Loss Of Nerve Tissue Research Articles

Cell-Free Extracts from Human Fat Tissue with a Hyaluronan-Based Hydrogel Attenuate Inflammation in a Spinal Cord Injury Model through M2 Microglia/Microphage Polarization.

Treatment for spinal cord injuries (SCIs) is often ineffective because SCIs result in a loss of nerve tissue, glial scar formation, local ischemia and secondary inflammation. The current promising strategy for SCI is the combination of bioactive materials and cytokines. Bioactive materials support the injured spinal cord, stabilize the morphology, and avoid excessive inflammatory responses. Fat extract (FE) is a cell-free liquid component containing a variety of cytokines extracted from human fat tissue using mechanical methods. In this research, a biocompatible HAMC (hyaluronan and methylcellulose) loaded with FE is used to treat a model of spinal cord contusion in mice. The composite not only inhibits death of neuro- and vascular cells and leads to the preservation of neural and vascular structure, but also modulates the inflammatory phenotype of macrophages in the locally injured region. Specifically, FE promotes the polarization of macrophages from an inflammatory M1 phenotype to an anti-inflammatory M2 phenotype. During the screening of the involved pathways, it is corroborated that activation of the STAT6/Arg-1 signaling pathway is involved in macrophage M2 polarization. In summary, FE is a promising treatment for SCI, as it is easy to obtain, nonimmunogenic, and effective.

Olfactory Mucosal Auto-transplantation in Spinal Cord Injury: A Clinical Trial, Saudi Arabia

Introduction: Spinal cord injury (SCI) results in loss of nervous tissue and consequently loss of motor and sensory function. Despite significant improvements in the early medical and surgical management of SCI, there is no effective treatment available that restores the injury-induced loss of function to a degree that an independent life can be guaranteed. Restoration of function and reversal of paralysis following SCI is among the most daunting challenges in all of neuroscience research.
 Methodology: We decided to study the outcomes in chronic SCI (CSCI) after autologous olfactory mucosal transplantation into the spinal cord following detethering of the cord. The human surgical procedure of autologous olfactory mucosal transplantation was first developed by Carlos Lima and his colleagues. These investigators provided guidance for the surgical procedures in this study and the procedures on the first six participants were performed in their presence.
 Result: Patients were screened at different centers in the kingdom. A stringent inclusion and exclusion criteria were applied. Patients for this clinical trial were selected from individuals that suffered an SCI at least 12 months before their assessment and were chronically paraplegic or tetraplegic. The final twenty participants were selected after screening more than 125 patients. While some of them were rejected for medical reasons, some refused to participate upon receiving a full briefing and some of them were unable to fulfill the required psychosocial criteria.
 Conclusion: The details of the patients and the changes observed in their conditions post olfactory mucosal auto-transplantation will be discussed in detail in oral presentation with graphic results with marked significant improvement in motor and sensory levels of SCI patients as compared to before transplantation of olfactory mucosa. Olfactory unsheathing cells (OECs) are glia cells and continuous axon extension and successful topographic targeting of the olfactory receptor neurons responsible for the sense of smell (olfaction). Due to this distinctive property, OECs have been trialed in human cell transplant therapies to assist in the repair of central nervous system injuries, particularly those of the spinal cord. Although many studies have reported neurological improvement, therapy remains inconsistent and requires further improvement.

Poly-3-hydroxybutyrate strips seeded with regenerative cells are effective promoters of peripheral nerve repair.

Peripheral nerve injuries are often associated with loss of nerve tissue and require a graft to bridge the gap. Autologous nerve grafts are still the 'gold standard' in reconstructive surgery but have several disadvantages, such as sacrifice of a functional nerve, neuroma formation and loss of sensation at the donor site. Bioengineered grafts represent a promising approach to address this problem. In this study, poly-3-hydroxybutyrate (PHB) strips were used to bridge a 10 mm rat sciatic nerve gap and their effects on long-term (12 weeks) nerve regeneration were compared. PHB strips were seeded with different cell types, either primary Schwann cells (SCs) or SC-like differentiated adipose-derived stem cells (dASCs) suspended in a fibrin glue matrix. The control group was PHB and fibrin matrix without cells. Functional and morphological properties of the regenerated nerve were assessed using walking track analysis, EMGs, muscle weight ratios and muscle and nerve histology. The animals treated with PHB strips seeded with SCs or dASCs showed significantly better functional ability than the control group. This correlated with less muscle atrophy and greater axon myelination in the cell groups. These findings suggest that the PHB strip seeded with cells provides a beneficial environment for nerve regeneration. Furthermore, dASCs, which are abundant and easily accessible, constitute an attractive cell source for future applications of cell therapy for the clinical repair of traumatic nerve injuries. Copyright © 2015 John Wiley & Sons, Ltd.

Muscle recovery after repair of short and long peripheral nerve gaps using fibrin conduits

Peripheral nerve injuries with loss of nervous tissue are a significant clinical problem and are currently treated using autologous nerve transplants. To avoid the need for donor nerve, which results in additional morbidity such as loss of sensation and scarring, alternative bridging methods have been sought. Recently we showed that an artificial nerve conduit moulded from fibrin glue is biocompatible to nerve regeneration. In this present study, we have used the fibrin conduit or a nerve graft to bridge either a 10 mm or 20 mm sciatic nerve gap and analyzed the muscle recovery in adult rats after 16 weeks. The gastrocnemius muscle weights of the operated side were similar for both gap sizes when treated with nerve graft. In contrast, muscle weight was 48.32 ± 4.96% of the contra-lateral side for the 10 mm gap repaired with fibrin conduit but only 25.20 ± 2.50% for the 20 mm gap repaired with fibrin conduit. The morphology of the muscles in the nerve graft groups showed an intact, ordered structure, with the muscle fibers grouped in fascicles whereas the 20 mm nerve gap fibrin group had a more chaotic appearance. The mean area and diameter of fast type fibers in the 20 mm gap repaired with fibrin conduits were significantly ( P < 0.01) worse than those of the corresponding 10 mm gap group. In contrast, both gap sizes treated with nerve graft showed similar fiber size. Furthermore, the 10 mm gaps repaired with either nerve graft or fibrin conduit showed similar muscle fiber size. These results indicate that the fibrin conduit can effectively treat short nerve gaps but further modification such as the inclusion of regenerative cells may be required to attain the outcomes of nerve graft for long gaps.

A clinical perspective of spinal cord injury

Spinal cord injury (SCI) results in loss of nervous tissue in the spinal cord and consequently loss of motor and sensory function. The impairments are permanent because endogenous repair events fail to restore the damaged axonal circuits that are involved in function. There is no treatment available that restores the injury-induced loss of function. The consequences of SCI are devastating physically and socially. The assessment of functional loss after SCI has been standardized in the larger part of the world. For medical care however there are no standards available. During the early phase, treatments that stabilize the patient's health and attempt to limit further neurological deterioration need to be implemented. During the later phase of SCI, the focus needs to be on prevention and/or treatment of secondary complications such as pain, pressure ulcers, and infections. Neuroprotective, axon growth-promoting and rehabilitative repair approaches are currently being tested but, so far, none of these has emerged as an effective treatment that reverses the consequences of SCI. Promising new repair approaches have emerged from the laboratory during the last years and entered the clinical arena including stem cell transplantation and functional electrical stimulation.

Biodegradable fibrin conduit promotes long-term regeneration after peripheral nerve injury in adult rats

Peripheral nerve injuries are often associated with loss of nerve tissue and require autologous nerve grafts to provide a physical substrate for axonal growth. Biosynthetic neural conduits could be an alternative treatment strategy in such injuries. The present study investigates the long-term effects of a tubular fibrin conduit on neuronal regeneration, axonal sprouting and recovery of muscle weight following peripheral nerve injury and repair in adult rats. Sciatic axotomy was performed proximally in the thigh to create a 10-mm gap between the nerve stumps. The injury gap was bridged by using a 14-mm-long fibrin glue conduit, entubulating 2 mm of the nerve stump at each end. A reversed autologous nerve graft was used as a control. The regenerative response from sensory and motor neurones was evaluated following retrograde labelling with Fast Blue fluorescent tracer. In control experiments, at 16 weeks following peripheral nerve grafting, 5184 (±574 standard error of mean (SEM)) sensory dorsal root ganglion neurones and 1001 (±37 SEM) spinal motor neurones regenerated across the distal nerve-graft interface. The fibrin conduit promoted regeneration of 60% of sensory neurones and 52% of motor neurones when compared to the control group. The total number of myelinated axons in the distal nerve stump in the fibrin-conduit group reached 86% of the control and the weight of gastrocnemius and soleus muscles recovered to 82% and 89% of the controls, respectively. The present results suggest that a tubular fibrin conduit can be used to promote neuronal regeneration following peripheral nerve injury.

Host strain-dependent difference in susceptibility in a rat model of herpes simplex type 1 encephalitis

Herpes simplex encephalitis (HSE) is characterized by severe focal brain inflammation leading to substantial loss of nervous tissue. The authors established a model of Herpes simplex virus type 1 (HSV)-1-induced acute encephalitis in the rat by injecting into the whiskers' area a virus strain isolated from a fatal human HSE case. The model might resemble natural propagation of HSV-1 in humans; spreading from the mouth and lips via the trigeminal nerve to trigeminal ganglia and subsequently entering the central nervous system (CNS). HSV-1 infected Dark Agouti (DA) rats developed a well-synchronized disease and died 5 days after inoculation. HSV-1 detection by quantitative polymerase chain reaction (qPCR), virus isolation and immunohistochemistry, magnetic resonance imaging, and histopathological examination verified dramatic encephalitis mainly in the brainstem, but also in the olfactory bulb and other segments of the brain of diseased rats. In contrast, Piebald Virol Glaxo (PVG) rats were completely resistant to disease, displaying a more rapid clearance of peripheral infection and no evidence of virus entering into neither the trigeminal ganglia nor the CNS. These results suggest a regulation of susceptibility to HSV-1-induced encephalitis at the level of peripheral infection and subsequent neuronal uptake/transport of the virus. This provides a basis for future positioning of genetic polymorphisms regulating HSE and for dissection of important pathogenetic mechanisms of this severe human disease.

Interfascicular autologous grafts in the repair of peripheral nerves: eight years experience

The author reports his experience with the repair of peripheral nerves using interfascicular autologous grafts. There were 52 lesions treated with more than 69% good results judged by motor and sensory recovery. Attention is focused on some factors that strongly influence recovery such as the length of the graft, the distal suture and loss of nerve tissue.

Peripheral nerve injuries: Studies in higher nonhuman primates

Two skeletally mature baboons underwent comparative neurorrhapies following transsection of both ulnar nerves without loss of nerve tissue. In baboon 1 there was no difference in objective evaluations at 12 months when an epineurial neurorrhaphy was compared to a perineurial fascicular neurorrhaphy. In baboon 2, the one that had interfacicular grafts in one upper extremity and an epineurial neurorrhaphy on the other side, there was significantly better functional return on the epineurial side than one the graft side. Grass and histological evaluation showed that the grafts retained their integrity and regenerating axons transversed the grafts well.

NEUROLOGIC SYMPTOMS FOLLOWING EXTENSIVE OCCLUSION OF THE COMMON OR INTERNAL CAROTID ARTERY

Occlusion of the carotid vessels is not a rare lesion. Since the introduction of surgical treatment for pulsating exophthalmos, intracranial aneurysms and uncontrollable nasal hemorrhage by ligation either of the common carotid or of the common and internal carotid arteries, many cases with neurologic residua have been reported. However, the changes following surgical ligation rarely show the clearcut syndromes produced by the extensive spontaneous closure of these vessels. The operations are usually performed on young persons in whom the collateral circulation seems satisfactory, so that the loss of nerve tissue is kept to a minimum. Even in the most extensive ligation, as practiced by Dandy1and others,1athe length of the vessels occluded is not as great as that produced by sudden thrombosis or by an embolus with a long thrombus behind it. When spontaneous closure of the carotid arteries on one side occurs, the thrombus may extend