely studied paradigm to investigate the genetic mechanisms that control the formation of neural circuits. However, these studies are often made difficult by the complex and shifting patterns in which different types of neurons and their connections are distributed throughout development. In the present paper we have reconstructed the three-dimensional architecture of the Drosophila optic lobe from the early larva to the adult. Based on specific markers, we were able to distinguish the populations of progenitors of the four optic neuropils and map the neurons and their connections. Our paper presents sets of annotated confocal z-projections and animated 3D digital models of these structures for representative stages. The data reveal the temporally coordinated growth of the optic neuropils, and clarify how the position and orientation of the neuropils and interconnecting tracts (inner and outer optic chiasm) changes over time. Finally, we have analyzed the emergence of the discrete layers of the medulla and lobula complex using the same markers (DN-cadherin, Brp) employed to systematically explore the structure and development of the central brain neuropil. Our work will facilitate experimental studies of the molecular mechanisms regulating neuronal fate and connectivity in the fly visual system, which bears many fundamental similarities with the retina of vertebrates.

A novel method of lengthening the accessory nerve for direct coaptation during nerve repair and nerve transfer procedures.

OBJECTIVE The accessory nerve is frequently repaired or used for nerve transfer. The length of accessory nerve available is often insufficient or marginal (under tension) for allowing direct coaptation during nerve repair or nerve transfer (neurotization), necessitating an interpositional graft. An attractive maneuver would facilitate lengthening of the accessory nerve for direct coaptation. The aim of the present study was to identify an anatomical method for such lengthening. METHODS In 20 adult cadavers, the C-2 or C-3 connections to the accessory nerve were identified medial to the sternocleidomastoid (SCM) muscle and the anatomy of the accessory nerve/cervical nerve fibers within the SCM was documented. The cervical nerve connections were cut. Lengths of the accessory nerve were measured. Samples of the cut C-2 and C-3 nerves were examined using immunohistochemistry. RESULTS The anatomy and adjacent neural connections within the SCM are complicated. However, after the accessory nerve was "detethered" from within the SCM and following transection, the additional length of the accessory nerve increased from a mean of 6 cm to a mean of 10.5 cm (increase of 4.5 cm) after cutting the C-2 connections, and from a mean of 6 cm to a mean length of 9 cm (increase of 3.5 cm) after cutting the C-3 connections. The additional length of accessory nerve even allowed direct repair of an infraclavicular target (i.e., the proximal musculocutaneous nerve). The cervical nerve connections were shown not to contain motor fibers. CONCLUSIONS An additional length of the accessory nerve made available in the posterior cervical triangle can facilitate direct repair or neurotization procedures, thus eliminating the need for an interpositional nerve graft, decreasing the time/distance for regeneration and potentially improving clinical outcomes.

Reinnervation post-Heart transplantation

Heart transplantation results in complete denervation of the donor heart with loss of afferent and efferent nerve connections. The majority of patients remain completely denervated during the first 6-12 months following transplantation. Evidence of reinnervation is usually found during the second year after transplantation and involve the myocardial muscle, sinoatrial node, and coronary vessels, but remains incomplete and regionally limited many years post-transplant. Restoration of cardiac innervation can improve exercise capacity as well as blood flow regulation in the coronary arteries, and hence improve quality of life. As yet, there is no evidence that the reinnervation process is associated with the occurrence of allograft-related events or survival.

Comparative quantitative assessment of the human corneal sub-basal nerve plexus by in vivo confocal microscopy and histological staining.

PurposeThis study was designed to compare and contrast quantitative data of the human corneal sub-basal nerve plexus (SBP) evaluated by two different methods: in vivo confocal microscopy (IVCM), and immunohistochemical staining of ex vivo donor corneas.MethodsSeven parameters of the SBP in large-scale IVCM mosaicking images from healthy subjects were compared with the identical parameters in ex vivo donor corneas stained by β-III-tubulin immunohistochemistry. Corneal nerve fiber length (CNFL), corneal nerve fiber density (CNFD), corneal nerve branch density (CNBD), average weighted corneal nerve fiber tortuosity (CNFTo), corneal nerve connection points (CNCP), average corneal nerve single-fiber length (CNSFL), and average weighted corneal nerve fiber thickness (CNFTh) were calculated using a dedicated, published algorithm and compared.ResultsOur experiments showed significantly higher values for CNFL (50.2 vs 21.4 mm/mm2), CNFD (1358.8 vs 277.3 nerve fibers/mm2), CNBD (847.6 vs 163.5 branches/mm2), CNFTo (0.095 vs 0.081 μm-1), and CNCP (49.4 vs 21.6 connections/mm2) in histologically staining specimens compared with IVCM images. In contrast, CNSFL values were higher in IVCM images than in histological specimens (32.1 vs 74.1 μm). No significant difference was observed in CNFTh (2.22 vs 2.20 μm) between the two groups.ConclusionsThe results of this study have shown that IVCM has an inherently lower resolution compared with ex vivo immunohistochemical staining of the corneal SBP and that this limitation leads to a systematic underestimation of several SBP parameters. Despite this shortcoming, IVCM is a vital clinical tool for in vivo characterization, quantitative clinical imaging, and evaluation of the human corneal SBP.

Progression of motor neuron disease is accelerated and the ability to recover is compromised with advanced age in rNLS8 mice.

In order to treat progressive paralysis in ALS patients, it is critical to develop a mouse that closely models human ALS in both pathology and also in the timing of these events. We have recently generated new TDP-43 bigenic mice (called rNLS8) with doxycycline (Dox)-suppressible expression of human TDP-43 (hTDP-43) harboring a defective nuclear localization signal (hTDP-43∆NLS) under the control of the NEFH promoter. Our previous studies characterized the pathology and disease course in young rNLS8 mice following induction of neuronal hTDP-43ΔNLS. We now seek to examine if the order and timing of pathologic events are changed in aged mice. We found that the expression of hTDP-43∆NLS in 12+ month old mice did not accelerate the appearance of neuromuscular abnormalities or motor neuron (MN) death in the lumbar spinal cord (SC), though disease progression was accelerated. However, following suppression of the transgene, important differences between young and aged rNLS8 mice emerged in functional motor recovery. We found that recovery was incomplete in aged mice relative to their younger treatment matched counterparts based on gross behavioral measures and physiological recordings from the animals’ gastrocnemius (GC) muscles, despite muscle reinnervation by surviving MNs. This is likely because the reinnervation most often only resulted in partial nerve and endplate connections and the muscle’s junctional folds were much more disorganized in aged rNLS8 mice. We believe that these studies will be an important basis for the future design and evaluation of therapies designed to slow denervation and promote re-innervation in adult ALS patients.

Neuropharmacologic Approaches to Restore the Brain's Microenvironment.

Maintaining the central nervous system microenvironment after injury, infection, inflammatory and degenerative diseases is contingent upon adequate control of glial homeostatic functions. Disease is caused by microbial, environmental and endogenous factors that compromise ongoing nervous system functions. The final result is neuronal injury, dropout and nerve connection loss, and these underlie the pathobiology of Alzheimer's and Parkinson's disease, amyotrophic lateral sclerosis, stroke, and bacterial, parasitic and viral infections. However, what promotes disease are homeostatic changes in the brain's microenvironment affected by innate glial immune pro-inflammatory and adaptive immune responses. These events disturb the brain's metabolic activities and communication abilities. How the process affects the brain's regulatory functions that can be harnessed for therapeutic gain is the subject at hand. Specific examples are provided that serve to modulate inflammation and improve disease outcomes specifically for HIV-associated neurocognitive disorders.

Endogenous spontaneous ultraweak photon emission in the formation of eye-specific retinogeniculate projections before birth.

In 1963, it was suggested [Sperry, R.W. (1963). Chemoaffinity in the orderly growth of nerve fiber patterns and connections. Proc. Natl. Acad. Sci. USA 50, 703-710.] that molecular cues can direct the development of orderly connections between the eye and the brain (the "chemoaffinity hypothesis"). In the same year, the amazing degree of functional accuracy of the visual pathway in the absence of any external light/photon perception prior to birth [Wiesel, T.N and Hubel, D.H. (1963). Single-cell responses in striate cortex of kittens deprived of vision in one eye. J. Neurophysiol. 26, 1003-1017.] was discovered. These recognitions revealed that the wiring of the visual system relies on innate cues. However, how the eye-specific retinogeniculate pathway can be developed before birth without any visual experience is still an unresolved issue. In the present paper, we suggest that Müller cells (functioning as optical fibers), Müller cell cone (i.e. the inner half of the foveola that is created of an inverted cone-shaped zone of Müller cells), discrete retinal noise of rods, and intrinsically photosensitive retinal ganglion cells might have key functions by means of retinal spontaneous ultraweak photon emission in the development of eye-specific retinogeniculate pathways prior to birth.

Oosorption in the stink bug Plautia stali: role of Juvenile hormone in the induction of oosorption

AbstractTo clarify the role of Juvenile hormone (JH) in the induction of oosorption in females of the stink bug Plautia stali Scott (Heteroptera: Pentatomidae), the effects of extirpation and implantation of the corpus cardiac‐corpus allatum complex (CC‐CA) are examined in fed and starved adults, respectively. Removal of CC‐CA induces oosorption in fed females, whereas CC‐CA implantation stimulates ovary development in starved females. Transection of the nervous connections between the brain and CC‐CA also exerts a stimulatory effect on ovary development. Uptake of yolk protein by the oocytes, assessed in terms of incorporation of a fluorescence dye, occurs on the day after food deprivation but ceases within 1 day after allatectomy. When females are deprived of food, beginning on day 3 of adult life, and treated with JH III skipped bisepoxide (JHSB3) on the same day, their ovaries develop in a dose‐dependent fashion. Approximately half of the starved females that received JHSB3 application on day 5 undergo oosorption in the terminal oocytes. This indicates that the critical starvation period for oosorption induction is approximately 2 days, and the earlier half of this period may reflect the time required for the brain to detect poor nutritional condition. During the latter half, in response to food deprivation, the brain inhibits JH biosynthesis by the corpus allatum through nervous connections, resulting in a low JH titre, which in turn induces oosorption.

Variation of the Musculocutaneous Nerve: A Case Report

In normal individuals the Musculocutaneous nerve is terminal branch of the lateral cord of the brachial plexus. During routine dissection conducted for undergraduates study in the Department of Anatomy, Tehran medical college, the Musculocutaneous nerve was found variation and two roots of median nerve have united and median nerve innervated muscles in one adult Iranian woman cadaver. In others words, Variations in the origins and distributions of the brachial plexus had been documented by previous researcher. Variations in the origin course, branching pattern, termination and connection of the Musculocutaneous nerve are not uncommon. Knowledge of these variations is important to the anatomist, orthopaedicans, neurologist and anesthetist.

Intraparotid Location of the Great Auricular Nerve: A New Anatomical Basis for Gustatory Sweating Syndrome.

Gustatory sweating syndrome (also known as Frey syndrome or auriculotemporal nerve syndrome) is thought to result from a lesion of the auriculotemporal nerve. A lesion of this nerve can lead to aberrant regeneration of nerve fibers to the sweat glands and blood vessels. The occurrence of signs outside the region of the auriculotemporal nerve prompted the author to search for another anatomical basis for this syndrome. The author dissected 46 great auricular nerves from their origin to the parotid gland and in the infratemporal fossa. The author investigated the different connections of the great auricular nerve with the facial nerve and the auriculotemporal nerve. The great auricular nerve was found to essentially be a parotid nerve. There was a set of intraparotid nerve connections on 14 of the 46 half-heads that were dissected. The author was able to discern three types of parotid great auricular nerve connections, which he designates as either type 1, connection with the trunk of the facial nerve and its branches; type 2, connection with the auriculotemporal nerve; or type 3, connection with the auriculotemporal nerve and the facial nerve with the formation of an intraparotid nerve circle. Having clearly established the nerve connections of the great auricular nerve, the author believes that it is primarily this nerve that is responsible for gustatory sweating syndrome. This allows for a better understanding of the sympathetic nervous system features and the manifestation of the syndrome outside the region of the auriculotemporal nerve.

The role of central nervous system connections in POTS and pediatric FGID

The role of central nervous system connections in POTS and pediatric FGID

Neural connections between the nervus intermedius and the facial and vestibulocochlear nerves in the cerebellopontine angle: an anatomic study.

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. 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. 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 0.1mm. 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. 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.