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Sample records for nerve injury model

  1. Reactive microglia after taste nerve injury: comparison to nerve injury models of chronic pain.

    PubMed

    Bartel, Dianna L; Finger, Thomas E

    2013-01-01

    The chorda tympani (CT), which innervates taste buds on the anterior portion of the tongue, is susceptible to damage during inner ear surgeries. Injury to the CT causes a disappearance of taste buds, which is concurrent with significant microglial responses at central nerve terminals in the nucleus of the solitary tract (nTS). The resulting taste disturbances that can occur may persist for months or years, long after the nerve and taste buds have regenerated. These persistent changes in taste sensation suggest alterations in central functioning and may be related to the microglial responses. This is reminiscent of nerve injuries that result in chronic pain, where microglial reactivity is essential in maintaining the altered sensation (i.e., pain). In these models, methods that diminish microglial responses also diminish the corresponding pain behavior. Although the CT nerve does not contain nociceptive pain fibers, the microglial reactivity after CT damage is similar to that described in pain models. Therefore, methods that decrease microglial responses in pain models were used here to test if they could also affect microglial reactivity after CT injury. Treatment with minocycline, an antibiotic that dampens pain responsive microglia, was largely ineffective in diminishing microglial responses after CT injury. In addition, signaling through the toll-like 4 receptor (TLR4) does not seem to be required after CT injury as blocking or deleting TLR4 had no effect on microglial reactivity. These results suggest that microglial responses following CT injury rely on different signaling mechanisms than those described in nerve injuries resulting in chronic pain.

  2. Misdirection of regenerating motor axons after nerve injury and repair in the rat sciatic nerve model

    PubMed Central

    de Ruiter, Godard C. W.; Malessy, Martijn J. A.; Alaid, Awad O.; Spinner, Robert J.; Engelstad, JaNean K.; Sorenson, E. J.; Kaufman, K. R.; Dyck, Peter J.; Windebank, Anthony J.

    2010-01-01

    Misdirection of regenerating axons is one of the factors that can explain the poor results often found after nerve injury and repair. In this study, we quantified the degree of misdirection and the effect on recovery of function after different types of nerve injury and repair in the rat sciatic nerve model; crush injury, direct coaptation, and autograft repair. Sequential tracing with retrograde labeling of the peroneal nerve before and 8 weeks after nerve injury and repair was performed to quantify the accuracy of motor axon regeneration. Digital video analysis of ankle motion was used to investigate the recovery of function. In addition, serial compound action potential recordings and nerve and muscle morphometry were performed. In our study, accuracy of motor axon regeneration was found to be limited; only 71% (±4.9%) of the peroneal motoneurons were correctly directed 2 months after sciatic crush injury, 42% (±4.2%) after direct coaptation, and 25% (±6.6%) after autograft repair. Recovery of ankle motion was incomplete after all types of nerve injury and repair and demonstrated a disturbed balance of ankle plantar and dorsiflexion. The number of motoneurons from which axons had regenerated was not significantly different from normal. The number of myelinated axons was significantly increased distal to the site of injury. Misdirection of regenerating motor axons is a major factor in the poor recovery of nerves that innervate different muscles. The results of this study can be used as basis for developing new nerve repair techniques that may improve the accuracy of regeneration. PMID:18448099

  3. ISCHEMIC MODEL OF OPTIC NERVE INJURY

    PubMed Central

    Cioffi, George A

    2005-01-01

    Purpose It is proposed that the anterior optic nerve is specifically susceptible to microcirculatory compromise contributing to the development of glaucomatous optic neuropathy. Methods Ischemic optic neuropathy was induced by delivering endothelin-1 (ET-1) to the retrobulbar space in one eye of 12 primates for 6 to 12 months. Regional ganglion cell axonal sizes and densities were compared with the normal, contralateral eyes. Results Without changes of intraocular pressure, mean axonal density was significantly decreased in ET-1 eyes compared to controls (P = .03, paired t test). Two-way matched-pair analysis of variance showed a significant effect of ET-1 on overall axonal density (P < .0001). Among the animals with significant axonal loss, the mean axonal loss was 11.6%, and loss varied from 4% to 21%. Axonal loss was commonly localized within specific quadrants. Five animals were examined for preferential axonal size loss. As a group, there appears to be a tendency toward preferential large axonal loss, but the mean axonal loss of large and small axons did not meet significant differences (P = .1) However, examination of individual animals with significant loss shows significantly greater loss of large axons as compared to the small axons in three of the animals. Conclusions Chronic optic nerve ischemia causes demonstrable and localized damage of the optic nerve, without intraocular pressure elevation. There is preferential loss of large retinal ganglion cell axons in animals with significant axonal loss. Ischemia-induced focal axonal loss is similar to human glaucoma and may represent a differential regional vulnerability. PMID:17057819

  4. Nerve Injuries in Athletes.

    ERIC Educational Resources Information Center

    Collins, Kathryn; And Others

    1988-01-01

    Over a two-year period this study evaluated the condition of 65 athletes with nerve injuries. These injuries represent the spectrum of nerve injuries likely to be encountered in sports medicine clinics. (Author/MT)

  5. Far-Infrared Therapy Promotes Nerve Repair following End-to-End Neurorrhaphy in Rat Models of Sciatic Nerve Injury

    PubMed Central

    Chen, Tai-Yuan; Yang, Yi-Chin; Sha, Ya-Na; Chou, Jiun-Rou

    2015-01-01

    This study employed a rat model of sciatic nerve injury to investigate the effects of postoperative low-power far-infrared (FIR) radiation therapy on nerve repair following end-to-end neurorrhaphy. The rat models were divided into the following 3 groups: (1) nerve injury without FIR biostimulation (NI/sham group); (2) nerve injury with FIR biostimulation (NI/FIR group); and (3) noninjured controls (normal group). Walking-track analysis results showed that the NI/FIR group exhibited significantly higher sciatic functional indices at 8 weeks after surgery (P < 0.05) compared with the NI/sham group. The decreased expression of CD4 and CD8 in the NI/FIR group indicated that FIR irradiation modulated the inflammatory process during recovery. Compared with the NI/sham group, the NI/FIR group exhibited a significant reduction in muscle atrophy (P < 0.05). Furthermore, histomorphometric assessment indicated that the nerves regenerated more rapidly in the NI/FIR group than in the NI/sham group; furthermore, the NI/FIR group regenerated neural tissue over a larger area, as well as nerve fibers of greater diameter and with thicker myelin sheaths. Functional recovery, inflammatory response, muscular reinnervation, and histomorphometric assessment all indicated that FIR radiation therapy can accelerate nerve repair following end-to-end neurorrhaphy of the sciatic nerve. PMID:25722734

  6. Low-level laser irradiation improves functional recovery and nerve regeneration in sciatic nerve crush rat injury model.

    PubMed

    Wang, Chau-Zen; Chen, Yi-Jen; Wang, Yan-Hsiung; Yeh, Ming-Long; Huang, Mao-Hsiung; Ho, Mei-Ling; Liang, Jen-I; Chen, Chia-Hsin

    2014-01-01

    The development of noninvasive approaches to facilitate the regeneration of post-traumatic nerve injury is important for clinical rehabilitation. In this study, we investigated the effective dose of noninvasive 808-nm low-level laser therapy (LLLT) on sciatic nerve crush rat injury model. Thirty-six male Sprague Dawley rats were divided into 6 experimental groups: a normal group with or without 808-nm LLLT at 8 J/cm(2) and a sciatic nerve crush injury group with or without 808-nm LLLT at 3, 8 or 15 J/cm(2). Rats were given consecutive transcutaneous LLLT at the crush site and sacrificed 20 days after the crush injury. Functional assessments of nerve regeneration were analyzed using the sciatic functional index (SFI) and hindlimb range of motion (ROM). Nerve regeneration was investigated by measuring the myelin sheath thickness of the sciatic nerve using transmission electron microscopy (TEM) and by analyzing the expression of growth-associated protein 43 (GAP43) in sciatic nerve using western blot and immunofluorescence staining. We found that sciatic-injured rats that were irradiated with LLLT at both 3 and 8 J/cm(2) had significantly improved SFI but that a significant improvement of ROM was only found in rats with LLLT at 8 J/cm(2). Furthermore, the myelin sheath thickness and GAP43 expression levels were significantly enhanced in sciatic nerve-crushed rats receiving 808-nm LLLT at 3 and 8 J/cm(2). Taken together, these results suggest that 808-nm LLLT at a low energy density (3 J/cm(2) and 8 J/cm(2)) is capable of enhancing sciatic nerve regeneration following a crush injury.

  7. Electrical Stimulation to Enhance Axon Regeneration After Peripheral Nerve Injuries in Animal Models and Humans.

    PubMed

    Gordon, Tessa

    2016-04-01

    Injured peripheral nerves regenerate their lost axons but functional recovery in humans is frequently disappointing. This is so particularly when injuries require regeneration over long distances and/or over long time periods. Fat replacement of chronically denervated muscles, a commonly accepted explanation, does not account for poor functional recovery. Rather, the basis for the poor nerve regeneration is the transient expression of growth-associated genes that accounts for declining regenerative capacity of neurons and the regenerative support of Schwann cells over time. Brief low-frequency electrical stimulation accelerates motor and sensory axon outgrowth across injury sites that, even after delayed surgical repair of injured nerves in animal models and patients, enhances nerve regeneration and target reinnervation. The stimulation elevates neuronal cyclic adenosine monophosphate and, in turn, the expression of neurotrophic factors and other growth-associated genes, including cytoskeletal proteins. Electrical stimulation of denervated muscles immediately after nerve transection and surgical repair also accelerates muscle reinnervation but, at this time, how the daily requirement of long-duration electrical pulses can be delivered to muscles remains a practical issue prior to translation to patients. Finally, the technique of inserting autologous nerve grafts that bridge between a donor nerve and an adjacent recipient denervated nerve stump significantly improves nerve regeneration after delayed nerve repair, the donor nerves sustaining the capacity of the denervated Schwann cells to support nerve regeneration. These reviewed methods to promote nerve regeneration and, in turn, to enhance functional recovery after nerve injury and surgical repair are sufficiently promising for early translation to the clinic.

  8. Traumatic facial nerve injury.

    PubMed

    Lee, Linda N; Lyford-Pike, Sofia; Boahene, Kofi Derek O

    2013-10-01

    Facial nerve trauma can be a devastating injury resulting in functional deficits and psychological distress. Deciding on the optimal course of treatment for patients with traumatic facial nerve injuries can be challenging, as there are many critical factors to be considered for each patient. Choosing from the great array of therapeutic options available can become overwhelming to both patients and physicians, and in this article, the authors present a systematic approach to help organize the physician's thought process.

  9. Nerve growth factor and associated nerve sprouting contribute to local mechanical hyperalgesia in a rat model of bone injury.

    PubMed

    Yasui, M; Shiraishi, Y; Ozaki, N; Hayashi, K; Hori, K; Ichiyanagi, M; Sugiura, Y

    2012-08-01

    To clarify the mechanism of tenderness after bone injury, we investigated changes in the withdrawal threshold to mechanical stimuli, nerve distribution and nerve growth factor (NGF)-expression in a rat model of bone injury without immobilization for bone injury healing. Rats were divided into three groups as follows: (1) rats incised in the skin and periosteum, followed by drilling a hole in the tibia [bone lesion group (BLG)]; (2) those incised in the skin and periosteum without bone drilling [periosteum lesion group (PLG)]; and (3) those incised in the skin [skin lesion group (SLG)]. Mechanical hyperalgesia continued for 28 days at a lesion in the BLG, 21 days in PLG and 5 days in SLG after treatments, respectively. Endochondral ossification was observed on days 5-28 in BLG and on days 5-21 in PLG. Nerve growth appeared in deep connective tissue (DCT) at day 28 in BLG. Nerve fibres increased in both cutaneous tissue and DCT at day 7 in PLG, but they were not found at day 28. Mechanical hyperalgesia accompanied with endochondral ossification and nerve fibres increasing at the lesion in both BLG and PLG. NGF was expressed in bone-regenerating cells during the bone injury healing. Anti-NGF and trk inhibitor K252a inhibited hyperalgesia in the different time course. This study shows that localized tenderness coincides with the bone healing and involves NGF expression and nerve sprouting after bone injury. The findings present underlying mechanisms and provide pathophysiological relevance of local tenderness to determination of bone fracture and its healing.

  10. Craniocerebral injury promotes the repair of peripheral nerve injury

    PubMed Central

    Wang, Wei; Gao, Jun; Na, Lei; Jiang, Hongtao; Xue, Jingfeng; Yang, Zhenjun; Wang, Pei

    2014-01-01

    The increase in neurotrophic factors after craniocerebral injury has been shown to promote fracture healing. Moreover, neurotrophic factors play a key role in the regeneration and repair of peripheral nerve. However, whether craniocerebral injury alters the repair of peripheral nerve injuries remains poorly understood. Rat injury models were established by transecting the left sciatic nerve and using a free-fall device to induce craniocerebral injury. Compared with sciatic nerve injury alone after 6–12 weeks, rats with combined sciatic and craniocerebral injuries showed decreased sciatic functional index, increased recovery of gastrocnemius muscle wet weight, recovery of sciatic nerve ganglia and corresponding spinal cord segment neuron morphologies, and increased numbers of horseradish peroxidase-labeled cells. These results indicate that craniocerebral injury promotes the repair of peripheral nerve injury. PMID:25374593

  11. Effect of Zofenopril on regeneration of sciatic nerve crush injury in a rat model

    PubMed Central

    2009-01-01

    Background Zofenopril is an antioxidant agent which has been shown to have beneficial effects in hypertension and heart failure. The aim of this study was to test the effects of Zofenopril on nerve regeneration and scarring in a rat model of peripheral nerve crush injury. Methods Twenty-one adult Sprague-Dawley rats underwent a surgical procedure involving right sciatic nerve crush injury. 15 mg/kg Zofenopril was administered orally to seven rats in group Z for seven days. Seven rats in group S received saline orally for seven days. Seven rats in the control group C received no drug after crush injury. Fourteenth and 42nd days after injury, functional and electromyography assessments of nerves were performed. Functional recovery was analyzed using a walking track assessment, and quantified using the sciatic functional index (SFI). After these evaluations, all rats were sacrificed and microscopic evaluations were performed. Results The Sciatic functional Index (SFI) in group Z on 14th day is different significantly from group S and group C (p = 0.037). But on 42nd day there was no difference between groups (p = 0.278). The statistical analyses of electromyelographic (EMG) studies showed that the latency in group Z is significantly different from group S (p = 0.006) and group C (p = 0.045). But on 42nd day there was no difference between groups like SFI (p = 0.147). The amplitude was evaluated better in group Z than others (p < 0.05). In microscopic evaluation, we observed the highest number of nerve regeneration in the group Z and the lowest in the group C. But it was not significant statistically. Conclusion Our results demonstrate that Zofenopril promotes the regeneration of peripheral nerve injuries in rat models. PMID:19508704

  12. N-Propionylmannosamine stimulates axonal elongation in a murine model of sciatic nerve injury.

    PubMed

    Witzel, Christian; Reutter, Werner; Stark, G Björn; Koulaxouzidis, Georgios

    2015-06-01

    Increasing evidence indicates that sialic acid plays an important role during nerve regeneration. Sialic acids can be modified in vitro as well as in vivo using metabolic oligosaccharide engineering of the N-acyl side chain. N-Propionylmannosamine (ManNProp) increases neurite outgrowth and accelerates the reestablishment of functional synapses in vitro. We investigated the influence of systemic ManNProp application using a specific in vivo mouse model. Using mice expressing axonal fluorescent proteins, we quantified the extension of regenerating axons, the number of regenerating axons, the number of arborising axons and the number of branches per axon 5 days after injury. Sciatic nerves from non-expressing mice were grafted into those expressing yellow fluorescent protein. We began a twice-daily intraperitoneal application of either peracetylated ManNProp (200 mg/kg) or saline solution 5 days before injury, and continued it until nerve harvest (5 days after transection). ManNProp significantly increased the mean distance of axonal regeneration (2.49 mm vs. 1.53 mm; P < 0.005) and the number of arborizing axons (21% vs. 16%; P = 0.008) 5 days after sciatic nerve grafting. ManNProp did not affect the number of regenerating axons or the number of branches per arborizing axon. The biochemical glycoengineering of the N-acyl side chain of sialic acid might be a promising approach for improving peripheral nerve regeneration.

  13. N-Propionylmannosamine stimulates axonal elongation in a murine model of sciatic nerve injury

    PubMed Central

    Witzel, Christian; Reutter, Werner; Stark, G. Björn; Koulaxouzidis, Georgios

    2015-01-01

    Increasing evidence indicates that sialic acid plays an important role during nerve regeneration. Sialic acids can be modified in vitro as well as in vivo using metabolic oligosaccharide engineering of the N-acyl side chain. N-Propionylmannosamine (ManNProp) increases neurite outgrowth and accelerates the reestablishment of functional synapses in vitro. We investigated the influence of systemic ManNProp application using a specific in vivo mouse model. Using mice expressing axonal fluorescent proteins, we quantified the extension of regenerating axons, the number of regenerating axons, the number of arborising axons and the number of branches per axon 5 days after injury. Sciatic nerves from non-expressing mice were grafted into those expressing yellow fluorescent protein. We began a twice-daily intraperitoneal application of either peracetylated ManNProp (200 mg/kg) or saline solution 5 days before injury, and continued it until nerve harvest (5 days after transection). ManNProp significantly increased the mean distance of axonal regeneration (2.49 mm vs. 1.53 mm; P < 0.005) and the number of arborizing axons (21% vs. 16%; P = 0.008) 5 days after sciatic nerve grafting. ManNProp did not affect the number of regenerating axons or the number of branches per arborizing axon. The biochemical glycoengineering of the N-acyl side chain of sialic acid might be a promising approach for improving peripheral nerve regeneration. PMID:26199617

  14. Long thoracic nerve injury.

    PubMed

    Wiater, J M; Flatow, E L

    1999-11-01

    Injury to the long thoracic nerve causing paralysis or weakness of the serratus anterior muscle can be disabling. Patients with serratus palsy may present with pain, weakness, limitation of shoulder elevation, and scapular winging with medial translation of the scapula, rotation of the inferior angle toward the midline, and prominence of the vertebral border. Long thoracic nerve dysfunction may result from trauma or may occur without injury. Fortunately, most patients experience a return of serratus anterior function with conservative treatment, but recovery may take as many as 2 years. Bracing often is tolerated poorly. Patients with severe symptoms in whom 12 months of conservative treatment has failed may benefit from surgical reconstruction. Although many surgical procedures have been described, the current preferred treatment is transfer of the sternal head of the pectoralis major tendon to the inferior angle of the scapula reinforced with fascia or tendon autograft. Many series have shown good to excellent results, with consistent improvement in function, elimination of winging, and reduction of pain.

  15. Peripheral nerve injury during anesthesia.

    PubMed

    Lieblich, S E

    1990-01-01

    A case is presented where a peripheral nerve injury occurred due to the pressure of a restraint buckle causing a postoperative motor and sensory deficit. Because these are iatrogenic injuries it is useful to review the mechanism of injury and means of prevention.

  16. Peripheral nerve injury during anesthesia.

    PubMed Central

    Lieblich, S. E.

    1990-01-01

    A case is presented where a peripheral nerve injury occurred due to the pressure of a restraint buckle causing a postoperative motor and sensory deficit. Because these are iatrogenic injuries it is useful to review the mechanism of injury and means of prevention. Images Figure 1 PMID:2096751

  17. A novel rat forelimb model of neuropathic pain produced by partial injury of the median and ulnar nerves.

    PubMed

    Yi, Hanju; Kim, Myung Ah; Back, Seung Keun; Eun, Jong Shin; Na, Heung Sik

    2011-05-01

    The vast majority of human peripheral nerve injuries occur in the upper limb, whereas the most animal studies have been conducted using the hindlimb models of neuropathic pain, involving damages of the sciatic or lumbar spinal nerve(s). We attempted to develop a rat forelimb model of peripheral neuropathy by partial injury of the median and ulnar nerves. The halves of each nerve were transected by microscissors at about 5mm proximal from the elbow joint and behavioral signs of neuropathic pain, such as mechanical and cold allodynia, and heat hyperalgesia, were monitored up to 126 days following nerve injury. Mechanical allodynia was assessed by measuring the forepaw withdrawal threshold to von Frey filaments, and cold allodynia was evaluated by measuring the time spent in lifting or licking the forepaw after applying acetone to it. Heat hyperalgesia was also monitored by investigating the forepaw withdrawal latencies using the Hargreaves' test. After the nerve injury, the experimental animals exhibited long-lasting clear neuropathic pain-like behaviors, such as reduced forepaw withdrawal threshold to von Frey filaments, the increased response duration of the forepaw to acetone application, and the decreased withdrawal latency to radiant heat stimulation. These behaviors were significantly alleviated by administration of gabapentin (5 or 50mg/kg, i.p.) in a dose-dependent manner. Therefore, these abnormal sensitivities are interpreted as the signs of neuropathic pain following injury of the median and ulnar nerves. Our rat forelimb model of neuropathic pain may be useful for studying human neuropathic pain and screening for valuable drug candidates.

  18. Quantitative Histologic Analysis of Muscle Micro-architecture Following Facial Nerve Injury in a Rodent Model

    PubMed Central

    Kim, Sang W; Knox, Christopher J; Weinberg, Julie; Heaton, James T

    2015-01-01

    Objective To describe denervation features of facial musculature following facial nerve injury in a rodent model. Methods Six female Wistar-Hannover rats underwent unilateral transection and immediate repair of the facial nerve. After 8 weeks, muscular bundles consisting of dilator naris and levator labii superioris from both sides were harvested. The specimens were fixed, cryo-cut, and stained with Masson's trichrome stain. Tissue sections were analyzed for average muscle cell diameter and the percentage of muscle specimen attributable to muscle cell cross-sectional area using Image J image processing software. The atrophic features of facial muscles ipsilateral to nerve transection and repair were quantified and compared to the contralateral, healthy side of the face. Results Weekly post-operative whisking assessment demonstrated the anticipated time course of whisking recovery, with all animals demonstrating the initiation of recovered movement by post-repair day 17, and progressing to approximately 25% recovered whisking amplitude (repaired side / healthy side) by the end of the 8 week survival period. We observed significant differences in the percentage of muscle specimen cross-sectional area (including connective tissues) attributable to muscle cell profiles (57% vs 29%; p=0.01), and total fiber counts (1,346 vs 794; p=0.02) for the normal side and the manipulated side, respectively. While the average cross-sectional area of individual muscle fibers was higher on the normal side (1,129µm2 vs 928µm2; p=0.39), this difference was not statistically significant. Conclusion Although reinnervation of rat facial muscles begins within three weeks after facial nerve transection and suture repair, after an 8-week survival period whisking remain substantially impaired and rats experience a substantial loss (approximately 40%) of muscle cells and a roughly parallel loss of muscle cell surface area (approximately 49%) in two facial muscles associated with the whisker

  19. Endogenous glucocorticoids improve myelination via Schwann cells after peripheral nerve injury: An in vivo study using a crush injury model.

    PubMed

    Morisaki, Shinsuke; Nishi, Mayumi; Fujiwara, Hiroyoshi; Oda, Ryo; Kawata, Mitsuhiro; Kubo, Toshikazu

    2010-06-01

    Glucocorticoids improve the symptoms of peripheral nerve disorders, such as carpal tunnel syndrome and peripheral neuropathy. The effects of glucocorticoids are mainly anti-inflammatory, but the mechanisms of their effects in peripheral nerve disorders remain unclear. Schwann cells of the peripheral nerves express glucocorticoid receptors (GR), and glucocorticoids enhance the rate of myelin formation in vitro. Therefore, it is possible that the clinical improvement of peripheral nerve disorders by glucocorticoids is due, at least in part, to the modulation of myelination. In this study, an adrenalectomy (ADX) was performed, and followed by a daily injection of either low dose (1 mg/kg) or high dose (10 mg/kg) corticosterone (CORT). We then simulated a crush injury of the sciatic nerves. A sham ADX operation, followed by a simulated crush injury, was conducted as a control. Immunohistochemistry showed that the nuclei of in vivo Schwann cells expressed GR and that glucocorticoids impacted the GR immunoreactivity of the Schwann cells. The mRNA and protein expression of myelin basic protein was significantly lower in the animals given ADX with vehicle than in the sham operation group. However, the expression was restored in the low-dose CORT replacement group. Morphological analyses showed that the ADX with vehicle group had a significantly lower myelin thickness than did the low-dose CORT replacement group and the sham operation group. These results suggest that endogenous glucocorticoids have an important role in myelination through the GR in Schwann cells after an in vivo peripheral nerve injury.

  20. Plasticity of DNA methylation in a nerve injury model of pain

    PubMed Central

    Gölzenleuchter, Meike; Kanwar, Rahul; Zaibak, Manal; Al Saiegh, Fadi; Hartung, Theresa; Klukas, Jana; Smalley, Regenia L; Cunningham, Julie M; Figueroa, Maria E; Schroth, Gary P; Therneau, Terry M; Banck, Michaela S; Beutler, Andreas S

    2015-01-01

    The response of the peripheral nervous system (PNS) to injury may go together with alterations in epigenetics, a conjecture that has not been subjected to a comprehensive, genome-wide test. Using reduced representation bisulfite sequencing, we report widespread remodeling of DNA methylation in the rat dorsal root ganglion (DRG) occurring within 24 h of peripheral nerve ligation, a neuropathy model of allodynia. Significant (P < 10−4) cytosine hyper- and hypo-methylation was found at thousands of CpG sites. Remodeling occurred outside of CpG islands. Changes affected genes with known roles in the PNS, yet methylome remodeling also involved genes that were not linked to neuroplasticity by prior evidence. Consistent with emerging models relying on genome-wide methylation and RNA-seq analysis of promoter regions and gene bodies, variation of methylation was not tightly linked with variation of gene expression. Furthermore, approximately 44% of the dynamically changed CpGs were located outside of genes. We compared their positions with the intergenic, tissue-specific differentially methylated CpGs (tDMCs) of an independent experimental set consisting of liver, spleen, L4 control DRG, and muscle. Dynamic changes affected those intergenic CpGs that were different between tissues (P < 10−15) and almost never the invariant portion of the methylome (those CpGs that were identical across all tissues). Our findings—obtained in mixed tissue—show that peripheral nerve injury leads to methylome remodeling in the DRG. Future studies may address which of the cell types found in the DRG, such as specific groups of neurons or non-neuronal cells are affected by which aspect of the observed methylome remodeling. PMID:25621511

  1. [Peripheral Nerve Injuries in Sports].

    PubMed

    Tettenborn, B; Mehnert, S; Reuter, I

    2016-09-01

    Peripheral nerve injuries due to sports are relatively rare but the exact incidence is not known due to a lack of epidemiological studies. Particular sports activities tend to cause certain peripheral nerve injuries including direct acute compression or stretching, repetitive compression and stretching over time, or another mechanism such as ischemia or laceration. These nerve lesions may be severe and delay or preclude the athlete's return to sports, especially in cases with delayed diagnosis. Repetitive and vigorous use or overuse makes the athlete vulnerable to disorders of the peripheral nerves, and sports equipment may cause compression of the nerves. Depending on etiology, the treatment is primarily conservative and includes physiotherapy, modification of movements and sports equipment, shoe inserts, splinting, antiphlogistic drugs, sometimes local administration of glucocorticoids or, lately, the use of extracorporeal shock waves. Most often, cessation of the offending physical activity is necessary. Surgery is only indicated in the rare cases of direct traumatic nerve injury or when symptoms are refractory to conservative therapy. Prognosis mainly depends on the etiology and the available options of modifying measures.This article is based on the publications "Reuter I, Mehnert S. Engpasssyndrome peripherer Nerven bei Sportlern". Akt Neurol 2012;39:292-308 and Sportverl Sportschad 2013;27:130-146.

  2. Exogenous nerve growth factor protects the hypoglossal nerve against crush injury

    PubMed Central

    Fan, Li-yuan; Wang, Zhong-chao; Wang, Pin; Lan, Yu-yan; Tu, Ling

    2015-01-01

    Studies have shown that sensory nerve damage can activate the p38 mitogen-activated protein kinase (MAPK) pathway, but whether the same type of nerve injury after exercise activates the p38MAPK pathway remains unclear. Several studies have demonstrated that nerve growth factor may play a role in the repair process after peripheral nerve injury, but there has been little research focusing on the hypoglossal nerve injury and repair. In this study, we designed and established rat models of hypoglossal nerve crush injury and gave intraperitoneal injections of exogenous nerve growth factor to rats for 14 days. p38MAPK activity in the damaged neurons was increased following hypoglossal nerve crush injury; exogenous nerve growth factor inhibited this increase in acitivity and increased the survival rate of motor neurons within the hypoglossal nucleus. Under transmission electron microscopy, we found that the injection of nerve growth factor contributed to the restoration of the morphology of hypoglossal nerve after crush injury. Our experimental findings indicate that exogenous nerve growth factor can protect damaged neurons and promote hypoglossal nerve regeneration following hypoglossal nerve crush injury. PMID:26889186

  3. 17β-Estradiol Promotes Schwann Cell Proliferation and Differentiation, Accelerating Early Remyelination in a Mouse Peripheral Nerve Injury Model

    PubMed Central

    Chen, Yan; Guo, Wenjie; Li, Wenjuan; Cheng, Meng; Hu, Ying; Xu, Wenming

    2016-01-01

    Estrogen induces oligodendrocyte remyelination in response to demyelination in the central nervous system. Our objective was to determine the effects of 17β-estradiol (E2) on Schwann cell function and peripheral nerve remyelination after injury. Adult male C57BL/6J mice were used to prepare the sciatic nerve transection injury model and were randomly categorized into control and E2 groups. To study myelination in vitro, dorsal root ganglion (DRG) explant culture was prepared using 13.5-day-old mouse embryos. Primary Schwann cells were isolated from the sciatic nerves of 1- to 3-day-old Sprague–Dawley rats. Immunostaining for myelin basic protein (MBP) expression and toluidine blue staining for myelin sheaths demonstrated that E2 treatment accelerates early remyelination in the “nerve bridge” region between the proximal and distal stumps of the transection injury site in the mouse sciatic nerve. The 5-bromo-2′-deoxyuridine incorporation assay revealed that E2 promotes Schwann cell proliferation in the bridge region and in the primary culture, which is blocked using AKT inhibitor MK2206. The in vitro myelination in the DRG explant culture determined showed that the MBP expression in the E2-treated group is higher than that in the control group. These results show that E2 promotes Schwann cell proliferation and myelination depending on AKT activation. PMID:27872858

  4. Goji fruit (Lycium barbarum) protects sciatic nerve function against crush injury in a model of diabetic stress.

    PubMed

    Simonyan, K V; Avetisyan, L G; Chavushyan, V A

    2016-09-01

    Excess fructose consumption causes changes in functioning of the central and peripheral nervous systems, which increase the vulnerability of peripheral nerves to traumatic injury. The aim of this study was to evaluate the electrophysiological parameters of responses of motoneurons of the spinal cord at high-frequency stimulation of the distal part of the injured sciatic nerve in a model of diabetic stress under action of Lycium barbarum (LB). Male albino rats were given with drinking water with 50% concentration of dietary fructose for 6 weeks. Starting on the 7th week a crush injury of the left sciatic nerve was carried out. Some of the animals received fructose post-injury for 3 weeks and some of the animals received fructose+dry LB fruits for 3 weeks. In the fructose+crush+LВ group a relatively proportional division of tetanic and posttetanic potentiation and depression in responses of ipsilateral and contralateral motoneurons was observed, which would suggest the modulatory role of LB in short-term synaptic plasticity formation. Generally, LB fruit is able to modulate central nervous system reorganization, amplifying positive adaptive changes that improve functional recovery and promote selective target reinnervation in high fructose-diet rats with sciatic nerve crush-injury.

  5. Extracranial spinal accessory nerve injury.

    PubMed

    Donner, T R; Kline, D G

    1993-06-01

    Eighty-three consecutive patients with extracranial accessory nerve injury seen over a 12-year period are reviewed. The most common etiology was iatrogenic injury to the nerve at the time of previous surgery. Such operations were usually minor in nature and often related to lymph node or benign tumor removal. Examination usually distinguished winging due to trapezius weakness from that of serratus anterior palsy. Trapezius weakness was seen in all cases. Sternocleidomastoid weakness was unusual. Patients with accessory palsy were evaluated by both clinical and electromyographic studies. Patients who exhibited no clinical or electrical evidence of regeneration were operated on (44 cases). Based on intraoperative nerve action potential studies, 8 lesions in continuity had neurolysis alone. Resection with repair either by end-to-end suture or by grafts was necessary in 31 cases. One case had suture removed from nerve, two had nerve placed into target muscle, and two had more proximal neurotization. Function was usually improved in both operative and nonoperative patients. Related anatomy is discussed.

  6. Chitooligosaccharide Inhibits Scar Formation and Enhances Functional Recovery in a Mouse Model of Sciatic Nerve Injury.

    PubMed

    Hou, Hongping; Zhang, Lihai; Ye, Zuguang; Li, Jianrong; Lian, Zijian; Chen, Chao; He, Rong; Peng, Bo; Xu, Qihua; Zhang, Guangping; Gan, Wenbiao; Tang, Peifu

    2016-05-01

    Chitooligosaccharide (COS) has been shown to induce fibroblast apoptosis, indicating that it could be used as a material to inhibit scar formation. In the present study, we used a mouse model of sciatic nerve injury (SNI) to determine the role of COS in scar inhibition and functional recovery. The animals were divided into three groups: SNI, SNI + vehicle, and SNI + COS group. We performed a series of functional and histological examinations at ctrl, 0 min, 14 days, and 42 days, including behavioral recovery, percentage of regenerating axons, degree of scar formation, vascular changes, type I and type III collagen ratio, and percentage of demyelinated axons. The SNI + COS group exhibited better recovery of sensory and motor function and less scar formation. Two-photon microscopy showed that the percentage of regenerating axons was highest in the SNI + COS group at 14 and 42 days. Our results suggested that COS can inhibit scar formation and enhance functional recovery by inducing fibroblast death, altering the proportion of different vascular diameters, changing the ratio of type I/type III collagen, and reducing the percentage of demyelinated axons. COS might be a useful drug in the treatment of SNI to reduce scar formation, but additional research is required to clarify the relevant molecular pathways.

  7. Pleiotrophin and peripheral nerve injury.

    PubMed

    Jin, Li; Jianghai, Chen; Juan, Liu; Hao, Kang

    2009-10-01

    The proto-oncogene pleiotrophin, discovered in 1989, was considered as a multifunctional growth factor, which played an important role in tumor occurrence, development, and central nervous system. The latest research showed that pleiotrophin signal pathway probably participated in neural repair after peripheral nerve injury, especially in the following critical points, such as the protection of spinal cord neuron, the promotion of the speed of neuron axon regeneration, the guidance of neuron axon regeneration, skeleton muscle reinnervation, and so on. It potentially plays a key role in the guidance of neural axon regeneration in peripheral nervous system and muscle reinnervation. With the deepening of related researches, pleiotrophin gene would become a controllable target for improving the repairing effect of peripheral nerve injury and reconstruction of the neuromuscular junction.

  8. Proximal versus Distal Nerve Transfer for Biceps Reinnervation—A Comparative Study in a Rat’s Brachial Plexus Injury Model

    PubMed Central

    McGrath, Aleksandra M.; Lu, Johnny Chuieng-Yi; Chang, Tommy Naj-Jen; Fang, Frank

    2016-01-01

    Background: The exact role of proximal and distal nerve transfers in reconstruction strategies of brachial plexus injury remains controversial. We compared proximal with distal nerve reconstruction strategies in a rat model of brachial plexus injury. Methods: In rats, the C6 spinal nerve with a nerve graft (proximal nerve transfer model, n = 30, group A) and 50% of ulnar nerve (distal nerve transfer model, n = 30, group B) were used as the donor nerves. The targets were the musculocutaneous nerve and the biceps muscle. Outcomes were recorded at 4, 8, 12, and 16 weeks postoperatively. Outcome parameters included grooming test, biceps muscle weight, compound muscle action potentials, tetanic contraction force, and axonal morphology of the donor and target nerves. Results: The axonal morphology of the 2 donor nerves revealed no significant difference. Time interval analysis in the proximal nerve transfer group showed peak axon counts at 12 weeks and a trend of improvement in all functional and physiologic parameters across all time points with statistically significant differences for grooming test, biceps compound action potentials, tetanic muscle contraction force, and muscle weight at 16 weeks. In contrast, in the distal nerve transfer group, the only statistically significant difference was observed between the 4 and 8 week time points, followed by a plateau from 8 to 16 weeks. Conclusions: Outcomes of proximal nerve transfers are ultimately superior to distal nerve transfers in our experimental model. Possible explanations for the superior results include a reduced need for cortical adaptation and higher proportions of motor units in the proximal nerve transfers. PMID:28293499

  9. Neuroprotective effect of docosahexaenoic acid nanoemulsion on erectile function in a rat model of bilateral cavernous nerve injury

    PubMed Central

    Liao, Chun-Hou; Wu, Yi-No; Chen, Bin-Huei; Lin, Ying-Hung; Ho, Hsiu-O; Chiang, Han-Sun

    2016-01-01

    There is an unmet need for treatment of erectile dysfunction resulting from radical prostatectomy and cavernous nerve (CN) injury. Given the neuroprotective properties of docosahexaenoic acid (DHA), we investigated its effect on penile functional and structural recovery in a rat model of bilateral cavernous nerve injury. Rats were subject to CN injury and received intraperitoneal administration of either vehicle or a DHA nanoemulsion (nano-DHA) at 10, 50, or 250 μg/kg. Functional testing and histological analyses were performed at 28 days post-injury. The maximum intracavernosal pressure (ICP) and other measures of erectile function were significantly higher in the nano-DHA groups than in the vehicle group (p < 0.05). The ratio of area of expression of neuronal nitric oxide synthase (nNOS)/β-III tubulin, numbers of axon and smooth muscle cell content were significantly higher in the 50 μg/kg nano-DHA group than in the vehicle group (p < 0.05). A qualitative increase in the smooth muscle cells/collagen ratio and decrease in apoptosis was observed in the nano-DHA groups relative to the vehicle group: however, these differences were not statistically significant. Our data demonstrate that nano-DHA, particularly the 50 μg/kg regimen, improves erectile function after bilateral CN injury in rats by neuroprotection and other anti-fibrotic and anti-apoptotic mechanisms. PMID:27625175

  10. Evaluation of PVA biodegradable electric conductive membranes for nerve regeneration in axonotmesis injuries: the rat sciatic nerve animal model.

    PubMed

    Ribeiro, Jorge; Caseiro, Ana Rita; Pereira, Tiago; Armada-da-Silva, Paulo Alexandre; Pires, Isabel; Prada, Justina; Amorim, Irina; Leal Reis, Inês; Amado, Sandra; Santos, José Domingos; Bompasso, Simone; Raimondo, Stefania; Varejão, Artur Severo Proença; Geuna, Stefano; Luís, Ana Lúcia; Maurício, Ana Colette

    2017-05-01

    The therapeutic effect of three polyvinyl alcohol (PVA) membranes loaded with electrically conductive materials - carbon nanotubes (PVA-CNTs) and polypyrrole (PVA-PPy) - were tested in vivo for neuro-muscular regeneration after an axonotmesis injury in the rat sciatic nerve. The membranes electrical conductivity measured was 1.5 ± 0.5 × 10(-6) S/m, 579 ± 0.6 × 10(-6) S/m, and 1837.5 ± 0.7 × 10(-6) S/m, respectively. At week-12, a residual motor and nociceptive deficit were present in all treated groups, but at week-12, a better recovery to normal gait pattern of the PVA-CNTs and PVA-PPy treated groups was observed. Morphometrical analysis demonstrated that PVA-CNTs group presented higher myelin thickness and lower g-ratio. The tibialis anterior muscle, in the PVA-PPy and PVA-CNTs groups showed a 9% and 19% increase of average fiber size area and a 5% and 10% increase of the "minimal Feret's diameter," respectively. No inflammation, degeneration, fibrosis or necrosis were detected in lung, liver, kidneys, spleen, and regional lymph nodes and absence of carbon deposits was confirmed with Von Kossa and Masson-Fontana stains. In conclusion, the membranes of PVA-CNTs and PVA-PPy are biocompatible and have electrical conductivity. The higher electrical conductivity measured in PVA-CNTs membrane might be responsible for the positive results on maturation of myelinated fibers. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 1267-1280, 2017.

  11. What Protects Certain Nerves from Stretch Injury?

    PubMed

    Schraut, Nicholas B; Walton, Sharon; Bou Monsef, Jad; Shott, Susan; Serici, Anthony; Soulii, Lioubov; Amirouche, Farid; Gonzalez, Mark H; Kerns, James M

    2016-01-01

    The human tibial nerves is less prone to injury following joint arthroplasty compared with the peroneal nerves. Besides the anatomical distribution, other features may confer protection from stretch injury. We therefore examined the size, shape and connective tissue distribution for the two nerves. The tibial and peroneal nerves from each side of nine fresh human cadavers we reharvested mid-thigh. Proximal segments manually stretched 20%-25% were fixed in aldehyde, while the adjacent distal segments were fixed in their natural length. Paraffin sections stained by Masson's trichrome method for connective tissue were examined by light microscopy. Tibial nerves had 2X more fascicles compared with the peroneal, but the axonal content appeared similar. Analysis showed that neither nerve had a significant reduction in cross sectional area of the fascicles following stretch. However, fascicles from stretched tibial nerves become significantly more oval compared with those from unstretched controls and peroneal nerves. Tibial nerves had a greater proportion that was extrafascicular tissue (50-55%) compared with peroneal nerves (38%-42%). This epineurium was typically adipose tissue. Perineurial thickness in both nerves was directly related to fascicular size. Tibial nerves have several unique histological features associated with size, shape and tissue composition compared with the peroneal nerve. We suggest that more fascicles with their tightly bound perineurium and more robust epineurium afford protection against stretch injury. Mechanical studies should clarify how size and shape contribute to nerve protection and/or neurapraxia.

  12. Convection enhanced drug delivery of BDNF through a microcannula in a rodent model to strengthen connectivity of a peripheral motor nerve bridge model to bypass spinal cord injury.

    PubMed

    Martin Bauknight, W; Chakrabarty, Samit; Hwang, Brian Y; Malone, Hani R; Joshi, Shailendra; Bruce, Jeffrey N; Sander Connolly, E; Winfree, Christopher J; Cunningham, Miles G; Martin, John H; Haque, Raqeeb

    2012-04-01

    Models employing peripheral nerve to bypass spinal cord injury (SCI), although highly promising, may benefit from improved nerve regeneration and motor bridge connectivity. Recent studies have demonstrated that neuronal growth factor-induced enhancement of endogenous neurorestoration may improve neuronal connectivity after severe neurologic injury, particularly if delivered intraparenchymally with zero-order kinetics. We sought to investigate the effect of convection-enhanced delivery of brain-derived neurotrophic factor (BDNF), a neuronal growth factor, on the connectivity of a peripheral motor-nerve bridge in a rodent model using electrophysiology and immunohistochemistry (IHC). Spinal cords of 29 female rats were hemisected at the L1 level. Ipsilateral T13 peripheral nerves were dissected from their muscular targets distally, while maintaining their connections with the spinal cord, and inserted caudal to the injury site to establish the nerve bridge. A microcannula attached to a six-week mini-osmotic pump was used to deliver either BDNF (n=12), saline (n=14), or fluorescein dye (n=3) directly into the spinal cord parenchyma between the site of nerve insertion and hemisection to a depth of 2mm into the area of the lateral motor pool. After four weeks, gastrocnemius muscle activation was assessed electromyographically in five animals from each group. Spinal cords were harvested and analyzed with IHC for cannula-associated injury, and nerve regeneration. Strength of motor bridge connection was illustrated by electrophysiology data. Intraspinal BDNF levels were measured using enzyme-linked immunosorbent assay. IHC revealed increased intraparenchymal BDNF concentration at the nerve bridge insertion site with evidence of minimal trauma from cannulation. BDNF infusion resulted in stronger connections between bridge nerves and spinal motor axons. Bridge nerve electrical stimulation in BDNF-treated rats evoked hind leg electromyogram responses of shorter latency and

  13. Feasibility of Human Amniotic Fluid Derived Stem Cells in Alleviation of Neuropathic Pain in Chronic Constrictive Injury Nerve Model

    PubMed Central

    Chiang, Chien-Yi; Liu, Shih-An; Sheu, Meei-Ling; Chen, Fu-Chou; Chen, Chun-Jung; Su, Hong-Lin; Pan, Hung-Chuan

    2016-01-01

    Purpose The neurobehavior of neuropathic pain by chronic constriction injury (CCI) of sciatic nerve is very similar to that in humans, and it is accompanied by a profound local inflammation response. In this study, we assess the potentiality of human amniotic fluid derived mesenchymal stem cells (hAFMSCs) for alleviating the neuropathic pain in a chronic constriction nerve injury model. Methods and Methods This neuropathic pain animal model was conducted by four 3–0 chromic gut ligatures loosely ligated around the left sciatic nerve in Sprague—Dawley rats. The intravenous administration of hAFMSCs with 5x105 cells was conducted for three consecutive days. Results The expression IL-1β, TNF-α and synaptophysin in dorsal root ganglion cell culture was remarkably attenuated when co-cultured with hAFMSCs. The significant decrease of PGP 9.5 in the skin after CCI was restored by administration of hAFMSCs. Remarkably increased expression of CD 68 and TNF-α and decreased S-100 and neurofilament expression in injured nerve were rescued by hAFMSCs administration. Increases in synaptophysin and TNF-α over the dorsal root ganglion were attenuated by hAFMSCs. Significant expression of TNF-α and OX-42 over the dorsal spinal cord was substantially attenuated by hAFMSCs. The increased amplitude of sensory evoked potential as well as expression of synaptophysin and TNF-α expression was alleviated by hAFMSCs. Human AFMSCs significantly improved the threshold of mechanical allodynia and thermal hyperalgesia as well as various parameters of CatWalk XT gait analysis. Conclusion Human AFMSCs administration could alleviate the neuropathic pain demonstrated in histomorphological alteration and neurobehavior possibly through the modulation of the inflammatory response. PMID:27441756

  14. Sesame oil improves functional recovery by attenuating nerve oxidative stress in a mouse model of acute peripheral nerve injury: role of Nrf-2.

    PubMed

    Hsu, Che-Chia; Huang, Hui-Cheng; Wu, Po-Ting; Tai, Ta-Wei; Jou, I-Ming

    2016-12-01

    Peripheral nervous injury (PNI) is a common form of trauma in modern society, especially in sport players. Despite the advance of therapy for PNI, the recovery of function can never reach the preinjury level after treatments. Recently, inhibiting neural oxidative stress shows a beneficial effect in improving functional recovery after PNI. In addition, sesame oil has been reported to possess the excellent antioxidative properties. However, whether sesame oil can improve the functional recovery after PNI by its antioxidative effect has never been investigated. Thirty mice were randomly divided into five groups of six: group I mice received sham operation; group II mice received sciatic nerve crush; and groups III-V mice daily ingested 0.5, 1 and 2 ml/kg of sesame oil for 6 days, respectively, after sciatic nerve crush. Oxidative stress, GAP43 and nuclear Nrf2 levels as well as spinal somatosensory evoked potentials were assessed on day 6, while paw withdrawal latency and sciatic function index were assessed on days 0, 3, and 6. Sesame oil significantly decreased lipid peroxidation and increased nuclear factor erythroid 2-related factor 2 and GAP43 expression in sciatic nerve. Furthermore, sesame oil improved electrophysiological and functional assessments in mice with sciatic nerve crush. In conclusion, sesame oil may improve nerve functional recovery by attenuating nerve oxidative stress in mouse acute peripheral nerve injury. Further, application of natural product sesame oil may be an alternative approach for improving nerve functional recovery in the clinical setting.

  15. Peripheral Nerve Injury: Stem Cell Therapy and Peripheral Nerve Transfer

    PubMed Central

    Sullivan, Robert; Dailey, Travis; Duncan, Kelsey; Abel, Naomi; Borlongan, Cesario V.

    2016-01-01

    Peripheral nerve injury can lead to great morbidity in those afflicted, ranging from sensory loss, motor loss, chronic pain, or a combination of deficits. Over time, research has investigated neuronal molecular mechanisms implicated in nerve damage, classified nerve injury, and developed surgical techniques for treatment. Despite these advancements, full functional recovery remains less than ideal. In this review, we discuss historical aspects of peripheral nerve injury and introduce nerve transfer as a therapeutic option, as well as an adjunct therapy to transplantation of Schwann cells and their stem cell derivatives for repair of the damaged nerve. This review furthermore, will provide an elaborated discussion on the sources of Schwann cells, including sites to harvest their progenitor and stem cell lines. This reflects the accessibility to an additional, concurrent treatment approach with nerve transfers that, predicated on related research, may increase the efficacy of the current approach. We then discuss the experimental and clinical investigations of both Schwann cells and nerve transfer that are underway. Lastly, we provide the necessary consideration that these two lines of therapeutic approaches should not be exclusive, but conversely, should be pursued as a combined modality given their mutual role in peripheral nerve regeneration. PMID:27983642

  16. A Novel Model for Acute Peripheral Nerve Injury in the Horse and Evaluation of the Effect of Mesenchymal Stromal Cells Applied In Situ on Nerve Regeneration: A Preliminary Study

    PubMed Central

    Cruz Villagrán, Claudia; Schumacher, Jim; Donnell, Robert; Dhar, Madhu S.

    2016-01-01

    Transplantation of mesenchymal stromal cells (MSCs) to sites of experimentally created nerve injury in laboratory animals has shown promising results in restoring nerve function. This approach for nerve regeneration has not been reported in horses. In this study, we first evaluated the in vitro ability of equine bone marrow-derived MSCs (EBM-MSCs) to trans-differentiate into Schwann-like cells and subsequently tested the MSCs in vivo for their potential to regenerate a transected nerve after implantation. The EBM-MSCs from three equine donors were differentiated into SCLs for 7 days, in vitro, in the presence of specialized differentiation medium and evaluated for morphological characteristics, by using confocal microscopy, and for protein characteristics, by using selected Schwann cell markers (GFAP and S100b). The EBM-MSCs were then implanted into the fascia surrounding the ramus communicans of one fore limb of three healthy horses after a portion of this nerve was excised. The excised portion of the nerve was examined histologically at the time of transection, and stumps of the nerve were examined histologically at day 45 after transplantation. The EBM-MSCs from all donors demonstrated morphological and protein characteristics of those of Schwann cells 7 days after differentiation. Nerves implanted with EBM-MSCs after nerve transection did not show evidence of nerve regeneration at day 45. Examination of peripheral nerves collected 45 days after injury and stem cell treatment revealed no histological differences between nerves treated with MSCs and those treated with isotonic saline solution (controls). The optimal delivery of MSCs and the model suitable to study the efficacy of MSCs in nerve regeneration should be investigated. PMID:27695697

  17. Application of implantable wireless biomicrosystem for monitoring nerve impedance of rat after sciatic nerve injury.

    PubMed

    Li, Yu-Ting; Peng, Chih-Wei; Chen, Lung-Tai; Lin, Wen-Shan; Chu, Chun-Hsun; Chen, Jia-Jin Jason

    2013-01-01

    Electrical stimulation is usually applied percutaneously for facilitating peripheral nerve regeneration. However, few studies have conducted long-term monitoring of the condition of nerve regeneration. This study implements an implantable biomicrosystem for inducing pulse current for aiding nerve repair and monitoring the time-course changes of nerve impedance for assessing nerve regeneration in sciatic nerve injury rat model. For long-term implantation, a transcutaneous magnetic coupling technique is adopted for power and data transmission. For in vivo study, the implanted module was placed in the rat's abdomen and the cuff electrode was wrapped around an 8-mm sciatic nerve gap of the rat for nerve impedance measurement for 42 days. One group of animals received monophasic constant current via the cuff electrode and a second group had no stimulation between days 8-21. The nerve impedance increased to above 150% of the initial value in the nerve regeneration groups with and without stimulation whereas the group with no nerve regeneration increased to only 113% at day 42. The impedance increase in nerve regeneration groups can be observed before evident functional recovery. Also, the nerve regeneration group that received electrical stimulation had relatively higher myelinated fiber density than that of no stimulation group, 20686 versus 11417 fiber/mm (2). The developed implantable biomicrosystem is proven to be a useful experimental tool for long-term stimulation in aiding nerve fiber growth as well as impedance assessment for understanding the time-course changes of nerve regeneration.

  18. Investigation of nerve injury through microfluidic devices

    PubMed Central

    Siddique, Rezina; Thakor, Nitish

    2014-01-01

    Traumatic injuries, both in the central nervous system (CNS) and peripheral nervous system (PNS), can potentially lead to irreversible damage resulting in permanent loss of function. Investigating the complex dynamics involved in these processes may elucidate the biological mechanisms of both nerve degeneration and regeneration, and may potentially lead to the development of new therapies for recovery. A scientific overview on the biological foundations of nerve injury is presented. Differences between nerve regeneration in the central and PNS are discussed. Advances in microtechnology over the past several years have led to the development of invaluable tools that now facilitate investigation of neurobiology at the cellular scale. Microfluidic devices are explored as a means to study nerve injury at the necessary simplification of the cellular level, including those devices aimed at both chemical and physical injury, as well as those that recreate the post-injury environment. PMID:24227311

  19. Motonuclear changes after cranial nerve injury and regeneration.

    PubMed

    Fernandez, E; Pallini, R; Lauretti, L; La Marca, F; Scogna, A; Rossi, G F

    1997-09-01

    Little is known about the mechanisms at play in nerve regeneration after nerve injury. Personal studies are reported regarding motonuclear changes after regeneration of injured cranial nerves, in particular of the facial and oculomotor nerves, as well as the influence that the natural molecule acetyl-L-carnitine (ALC) has on post-axotomy cranial nerve motoneuron degeneration after facial and vagus nerve lesions. Adult and newborn animal models were used. Massive motoneuron response after nerve section and reconstruction was observed in the motonuclei of all nerves studied. ALC showed to have significant neuroprotective effects on the degeneration of axotomized motoneurons. Complex quantitative, morphological and somatotopic nuclear changes occurred that sustain new hypotheses regarding the capacities of motoneurons to regenerate and the possibilities of new neuron proliferation. The particularities of such observations are described and discussed.

  20. Spinal Autofluorescent Flavoprotein Imaging in a Rat Model of Nerve Injury-Induced Pain and the Effect of Spinal Cord Stimulation

    PubMed Central

    Jongen, Joost L. M.; Smits, Helwin; Pederzani, Tiziana; Bechakra, Malik; Hossaini, Mehdi; Koekkoek, Sebastiaan K.; Huygen, Frank J. P. M.; De Zeeuw, Chris I.; Holstege, Jan C.; Joosten, Elbert A. J.

    2014-01-01

    Nerve injury may cause neuropathic pain, which involves hyperexcitability of spinal dorsal horn neurons. The mechanisms of action of spinal cord stimulation (SCS), an established treatment for intractable neuropathic pain, are only partially understood. We used Autofluorescent Flavoprotein Imaging (AFI) to study changes in spinal dorsal horn metabolic activity. In the Seltzer model of nerve-injury induced pain, hypersensitivity was confirmed using the von Frey and hotplate test. 14 Days after nerve-injury, rats were anesthetized, a bipolar electrode was placed around the affected sciatic nerve and the spinal cord was exposed by a laminectomy at T13. AFI recordings were obtained in neuropathic rats and a control group of naïve rats following 10 seconds of electrical stimulation of the sciatic nerve at C-fiber strength, or following non-noxious palpation. Neuropathic rats were then treated with 30 minutes of SCS or sham stimulation and AFI recordings were obtained for up to 60 minutes after cessation of SCS/sham. Although AFI responses to noxious electrical stimulation were similar in neuropathic and naïve rats, only neuropathic rats demonstrated an AFI-response to palpation. Secondly, an immediate, short-lasting, but strong reduction in AFI intensity and area of excitation occurred following SCS, but not following sham stimulation. Our data confirm that AFI can be used to directly visualize changes in spinal metabolic activity following nerve injury and they imply that SCS acts through rapid modulation of nociceptive processing at the spinal level. PMID:25279562

  1. Botulinum neurotoxin type A counteracts neuropathic pain and facilitates functional recovery after peripheral nerve injury in animal models.

    PubMed

    Marinelli, S; Luvisetto, S; Cobianchi, S; Makuch, W; Obara, I; Mezzaroma, E; Caruso, M; Straface, E; Przewlocka, B; Pavone, F

    2010-11-24

    A growing interest was recently focused on the use of Botulinum neurotoxin serotype A (BoNT/A) for fighting pain. The aim of this study was to investigate the effects of BoNT/A on neuropathic pain. It was observed that BoNT/A is able to counteract neuropathic pain induced by chronic constriction injury (CCI) to the sciatic nerve both in mice and in rats. This effect is already present after a single intraplantar (i.pl.) or intrathecal (i.t.) neurotoxin administration that significantly reduces the sciatic nerve ligation-induced mechanical allodynia in mice and rats and thermal hyperalgesia in rats. This effect was evident starting 24 h after the administration of BoNT/A and it was long-lasting, being present 81 or 25 days after i.pl. injection of the higher dose in mice (15 pg/paw) and rats (75 pg/paw), respectively, and 35 days after i.t. injection in rats (75 pg/rat). Moreover, BoNT/A-injected mice showed a quicker recovery of the walking pattern and weight bearing compared to control groups. The behavioral improvement was accompanied by structural modifications, as revealed by the expression of cell division cycle 2 (Cdc2) and growth associated protein 43 (GAP-43) regeneration associated proteins, investigated by immunofluorescence and Western blotting in the sciatic nerve, and by the immunofluorescence expression of S100β and glial fibrillary acidic protein (GFAP) Schwann cells proteins. In conclusion, the present research demonstrate long-lasting anti-allodynic and anti-hyperalgesic effects of BoNT/A in animal models of neuropathic pain together with an acceleration of regenerative processes in the injured nerve, as evidenced by both behavioral and immunohistochemistry/blotting analysis. These results may have important implications in the therapy of neuropathic pain.

  2. Expression changes of nerve cell adhesion molecules L1 and semaphorin 3A after peripheral nerve injury

    PubMed Central

    He, Qian-ru; Cong, Meng; Chen, Qing-zhong; Sheng, Ya-feng; Li, Jian; Zhang, Qi; Ding, Fei; Gong, Yan-pei

    2016-01-01

    The expression of nerve cell adhesion molecule L1 in the neuronal growth cone of the central nervous system is strongly associated with the direction of growth of the axon, but its role in the regeneration of the peripheral nerve is still unknown. This study explored the problem in a femoral nerve section model in rats. L1 and semaphorin 3A mRNA and protein expressions were measured over the 4-week recovery period. Quantitative polymerase chain reaction showed that nerve cell adhesion molecule L1 expression was higher in the sensory nerves than in motor nerves at 2 weeks after injury, but vice versa for the expression of semaphorin 3A. Western blot assay results demonstrated that nerve cell adhesion molecule L1 expression was higher in motor nerves than in the sensory nerves at the proximal end after injury, but its expression was greater in the sensory nerves at 2 weeks. Semaphorin 3A expression was higher in the motor nerves than in the sensory nerves at 3 days and 1 week after injury. Nerve cell adhesion molecule L1 and semaphorin 3A expressions at the distal end were higher in the motor nerves than in the sensory nerves at 3 days, 1 and 2 weeks. Immunohistochemical staining results showed that nerve cell adhesion molecule L1 expression at the proximal end was greater in the sensory nerves than in the motor nerves; semaphorin 3A expression was higher in the motor nerves than in the sensory nerves at 2 weeks after injury. Taken together, these results indicated that nerve cell adhesion molecules L1 and semaphorin 3A exhibited different expression patterns at the proximal and distal ends of sensory and motor nerves, and play a coordinating role in neural chemotaxis regeneration. PMID:28197202

  3. Ursolic acid induces neural regeneration after sciatic nerve injury

    PubMed Central

    Liu, Biao; Liu, Yan; Yang, Guang; Xu, Zemin; Chen, Jiajun

    2013-01-01

    In this study, we aimed to explore the role of ursolic acid in the neural regeneration of the injured sciatic nerve. BALB/c mice were used to establish models of sciatic nerve injury through unilateral sciatic nerve complete transection and microscopic anastomosis at 0.5 cm below the ischial tube-rosity. The successfully generated model mice were treated with 10, 5, or 2.5 mg/kg ursolic acid via intraperitoneal injection. Enzyme-linked immunosorbent assay results showed that serum S100 protein expression level gradually increased at 1–4 weeks after sciatic nerve injury, and significantly decreased at 8 weeks. As such, ursolic acid has the capacity to significantly increase S100 protein expression levels. Real-time quantitative PCR showed that S100 mRNA expression in the L4–6 segments on the injury side was increased after ursolic acid treatment. In addition, the muscular mass index in the soleus muscle was also increased in mice treated with ursolic acid. Toluidine blue staining revealed that the quantity and average diameter of myelinated nerve fibers in the injured sciatic nerve were significantly increased after treatment with ursolic acid. 10 and 5 mg/kg of ursolic acid produced stronger effects than 2.5 mg/kg of ursolic acid. Our findings indicate that ursolic acid can dose-dependently increase S100 expression and promote neural regeneration in BALB/c mice following sciatic nerve injury. PMID:25206561

  4. Optical Detection of Early Damage in Retinal Ganglion Cells in a Mouse Model of Partial Optic Nerve Crush Injury

    PubMed Central

    Yi, Ji; Puyang, Zhen; Feng, Liang; Duan, Lian; Liang, Peiji; Backman, Vadim; Liu, Xiaorong; Zhang, Hao F.

    2016-01-01

    Purpose Elastic light backscattering spectroscopy (ELBS) has exquisite sensitivity to the ultrastructural properties of tissue and thus has been applied to detect various diseases associated with ultrastructural alterations in their early stages. This study aims to test whether ELBS can detect early damage in retinal ganglion cells (RGCs). Methods We used a mouse model of partial optic nerve crush (pONC) to induce rapid RGC death. We confirmed RGC loss by axon counting and characterized the changes in retinal morphology by optical coherence tomography (OCT) and in retinal function by full-field electroretinogram (ERG), respectively. To quantify the ultrastructural properties, elastic backscattering spectroscopic analysis was implemented in the wavelength-dependent images recorded by reflectance confocal microscopy. Results At 3 days post-pONC injury, no significant change was found in the thickness of the RGC layer or in the mean amplitude of the oscillatory potentials measured by OCT and ERG, respectively; however, we did observe a significantly decreased number of axons compared with the controls. At 3 days post-pONC, we used ELBS to calculate the ultrastructural marker (D), the shape factor quantifying the shape of the local mass density correlation functions. It was significantly reduced in the crushed eyes compared with the controls, indicating the ultrastructural fragmentation in the crushed eyes. Conclusions Elastic light backscattering spectroscopy detected ultrastructural neuronal damage in RGCs following the pONC injury when OCT and ERG tests appeared normal. Our study suggests a potential clinical method for detecting early neuronal damage prior to anatomical alterations in the nerve fiber and ganglion cell layers. PMID:27784071

  5. Human umbilical cord blood mononuclear cells and chorionic plate-derived mesenchymal stem cells promote axon survival in a rat model of optic nerve crush injury.

    PubMed

    Chung, Sokjoong; Rho, Seungsoo; Kim, Gijin; Kim, So-Ra; Baek, Kwang-Hyun; Kang, Myungseo; Lew, Helen

    2016-05-01

    The use of mesenchymal stem cells (MSCs) in cell therapy in regenerative medicine has great potential, particularly in the treatment of nerve injury. Umbilical cord blood (UCB) reportedly contains stem cells, which have been widely used as a hematopoietic source and may have therapeutic potential for neurological impairment. Although ongoing research is dedicated to the management of traumatic optic nerve injury using various measures, novel therapeutic strategies based on the complex underlying mechanisms responsible for optic nerve injury, such as inflammation and/or ischemia, are required. In the present study, a rat model of optic nerve crush (ONC) injury was established in order to examine the effects of transplanting human chorionic plate-derived MSCs (CP‑MSCs) isolated from the placenta, as well as human UCB mononuclear cells (CB-MNCs) on compressed rat optic nerves. Expression markers for inflammation, apoptosis, and optic nerve regeneration were analyzed, as well as the axon survival rate by direct counting. Increased axon survival rates were observed following the injection of CB‑MNCs at at 1 week post-transplantation compared with the controls. The levels of growth-associated protein-43 (GAP‑43) were increased after the injection of CB‑MNCs or CP‑MSCs compared with the controls, and the expression levels of hypoxia-inducible factor-1α (HIF-1α) were also significantly increased following the injection of CB-MNCs or CP-MSCs. ERM-like protein (ERMN) and SLIT-ROBO Rho GTPase activating protein 2 (SRGAP2) were found to be expressed in the optic nerves of the CP‑MSC-injected rats with ONC injury. The findings of our study suggest that the administration of CB‑MNCs or CP‑MSCs may promote axon survival through systemic concomitant mechanisms involving GAP‑43 and HIF‑1α. Taken together, these findings provide further understanding of the mechanisms repsonsible for optic nerve injury and may aid in the development of novel cell

  6. Human umbilical cord blood mononuclear cells and chorionic plate-derived mesenchymal stem cells promote axon survival in a rat model of optic nerve crush injury

    PubMed Central

    CHUNG, SOKJOONG; RHO, SEUNGSOO; KIM, GIJIN; KIM, SO-RA; BAEK, KWANG-HYUN; KANG, MYUNGSEO; LEW, HELEN

    2016-01-01

    The use of mesenchymal stem cells (MSCs) in cell therapy in regenerative medicine has great potential, particularly in the treatment of nerve injury. Umbilical cord blood (UCB) reportedly contains stem cells, which have been widely used as a hematopoietic source and may have therapeutic potential for neurological impairment. Although ongoing research is dedicated to the management of traumatic optic nerve injury using various measures, novel therapeutic strategies based on the complex underlying mechanisms responsible for optic nerve injury, such as inflammation and/or ischemia, are required. In the present study, a rat model of optic nerve crush (ONC) injury was established in order to examine the effects of transplanting human chorionic plate-derived MSCs (CP-MSCs) isolated from the placenta, as well as human UCB mononuclear cells (CB-MNCs) on compressed rat optic nerves. Expression markers for inflammation, apoptosis, and optic nerve regeneration were analyzed, as well as the axon survival rate by direct counting. Increased axon survival rates were observed following the injection of CB-MNCs at at 1 week post-transplantation compared with the controls. The levels of growth-associated protein-43 (GAP-43) were increased after the injection of CB-MNCs or CP-MSCs compared with the controls, and the expression levels of hypoxia-inducible factor-1α (HIF-1α) were also significantly increased following the injection of CB-MNCs or CP-MSCs. ERM-like protein (ERMN) and SLIT-ROBO Rho GTPase activating protein 2 (SRGAP2) were found to be expressed in the optic nerves of the CP-MSC-injected rats with ONC injury. The findings of our study suggest that the administration of CB-MNCs or CP-MSCs may promote axon survival through systemic concomitant mechanisms involving GAP-43 and HIF-1α. Taken together, these findings provide further understanding of the mechanisms repsonsible for optic nerve injury and may aid in the development of novel cell-based therapeutic strategies with

  7. Nerve Injury in Athletes Caused by Cryotherapy

    PubMed Central

    Malone, Terry R.; Engelhardt, David L.; Kirkpatrick, John S.; Bassett, Frank H.

    1992-01-01

    Cryotherapy is a therapeutic modality frequently used in the treatment of athletic injuries. In very rare circumstances, inappropriate use in some individuals can lead to nerve injury resulting in temporary or permanent disability of the athlete. Six cases of cold-induced peripheral nerve injury from 1988 to 1991 at the Sports Medicine Center at Duke University are reported. Although disability can be severe and can render an athlete unable to compete for several months, each of these cases resolved spontaneously. Whereas the application of this modality is typically quite safe and beneficial, clinicians must be aware of the location of major peripheral nerves, the thickness of the overlying subcutaneous fat, the method of application (with inherent or additional compression), the duration of tissue cooling, and the possible cryotherapy sensibility of some individuals. PMID:16558167

  8. Puerarin accelerates neural regeneration after sciatic nerve injury

    PubMed Central

    Wu, Minfei; Zhao, Guanjie; Yang, Xiaoyu; Peng, Chuangang; Zhao, Jianwu; Liu, Jun; Li, Rui; Gao, Zhongli

    2014-01-01

    Puerarin is a natural isoflavone isolated from plants of the genus Pueraria and functions as a protector against cerebral ischemia. We hypothesized that puerarin can be involved in the repair of peripheral nerve injuries. To test this hypothesis, doses of 10, 5, or 2.5 mg/kg per day puerarin (8-(β-D-Glucopyranosyl-7-hydroxy-3-(4-hydroxyphenyl)-4H-1-benzopyran-4-one) were injected intraperitoneally into mouse models of sciatic nerve injury. Puerarin at the middle and high doses significantly up-regulated the expression of growth-associated protein 43 in the L4–6 segments of the spinal cord from mice at 1, 2, and 4 weeks after modeling, and reduced the atrophy of the triceps surae on the affected side and promoted the regeneration of nerve fibers of the damaged spinal cord at 8 weeks after injury. We conclude that puerarin exerts an ongoing role to activate growth-associated protein 43 in the corresponding segment of the spinal cord after sciatic nerve injury, thus contributing to neural regeneration after sciatic nerve injuries. PMID:25206860

  9. Effect of PACAP in Central and Peripheral Nerve Injuries

    PubMed Central

    Tamas, Andrea; Reglodi, Dora; Farkas, Orsolya; Kovesdi, Erzsebet; Pal, Jozsef; Povlishock, John T.; Schwarcz, Attila; Czeiter, Endre; Szanto, Zalan; Doczi, Tamas; Buki, Andras; Bukovics, Peter

    2012-01-01

    Pituitary adenylate cyclase activating polypeptide (PACAP) is a bioactive peptide with diverse effects in the nervous system. In addition to its more classic role as a neuromodulator, PACAP functions as a neurotrophic factor. Several neurotrophic factors have been shown to play an important role in the endogenous response following both cerebral ischemia and traumatic brain injury and to be effective when given exogenously. A number of studies have shown the neuroprotective effect of PACAP in different models of ischemia, neurodegenerative diseases and retinal degeneration. The aim of this review is to summarize the findings on the neuroprotective potential of PACAP in models of different traumatic nerve injuries. Expression of endogenous PACAP and its specific PAC1 receptor is elevated in different parts of the central and peripheral nervous system after traumatic injuries. Some experiments demonstrate the protective effect of exogenous PACAP treatment in different traumatic brain injury models, in facial nerve and optic nerve trauma. The upregulation of endogenous PACAP and its receptors and the protective effect of exogenous PACAP after different central and peripheral nerve injuries show the important function of PACAP in neuronal regeneration indicating that PACAP may also be a promising therapeutic agent in injuries of the nervous system. PMID:22942712

  10. Electrical Stimulation Enhances Reinnervation After Nerve Injury

    PubMed Central

    2015-01-01

    Electrical muscle stimulation following peripheral nerve injury has been a controversial method of treatment due primarily to the inconsistent literature surrounding it. In this presentation transcript I outline ongoing experiments investigating a clinically translatable daily muscle stimulation paradigm in rats following nerve injury. Results show that reinnervation of muscle and functional behavioural metrics are enhanced with daily stimulation with upregulation of intramuscular neurotrophic factors as a potential mechanism. In addition, the impact of stimulation on terminal sprouting, a mentioned negative aspect of electrical muscle stimulation, was a minor contributor to long term functional reinnervation of stimulated muscles in our studies. PMID:26913163

  11. Prevention and Management of Nerve Injuries in Thoracic Surgery.

    PubMed

    Auchincloss, Hugh G; Donahue, Dean M

    2015-11-01

    Nerve injuries can cause substantial morbidity after thoracic surgical procedures. These injuries are preventable, provided that the surgeon has a thorough understanding of the anatomy and follows important surgical principles. When nerve injuries occur, it is important to recognize the options available in the immediate and postoperative settings, including expectant management, immediate nerve reconstruction, or auxiliary procedures. This article covers the basic anatomy and physiology of nerves and nerve injuries, an overview of techniques in nerve reconstruction, and a guide to the nerves most commonly involved in thoracic operative procedures.

  12. Fate of combat nerve injury

    DTIC Science & Technology

    2012-11-01

    Exoskeletal Orthosis are promising, even in patients complicated by the presence of a foot drop (0/5 motor strength to the peroneal nerve), allowing them...after limb salvage. J Trauma. 2011;71:S120 S124. 32. Patzkowski JC, Blanck RV, Owens JG, et al. Can an ankle-foot orthosis change hearts and minds? J

  13. GLIAL RESPONSES AFTER CHORDA TYMPANI NERVE INJURY

    PubMed Central

    Bartel, Dianna L.

    2013-01-01

    The chorda tympani (CT) nerve innervates lingual taste buds and is susceptible to damage during dental and inner ear procedures. Interruption of the CT results in a disappearance of taste buds, which can be accompanied by taste disturbances. Because the CT usually regenerates to reinnervate taste buds successfully in a few weeks, a persistence of taste disturbances may indicate alterations in central nervous function. Peripheral injury to other sensory nerves leads to glial responses at central terminals, which actively contribute to abnormal sensations arising from nerve damage. Therefore, the current study examined microglial and astrocytic responses in the first central gustatory relay -the nucleus of the solitary tract (nTS)- after transection of the CT. Damage to the CT resulted in significant microglial responses in terms of morphological reactivity and an increased density of microglial cells from 2-20 days after injury. This increased microglial population primarily resulted from microglial proliferation from 1.5-3 days, which was supplemented by microglial migration within sub-divisions of the nTS between days 2-3. Unlike other nerve injuries, CT injury did not result in recruitment of bone marrow-derived precursors. Astrocytes also reacted in the nTS with increased levels of GFAP by 3 days, although none showed evidence of cell division. GFAP levels remained increased at 30 days by which time microglial responses had resolved. These results show that nerve damage to the CT results in central glial responses, which may participate in long lasting taste alterations following CT lesion. PMID:22315167

  14. N-11C-Methyl-Dopamine PET Imaging of Sympathetic Nerve Injury in a Swine Model of Acute Myocardial Ischemia: A Comparison with 13N-Ammonia PET

    PubMed Central

    Zhou, Weina; Wang, Xiangcheng; He, Yulin; Nie, Yongzhen; Zhang, Guojian; Wang, Cheng; Wang, Chunmei; Wang, Xuemei

    2016-01-01

    Objective. Using a swine model of acute myocardial ischemia, we sought to validate N-11C-methyl-dopamine (11C-MDA) as an agent capable of imaging cardiac sympathetic nerve injury. Methods. Acute myocardial ischemia was surgically generated in Chinese minipigs. ECG and serum enzyme levels were used to detect the presence of myocardial ischemia. Paired 11C-MDA PET and 13N-ammonia PET scans were performed at baseline, 1 day, and 1, 3, and 6 months after surgery to relate cardiac sympathetic nerve injury to blood perfusion. Results. Seven survived the surgical procedure. The ECG-ST segment was depressed, and levels of the serum enzymes increased. Cardiac uptake of tracer was quantified as the defect volume. Both before and immediately after surgery, the images obtained with 11C-MDA and 13N-ammonia were similar. At 1 to 6 months after surgery, however, 11C-MDA postsurgical left ventricular myocardial defect volume was significantly greater compared to 13N-ammonia. Conclusions. In the Chinese minipig model of acute myocardial ischemia, the extent of the myocardial defect as visualized by 11C-MDA is much greater than would be suggested by blood perfusion images, and the recovery from myocardial sympathetic nerve injury is much slower than the restoration of blood perfusion. 11C-MDA PET may provide additional biological information during recovery from ischemic heart disease. PMID:27034950

  15. Vitamin B complex and vitamin B12 levels after peripheral nerve injury

    PubMed Central

    Altun, Idiris; Kurutaş, Ergül Belge

    2016-01-01

    The aim of the present study was to evaluate whether tissue levels of vitamin B complex and vitamin B12 were altered after crush-induced peripheral nerve injury in an experimental rat model. A total of 80 male Wistar rats were randomized into one control (n = 8) and six study groups (1, 6, 12, 24 hours, 3, and 7 days after experimental nerve injury; n = 12 for each group). Crush-induced peripheral nerve injury was performed on the sciatic nerves of rats in six study groups. Tissue samples from the sites of peripheral nerve injury were obtained at 1, 6, 12, 24 hours, 3 and 7 days after experimental nerve injury. Enzyme-linked immunosorbent assay results showed that tissue levels of vitamin B complex and vitamin B12 in the injured sciatic nerve were significantly greater at 1 and 12 hours after experimental nerve injury, while they were significantly lower at 7 days than in control group. Tissue level of vitamin B12 in the injured sciatic nerve was significantly lower at 1, 6, 12 and 24 hours than in the control group. These results suggest that tissue levels of vitamin B complex and vitamin B12 vary with progression of crush-induced peripheral nerve injury, and supplementation of these vitamins in the acute period may be beneficial for acceleration of nerve regeneration. PMID:27335572

  16. Exploring vocal recovery after cranial nerve injury in Bengalese finches.

    PubMed

    Urbano, Catherine M; Peterson, Jennifer R; Cooper, Brenton G

    2013-02-08

    Songbirds and humans use auditory feedback to acquire and maintain their vocalizations. The Bengalese finch (Lonchura striata domestica) is a songbird species that rapidly modifies its vocal output to adhere to an internal song memory. In this species, the left side of the bipartite vocal organ is specialized for producing louder, higher frequencies (≥2.2kHz) and denervation of the left vocal muscles eliminates these notes. Thus, the return of higher frequency notes after cranial nerve injury can be used as a measure of vocal recovery. Either the left or right side of the syrinx was denervated by resection of the tracheosyringeal portion of the hypoglossal nerve. Histologic analyses of syringeal muscle tissue showed significant muscle atrophy in the denervated side. After left nerve resection, songs were mainly composed of lower frequency syllables, but three out of five birds recovered higher frequency syllables. Right nerve resection minimally affected phonology, but it did change song syntax; syllable sequence became abnormally stereotyped after right nerve resection. Therefore, damage to the neuromuscular control of sound production resulted in reduced motor variability, and Bengalese finches are a potential model for functional vocal recovery following cranial nerve injury.

  17. Statins alleviate experimental nerve injury-induced neuropathic pain.

    PubMed

    Shi, Xiang Qun; Lim, Tony K Y; Lee, Seunghwan; Zhao, Yuan Qing; Zhang, Ji

    2011-05-01

    The statins are a well-established class of drugs that lower plasma cholesterol levels by inhibiting HMG-CoA (3-hydroxy-3-methyl-glutaryl-coenzyme A) reductase. They are widely used for the treatment of hypercholesterolemia and for the prevention of coronary heart disease. Recent studies suggest that statins have anti-inflammatory effects beyond their lipid-lowering properties. We sought to investigate whether statins could affect neuropathic pain by mediating nerve injury-associated inflammatory responses. The effects of hydrophilic rosuvastatin and lipophilic simvastatin were examined in the mouse partial sciatic nerve ligation model. Systemic daily administration of either statin from days 0 to 14 completely prevented the development of mechanical allodynia and thermal hyperalgesia. When administered from days 8 to 14 after injury, both statins dose-dependently reduced established hypersensitivity. After treatment, the effects of the statins were washed out within 2 to 7 days, depending on dose. Effects of both statins in alleviating mechanical allodynia were further confirmed in a different injury-associated neuropathic pain model, mental nerve chronic constriction, in rats. Both statins were able to abolish interleukin-1β expression in sciatic nerve triggered by nerve ligation. Additionally, quantitative analysis with Iba-1 and glial fibrillary acid protein immunoreactivity demonstrated that rosuvastatin and simvastatin significantly reduced the spinal microglial and astrocyte activation produced by sciatic nerve injury. The increase of interleukin-1β mRNA in the ipsilateral side of spinal cords was also reduced by the treatment of either statin. We identified a potential new application of statins in the treatment of neuropathic pain. The pain-alleviating effects of statins are likely attributable to their immunomodulatory effects.

  18. Effect of icariin in combination with daily sildenafil on penile atrophy and erectile dysfunction in a rat model of bilateral cavernous nerves injury.

    PubMed

    Xu, Y; Xin, H; Wu, Y; Guan, R; Lei, H; Fu, X; Xin, Z; Yang, Y

    2017-03-10

    The commonly utilized phosphodiesterase type 5 inhibitors do not lead to satisfactory penile erection after radical prostatectomy mainly because of insufficient nitric oxide drive from the damaged cavernous nerves. The aim of this study was to assess the efficacy and mechanisms of icariin in combination with daily sildenafil on neurogenic erectile dysfunction and penile atrophy in a rat model of bilateral cavernous nerves injury. Sixty male Sprague-Dawley rats injected with 5-ethynyl-2-deoxyuridine (50 mg/kg) at postnatal day 1 for the purpose of tracking endogenous stem cells in penis. Forty-eight rats of bilateral cavernous nerves injury were randomized equally into gavage feeding of vehicle, sildenafil (10 mg/kg), icariin (1.5 mg/kg) and sildenafil + icariin, respectively. Twelve sham-operated rats served as control. The intracavernous pressure and mean arterial pressure was measured and mid-penile cross sections were histologically examined 5 weeks after surgery. Western blotting of cavernous tissue protein was also performed. Animals treated with sildenafil + icariin had significantly higher mean intracavernous pressure/mean arterial pressure ratio relative to other rats with bilateral cavernous nerves injury (p < 0.05). The circumference and mean cross-sectional area of the paired corpus cavernosum were effectively preserved in the sildenafil + icariin. Treatment with sildenafil + icariin significantly increased the cavernous cyclic guanosine monophosphate concentration compared with the icariin group (p < 0.05). In addition, the numbers of neuronal nitric oxide synthase-positive nerves and 5-ethynyl-2-deoxyuridine-positive cells co-expressing S100 in the icariin-treated groups were greater compared with the bilateral cavernous nerves injury control group (p < 0.05). These data suggest that the combined use of icariin and daily sildenafil holds promise as a potential therapy for neurogenic erectile dysfunction in the future. The underlying

  19. Radial head fracture associated with posterior interosseous nerve injury.

    PubMed

    Terra, Bernardo Barcellos; Sassine, Tannus Jorge; Lima, Guilherme de Freitas; Rodrigues, Leandro Marano; Padua, David Victoria Hoffmann; Nadai, Anderson de

    2016-01-01

    Fractures of the radial head and radial neck correspond to 1.7-5.4% of all fractures and approximately 30% may present associated injuries. In the literature, there are few reports of radial head fracture with posterior interosseous nerve injury. This study aimed to report a case of radial head fracture associated with posterior interosseous nerve injury.

  20. Lentiviral-mediated transfer of CDNF promotes nerve regeneration and functional recovery after sciatic nerve injury in adult rats

    SciTech Connect

    Cheng, Lei; Liu, Yi; Zhao, Hua; Zhang, Wen; Guo, Ying-Jun; Nie, Lin

    2013-10-18

    Highlights: •CDNF was successfully transfected by a lentiviral vector into the distal sciatic nerve. •CDNF improved S-100, NF200 expression and nerve regeneration after sciatic injury. •CDNF improved the remyelination and thickness of the regenerated sciatic nerve. •CDNF improved gastrocnemius muscle weight and sciatic functional recovery. -- Abstract: Peripheral nerve injury is often followed by incomplete and unsatisfactory functional recovery and may be associated with sensory and motor impairment of the affected limb. Therefore, a novel method is needed to improve the speed of recovery and the final functional outcome after peripheral nerve injuries. This report investigates the effect of lentiviral-mediated transfer of conserved dopamine neurotrophic factor (CDNF) on regeneration of the rat peripheral nerve in a transection model in vivo. We observed notable overexpression of CDNF protein in the distal sciatic nerve after recombinant CDNF lentiviral vector application. We evaluated sciatic nerve regeneration after surgery using light and electron microscopy and the functional recovery using the sciatic functional index and target muscle weight. HE staining revealed better ordered structured in the CDNF-treated group at 8 weeks post-surgery. Quantitative analysis of immunohistochemistry of NF200 and S-100 in the CDNF group revealed significant improvement of axonal and Schwann cell regeneration compared with the control groups at 4 weeks and 8 weeks after injury. The thickness of the myelination around the axons in the CDNF group was significantly higher than in the control groups at 8 weeks post-surgery. The CDNF group displayed higher muscle weights and significantly increased sciatic nerve index values. Our findings suggest that CDNF gene therapy could provide durable and stable CDNF protein concentration and has the potential to enhance peripheral nerve regeneration, morphological and functional recovery following nerve injury, which suggests a

  1. The treatment of peripheral nerve injuries using irradiated allografts and temporary host immunosuppression (in a rat model)

    SciTech Connect

    Easterling, K.J.; Trumble, T.E. )

    1990-10-01

    Irradiation of allografts prior to transplantation and host immunosuppression with cyclosporin-A were studied separately and in combination as means of lessening the rejection of transplanted peripheral nerve tissue. Lewis and Brown Norway rats were used in the animal model, as they differ at both major and minor histocompatibility loci. Sciatic nerve grafts (2.5 cm) were used and the animals were followed for 16 weeks after nerve grafting. The outcome was studied by functional measurements (sensory testing, gait analysis, joint flexion contracture, and muscle weight), as well as by measurements of biochemical and histologic parameters (hydroxyproline concentration and axon counts, respectively). Sensory testing was not reliable because of crossover innervation by the saphenous nerve. Evaluation by standard gait-testing techniques was found to be unsatisfactory. However, the allografted animals receiving cyclosporin-A had significantly smaller flexion contractures, compared to the allografted animals without immunosuppression (17 degrees +/- 12 degrees vs. 44 degrees +/- 13 degrees and 51 degrees +/- 13 degrees, p less than 0.005). Allografted animals receiving short-term cyclosporin-A had contractures that were not significantly different from those seen in isografted control animals (17 degrees +/- 12 degrees vs. 22 degrees +/- 15 degrees, NS). Muscle hydroxyproline concentration analysis revealed a lower hydroxyproline concentration among the allografted groups that received irradiated allografts, compared to groups receiving nonirradiated allogeneic grafts. The studies of muscle hydroxyproline concentration and muscle weight both showed substantial reinnervation, even in allografted animals without pretreatment of the grafts or immunosuppression of the recipient animal.

  2. Recombinant hNeuritin Promotes Structural and Functional Recovery of Sciatic Nerve Injury in Rats

    PubMed Central

    Wang, Haiyan; Li, Xinli; Shan, Liya; Zhu, Jingling; Chen, Rong; Li, Yuan; Yuan, Wumei; Yang, Lei; Huang, Jin

    2016-01-01

    Neuritin is a new neurotropic factor implicated in nervous system development and plasticity. Studies have shown that Neuritin is upregulated in injured nerves, suggesting that it is involved in nerve repair. To test this hypothesis, we investigated whether recombinant human Neuritin could restore nerve structure and function in a rat model of sciatic nerve injury. Neuritin treatment had a dose-dependent effect on functional recovery 4 weeks after injury, as determined by the walking-track test. Similar trends were observed for gastrocnemius muscular strength and nerve conduction velocity. Additionally, sciatic nerve fiber density and organization as well as degree of remyelination were increased, while growth-associated protein 43 and neurofilament 200 expression was upregulated upon treatment with Neuritin. These findings demonstrate that Neuritin stimulates nerve regeneration and functional recovery and thus promotes the repair of injured sciatic nerves. PMID:28066172

  3. Injections of adipose tissue-derived stem cells and stem cell lysate improve recovery of erectile function in a rat model of cavernous nerve injury

    PubMed Central

    Albersen, Maarten; Fandel, Thomas M.; Lin, Guiting; Wang, Guifang; Banie, Lia; Lin, Ching-Shwun; Lue, Tom F.

    2013-01-01

    Introduction Erectile dysfunction (ED) remains a major complication after radical prostatectomy. The use of adipose tissue-derived stem cells (ADSC) has shown promising results for the treatment of ED. However, the mechanisms of action for stem cell therapy remain controversial, with increasing evidence pointing to paracrine pathways. Aim To determine the effects and to identify the mechanism of action of ADSC and ADSC-derived lysate in a rat model of cavernous nerve (CN) crush injury. Methods Thirty-two male Sprague-Dawley rats were randomly divided into four equal groups: one group underwent sham operation, while three groups underwent bilateral CN crush. Crush-injury groups were treated at the time of injury with intracavernous injection of ADSC, lysate, or vehicle only (injured controls). Erectile function was assessed by cavernous nerve electrostimulation at 4 weeks. Penile tissue was collected for histology. Main Outcome Measures Intracavernous pressure increase upon CN stimulation; neuronal nitric oxide synthase (nNOS) content in the dorsal penile nerve; smooth muscle content, collagen content, and number of apoptotic cells in the corpus cavernosum. Results Both ADSC and lysate treatments resulted in significant recovery of erectile function, as compared to vehicle treatment. nNOS content was preserved in both the ADSC and lysate group, with significantly higher expression compared to vehicle-treated animals. There was significantly less fibrosis and a significant preservation of smooth muscle content in the ADSC and lysate groups compared to injured controls. The observed functional improvement after lysate injection supports the hypothesis that ADSC act through release of intracellular preformed substances or by active secretion of certain biomolecules. The underlying mechanism of recovery appears to involve neuron preservation and cytoprotection by inhibition of apoptosis. Conclusions Penile injection of both ADSC and ADSC-derived lysate can improve

  4. Cell proliferation and apoptosis in optic nerve and brain integration centers of adult trout Oncorhynchus mykiss after optic nerve injury.

    PubMed

    Pushchina, Evgeniya V; Shukla, Sachin; Varaksin, Anatoly A; Obukhov, Dmitry K

    2016-04-01

    Fishes have remarkable ability to effectively rebuild the structure of nerve cells and nerve fibers after central nervous system injury. However, the underlying mechanism is poorly understood. In order to address this issue, we investigated the proliferation and apoptosis of cells in contralateral and ipsilateral optic nerves, after stab wound injury to the eye of an adult trout Oncorhynchus mykiss. Heterogenous population of proliferating cells was investigated at 1 week after injury. TUNEL labeling gave a qualitative and quantitative assessment of apoptosis in the cells of optic nerve of trout 2 days after injury. After optic nerve injury, apoptotic response was investigated, and mass patterns of cell migration were found. The maximal concentration of apoptotic bodies was detected in the areas of mass clumps of cells. It is probably indicative of massive cell death in the area of high phagocytic activity of macrophages/microglia. At 1 week after optic nerve injury, we observed nerve cell proliferation in the trout brain integration centers: the cerebellum and the optic tectum. In the optic tectum, proliferating cell nuclear antigen (PCNA)-immunopositive radial glia-like cells were identified. Proliferative activity of nerve cells was detected in the dorsal proliferative (matrix) area of the cerebellum and in parenchymal cells of the molecular and granular layers whereas local clusters of undifferentiated cells which formed neurogenic niches were observed in both the optic tectum and cerebellum after optic nerve injury. In vitro analysis of brain cells of trout showed that suspension cells compared with monolayer cells retain higher proliferative activity, as evidenced by PCNA immunolabeling. Phase contrast observation showed mitosis in individual cells and the formation of neurospheres which gradually increased during 1-4 days of culture. The present findings suggest that trout can be used as a novel model for studying neuronal regeneration.

  5. Cell proliferation and apoptosis in optic nerve and brain integration centers of adult trout Oncorhynchus mykiss after optic nerve injury

    PubMed Central

    Pushchina, Evgeniya V.; Shukla, Sachin; Varaksin, Anatoly A.; Obukhov, Dmitry K.

    2016-01-01

    Fishes have remarkable ability to effectively rebuild the structure of nerve cells and nerve fibers after central nervous system injury. However, the underlying mechanism is poorly understood. In order to address this issue, we investigated the proliferation and apoptosis of cells in contralateral and ipsilateral optic nerves, after stab wound injury to the eye of an adult trout Oncorhynchus mykiss. Heterogenous population of proliferating cells was investigated at 1 week after injury. TUNEL labeling gave a qualitative and quantitative assessment of apoptosis in the cells of optic nerve of trout 2 days after injury. After optic nerve injury, apoptotic response was investigated, and mass patterns of cell migration were found. The maximal concentration of apoptotic bodies was detected in the areas of mass clumps of cells. It is probably indicative of massive cell death in the area of high phagocytic activity of macrophages/microglia. At 1 week after optic nerve injury, we observed nerve cell proliferation in the trout brain integration centers: the cerebellum and the optic tectum. In the optic tectum, proliferating cell nuclear antigen (PCNA)-immunopositive radial glia-like cells were identified. Proliferative activity of nerve cells was detected in the dorsal proliferative (matrix) area of the cerebellum and in parenchymal cells of the molecular and granular layers whereas local clusters of undifferentiated cells which formed neurogenic niches were observed in both the optic tectum and cerebellum after optic nerve injury. In vitro analysis of brain cells of trout showed that suspension cells compared with monolayer cells retain higher proliferative activity, as evidenced by PCNA immunolabeling. Phase contrast observation showed mitosis in individual cells and the formation of neurospheres which gradually increased during 1–4 days of culture. The present findings suggest that trout can be used as a novel model for studying neuronal regeneration. PMID:27212918

  6. Nerve Injuries of the Upper Extremity

    MedlinePlus

    ... of individual nerve fibers and surrounding outer sheath (“insulation”) Figure 2: Nerve repair with realignment of bundles © ... of individual nerve fibers and surrounding outer sheath insulation Figure 2 - Nerve repair with realignment of bundles ...

  7. A Novel Animal Model of Partial Optic Nerve Transection Established Using an Optic Nerve Quantitative Amputator

    PubMed Central

    Wang, Xu; Li, Ying; He, Yan; Liang, Hong-Sheng; Liu, En-Zhong

    2012-01-01

    Background Research into retinal ganglion cell (RGC) degeneration and neuroprotection after optic nerve injury has received considerable attention and the establishment of simple and effective animal models is of critical importance for future progress. Methodology/Principal Findings In the present study, the optic nerves of Wistar rats were semi-transected selectively with a novel optic nerve quantitative amputator. The variation in RGC density was observed with retro-labeled fluorogold at different time points after nerve injury. The densities of surviving RGCs in the experimental eyes at different time points were 1113.69±188.83 RGC/mm2 (the survival rate was 63.81% compared with the contralateral eye of the same animal) 1 week post surgery; 748.22±134.75 /mm2 (46.16% survival rate) 2 weeks post surgery; 505.03±118.67 /mm2 (30.52% survival rate) 4 weeks post surgery; 436.86±76.36 /mm2 (24.01% survival rate) 8 weeks post surgery; and 378.20±66.74 /mm2 (20.30% survival rate) 12 weeks post surgery. Simultaneously, we also measured the axonal distribution of optic nerve fibers; the latency and amplitude of pattern visual evoke potentials (P-VEP); and the variation in pupil diameter response to pupillary light reflex. All of these observations and profiles were consistent with post injury variation characteristics of the optic nerve. These results indicate that we effectively simulated the pathological process of primary and secondary injury after optic nerve injury. Conclusions/Significance The present quantitative transection optic nerve injury model has increased reproducibility, effectiveness and uniformity. This model is an ideal animal model to provide a foundation for researching new treatments for nerve repair after optic nerve and/or central nerve injury. PMID:22973439

  8. Neuroprotective effects of vagus nerve stimulation on traumatic brain injury.

    PubMed

    Zhou, Long; Lin, Jinhuang; Lin, Junming; Kui, Guoju; Zhang, Jianhua; Yu, Yigang

    2014-09-01

    Previous studies have shown that vagus nerve stimulation can improve the prognosis of traumatic brain injury. The aim of this study was to elucidate the mechanism of the neuroprotective effects of vagus nerve stimulation in rabbits with brain explosive injury. Rabbits with brain explosive injury received continuous stimulation (10 V, 5 Hz, 5 ms, 20 minutes) of the right cervical vagus nerve. Tumor necrosis factor-α, interleukin-1β and interleukin-10 concentrations were detected in serum and brain tissues, and water content in brain tissues was measured. Results showed that vagus nerve stimulation could reduce the degree of brain edema, decrease tumor necrosis factor-α and interleukin-1β concentrations, and increase interleukin-10 concentration after brain explosive injury in rabbits. These data suggest that vagus nerve stimulation may exert neuroprotective effects against explosive injury via regulating the expression of tumor necrosis factor-α, interleukin-1β and interleukin-10 in the serum and brain tissue.

  9. Neuroprotective effects of vagus nerve stimulation on traumatic brain injury

    PubMed Central

    Zhou, Long; Lin, Jinhuang; Lin, Junming; Kui, Guoju; Zhang, Jianhua; Yu, Yigang

    2014-01-01

    Previous studies have shown that vagus nerve stimulation can improve the prognosis of traumatic brain injury. The aim of this study was to elucidate the mechanism of the neuroprotective effects of vagus nerve stimulation in rabbits with brain explosive injury. Rabbits with brain explosive injury received continuous stimulation (10 V, 5 Hz, 5 ms, 20 minutes) of the right cervical vagus nerve. Tumor necrosis factor-α, interleukin-1β and interleukin-10 concentrations were detected in serum and brain tissues, and water content in brain tissues was measured. Results showed that vagus nerve stimulation could reduce the degree of brain edema, decrease tumor necrosis factor-α and interleukin-1β concentrations, and increase interleukin-10 concentration after brain explosive injury in rabbits. These data suggest that vagus nerve stimulation may exert neuroprotective effects against explosive injury via regulating the expression of tumor necrosis factor-α, interleukin-1β and interleukin-10 in the serum and brain tissue. PMID:25368644

  10. Peripheral nerve injuries in athletes. Treatment and prevention.

    PubMed

    Lorei, M P; Hershman, E B

    1993-08-01

    Peripheral nerve lesions are uncommon but serious injuries which may delay or preclude an athlete's safe return to sports. Early, accurate anatomical diagnosis is essential. Nerve lesions may be due to acute injury (e.g. from a direct blow) or chronic injury secondary to repetitive microtrauma (entrapment). Accurate diagnosis is based upon physical examination and a knowledge of the relative anatomy. Palpation, neurological testing and provocative manoeuvres are mainstays of physical diagnosis. Diagnostic suspicion can be confirmed by electrophysiological testing, including electromyography and nerve conduction studies. Proper equipment, technique and conditioning are the keys to prevention. Rest, anti-inflammatories, physical therapy and appropriate splinting are the mainstays of treatment. In the shoulder, spinal accessory nerve injury is caused by a blow to the neck and results in trapezius paralysis with sparing of the sternocleidomastoid muscle. Scapular winging results from paralysis of the serratus anterior because of long thoracic nerve palsy. A lesion of the suprascapular nerve may mimic a rotator cuff tear with pain a weakness of the rotator cuff. Axillary nerve injury often follows anterior shoulder dislocation. In the elbow region, musculocutaneous nerve palsy is seen in weightlifters with weakness of the elbow flexors and dysesthesias of the lateral forearm. Pronator syndrome is a median nerve lesion occurring in the proximal forearm which is diagnosed by several provocative manoeuvres. Posterior interosseous nerve entrapment is common among tennis players and occurs at the Arcade of Froshe--it results in weakness of the wrist and metacarpophalangeal extensors. Ulnar neuritis at the elbow is common amongst baseball pitchers. Carpal tunnel syndrome is a common neuropathy seen in sport and is caused by median nerve compression in the carpal tunnel. Paralysis of the ulnar nerve at the wrist is seen among bicyclists resulting in weakness of grip and

  11. Piriformis syndrome surgery causing severe sciatic nerve injury.

    PubMed

    Justice, Phillip E; Katirji, Bashar; Preston, David C; Grossman, Gerald E

    2012-09-01

    Piriformis syndrome is a controversial entrapment neuropathy in which the sciatic nerve is thought to be compressed by the piriformis muscle. Two patients developed severe left sciatic neuropathy after piriformis muscle release. One had a total sciatic nerve lesion, whereas the second had a predominantly high common peroneal nerve lesion. Follow-up studies showed reinnervation of the hamstrings only. We conclude that piriformis muscle surgery may be hazardous and result in devastating sciatic nerve injury.

  12. “Three Methods and Three Points” regulates p38 mitogen-activated protein kinase in the dorsal horn of the spinal cord in a rat model of sciatic nerve injury

    PubMed Central

    Guo, Xin; Yu, Tian-yuan; Steven, Wong; Jia, Wen-duan; Ma, Chi; Tao, Yan-hong; Yang, Chao; Lv, Tao-tao; Wu, Shuai; Lu, Meng-qian; Liu, Jia-li

    2016-01-01

    Tuina is a traditional Chinese treatment for sensory disturbances caused by peripheral nerve injury and related diseases. Our previous studies showed that tuina regulates relevant regions and indices of the spinal dorsal horn using the Dian, Bo, and Rou method in Yinmen (BL37), Yanglingquan (GB34), and Weizhong (BL40). Treatment prevents muscle atrophy, protects spinal cord neurons, and promotes sciatic nerve repair. The mechanisms of action of tuina for treating peripheral nerve injury remain poorly understood. This study established rat models of sciatic nerve injury using the crushing method. Rats received Chinese tuina in accordance with the principle of “Three Methods and Three Points,” once daily for 20 days. Tuina intervention reduced paw withdrawal latency and improved wet weight of the gastrocnemius muscle, as well as promoting morphological recovery of sciatic nerve fibers, Schwann cells, and axons. The protein expression levels of phospho-p38 mitogen-activated protein kinase, tumor necrosis factor-α, and interleukin-1β also decreased. These findings indicate that “Three Methods and Three Points” promoted morphological recovery and improved behavior of rats with peripheral nerve injury. PMID:28197201

  13. Nerve injury complicating multiligament knee injury: current concepts and treatment algorithm.

    PubMed

    Mook, William Randolph; Ligh, Cassandra A; Moorman, Claude T; Leversedge, Fraser J

    2013-06-01

    Multiligament knee injuries account for <0.02% of all orthopaedic injuries, and 16% to 40% of these patients suffer associated injury to the common peroneal nerve (CPN). The proximity of the CPN to the proximal fibula predisposes the nerve to injury during local trauma and dislocation; the nerve is highly vulnerable to stretch injury during varus stress, particularly in posterolateral corner injuries. CPN injuries have a poor prognosis compared with that of other peripheral nerve injuries. Management is determined based on the severity and location of nerve injury, timing of presentation, associated injuries requiring surgical management, and the results of serial clinical evaluations and electrodiagnostic studies. Nonsurgical treatment options include orthosis wear and physical therapy. Surgical management includes one or more of the following: neurolysis, primary nerve repair, intercalary nerve grafting, tendon transfer, and nerve transfer. Limited evidence supports the use of early one-stage nerve reconstruction combined with tendon transfer; however, optimal management of these rare injuries continues to change, and treatment should be individualized.

  14. Neuronal plasticity of trigeminal ganglia in mice following nerve injury

    PubMed Central

    Lynds, Randi; Lyu, Chuang; Lyu, Gong-Wei; Shi, Xie-Qi; Rosén, Annika; Mustafa, Kamal; Shi, Tie-Jun Sten

    2017-01-01

    Background Nerve injury may induce neuropathic pain. In studying the mechanisms of orofacial neuropathic pain, attention has been paid to the plastic changes that occur in the trigeminal ganglia (TGs) and nucleus in response to an injury of the trigeminal nerve branches. Previous studies have explored the impact of sciatic nerve injury on dorsal root ganglia (DRGs) and it has shown dramatic changes in the expression of multiple biomarkers. In large, the changes in biomarker expression in TGs after trigeminal nerve injury are similar to that in DRGs after sciatic nerve injury. However, important differences exist. Therefore, there is a need to study the plasticity of biomarkers in TGs after nerve injury in the context of the development of neuropathic pain-like behaviors. Aim The aim of this study was to investigate the plasticity of biomarkers associated with chronic persistent pain in TGs after trigeminal nerve injury. Materials and methods To mimic the chronic nature of the disorder, we used an intraoral procedure to access the infraorbital nerve (ION) and induced a nerve injury in mice. Immunohistochemistry and quantification were used for revealing the expression level of each biomarker in TGs after nerve injury. Results Two weeks after partial ION injury, immunohistochemistry results showed strongly upregulated expressions of activating transcription factor 3 and neuropeptide Y (NPY) in the ipsilateral TGs. Microglial cells were also activated after nerve injury. In regard to positive neuronal profile counting, however, no significant difference in expression was observed in galanin, substance P, calcitonin gene-related peptide, neuronal nitric oxide synthase, phosphorylated AKT, or P2X3 in ipsilateral TGs when compared to contralateral TGs. Conclusion In this study, the expression and regulation of biomarkers in TGs have been observed in response to trigeminal nerve injury. Our results suggest that NPY and Iba1 might play crucial roles in the pathogenesis of

  15. Meta-analysis of recurrent laryngeal nerve injury in thyroid surgery with or without intraoperative nerve monitoring.

    PubMed

    Rulli, F; Ambrogi, V; Dionigi, G; Amirhassankhani, S; Mineo, T C; Ottaviani, F; Buemi, A; DI Stefano, P; Mourad, M

    2014-08-01

    Intraoperative nerve monitoring (IONM) aimed at reducing the injuries of recurrent laryngeal nerve during thyroidectomy is controversial. We conducted a meta-analysis to assess the incidence of nerve injuries with or without IONM. Studies published from January 1994 to February 2012 in English language on humans were identified. Heterogeneity of studies was checked by the Higgins test. Summary estimates of predictive values of injury were made using the Mantel-Haenszel test based on the fixed-effects model. Publication bias was assessed by a funnel plot and Egger's method. Eight articles were selected accounting a total of 5257 nerves at risk. IONM revealed a significant impact in preventing transient injuries (positive predictive value = 5% [95% CI: 2-8], negative = 96% [95% CI: 91-100], relative risk = 0.73 [95% CI: 0.54-0.98], p = 0.035), whereas they failed to demonstrate effect on permanent injuries (positive predictive value = 2% [95% CI: 0.6-3.8], negative 99% [95% CI: 97-100], relative risk = 0.73 [95% CI: 0.44-1.23], p = 0.235). This meta-analysis demonstrated the merit of IONM in preventing transient injury during thyroidectomy. No advantage was found in permanent injuries.

  16. Dexamethasone enhanced functional recovery after sciatic nerve crush injury in rats.

    PubMed

    Feng, Xinhong; Yuan, Wei

    2015-01-01

    Dexamethasone is currently used for the treatment of peripheral nerve injury, but its mechanisms of action are not completely understood. Inflammation/immune response at the site of nerve lesion is known to be an essential trigger of the pathological changes that have a critical impact on nerve repair and regeneration. In this study, we observed the effects of various doses of dexamethasone on the functional recovery after sciatic nerve crush injury in a rat model. Motor functional recovery was monitored by walking track analysis and gastrocnemius muscle mass ratio. The myelinated axon number was counted by morphometric analysis. Rats administered dexamethasone by local intramuscular injection had a higher nerve function index value, increased gastrocnemius muscle mass ratio, reduced Wallerian degeneration severity, and enhanced regenerated myelinated nerve fibers. Immunohistochemical analysis was performed for CD3 expression, which is a marker for T-cell activation, and infiltration in the sciatic nerve. Dexamethasone-injected rats had fewer CD3-positive cells compared to controls. Furthermore, we found increased expression of GAP-43, which is a factor associated with development and plasticity of the nervous system, in rat nerves receiving dexamethasone. These results provide strong evidence that dexamethasone enhances sciatic nerve regeneration and function recovery in a rat model of sciatic nerve injury through immunosuppressive and potential neurotrophic effects.

  17. Intraoperative peripheral nerve injury in colorectal surgery. An update.

    PubMed

    Colsa Gutiérrez, Pablo; Viadero Cervera, Raquel; Morales-García, Dieter; Ingelmo Setién, Alfredo

    2016-03-01

    Intraoperative peripheral nerve injury during colorectal surgery procedures is a potentially serious complication that is often underestimated. The Trendelenburg position, use of inappropriately padded armboards and excessive shoulder abduction may encourage the development of brachial plexopathy during laparoscopic procedures. In open colorectal surgery, nerve injuries are less common. It usually involves the femoral plexus associated with lithotomy position and self-retaining retractor systems. Although in most cases the recovery is mostly complete, treatment consists of physical therapy to prevent muscular atrophy, protection of hypoesthesic skin areas and analgesics for neuropathic pain. The aim of the present study is to review the incidence, prevention and management of intraoperative peripheral nerve injury.

  18. Gait analysis in rats with peripheral nerve injury.

    PubMed

    Yu, P; Matloub, H S; Sanger, J R; Narini, P

    2001-02-01

    Rats are commonly used to study peripheral nerve repair and grafting. The traditional footprint method to assess functional recovery is messy, indirect, and not useful when contractures develop in the animal model. The aim of the present study was to establish an accurate, reproducible, but simple, method to assess dynamic limb function. The basic quantitative aspects of a normal gait were characterized from 59 recorded walks in 23 rats. The video was digitized and analyzed frame by frame on a personal computer. Seven parameters of the gait were assessed: (1) walking speed; (2) stance phase, swing phase and right to left stance/swing ratio; (3) step length and step length ratio; (4) ankle angles at terminal stance and midswing; (5) tail height; (6) midline deviation; and (7) tail deviation. These gait parameters were then applied to groups of animals with sciatic (group S), tibial (group T), and peroneal (group P) nerve injuries. A discriminant analysis was performed to analyze each parameter and to compute a functional score. We found that the video gait analysis was superior to the footprint method and believe it will be very useful in future studies on peripheral nerve injury.

  19. Antioxidative mechanism of Lycium barbarum polysaccharides promotes repair and regeneration following cavernous nerve injury

    PubMed Central

    Zhao, Zhan-kui; Yu, Hong-lian; Liu, Bo; Wang, Hui; Luo, Qiong; Ding, Xie-gang

    2016-01-01

    Polysaccharides extracted from Lycium barbarum exhibit antioxidant properties. We hypothesized that these polysaccharides resist oxidative stress-induced neuronal damage following cavernous nerve injury. In this study, rat models were intragastrically administered Lycium barbarum polysaccharides for 2 weeks at 1, 7, and 14 days after cavernous nerve injury. Serum superoxide dismutase and glutathione peroxidase activities significantly increased at 1 and 2 weeks post-injury. Serum malondialdehyde levels decreased at 2 and 4 weeks. At 12 weeks, peak intracavernous pressure, the number of myelinated axons and nicotinamide adenine dinucleotide phosphate-diaphorase-positive nerve fibers, levels of phospho-endothelial nitric oxide synthase protein and 3-nitrotyrosine were higher in rats administered at 1 day post-injury compared with rats administered at 7 and 14 days post-injury. These findings suggest that application of Lycium barbarum polysaccharides following cavernous nerve crush injury effectively promotes nerve regeneration and erectile functional recovery. This neuroregenerative effect was most effective in rats orally administered Lycium barbarum polysaccharides at 1 day after cavernous nerve crush injury. PMID:27651780

  20. Investigation of infraorbital nerve injury following zygomaticomaxillary complex fractures.

    PubMed

    Sakavicius, D; Juodzbalys, G; Kubilius, R; Sabalys, G P

    2008-12-01

    The aim of this study was to investigate the severity of infraorbital nerve injury following zygomaticomaxillary complex fractures and to estimate the treatment methods facilitating its functional recovery. A total of 478 patients with unilateral zygomaticomaxillary complex fractures were treated. Infraorbital nerve sensory disturbances were diagnosed in 64.4% of the patients. Injury of the infraorbital nerve was expressed as asymmetry index, which was calculated as a ratio between the affected side and the intact side electric pain detection thresholds at the innervation zone skin before treatment and 14 days, 1, 3, 6 and 12 months postoperatively. A mean asymmetry index of 0.6 +/- 0.03 and 1.9 +/- 0.5 was registered for 57 (11.9%) patients with hyperalgesia and for 251 (52.5%) patients with hypoalgesia, respectively. As a result of retrospective analysis of infraorbital nerve sensory disturbances and its functional recovery, infraorbital nerve injury severity was classified as mild, moderate and severe. It was found that the dynamics and outcome of the functional infraorbital nerve recovery depend on the severity of the injury and the presence of infraorbital canal damage. Function was completely recovered within 3 months after treatment in cases with mild nerve injury. In moderate cases, complete recovery was seen within 6 months and in 34.6% of the severe cases, within a 12-month period after treatment when infraorbital nerve decompression was performed according to the stated indication. Treatment based on infraorbital nerve injury classification offers a better prognosis for complete recovery of the infraorbital nerve function.

  1. Neuroprotective effects of ultrasound-guided nerve growth factor injections after sciatic nerve injury

    PubMed Central

    Li, Hong-fei; Wang, Yi-ru; Huo, Hui-ping; Wang, Yue-xiang; Tang, Jie

    2015-01-01

    Nerve growth factor (NGF) plays an important role in promoting neuroregeneration after peripheral nerve injury. However, its effects are limited by its short half-life; it is therefore important to identify an effective mode of administration. High-frequency ultrasound (HFU) is increasingly used in the clinic for high-resolution visualization of tissues, and has been proposed as a method for identifying and evaluating peripheral nerve damage after injury. In addition, HFU is widely used for guiding needle placement when administering drugs to a specific site. We hypothesized that HFU guiding would optimize the neuroprotective effects of NGF on sciatic nerve injury in the rabbit. We performed behavioral, ultrasound, electrophysiological, histological, and immunohistochemical evaluation of HFU-guided NGF injections administered immediately after injury, or 14 days later, and compared this mode of administration with intramuscular NGF injections. Across all assessments, HFU-guided NGF injections gave consistently better outcomes than intramuscular NGF injections administered immediately or 14 days after injury, with immediate treatment also yielding better structural and functional results than when the treatment was delayed by 14 days. Our findings indicate that NGF should be administered as early as possible after peripheral nerve injury, and highlight the striking neuroprotective effects of HFU-guided NGF injections on peripheral nerve injury compared with intramuscular administration. PMID:26807123

  2. Neuroprotective effects of ultrasound-guided nerve growth factor injections after sciatic nerve injury.

    PubMed

    Li, Hong-Fei; Wang, Yi-Ru; Huo, Hui-Ping; Wang, Yue-Xiang; Tang, Jie

    2015-11-01

    Nerve growth factor (NGF) plays an important role in promoting neuroregeneration after peripheral nerve injury. However, its effects are limited by its short half-life; it is therefore important to identify an effective mode of administration. High-frequency ultrasound (HFU) is increasingly used in the clinic for high-resolution visualization of tissues, and has been proposed as a method for identifying and evaluating peripheral nerve damage after injury. In addition, HFU is widely used for guiding needle placement when administering drugs to a specific site. We hypothesized that HFU guiding would optimize the neuroprotective effects of NGF on sciatic nerve injury in the rabbit. We performed behavioral, ultrasound, electrophysiological, histological, and immunohistochemical evaluation of HFU-guided NGF injections administered immediately after injury, or 14 days later, and compared this mode of administration with intramuscular NGF injections. Across all assessments, HFU-guided NGF injections gave consistently better outcomes than intramuscular NGF injections administered immediately or 14 days after injury, with immediate treatment also yielding better structural and functional results than when the treatment was delayed by 14 days. Our findings indicate that NGF should be administered as early as possible after peripheral nerve injury, and highlight the striking neuroprotective effects of HFU-guided NGF injections on peripheral nerve injury compared with intramuscular administration.

  3. “Early Evaluation of Nerve Regeneration After Nerve Injury and Repair Using Functional Connectivity MRI”

    PubMed Central

    Li, Rupeng; Hettinger, Patrick C.; Liu, Xiping; Machol, Jacques; Yan, Ji-Geng; Matloub, Hani S.; Hyde, James S.

    2014-01-01

    Resting state functional connectivity magnetic resonance imaging (fcMRI) studies in rat brain show brain reorganization caused by nerve injury and repair. In this study, distinguishable differences were found in healthy, nerve transection without repair (R+) and nerve transection with repair (R−) groups in the subacute stage (two weeks after initial injury). Only forepaw on the healthy side was used to determine seed voxel regions in this study. Disturbance of neuronal network in the primary sensory region of cortex occurs within two hours after initial injury, and the network pattern was restored in R+ group in subacute stage, while the disturbed pattern remained in R− group. These are the central findings of the study. This technique provides a novel way of detecting and monitoring the effectiveness of peripheral nerve injury treatment in the early stage and potentially offers a tool for clinicians to avoid poor clinical outcomes. PMID:24515926

  4. Biomechanical analysis of optic nerve injury treated by compound light granules and ciliary neurotrophic factor☆

    PubMed Central

    Jiang, Yuying; Xu, Haitao; Liu, Jingxiang; Li, Peng; Wu, Yazhen

    2012-01-01

    In this study, rabbit models of optic nerve injury were reproduced by the clamp method. After modeling, rabbit models were given one injection of 50 ng recombinant human ciliary neurotrophic factor into the vitreous body and/or intragastric injection of 4 g/kg compound light granules containing Radix Angelicae Sinensis and Raidix Paeoniae Alba at 4 days after modeling, once per day for 30 consecutive days. After administration, the animals were sacrificed and the intraorbital optic nerve was harvested. Hematoxylin-eosin staining revealed that the injured optic nerve was thinner and optic nerve fibers were irregular. After treatment with recombinant human ciliary neurotrophic factor, the arrangement of optic nerve fibers was disordered but they were not markedly thinner. After treatment with compound light granules, the arrangement of optic nerve fibers was slightly disordered and their structure was intact. After combined treatment with recombinant human ciliary neurotrophic factor and compound light granules, the arrangement of optic nerve fibers was slightly disordered and the degree of injury was less than after either treatment alone. Results of tensile mechanical testing of the optic nerve showed that the tensile elastic limit strain, elastic limit stress, maximum stress and maximum strain of the injured optic nerve were significantly lower than the normal optic nerve. After treatment with recombinant human ciliary neurotrophic factor and/or compound light granules, the tensile elastic limit strain, elastic limit stress, maximum stress and maximum strain of the injured optic nerve were significantly increased, especially after the combined treatment. These experimental findings indicate that compound light granules and ciliary neurotrophic factor can alleviate optic nerve injury at the histological and biochemical levels, and the combined treatment is more effective than either treatment alone. PMID:25317141

  5. Vagal nerve stimulation protects against burn-induced intestinal injury through activation of enteric glia cells

    PubMed Central

    Costantini, Todd W.; Bansal, Vishal; Krzyzaniak, Michael; Putnam, James G.; Peterson, Carrie Y.; Loomis, William H.; Wolf, Paul; Baird, Andrew; Eliceiri, Brian P.

    2010-01-01

    The enteric nervous system may have an important role in modulating gastrointestinal barrier response to disease through activation of enteric glia cells. In vitro studies have shown that enteric glia activation improves intestinal epithelial barrier function by altering the expression of tight junction proteins. We hypothesized that severe injury would increase expression of glial fibrillary acidic protein (GFAP), a marker of enteric glial activation. We also sought to define the effects of vagal nerve stimulation on enteric glia activation and intestinal barrier function using a model of systemic injury and local gut mucosal involvement. Mice with 30% total body surface area steam burn were used as model of severe injury. Vagal nerve stimulation was performed to assess the role of parasympathetic signaling on enteric glia activation. In vivo intestinal permeability was measured to assess barrier function. Intestine was collected to investigate changes in histology; GFAP expression was assessed by quantitative PCR, by confocal microscopy, and in GFAP-luciferase transgenic mice. Stimulation of the vagus nerve prevented injury-induced intestinal barrier injury. Intestinal GFAP expression increased at early time points following burn and returned to baseline by 24 h after injury. Vagal nerve stimulation prior to injury increased GFAP expression to a greater degree than burn alone. Gastrointestinal bioluminescence was imaged in GFAP-luciferase transgenic animals following either severe burn or vagal stimulation and confirmed the increased expression of intestinal GFAP. Injection of S-nitrosoglutathione, a signaling molecule released by activated enteric glia cells, following burn exerts protective effects similar to vagal nerve stimulation. Intestinal expression of GFAP increases following severe burn injury. Stimulation of the vagus nerve increases enteric glia activation, which is associated with improved intestinal barrier function. The vagus nerve may mediate the

  6. Identification of Changes in Gene expression of rats after Sensory and Motor Nerves Injury.

    PubMed

    Wang, Yu; Guo, Zhi-Yuan; Sun, Xun; Lu, Shi-Bi; Xu, Wen-Jing; Zhao, Qing; Peng, Jiang

    2016-06-02

    Wallerian degeneration is a sequence of events in the distal stump of axotomized nerves. Despite large numbers of researches concentrating on WD, the biological mechanism still remains unclear. Hence we constructed a rat model with both motor and sensory nerves injury and then conducted a RNA-seq analysis. Here the rats were divided into the 4 following groups: normal motor nerves (NMN), injured motor nerves (IMN), normal sensory nerves (NSN) and injured sensory nerves (ISN). The transcriptomes of rats were sequenced by the Illumina HiSeq. The differentially expressed genes (DEGs) of 4 combinations including NMN vs. IMN, NSN vs. ISN, NMN vs. NSN and IMN vs. ISN were identified respectively. For the above 4 combinations, we identified 1666, 1514, 95 and 17 DEGs. We found that NMN vs. IMN shared the most common genes with NSN vs. ISN indicating common mechanisms between motor nerves injury and sensory nerves injury. At last, we performed an enrichment analysis and observed that the DEGs of NMN vs IMN and NSN vs. ISN were significantly associated with binding and activity, immune response, biosynthesis, metabolism and development. We hope our study may shed light on the molecular mechanisms of nerves degeneration and regeneration during WD.

  7. An unusual presentation of whiplash injury: long thoracic and spinal accessory nerve injury

    PubMed Central

    Omar, N.; Srinivasan, M. S.

    2007-01-01

    Whiplash injuries from motor vehicle accidents are very common. The usual presentation and course of this condition normally results in resolution of symptoms within a few weeks. Brachial plexus traction injuries without any bone or joint lesion of the cervical spine have been reported before. We report a case where a gentleman was involved in a rear end vehicle collision, sustained a whiplash injury and was later found to have a long thoracic nerve palsy and spinal accessory nerve palsy. Although isolated injuries of both nerves following a whiplash injury have been reported, combined injury of the two nerves following a whiplash injury is very uncommon and is being reported for the first time. PMID:17587067

  8. Nerve injury and neuropathic pain — A question of age

    PubMed Central

    Fitzgerald, Maria; McKelvey, Rebecca

    2016-01-01

    The effects of peripheral nerve injury on somatosensory processing and pain are highly dependent upon the age at which the damage occurs. Adult nerve injury rapidly triggers neuropathic pain, but this is not so if the same nerve injury is performed in animals below postnatal day (P) 28, consistent with observations in paediatric patients. However, longitudinal studies show that pain hypersensitivity emerges later in life, when the animal reaches adolescence, an observation that could be of clinical importance. Here we discuss the evidence that the central consequences of nerve damage are critically determined by the status of neuroimmune regulation at different ages. In the first postnatal weeks, when spinal somatosensory circuits are undergoing synaptic reorganisation, the ‘default’ neuroimmune response is skewed in an anti-inflammatory direction, suppressing the excitation of dorsal horn neurons and preventing the onset of neuropathic pain. As animals grow up and the central nervous system matures, the neuroimmune profile shifts in a pro-inflammatory direction, unmasking a ‘latent’ pain response to an earlier nerve injury. The data predicts that nerve injury in infancy and childhood could go unnoticed at the time, but emerge as clinically ‘unexplained’ or ‘functional’ pain in adolescence. PMID:26220898

  9. Long thoracic nerve injury due to an electric burn.

    PubMed

    Still, J M; Law, E J; Duncan, J W; Hughes, H F

    1996-01-01

    A 19-year-old white man was burned over 7.5% of his body when he sustained an electric injury from a transformer. There was no associated fall or loss of consciousness. Debridement and grafting were required. The patient had some transient weakness of the muscles of his right arm associated with lower cervical nerve-root injury. This subsequently improved. He also was found to have paralysis of the serratus anterior muscle, with winging of the scapula due to long thoracic nerve injury. This has not improved. A surgical procedure suggested to improve function of the shoulder was rejected by the patient. This is only the second case reported of long thoracic nerve injury due to an electric burn of which we are aware.

  10. Blockade of transient receptor potential cation channel subfamily V member 1 promotes regeneration after sciatic nerve injury

    PubMed Central

    Ren, Fei; Zhang, Hong; Qi, Chao; Gao, Mei-ling; Wang, Hong; Li, Xia-qing

    2015-01-01

    The transient receptor potential cation channel subfamily V member 1 (TRPV1) provides the sensation of pain (nociception). However, it remains unknown whether TRPV1 is activated after peripheral nerve injury, or whether activation of TRPV1 affects neural regeneration. In the present study, we established rat models of unilateral sciatic nerve crush injury, with or without pretreatment with AMG517 (300 mg/kg), a TRPV1 antagonist, injected subcutaneously into the ipsilateral paw 60 minutes before injury. At 1 and 2 weeks after injury, we performed immunofluorescence staining of the sciatic nerve at the center of injury, at 0.3 cm proximal and distal to the injury site, and in the dorsal root ganglia. Our results showed that Wallerian degeneration occurred distal to the injury site, and neurite outgrowth and Schwann cell regeneration occurred proximal to the injury. The number of regenerating myelinated and unmyelinated nerve clusters was greater in the AMG517-pretreated rats than in the vehicle-treated group, most notably 2 weeks after injury. TRPV1 expression in the injured sciatic nerve and ipsilateral dorsal root ganglia was markedly greater than on the contralateral side. Pretreatment with AMG517 blocked this effect. These data indicate that TRPV1 is activated or overexpressed after sciatic nerve crush injury, and that blockade of TRPV1 may accelerate regeneration of the injured sciatic nerve. PMID:26487864

  11. Meaningful power grip recovery after salvage reconstruction of a median nerve avulsion injury with a pedicled vascularized ulnar nerve

    PubMed Central

    Van Slyke, Aaron C; Jansen, Leigh A; Hynes, Sally; Hicks, Jane; Bristol, Sean; Carr, Nicholas

    2015-01-01

    In cases of median nerve injury alongside an unsalvageable ulnar nerve, a vascularized ulnar nerve graft to reconstruct the median nerve is a viable option. While restoration of median nerve sensation is consistently reported, recovery of significant motor function is less frequently observed. The authors report a case involving a previously healthy man who sustained upper arm segmental median and ulnar nerve injuries and, after failure of sural nerve grafts, was treated with a pedicled vascularized ulnar nerve graft to restore median nerve function. Long-term follow-up showed near full fist, with 12 kg of grip strength, key pinch with 1.5 kg of strength and protective sensation in the median nerve distribution. The present case demonstrates that pedicled ulnar vascularized nerve grafts can provide significant improvements to median nerve sensory and motor function in a heavily scarred environment. PMID:26665144

  12. Epigenomic Regulation of Schwann Cell Reprogramming in Peripheral Nerve Injury

    PubMed Central

    Ma, Ki H.; Hung, Holly A.

    2016-01-01

    The rapid and dynamic transcriptional changes of Schwann cells in response to injury are critical to peripheral nerve repair, yet the epigenomic reprograming that leads to the induction of injury-activated genes has not been characterized. Polycomb Repressive Complex 2 (PRC2) catalyzes the trimethylation of lysine 27 of histone H3 (H3K27me3), which produces a transcriptionally repressive chromatin environment. We find that many promoters and/or gene bodies of injury-activated genes of mature rat nerves are occupied with H3K27me3. In contrast, the majority of distal enhancers that gain H3K27 acetylation after injury are not repressed by H3K27 methylation before injury, which is normally observed in developmentally poised enhancers. Injury induces demethylation of H3K27 in many genes, such as Sonic hedgehog (Shh), which is silenced throughout Schwann cell development before injury. In addition, experiments using a Schwann cell-specific mouse knock-out of the Eed subunit of PRC2 indicate that demethylation is a rate-limiting step in the activation of such genes. We also show that some transcription start sites of H3K27me3-repressed injury genes of uninjured nerves are bound with a mark of active promoters H3K4me3, for example, Shh and Gdnf, and the reduction of H3K27me3 results in increased trimethylation of H3K4. Our findings identify reversal of polycomb repression as a key step in gene activation after injury. SIGNIFICANCE STATEMENT Peripheral nerve regeneration after injury is dependent upon implementation of a novel genetic program in Schwann cells that supports axonal survival and regeneration. Identifying means to enhance Schwann cell reprogramming after nerve injury could be used to foster effective remyelination in the treatment of demyelinating disorders and in identifying pathways involved in regenerative process of myelination. Although recent progress has identified transcriptional determinants of successful reprogramming of the Schwann cell transcriptome

  13. Facial reanimation after facial nerve injury using hypoglossal to facial nerve anastomosis: the gruppo otologico experience.

    PubMed

    Tanbouzi Husseini, Sami; Kumar, David Victor; De Donato, Giuseppe; Almutair, Tamama; Sanna, Mario

    2013-12-01

    To evaluate the results of facial nerve reanimation after facial nerve injury by means of hypoglossal to facial nerve anastomosis. Retrospective case review. Private neuro-otologic and cranial base quaternary referral center. Sixty patients underwent hypoglossal to facial nerve anastomosis for facial nerve reanimation between April 1987 and December 2010. Only forty patients completed a minimal follow up of 24 months at the time of evaluation and were included in the study population. Facial nerve paralysis was present for a mean duration of 11.3 months (range 2-42 months) and all the patients had a HB grade VI prior their surgery. Final facial nerve motor function. The most common cause of facial paralysis was vestibular Schwannoma surgery. All the patients achieved a postoperative HB grade III or IV after a mean follow-up time of 20 months. The facial movements were detected after a period that ranged from ranged from 5 to 9 months. Only 4 patients suffered from difficulties during eating and drinking and three of them had associated lower cranial nerve deficit. Despite the various techniques in facial reanimation following total facial nerve paralysis, the end to end of hypoglossal to facial nerve anastomosis remains one of the best treatments in cases of viable distal facial stump and nonatrophic musculature.

  14. Difference in intraosseous blood vessel volume and number in osteoporotic model mice induced by spinal cord injury and sciatic nerve resection.

    PubMed

    Ding, Wen-Ge; Yan, Wei-hong; Wei, Zhao-Xiang; Liu, Jin-Bo

    2012-07-01

    In the present study, we examined intraosseous blood vessel parameters of the tibial metaphysis in mice using microcomputed tomography (µCT) to investigate the relationship between post-nerve-injury osteoporosis and local intraosseous blood vessel volume and number. Mice were randomly divided into groups receiving spinal cord injury (SCI), sciatic nerve resection group (NX), or intact controls (30 mice/group). Four weeks after surgery, mice were perfused with silicone and the distribution of intraosseous blood vessels analyzed by μCT. The bone density, μCT microstructure, biomechanical properties, and the immunohistochemical and biochemical indicators of angiogenesis were also measured. The SCI group showed significantly reduced tibial metaphysis bone density, μCT bone microstructure, tibial biomechanical properties, indicators of angiogenesis, and intraosseous blood vessel parameters compared to the NX group. Furthermore, the spinal cord-injured mice exhibited significantly decreased intraosseous blood vessel volume and number during the development of osteoporosis. In conclusion, these data suggest that decreased intraosseous blood vessel volume and number may play an important role in the development of post-nerve-injury osteoporosis.

  15. Role of Intraoperative Nerve Monitoring During Parathyroidectomy to Prevent Recurrent Laryngeal Nerve Injury

    PubMed Central

    Assad, Salman; Assad, Shuja

    2016-01-01

    Injury to the recurrent laryngeal nerve (RLN) is a well known, though less frequent, complication of parathyroid surgery. In recent years, the use of intraoperative nerve monitoring (IONM) has gained popularity amongst surgeons when operating on thyroid gland; however, its utilization in parathyroid surgery is not established. This trend continues to rise, despite multiple studies documenting no statistically significant difference that IONM decreases the incidence of RLN injury. Most surgeons use this technology as an adjunct to visualization alone for identification of RLN. The purpose of this review is to discuss the possible role of IONM in parathyroid surgery with regards to the accuracy, efficacy, and recent trends in the utilization of this technology. There is insufficient evidence that IONM reduces the risk of RLN injury in parathyroidectomy. Although IONM may decrease the likelihood of nerve injury by helping to identify and map the RLN during thyroidectomy, we did not find studies exclusive to parathyroid surgery to see if its use can be supported for parathyroidectomy. Despite this lack of evidence, we believe that IONM is a promising adjunct to visualization alone in detecting nerve structures during neck dissection, but more clinical trials are warranted to establish its role in preventing nerve injury in parathyroid surgery. PMID:28003944

  16. CONSERVATIVE REHABILITATION OF SCIATIC NERVE INJURY FOLLOWING HAMSTRING TEAR

    PubMed Central

    Reuteman, Paul

    2010-01-01

    Study Design: Resident's case report Background: There have been only a few case reports in the literature mentioning sciatic nerve injury following a hamstring tear. In previous cases surgical intervention was performed to debride scar tissue around the sciatic nerve with the goal of full return to function for the patient. Objectives: The purpose of this case report is to describe the conservative interventions that allowed for recovery from a hamstring tear with sciatic nerve involvement. Case Description: The subject was a 53 year old female who developed foot drop and weakness in the common fibular nerve distribution following a grade 3 hamstring injury sustained during Nordic skiing. Nerve function and strength gradually returned over the course of several months of conservative rehabilitation which included on neural gliding and strengthening exercises. Outcomes: At 18 months post injury, the subject had returned to 95% of full sport function and 98% of full function with activities of daily living, as rated by the Hip Outcome Scale, and had full strength with manual muscle testing. Isokinetic testing revealed strength deficits of 11–23% in knee flexion peak torque at 60 degrees/second and 180 degrees/second respectively. Discussion: Sciatic nerve injury is a rare, but important potential consequence of severe hamstring strains. Clinicians should be cognizant of the potential injury to the nerve tissue following hamstring strains, so they may be dealt with in a prompt and appropriate manner. The use of neural gliding may be worth considering for a prophylactic effect following hamstring strains. PMID:21589670

  17. Identification of the effects of peripheral nerves injury on the muscle control - A review

    NASA Astrophysics Data System (ADS)

    Cabaj, Anna; Zmyslowski, Wojciech

    2011-01-01

    Impairment of motor function following peripheral nerve injury is a serious clinical problem. Generally nerve injury leads to erroneous control of muscle activity that results in gait and voluntary movement abnormalities followed by muscle atrophy. This article presents a review of studies on the effects of peripheral nerve injury on the motor system performed on animal models. We focused our attention on the results that are fundamental for better understanding of the degenerative and regenerative processes induced by nerve injury as well as of the mechanisms of structural changes in neuronal networks controlling movement. Quoted results are also important for clinical applications because they allow to develop new diagnostic and therapeutic techniques that can be used after nerve injury inducing motor deficits. However, till now no efficient therapy inducing satisfactory recovery was found. There is still a need to continue an advanced basic research directed to develop effective therapies. Thus the aim of this review is to compare the results of recent studies performed on various animal models in order to propose new methods for identification of mechanisms responsible for muscle deficits and propose targets for new pharmacological therapies.

  18. [Incarcerated epitrochlear fracture with a cubital nerve injury].

    PubMed

    Moril-Peñalver, L; Pellicer-Garcia, V; Gutierrez-Carbonell, P

    2013-01-01

    Injuries of the medial epicondyle are relatively common, mostly affecting children between 7 and 15 years. The anatomical characteristics of this apophysis can make diagnosis difficult in minimally displaced fractures. In a small percentage of cases, the fractured fragment may occupy the retroepitrochlear groove. The presence of dysesthesias in the territory of the ulnar nerve requires urgent open reduction of the incarcerated fragment. A case of a seven-year-old male patient is presented, who required surgical revision due to a displaced medial epicondyle fracture associated with ulnar nerve injury. A review of the literature is also made.

  19. Treatment of peroneal nerve injuries with simultaneous tendon transfer and nerve exploration

    PubMed Central

    2014-01-01

    Background Common peroneal nerve palsy leading to foot drop is difficult to manage and has historically been treated with extended bracing with expectant waiting for return of nerve function. Peroneal nerve exploration has traditionally been avoided except in cases of known traumatic or iatrogenic injury, with tendon transfers being performed in a delayed fashion after exhausting conservative treatment. We present a new strategy for management of foot drop with nerve exploration and concomitant tendon transfer. Method We retrospectively reviewed a series of 12 patients with peroneal nerve palsies that were treated with tendon transfer from 2005 to 2011. Of these patients, seven were treated with simultaneous peroneal nerve exploration and repair at the time of tendon transfer. Results Patients with both nerve repair and tendon transfer had superior functional results with active dorsiflexion in all patients, compared to dorsiflexion in 40% of patients treated with tendon transfers alone. Additionally, 57% of patients treated with nerve repair and tendon transfer were able to achieve enough function to return to running, compared to 20% in patients with tendon transfer alone. No patient had full return of native motor function resulting in excessive dorsiflexion strength. Conclusion The results of our limited case series for this rare condition indicate that simultaneous nerve repair and tendon transfer showed no detrimental results and may provide improved function over tendon transfer alone. PMID:25099247

  20. Effect of subcutaneous administration of calcium channel blockers on nerve injury-induced hyperalgesia.

    PubMed

    White, D M; Cousins, M J

    1998-08-10

    Recent studies suggest that calcium contributes to peripheral neural mechanisms of hyperalgesia associated with nerve damage. In this animal behavioural study, we examined further the contribution of calcium in neuropathic pain by testing whether subcutaneous administration of either a calcium chelating agent or voltage-dependent calcium channel blockers attenuate nerve injury-induced hyperalgesia to mechanical stimulation. Studies were carried out in animals with partially ligated sciatic nerves, an established animal model of neuropathic pain. The nociceptive flexion reflex was quantified using an Ugo Basile Analgesymeter. Partial nerve injury induced a significant decrease in mechanical threshold compared to the sham operated controls. Daily subcutaneous injections of the calcium chelating agent, Quin 2 (20 microgram/2.5 microliter), significantly attenuated the nerve injury-induced hyperalgesia. Similarly, SNX-111, a N-type channel blocker, also significantly attenuated the nerve injury-induced hyperalgesia. SNX-230, a P and/or Q-type channel blocker, and nifedipine, a L-type channel blocker, had no effect on the hyperalgesia to mechanical stimulation. In control experiments, SNX-111 had no effect on mechanical thresholds when administered subcutaneously in either the hindpaw of normal animals or the back of the neck in nerve injury animals. This study shows that neuropathic pain involves a local calcium-dependent mechanism in the receptive field of intact neurons of an injured nerve, since it can be alleviated by subcutaneous injections of either a calcium chelating agent or SNX-111, a N-type calcium channel blocker. These agents may be effective, peripherally acting therapeutic agents for neuropathic pain.

  1. Clinical Relevance of Cranial Nerve Injury following Carotid Endarterectomy

    PubMed Central

    Fokkema, M.; de Borst, G.J.; Nolan, B.W.; Indes, J.; Buck, D.B.; Lo, R.C.; Moll, F.L.; Schermerhorn, M.L.

    2014-01-01

    Objectives The benefit of carotid endarterectomy (CEA) may be diminished by cranial nerve injury (CNI). Using a quality improvement registry, we aimed to identify the nerves affected, duration of symptoms (transient vs. persistent), and clinical predictors of CNI. Methods We identified all patients undergoing CEA in the Vascular Study Group of New England (VSGNE) between 2003 and 2011. Surgeon-observed CNI rate was determined at discharge (postoperative CNI) and at follow-up to determine persistent CNI (CNIs that persisted at routine follow-up visit). Hierarchical multivariable model controlling for surgeon and hospital was used to assess independent predictors for postoperative CNI. Results A total of 6,878 patients (33.8% symptomatic) were included for analyses. CNI rate at discharge was 5.6% (n = 382). Sixty patients (0.7%) had more than one nerve affected. The hypoglossal nerve was most frequently involved (n = 185, 2.7%), followed by the facial (n = 128, 1.9%), the vagus (n = 49, 0.7%), and the glossopharyngeal (n = 33, 0.5%) nerve. The vast majority of these CNIs were transient; only 47 patients (0.7%) had a persistent CNI at their follow-up visit (median 10.0 months, range 0.3–15.6 months). Patients with perioperative stroke (0.9%, n = 64) had significantly higher risk of CNI (n = 15, CNI risk 23.4%, p < .01). Predictors for CNI were urgent procedures (OR 1.6, 95% CI 1.2–2.1, p < .01), immediate re-exploration after closure under the same anesthetic (OR 2.0, 95% CI 1.3–3.0, p < .01), and return to the operating room for a neurologic event or bleeding (OR 2.3, 95% CI 1.4–3.8, p < .01), but not redo CEA (OR 1.0, 95% CI 0.5–1.9, p = .90) or prior cervical radiation (OR 0.9, 95% CI 0.3–2.5, p = .80). Conclusions As patients are currently selected in the VSGNE, persistent CNI after CEA is rare. While conditions of urgency and (sub)acute reintervention carried increased risk for postoperative CNI, a history of prior ipsilateral CEA or cervical

  2. Synaptic ultrastructure changes in trigeminocervical complex posttrigeminal nerve injury.

    PubMed

    Park, John; Trinh, Van Nancy; Sears-Kraxberger, Ilse; Li, Kang-Wu; Steward, Oswald; Luo, Z David

    2016-02-01

    Trigeminal nerves collecting sensory information from the orofacial area synapse on second-order neurons in the dorsal horn of subnucleus caudalis and cervical C1/C2 spinal cord (Vc/C2, or trigeminocervical complex), which is critical for sensory information processing. Injury to the trigeminal nerves may cause maladaptive changes in synaptic connectivity that plays an important role in chronic pain development. Here we examined whether injury to the infraorbital nerve, a branch of the trigeminal nerves, led to synaptic ultrastructural changes when the injured animals have developed neuropathic pain states. Transmission electron microscopy was used to examine synaptic profiles in Vc/C2 at 3 weeks postinjury, corresponding to the time of peak behavioral hypersensitivity following chronic constriction injury to the infraorbital nerve (CCI-ION). Using established criteria, synaptic profiles were classified as associated with excitatory (R-), inhibitory (F-), and primary afferent (C-) terminals. Each type was counted within the superficial dorsal horn of the Vc/C2 and the means from each rat were compared between sham and injured animals; synaptic contact length was also measured. The overall analysis indicates that rats with orofacial pain states had increased numbers and decreased mean synaptic length of R-profiles within the Vc/C2 superficial dorsal horn (lamina I) 3 weeks post-CCI-ION. Increases in the number of excitatory synapses in the superficial dorsal horn of Vc/C2 could lead to enhanced activation of nociceptive pathways, contributing to the development of orofacial pain states.

  3. Intact subepidermal nerve fibers mediate mechanical hypersensitivity via the activation of protein kinase C gamma in spared nerve injury

    PubMed Central

    Ko, Miau-Hwa; Yang, Ming-Ling; Youn, Su-Chung; Tseng, To-Jung

    2016-01-01

    Background Spared nerve injury is an important neuropathic pain model for investigating the role of intact primary afferents in the skin on pain hypersensitivity. However, potential cellular mechanisms remain poorly understood. In phosphoinositide-3 kinase pathway, pyruvate dehydrogenase kinase 1 (PDK1) participates in the regulation of neuronal plasticity for central sensitization. The downstream cascades of PDK1 include: (1) protein kinase C gamma (PKCγ) controls the trafficking and phosphorylation of ionotropic glutamate receptor; (2) protein kinase B (Akt)/the mammalian target of rapamycin (mTOR) signaling is responsible for local protein synthesis. Under these statements, we therefore hypothesized that an increase of PKCγ activation and mTOR-dependent PKCγ synthesis in intact primary afferents after SNI might contribute to pain hypersensitivity. Results The variants of spared nerve injury were performed in Sprague-Dawley rats by transecting any two of the three branches of the sciatic nerve, leaving only one branch intact. Following SNIt (spared tibial branch), mechanical hyperalgesia and mechanical allodynia, but not thermal hyperalgesia, were significantly induced. In the first footpad, normal epidermal innervations were verified by the protein gene product 9.5 (PGP9.5)- and growth-associated protein 43 (GAP43)-immunoreactive (IR) intraepidermal nerve fibers (IENFs) densities. Furthermore, the rapid increases of phospho-PKCγ- and phospho-mTOR-IR subepidermal nerve fibers (SENFs) areas were distinct gathered from the results of PGP9.5-, GAP43-, and neurofilament 200 (NF200)-IR SENFs areas. The efficacy of PKC inhibitor (GF 109203X) or mTOR complex 1 inhibitor (rapamycin) for attenuating mechanical hyperalgesia and mechanical allodynia by intraplantar injection was dose-dependent. Conclusions From results obtained in this study, we strongly recommend that the intact SENFs persistently increase PKCγ activation and mTOR-dependent PKCγ synthesis participate

  4. Peptide therapy with pentadecapeptide BPC 157 in traumatic nerve injury.

    PubMed

    Gjurasin, Miroslav; Miklic, Pavle; Zupancic, Bozidar; Perovic, Darko; Zarkovic, Kamelija; Brcic, Luka; Kolenc, Danijela; Radic, Bozo; Seiwerth, Sven; Sikiric, Predrag

    2010-02-25

    We focused on the healing of rat transected sciatic nerve and improvement made by stable gastric pentadecapeptide BPC 157 (10 microg, 10ng/kg) applied shortly after injury (i) intraperitoneally/intragastrically/locally, at the site of anastomosis, or after (ii) non-anastomozed nerve tubing (7 mm nerve segment resected) directly into the tube. Improvement was shown clinically (autotomy), microscopically/morphometrically and functionally (EMG, one or two months post-injury, walking recovery (sciatic functional index (SFI)) at weekly intervals). BPC 157-rats exhibited faster axonal regeneration: histomorphometrically (improved presentation of neural fascicles, homogeneous regeneration pattern, increased density and size of regenerative fibers, existence of epineural and perineural regeneration, uniform target orientation of regenerative fibers, and higher proportion of neural vs. connective tissue, all fascicles in each nerve showed increased diameter of myelinated fibers, thickness of myelin sheet, number of myelinated fibers per area and myelinated fibers as a percentage of the nerve transected area and the increased blood vessels presentation), electrophysiologically (increased motor action potentials), functionally (improved SFI), the autotomy absent. Thus, BPC 157 markedly improved rat sciatic nerve healing.

  5. (-)-Epigallocatechin-3-gallate (EGCG) attenuates peripheral nerve degeneration in rat sciatic nerve crush injury.

    PubMed

    Renno, Waleed M; Al-Maghrebi, May; Alshammari, Ahmad; George, Preethi

    2013-02-01

    Recently, we have shown that green tea (GT) consumption improves both reflexes and sensation in unilateral chronic constriction injury to the sciatic nerve. Considering the substantial neuroprotective properties of GT polyphenols, we sought to investigate whether (-)-epigallocatechin-3-gallate (EGCG) could protect the sciatic nerve and improve functional impairments induced by a crushing injury. We also examined whether neuronal cell apoptosis induced by the crushing injury is affected by EGCG treatment. Histological examination of sciatic nerves from EGCG-treated (50mg/kg; i.p.) showed that axonotmized rats had a remarkable axonal and myelin regeneration with significant decrease in the number of myelinated axonal fibers compared to vehicle-treated crush group. Similarly, ultrastructural evaluation of EGCG-treated nerves displayed normal unmyelinated and myelinated axons with regular myelin sheath thickness and normalized appearance of Schmidt-Lantermann clefts. Extracellular matrix displayed normal collagen fibers appearance with distinctively organized distribution similar to sham animals. Analysis of foot position and extensor postural thrust test showed a progressive and faster recovery in the EGCG-treated group compared to vehicle-treated animals. EGCG-treated rats showed significant increase in paw withdrawal thresholds to mechanical stimulation compared to vehicle-treated crush group. EGCG treatment also restored the mRNA expression of Bax, Bcl-2 and survivin but not that of p53 to sham levels on days 3 and 7 post-injury. Our results demonstrate that EGCG treatment enhanced functional recovery, advanced morphological nerve rescue and accelerated nerve regeneration following crush injury partly due to the down regulation of apoptosis related genes.

  6. Nanostructured Guidance for Peripheral Nerve Injuries: A Review with a Perspective in the Oral and Maxillofacial Area

    PubMed Central

    Sivolella, Stefano; Brunello, Giulia; Ferrarese, Nadia; Puppa, Alessandro Della; D’Avella, Domenico; Bressan, Eriberto; Zavan, Barbara

    2014-01-01

    Injury to peripheral nerves can occur as a result of various surgical procedures, including oral and maxillofacial surgery. In the case of nerve transaction, the gold standard treatment is the end-to-end reconnection of the two nerve stumps. When it cannot be performed, the actual strategies consist of the positioning of a nerve graft between the two stumps. Guided nerve regeneration using nano-structured scaffolds is a promising strategy to promote axon regeneration. Biodegradable electrospun conduits composed of aligned nanofibers is a new class of devices used to improve neurite extension and axon outgrowth. Self assembled peptide nanofibrous scaffolds (SAPNSs) demonstrated promising results in animal models for central nervous system injuries, and, more recently, for peripheral nerve injury. Aims of this work are (1) to review electrospun and self-assembled nanofibrous scaffolds use in vitro and in vivo for peripheral nerve regeneration; and (2) its application in peripheral nerve injuries treatment. The review focused on nanofibrous scaffolds with a diameter of less than approximately 250 nm. The conjugation in a nano scale of a natural bioactive factor with a resorbable synthetic or natural material may represent the best compromise providing both biological and mechanical cues for guided nerve regeneration. Injured peripheral nerves, such as trigeminal and facial, may benefit from these treatments. PMID:24562333

  7. Isolated optic nerve oedema as unusual presentation of electric injury.

    PubMed

    Izzy, Saef; Deeb, Wissam; Peters, George B; Mitchell, Ann

    2014-10-15

    A 45-year-old man with no significant medical history presented following an electric current injury (380 V). He developed multiple systemic injuries including third degree burns and after 1 week of hospitalisation he reported unilateral visual changes. Examination suggested the presence of optic nerve oedema without evidence of haemorrhage, exudate or vessel abnormality. This was considered to be related to the electric shock. A trial of corticosteroids was considered. He was followed up to 5 months in clinic and was noted to have developed unilateral optic atrophy and no other systemic manifestations. Initial and 5 months follow-up optic nerve colour photograph and optical coherence topography were documented. The present case highlights the fact that electric current injury can present with only a unilateral ischaemic optic neuropathy, the need for early diagnosis for timely treatment and the controversial role of corticosteroids.

  8. Nuclear factor-kappa B decoy suppresses nerve injury and improves mechanical allodynia and thermal hyperalgesia in a rat lumbar disc herniation model

    PubMed Central

    Suzuki, Munetaka; Inoue, Gen; Gemba, Takefumi; Watanabe, Tomoko; Ito, Toshinori; Koshi, Takana; Yamauchi, Kazuyo; Yamashita, Masaomi; Orita, Sumihisa; Eguchi, Yawara; Ochiai, Nobuyasu; Kishida, Shunji; Takaso, Masashi; Aoki, Yasuchika; Takahashi, Kazuhisa

    2009-01-01

    Nuclear factor-kappa B (NF-κB) is a gene transcriptional regulator of inflammatory cytokines. We investigated the transduction efficiency of NF-κB decoy to dorsal root ganglion (DRG), as well as the decrease in nerve injury, mechanical allodynia, and thermal hyperalgesia in a rat lumbar disc herniation model. Forty rats were used in this study. NF-κB decoy–fluorescein isothiocyanate (FITC) was injected intrathecally at the L5 level in five rats, and its transduction efficiency into DRG measured. In another 30 rats, mechanical pressure was placed on the DRG at the L5 level and nucleus pulposus harvested from the rat coccygeal disc was transplanted on the DRG. Rats were classified into three groups of ten animals each: a herniation + decoy group, a herniation + oligo group, and a herniation only group. For behavioral testing, mechanical allodynia and thermal hyperalgesia were evaluated. In 15 of the herniation rats, their left L5 DRGs were resected, and the expression of activating transcription factor 3 (ATF-3) and calcitonin gene-related peptide (CGRP) was evaluated immunohistochemically compared to five controls. The total transduction efficiency of NF-κB decoy–FITC in DRG neurons was 10.8% in vivo. The expression of CGRP and ATF-3 was significantly lower in the herniation + decoy group than in the other herniation groups. Mechanical allodynia and thermal hyperalgesia were significantly suppressed in the herniation + decoy group. NF-κB decoy was transduced into DRGs in vivo. NF-κB decoy may be useful as a target for clarifying the mechanism of sciatica caused by lumbar disc herniation. PMID:19308465

  9. Nuclear factor-kappa B decoy suppresses nerve injury and improves mechanical allodynia and thermal hyperalgesia in a rat lumbar disc herniation model.

    PubMed

    Suzuki, Munetaka; Inoue, Gen; Gemba, Takefumi; Watanabe, Tomoko; Ito, Toshinori; Koshi, Takana; Yamauchi, Kazuyo; Yamashita, Masaomi; Orita, Sumihisa; Eguchi, Yawara; Ochiai, Nobuyasu; Kishida, Shunji; Takaso, Masashi; Aoki, Yasuchika; Takahashi, Kazuhisa; Ohtori, Seiji

    2009-07-01

    Nuclear factor-kappa B (NF-kappaB) is a gene transcriptional regulator of inflammatory cytokines. We investigated the transduction efficiency of NF-kappaB decoy to dorsal root ganglion (DRG), as well as the decrease in nerve injury, mechanical allodynia, and thermal hyperalgesia in a rat lumbar disc herniation model. Forty rats were used in this study. NF-kappaB decoy-fluorescein isothiocyanate (FITC) was injected intrathecally at the L5 level in five rats, and its transduction efficiency into DRG measured. In another 30 rats, mechanical pressure was placed on the DRG at the L5 level and nucleus pulposus harvested from the rat coccygeal disc was transplanted on the DRG. Rats were classified into three groups of ten animals each: a herniation + decoy group, a herniation + oligo group, and a herniation only group. For behavioral testing, mechanical allodynia and thermal hyperalgesia were evaluated. In 15 of the herniation rats, their left L5 DRGs were resected, and the expression of activating transcription factor 3 (ATF-3) and calcitonin gene-related peptide (CGRP) was evaluated immunohistochemically compared to five controls. The total transduction efficiency of NF-kappaB decoy-FITC in DRG neurons was 10.8% in vivo. The expression of CGRP and ATF-3 was significantly lower in the herniation + decoy group than in the other herniation groups. Mechanical allodynia and thermal hyperalgesia were significantly suppressed in the herniation + decoy group. NF-kappaB decoy was transduced into DRGs in vivo. NF-kappaB decoy may be useful as a target for clarifying the mechanism of sciatica caused by lumbar disc herniation.

  10. Locally Produced BDNF Promotes Sclerotic Change in Alveolar Bone after Nerve Injury

    PubMed Central

    Ida-Yonemochi, Hiroko; Yamada, Yurie; Yoshikawa, Hiroyuki

    2017-01-01

    Brain-derived neurotrophic factor (BDNF), which is released due to nerve injury, is known to promote the natural healing of injured nerves. It is often observed that damage of mandibular canal induces local sclerotic changes in alveolar bone. We reported that peripheral nerve injury promotes the local production of BDNF; therefore, it was possible to hypothesize that peripheral nerve injury affects sclerotic changes in the alveolar bone. This study aimed to evaluate the effect of BDNF on osteogenesis using in vitro osteoblast-lineage cell culture and an in vivo rat osteotomy model. MC3T3-E1 cells were cultured with BDNF and were examined for cell proliferative activity, chemotaxis and mRNA expression levels of osteoblast differentiation markers. For in vivo study, inferior alveolar nerve (IAN) injury experiments and mandibular cortical osteotomy were performed using a rat model. In the osteotomy model, exogenous BDNF was applied to bone surfaces after corticotomy of the mandible, and we morphologically analyzed the new bone formation. As a result, mRNA expression of osteoblast differentiation marker, osteocalcin, was significantly increased by BDNF, although cell proliferation and migration were not affected. In the in vivo study, osteopontin-positive new bone formation was significantly accelerated in the BDNF-grafted groups, and active bone remodeling, involving trkB-positive osteoblasts and osteocytes, continued after 28 days. In conclusion, BDNF stimulated the differentiation of MC3T3-E1 cells and it promoted new bone formation and maturation. These results suggested that local BDNF produced by peripheral nerve injury contributes to accelerating sclerotic changes in the alveolar bone. PMID:28072837

  11. Anterograde Degeneration along the Visual Pathway after Optic Nerve Injury

    PubMed Central

    Graham, Stuart L.; Klistorner, Alexander

    2012-01-01

    Purpose To investigate anterograde degenerative changes along the visual pathway in a rat model of optic nerve axotomy. Methods Optic nerve transection was performed in adult Sprague-Dawley rats. Animals were sacrificed at regular time intervals and tissues harvested. Immunoblotting followed by densitometric analysis was used to determine the phosphorylation profile of Akt in the dorsal lateral geniculate nucleus (dLGN) and the primary visual cortex (V1). The neuronal cell size and cell density were measured in the dLGN and the V1 using Nissl staining. The prevalence of apoptosis was characterized by terminal deoxynucleotidyl-transferase-mediated biotin-dUTP nick end labelling (TUNEL) histochemistry. Caspase-3 antibodies were also used to identify apoptotic cells. Neurons and astrocytes were detected using NeuN and glial fibrillary acidic protein (GFAP), respectively. Results An early and sustained loss of Akt phosphorylation was observed after optic nerve transection in both dLGN and V1. At week one, a decrease in the neuronal cell size (50.5±4.9 vs 60.3±5.0 µm2, P = 0.042) and an increase of TUNEL positive cells (7.9±0.6 vs 1.4±0.5 ×102 cells/mm2, P<0.001) were evident in the dLGN but not in V1. A significant decline in neuronal cell number (14.5±0.1 vs 17.4±1.3 ×102 cells/mm2, P = 0.048), cell size (42.5±4.3 vs 62.1±4.7 µm2, P = 0.001) and an increase in apoptotic cells (5.6±0.5 vs 2.0±0.4 ×102 cells/mm2, P<0.001) appeared in V1 initially at one month post-transection. The changes in the visual pathway continued through two months. Both neuronal cells and GFAP-positive glial cells were affected in this anterograde degeneration along the visual pathway. Conclusions Anterograde degeneration along the visual pathway takes place in target relay (LGN) and visual cortex following the optic nerve injury. Apoptosis was observed in both neural and adjacent glial cells. Reduction of Akt phosphorylation preceded cellular and apoptotic changes

  12. Rat rotator cuff muscle responds differently from hindlimb muscle to a combined tendon-nerve injury.

    PubMed

    Davies, Michael R; Ravishankar, Bharat; Laron, Dominique; Kim, Hubert T; Liu, Xuhui; Feeley, Brian T

    2015-07-01

    Rotator cuff tears (RCTs) are among the most common musculoskeletal injuries seen by orthopaedic surgeons. Clinically, massive cuff tears lead to unique pathophysiological changes in rotator cuff muscle, including atrophy, and massive fatty infiltration, which are rarely seen in other skeletal muscles. Studies in a rodent model for RCT have demonstrated that these histologic findings are accompanied by activation of the Akt/mammalian target of rapamycin (mTOR) and transforming growth factor-β (TGF-β) pathways following combined tendon-nerve injury. The purpose of this study was to compare the histologic and molecular features of rotator cuff muscle and gastrocnemius muscle--a major hindlimb muscle, following combined tendon-nerve injury. Six weeks after injury, the rat gastrocnemius did not exhibit notable fatty infiltration compared to the rotator cuff. Likewise, the adipogenic markers SREBP-1 and PPARγ as well as the TGF-β canonical pathway were upregulated in the rotator cuff, but not the gastrocnemius. Our study suggests that the rat rotator cuff and hindlimb muscles differ significantly in their response to a combined tendon-nerve injury. Clinically, these findings highlight the unique response of the rotator cuff to injury, and may begin to explain the poor outcomes of massive RCTs compared to other muscle-tendon injuries.

  13. Ingenuity Pathway Analysis of Gene Expression Profiles in Distal Nerve Stump following Nerve Injury: Insights into Wallerian Degeneration

    PubMed Central

    Yu, Jun; Gu, Xiaosong; Yi, Sheng

    2016-01-01

    Nerve injury is a common and difficult clinical problem worldwide with a high disability rate. Different from the central nervous system, the peripheral nervous system is able to regenerate after injury. Wallerian degeneration in the distal nerve stump contributes to the construction of a permissible microenvironment for peripheral nerve regeneration. To gain new molecular insights into Wallerian degeneration, this study aimed to identify differentially expressed genes and elucidate significantly involved pathways and cellular functions in the distal nerve stump following nerve injury. Microarray analysis showed that a few genes were differentially expressed at 0.5 and 1 h post nerve injury and later on a relatively larger number of genes were up-regulated or down-regulated. Ingenuity pathway analysis indicated that inflammation and immune response, cytokine signaling, cellular growth and movement, as well as tissue development and function were significantly activated following sciatic nerve injury. Notably, a cellular function highly related to nerve regeneration, which is called Nervous System Development and Function, was continuously activated from 4 days until 4 weeks post injury. Our results may provide further understanding of Wallerian degeneration from a genetic perspective, thus aiding the development of potential therapies for peripheral nerve injury. PMID:27999531

  14. Iatrogenic Injury to the Long Thoracic Nerve

    PubMed Central

    Bizzarri, Federico; Davoli, Giuseppe; Bouklas, Dimitri; Oricchio, Luca; Frati, Giacomo; Neri, Eugenio

    2001-01-01

    After heart surgery, complications affecting the brachial plexus have been reported in 2% to 38% of cases. The long thoracic nerve is vulnerable to damage at various levels, due to its long and superficial course. This nerve supplies the serratus anterior muscle, which has an important role in the abduction and elevation of the superior limb; paralysis of the serratus anterior causes “winged scapula,” a condition in which the arm cannot be lifted higher than 90° from the side. Unfortunately, the long thoracic nerve can be damaged by a wide variety of traumatic and nontraumatic occurrences, ranging from viral or nonviral disease to improper surgical technique, to the position of the patient during transfer to a hospital bed. Our patient, a 62-year-old man with triple-vessel disease, underwent myocardial revascularization in which right and left internal thoracic arteries and the left radial artery were grafted to the right coronary, descending anterior, and obtuse marginal arteries, respectively. Despite strong recovery and an apparently good postoperative course, the patient sued for damages due to subsequent winging of the left scapula. In this instance, the legal case has less to do with the cause of the lesion (which remains unclear) than with failure to adequately inform the patient of possible complications at the expense of the nervous system. The lesson is that each patient must receive detailed written and oral explanation of the potential benefits and all conceivable risks of a procedure. (Tex Heart Inst J 2001;28:315–7) PMID:11777160

  15. Late radiation injury to muscle and peripheral nerves

    SciTech Connect

    Gillette, E.L.; Powers, B.E.; Vujaskovic, Z.

    1995-03-30

    Late radiation injury to muscles and peripheral nerves is infrequently observed. However, the success of radiation oncology has led to longer patient survival, providing a greater opportunity for late effects to develop, increase in severity and, possibly, impact the quality of life of the patient. In addition, when radiation therapy is combined with surgery and/or chemotherapy, the risk of late complications is likely to increase. It is clear that the incidence of complications involving muscles and nerves increases with time following radiation. The influence of volume has yet to be determined; however, an increased volume is likely to increase the risk of injury to muscles and nerves. Experimental and clinical studies have indicated that the {alpha}/{beta} ratio for muscle is approximately 4 Gy and, possibly, 2 Gy for peripheral nerve, indicating the great influence of fractionation on response of these tissues. This is of concern for intraoperative radiation therapy, and for high dose rate brachytherapy. This review of clinical and experimental data discusses the response of muscle and nerves late after radiation therapy. A grading system has been proposed and endpoints suggested. 36 refs., 3 figs., 3 tabs.

  16. Spatiotemporal expression of postsynaptic density 95 in rat retina after optic nerve injury.

    PubMed

    Li, Chen; Zhou, Yi; Liu, ZhiQiang; Tuo, JingSheng; Hu, Nan; Guan, HuaiJin

    2012-03-01

    Postsynaptic density protein 95 (PSD95) contains three PSD95/Drosophilia disk large/ZO-1[PDZ] homology domains and links neuronal nitric oxide synthase (nNOS) with the N-methyl-D: -aspartic acid receptor. Previous studies showed that the assembly of PSD95/nNOS signaling played an important role in rat ischemic brain injury. In this study, we aimed to elucidate the changes of PSD95 expression and location in retina after optic nerve crush. The optic nerve injury model of rats was created by crushing optic nerve at 2 mm retrobulbarly. Real-time PCR and Western blot analysis were used to analyze mRNA and protein expression of PSD95. The spatial distribution of PSD95 were evaluated by immunohistochemistry. Immunofluorescence was performed to observe the co-localization of PSD95. The PSD95 expression diminished at 1 day and elevated and peaked on the 7th day of post-injury. The mRNA and protein levels of PSD95 underwent the similar change. The association of PSD95 and rhodopsin was detected by immunofluorescence double staining. The injury-induced expression of PSD95 was physically co-existed with active caspase-3 (apoptotic marker) and nNOS. The spatiotemporal changes of PSD95 expression suggests that this protein likely to play a role in the degenerative process of never cells induced by optic nerve injury in the retina.

  17. Synaptic ultrastructure changes in trigeminocervical complex post trigeminal nerve injury

    PubMed Central

    Park, John; Trinh, Van Nancy; Sears-Kraxberger, Ilse; Li, Kang-Wu; Steward, Oswald; Luo, Z. David

    2015-01-01

    Trigeminal nerves collecting sensory information from the orofacial area synapse on second order neurons in the dorsal horn of subnucleus caudalis and cervical C1/C2 spinal cord (Vc/C2, or trigeminocervical complex), which is critical for sensory information processing. Injury to the trigeminal nerves may cause maladaptive changes in synaptic connectivity that plays an important role in chronic pain development. Here, we examined whether injury to the infraorbital nerve, a branch of the trigeminal nerves, led to synaptic ultrastructural changes when the injured animals have developed neuropathic pain states. Transmission electron microscopy was used to examine synaptic profiles in Vc/C2 at three-weeks post-injury, corresponding to the time of peak behavioral hypersensitivity following chronic constriction injury to the infraorbital nerve (CCI-ION). Using established criteria, synaptic profiles were classified as associated with excitatory (R-), inhibitory (F-), and primary afferent (C-) terminals. Each type was counted within the superficial dorsal horn of the Vc/C2 and the means from each rat were compared between sham and injured animals; synaptic contact length was also measured. The overall analysis indicates that rats with orofacial pain states had increased numbers and decreased mean synaptic length of R-profiles within the Vc/C2 superficial dorsal horn (lamina I) three-weeks post CCI-ION. Increases in the number of excitatory synapses in the superficial dorsal horn of Vc/C2 could lead to enhanced activation of nociceptive pathways, contributing to the development of orofacial pain states. PMID:26132987

  18. Reverse transcription quantitative real-time polymerase chain reaction reference genes in the spared nerve injury model of neuropathic pain: validation and literature search

    PubMed Central

    2013-01-01

    Background The reverse transcription quantitative real-time polymerase chain reaction (RT-qPCR) is a widely used, highly sensitive laboratory technique to rapidly and easily detect, identify and quantify gene expression. Reliable RT-qPCR data necessitates accurate normalization with validated control genes (reference genes) whose expression is constant in all studied conditions. This stability has to be demonstrated. We performed a literature search for studies using quantitative or semi-quantitative PCR in the rat spared nerve injury (SNI) model of neuropathic pain to verify whether any reference genes had previously been validated. We then analyzed the stability over time of 7 commonly used reference genes in the nervous system – specifically in the spinal cord dorsal horn and the dorsal root ganglion (DRG). These were: Actin beta (Actb), Glyceraldehyde-3-phosphate dehydrogenase (GAPDH), ribosomal proteins 18S (18S), L13a (RPL13a) and L29 (RPL29), hypoxanthine phosphoribosyltransferase 1 (HPRT1) and hydroxymethylbilane synthase (HMBS). We compared the candidate genes and established a stability ranking using the geNorm algorithm. Finally, we assessed the number of reference genes necessary for accurate normalization in this neuropathic pain model. Results We found GAPDH, HMBS, Actb, HPRT1 and 18S cited as reference genes in literature on studies using the SNI model. Only HPRT1 and 18S had been once previously demonstrated as stable in RT-qPCR arrays. All the genes tested in this study, using the geNorm algorithm, presented gene stability values (M-value) acceptable enough for them to qualify as potential reference genes in both DRG and spinal cord. Using the coefficient of variation, 18S failed the 50% cut-off with a value of 61% in the DRG. The two most stable genes in the dorsal horn were RPL29 and RPL13a; in the DRG they were HPRT1 and Actb. Using a 0.15 cut-off for pairwise variations we found that any pair of stable reference gene was sufficient for the

  19. Dorsal clitoral nerve injury following transobturator midurethral sling

    PubMed Central

    Moss, Chailee F; Damitz, Lynn A; Gracely, Richard H; Mintz, Alice C; Zolnoun, Denniz A; Dellon, A Lee

    2016-01-01

    Introduction Transobturator slings can be successfully used to treat stress urinary incontinence and improve quality of life through a minimally invasive vaginal approach. Persistent postoperative pain can occur and pose diagnostic and therapeutic dilemmas. Following a sling procedure, a patient complained of pinching clitoral and perineal pain. Her symptoms of localized clitoral pinching and pain became generalized over the ensuing years, eventually encompassing the entire left vulvovaginal region. Aim The aim of this study was to highlight the clinical utility of conventional pain management techniques used for the evaluation and management of patients with postoperative pain following pelvic surgery. Methods We described a prototypical patient with persistent pain in and around the clitoral region complicating the clinical course of an otherwise successful sling procedure. We specifically discussed the utility of bedside sensory assessment techniques and selective nerve blocks in the evaluation and management of this prototypical patient. Results Neurosensory assessments and a selective nerve block enabled us to trace the source of the patient’s pain to nerve entrapment along the dorsal nerve of the clitoris. We then utilized a nerve stimulator-guided hydrodissection technique to release the scar contracture Conclusion This case demonstrates that the dorsal nerve of the clitoris is vulnerable to injury directly and/or indirectly. Assimilation of a time-honored pain management construct for the evaluation and management of patients’ pain may improve outcomes while obviating the need for invasive surgery. PMID:27729812

  20. Intranasal nerve growth factor bypasses the blood-brain barrier and affects spinal cord neurons in spinal cord injury

    PubMed Central

    Aloe, Luigi; Bianchi, Patrizia; De Bellis, Alberto; Soligo, Marzia; Rocco, Maria Luisa

    2014-01-01

    The purpose of this work was to investigate whether, by intranasal administration, the nerve growth factor bypasses the blood-brain barrier and turns over the spinal cord neurons and if such therapeutic approach could be of value in the treatment of spinal cord injury. Adult Sprague-Dawley rats with intact and injured spinal cord received daily intranasal nerve growth factor administration in both nostrils for 1 day or for 3 consecutive weeks. We found an increased content of nerve growth factor and enhanced expression of nerve growth factor receptor in the spinal cord 24 hours after a single intranasal administration of nerve growth factor in healthy rats, while daily treatment for 3 weeks in a model of spinal cord injury improved the deficits in locomotor behaviour and increased spinal content of both nerve growth factor and nerve growth factor receptors. These outcomes suggest that the intranasal nerve growth factor bypasses blood-brain barrier and affects spinal cord neurons in spinal cord injury. They also suggest exploiting the possible therapeutic role of intranasally delivered nerve growth factor for the neuroprotection of damaged spinal nerve cells. PMID:25206755

  1. The Effect of Sildenafil on Recuperation from Sciatic Nerve Injury in Rats

    PubMed Central

    Korkmaz, Mehmet Fatih; Parlakpınar, Hakan; Ceylan, Mehmet Fethi; Ediz, Levent; Şamdancı, Emine; Kekilli, Ersoy; Sağır, Mustafa

    2016-01-01

    Background: Severe functional and anatomical defects can be detected after the peripheral nerve injury. Pharmacological approaches are preferred rather than surgical treatment in the treatment of nerve injuries. Aims: The aim of this study is to perform histopathological, functional and bone densitometry examinations of the effects of sildenafil on nerve regeneration in a rat model of peripheral nerve crush injury. Study Design: Animal experiment. Methods: The study included a total of thirty adult Sprague-Dawley rats that were divided into three groups of ten rats each. In all rats, a crush injury was created by clamping the right sciatic nerve for one minute. One day before the procedure, rats in group 1 were started on a 28-day treatment consisting of a daily dose of 20 mg/kg body weight sildenafil citrate given orally via a nasogastric tube, while the rats in group 2 were started on an every-other-day dose of 10 mg/kg body weight sildenafil citrate. Rats from group 3 were not administered any drugs. Forty-two days after the nerve damage was created, functional and histopathological examination of both sciatic nerves and bone densitometric evaluation of the extremities were conducted. Results: During the rotarod test, rats from group 3 spent the least amount of time on the rod compared to the drug treatment groups at speeds of 20 rpm, 30 rpm and 40 rpm. In addition, the duration for which each animal could stay on the rod throughout the accelerod test significantly reduced in rats from group 3 compared to rats from groups 1 and 2 in the 4-min test. For the hot-plate latency time, there were no differences among the groups in either the basal level or after sciatic nerve injury. Moreover, there was no significant difference between the groups in terms of the static sciatic index (SSI) on the 42nd day (p=0.147). The amplitude was better evaluated in group 1 compared to the other two groups (p<0.05). Under microscopic evaluation, we observed the greatest amount of

  2. Ethical considerations in elective amputation after traumatic peripheral nerve injuries

    PubMed Central

    Myers, Keith P.; Holloway, Robert G.; Landau, Mark E.

    2014-01-01

    Summary Traumatic peripheral nerve injuries often complicate extremity trauma, and may cause substantial functional deficits. We have encountered patients who request amputation of such injured extremities, with the goal of prosthetic replacement as a means to restore function. Data on long-term outcomes of limb salvage vs amputation are limited and somewhat contradictory, leaving how to respond to such requests in the hands of the treating physician. We present example cases, drawn from our experience with wounded soldiers in a peripheral nerve injury clinic, in order to facilitate discussion of the ways in which these patients stress the system of medical decision-making while identifying ethical questions central to responding to these requests. PMID:25279253

  3. HuD-mediated distinct BDNF regulatory pathways promote regeneration after nerve injury.

    PubMed

    Sanna, Maria Domenica; Ghelardini, Carla; Galeotti, Nicoletta

    2017-03-15

    Up-regulation of brain-derived neurotrophic factor (BDNF) synthesis is an important mechanism of peripheral nerve regeneration after injury. However, the cellular and molecular mechanisms underlying this process are not fully understood. This study examines the role of BDNF in the spared nerve injury (SNI) mice model. Protein expression and cellular localization were investigated in the dorsal root ganglia (DRG) and spinal cord by western blotting and immunofluorescence experiments respectively. BDNF protein was markedly increased 3 and 7days post-injury in the spinal cord and DRG. Following nerve injury sensory neurons produce molecules to promote regeneration, such as growth-associated protein 43 (GAP-43) and cytoskeletal proteins. Our results show that the expression of GAP-43 was increased in the DRG and spinal cord while, an increased of p-NFH content was detected in the spinal cord, with no modification in the DRG. Both events were counteracted by the administration of an anti-BDNF antibody. In DRG of SNI mice we also detected an increase of HuD expression, a RNA-binding protein known to stabilize BDNF and GAP-43 mRNA. Silencing of HuD prevented the nerve injury-induced BDNF and GAP-43 enhanced expression in the DRG. HuD-mediated BDNF synthesis in the primary sensory neurons, is followed by an anterograde transport of the neurotrophin to the central terminals of the primary afferents in the spinal dorsal horn, to modulate GAP-43 and NFH activation. Our data suggest that BDNF, GAP-43 and p-NFH proteins increase are linked events required for the enhanced regeneration after nerve injury.

  4. Phonatory characteristics of patients undergoing thyroidectomy without laryngeal nerve injury.

    PubMed

    Hong, K H; Kim, Y K

    1997-10-01

    Complications that arise after thyroid surgery may be associated with infection, hemorrhage, hormonal problems, and laryngeal nerve injury. Voice alteration after thyroidectomy is usually caused by recurrent or superior laryngeal nerve injury. This voice dysfunction may also be associated with laryngotracheal fixation with impairment of vertical movement or by temporary malfunction of the strap muscles after surgery. In this study, we evaluated the voice function phonetically before and after thyroidectomy in 54 patients, although function of the recurrent and superior laryngeal nerves was normal. During surgery, the superior and recurrent laryngeal nerves were identified and protected, and after surgery electromyographic testing of the cricothyroid muscle was performed. Typical voice symptoms after surgery were easy fatigue during phonation and difficulty with high pitch and singing voice. Acoustic analysis revealed that the phonation time and fundamental frequency were not changed after surgery, but the speaking fundamental frequency, range of speaking fundamental frequency, and vocal range were significantly diminished after surgery. These data allowed us to suggest that the cause of voice dysfunction is not seen in neural lesions, but in a disturbance of the extralaryngeal skeleton. These voice changes emphasize the importance of the extralaryngeal mechanism for pitch control.

  5. Tips to avoid nerve injury in elbow arthroscopy

    PubMed Central

    Hilgersom, Nick F J; Oh, Luke S; Flipsen, Mark; Eygendaal, Denise; van den Bekerom, Michel P J

    2017-01-01

    Elbow arthroscopy is a technical challenging surgical procedure because of close proximity of neurovascular structures and the limited articular working space. With the rising number of elbow arthroscopies being performed nowadays due to an increasing number of surgeons performing this procedure and a broader range of indications, a rise in complications is foreseen. With this editorial we hope to create awareness of possible complications of elbow arthroscopy, particularly nerve injuries, and provide a guideline to avoid complications during elbow arthroscopy. PMID:28251060

  6. Bruxism elicited by inferior alveolar nerve injury: a case report.

    PubMed

    Melis, Marcello; Coiana, Carlo; Secci, Simona

    2012-02-01

    The aim of this case report is to describe the history of a patient who received an injury to the right inferior alveolar nerve after placement of a dental implant, with bruxism noted afterward. The symptoms were managed by the use of an occlusal appliance worn at night and occasionally during the day, associated with increased awareness of parafunction during the day to reduce muscle pain and fatigue. Paresthesia of the teeth, gingiva, and lower lip persisted but were reduced during appliance use.

  7. Effect of Frankincense Extract on Nerve Recovery in the Rat Sciatic Nerve Damage Model

    PubMed Central

    Jiang, Xiaowen; Ma, Jun; Wei, Qingwei; Feng, Xinxin; Qiao, Lu; Liu, Lin; Zhang, Binqing; Yu, Wenhui

    2016-01-01

    This study investigated the effect of frankincense extract on peripheral nerve regeneration in a crush injury rat model. Forty-eight Sprague-Dawley rats were randomly divided into four groups: control and frankincense extract low-, medium-, and high-dose groups. At days 7, 14, 21, and 28 following the surgery, nerve regeneration and functional recovery were evaluated using the sciatic functional index (SFI), expression of GAP-43, and the proliferation of Schwann cells (SCs) in vivo and in vitro. At day 7, the SFI in the frankincense extract high-dose group was significantly improved compared with the control group. After day 14, SFI was significantly improved in the medium- and high-dose groups. There was no significant difference in GAP-43 expression among the groups at day 7. However, after day 14, expression of GAP-43 in the high-dose group was higher than that in the control group. Histological evaluation showed that the injured nerve of frankincense extract high-dose group recovered better than the other groups 28 days after surgery. Further, S100 immunohistochemical staining, MTT colorimetry, and flow cytometry assays all showed that frankincense extract could promote the proliferation of SCs. In conclusion, frankincense extract is able to promote sciatic nerve regeneration and improve the function of a crushed sciatic nerve. This study provides a new direction for the repair of peripheral nerve injury. PMID:27143985

  8. Injury of the Inferior Alveolar Nerve during Implant Placement: a Literature Review

    PubMed Central

    Wang, Hom-Lay; Sabalys, Gintautas

    2011-01-01

    ABSTRACT Objectives The purpose of present article was to review aetiological factors, mechanism, clinical symptoms, and diagnostic methods as well as to create treatment guidelines for the management of inferior alveolar nerve injury during dental implant placement. Material and Methods Literature was selected through a search of PubMed, Embase and Cochrane electronic databases. The keywords used for search were inferior alveolar nerve injury, inferior alveolar nerve injuries, inferior alveolar nerve injury implant, inferior alveolar nerve damage, inferior alveolar nerve paresthesia and inferior alveolar nerve repair. The search was restricted to English language articles, published from 1972 to November 2010. Additionally, a manual search in the major anatomy, dental implant, periodontal and oral surgery journals and books were performed. The publications there selected by including clinical, human anatomy and physiology studies. Results In total 136 literature sources were obtained and reviewed. Aetiological factors of inferior alveolar nerve injury, risk factors, mechanism, clinical sensory nerve examination methods, clinical symptoms and treatment were discussed. Guidelines were created to illustrate the methods used to prevent and manage inferior alveolar nerve injury before or after dental implant placement. Conclusions The damage of inferior alveolar nerve during the dental implant placement can be a serious complication. Clinician should recognise and exclude aetiological factors leading to nerve injury. Proper presurgery planning, timely diagnosis and treatment are the key to avoid nerve sensory disturbances management. PMID:24421983

  9. Peripheral nerve regeneration following transection injury to rat sciatic nerve by local application of adrenocorticotropic hormone.

    PubMed

    Mohammadi, Rahim; Yadegarazadi, Mohammad-Javad; Amini, Keyvan

    2014-09-01

    The objective of this study was to assess local effect of adrenocorticotropic hormone (ACTH) on the functional recovery of the sciatic nerve in a transection model. Sixty male healthy white Wistar rats were randomized into four experimental groups of 15 animals each: In the sham-operated group (SHAM), the sciatic nerve was exposed and manipulated. In the transected group (TC), the left sciatic nerve was transected and the cut nerve ends were fixed in the adjacent muscle. In the silicone graft group (SIL) a 10-mm defect was made and bridged using a silicone tube. The graft was filled with phosphated-buffer saline alone. In the treatment group a silicone tube (SIL/ACTH) was filled with 10 μL ACTH (0.1 mg/mL). Each group was subdivided into three subgroups of five animals each and regenerated nerve fibres were studied at 4, 8 and 12 weeks post operation. Behavioral testing, functional, gastrocnemius muscle mass and morphometric indices showed earlier regeneration of axons in SIL/ACTH than in SIL group (p < 0.05). Immunohistochemistry clearly showed more positive location of reactions to S-100 in SIL/ACTH than in SIL group. ACTH improved functional recovery and morphometric indices of sciatic nerve. This finding supports role of ACTH after peripheral nerve repair and may have clinical implications for the surgical management of patients after nerve transection.

  10. Distinct degree of radiculopathy at different levels of peripheral nerve injury

    PubMed Central

    2012-01-01

    Background Lumbar radiculopathy is a common clinical problem, characterized by dorsal root ganglion (DRG) injury and neural hyperactivity causing intense pain. However, the mechanisms involved in DRG injury have not been fully elucidated. Furthermore, little is known about the degree of radiculopathy at the various levels of nerve injury. The purpose of this study is to compare the degree of radiculopathy injury at the DRG and radiculopathy injury proximal or distal to the DRG. Results The lumbar radiculopathy rat model was created by ligating the L5 nerve root 2 mm proximal to the DRG or 2 mm distal to the DRG with 6.0 silk. We examined the degree of the radiculopathy using different points of mechanical sensitivity, immunohistochemistry and in vivo patch-clamp recordings, 7 days after surgery. The rats injured distal to the DRG were more sensitive than those rats injured proximal to the DRG in the behavioral study. The number of activated microglia in laminas I–II of the L5 segmental level was significantly increased in rats injured distal to the DRG when compared with rats injured proximal to the DRG. The amplitudes and frequencies of EPSC in the rats injured distal to the DRG were higher than those injured proximal to the DRG. The results indicated that there is a different degree of radiculopathy at the distal level of nerve injury. Conclusions Our study examined the degree of radiculopathy at different levels of nerve injury. Severe radiculopathy occurred in rats injured distal to the DRG when compared with rats injured proximal to the DRG. This finding helps to correctly diagnose a radiculopathy. PMID:22537715

  11. Nerve injury associated with orthognathic surgery. Part 2: inferior alveolar nerve.

    PubMed

    McLeod, N M H; Bowe, D C

    2016-05-01

    The inferior alveolar nerve (IAN) is the most commonly injured structure during mandibular osteotomies. The prevalence of temporary injury has been reported as 70/100 patients (95% CI 67 to 73/100) or 56/100 nerves (95% CI 46 to 65/100), and the prevalence of permanent alteration in sensation was 33/100 patients (95% CI 30 to 35/100) or 20/100 nerves (95% CI 18 to 21/100) when assessed subjectively. The prevalence varied significantly between different operations (p<0.0001). It was significantly higher for sagittal split osteotomy (SSO) combined with genioplasty than for SSO alone (p<0.0001) or vertical ramus osteotomy (VRO) (p<0.0001). Injury may result from traction during stripping or manipulation of the distal fragment, incorrect placement of the cuts, or misjudged placement of fixation in ramus ostotomy. During SSO, they can occur during retraction to make cuts in the medial ramus, when the bone is cut or split, and on fixation. The impact of injury is generally said to be low as it does not seem to affect patients' opinions about the operation.

  12. Risk of injury to vascular-nerve bundle after calcaneal fracture: comparison among three techniques

    PubMed Central

    Labronici, Pedro José; Reder, Vitor Rodrigues; de Araujo Marins Filho, Guilherme Ferreira; Pires, Robinson Esteves Santos; Fernandes, Hélio Jorge Alvachian; Mercadante, Marcelo Tomanik

    2016-01-01

    Objective To ascertain whether the number of screws or pins placed in the calcaneus might increase the risk of injury when three different techniques for treating calcaneal fractures. Method 126 radiographs of patients who suffered displaced calcaneal fractures were retrospectively analyzed. Three surgical techniques were analyzed on an interobserver basis: 31 radiographs of patients treated using plates that were not specific for the calcaneus, 48 using specific plates and 47 using an external fixator. The risk of injury to the anatomical structures in relation to each Kirschner wire or screw was determined using a graded system in accordance with the Licht classification. The total risk of injury to the anatomical structures through placement of more than one wire/screw was quantified using the additive law of probabilities for the product, for independent events. Results All of the models presented high explanatory power for the risk evaluated, since the coefficient of determination values (R2) were greater than 98.6 for all the models. Therefore, the set of variables studied explained more than 98.6% of the variations in the risks of injury to arteries, veins or nerves and can be classified as excellent models for prevention of injuries. Conclusion The risk of injury to arteries, veins or nerves is not defined by the total number of pins/screws. The region and the number of pins/screws in each region define and determine the best distribution of the risk. PMID:27069891

  13. Prevention of iatrogenic inferior alveolar nerve injuries in relation to dental procedures.

    PubMed

    Renton, T

    2010-09-01

    This article aims to review current hypotheses on the aetiology and prevention of inferior alveolar nerve (IAN) injuries in relation to dental procedures. The inferior alveolar nerve can be damaged during many dental procedures, including administration of local anaesthetic, implant bed preparation and placement, endodontics, third molar surgery and other surgical interventions. Damage to sensory nerves can result in anaesthesia, paraesthesia, pain, or a combination of the three. Pain is common in inferior alveolar nerve injuries, resulting in significant functional problems. The significant disability associated with these nerve injuries may also result in increasing numbers of medico-legal claims. Many of these iatrogenic nerve injuries can be avoided with careful patient assessment and planning. Furthermore, if the injury occurs there are emerging strategies that may facilitate recovery. The emphasis of this review is on how we may prevent these injuries and facilitate resolution in the early post surgical phase.

  14. Combined common peroneal and tibial nerve injury after knee dislocation: one injury or two? An MRI-clinical correlation.

    PubMed

    Reddy, Chandan G; Amrami, Kimberly K; Howe, Benjamin M; Spinner, Robert J

    2015-09-01

    OBJECT Knee dislocations are often accompanied by stretch injuries to the common peroneal nerve (CPN). A small subset of these injuries also affect the tibial nerve. The mechanism of this combined pattern could be a single longitudinal stretch injury of the CPN extending to the sciatic bifurcation (and tibial division) or separate injuries of both the CPN and tibial nerve, either at the level of the tibiofemoral joint or distally at the soleal sling and fibular neck. The authors reviewed cases involving patients with knee dislocations with CPN and tibial nerve injuries to determine the localization of the combined injury and correlation between degree of MRI appearance and clinical severity of nerve injury. METHODS Three groups of cases were reviewed. Group 1 consisted of knee dislocations with clinical evidence of nerve injury (n = 28, including 19 cases of complete CPN injury); Group 2 consisted of knee dislocations without clinical evidence of nerve injury (n = 19); and Group 3 consisted of cases of minor knee trauma but without knee dislocation (n = 14). All patients had an MRI study of the knee performed within 3 months of injury. MRI appearance of tibial and common peroneal nerve injury was scored by 2 independent radiologists in 3 zones (Zone I, sciatic bifurcation; Zone II, knee joint; and Zone III, soleal sling and fibular neck) on a severity scale of 1-4. Injury signal was scored as diffuse or focal for each nerve in each of the 3 zones. A clinical score was also calculated based on Medical Research Council scores for strength in the tibial and peroneal nerve distributions, combined with electrophysiological data, when available, and correlated with the MRI injury score. RESULTS Nearly all of the nerve segments visualized in Groups 1 and 2 demonstrated some degree of injury on MRI (95%), compared with 12% of nerve segments in Group 3. MRI nerve injury scores were significantly more severe in Group 1 relative to Group 2 (2.06 vs 1.24, p < 0.001) and Group

  15. Schwann cells express erythropoietin receptor and represent a major target for Epo in peripheral nerve injury.

    PubMed

    Li, Xiaoqing; Gonias, Steven L; Campana, W Marie

    2005-09-01

    Erythropoietin (Epo) expresses potent neuroprotective activity in the peripheral nervous system; however, the underlying mechanism remains incompletely understood. In this study, we demonstrate that Epo is upregulated in sciatic nerve after chronic constriction injury (CCI) and crush injury in rats, largely due to local Schwann cell production. In uninjured and injured nerves, Schwann cells also express Epo receptor (EpoR), and its expression is increased during Wallerian degeneration. CCI increased the number of Schwann cells at the injury site and the number was further increased by exogenously administered recombinant human Epo (rhEpo). To explore the activity of Epo in Schwann cells, primary cultures were established. These cells expressed cell-surface Epo receptors, with masses of 71 and 62 kDa, as determined by surface protein biotinylation and affinity precipitation. The 71-kDa species was rapidly but transiently tyrosine-phosphorylated in response to rhEpo. ERK/MAP kinase was also activated in rhEpo-treated Schwann cells; this response was blocked by pharmacologic antagonism of JAK-2. RhEpo promoted Schwann cell proliferation, as determined by BrdU incorporation. Cell proliferation was ERK/MAP kinase-dependent. These results support a model in which Schwann cells are a major target for Epo in injured peripheral nerves, perhaps within the context of an autocrine signaling pathway. EpoR-induced cell signaling and Schwann cell proliferation may protect injured peripheral nerves and promote regeneration.

  16. Nerve Cross-Bridging to Enhance Nerve Regeneration in a Rat Model of Delayed Nerve Repair

    PubMed Central

    2015-01-01

    There are currently no available options to promote nerve regeneration through chronically denervated distal nerve stumps. Here we used a rat model of delayed nerve repair asking of prior insertion of side-to-side cross-bridges between a donor tibial (TIB) nerve and a recipient denervated common peroneal (CP) nerve stump ameliorates poor nerve regeneration. First, numbers of retrogradely-labelled TIB neurons that grew axons into the nerve stump within three months, increased with the size of the perineurial windows opened in the TIB and CP nerves. Equal numbers of donor TIB axons regenerated into CP stumps either side of the cross-bridges, not being affected by target neurotrophic effects, or by removing the perineurium to insert 5-9 cross-bridges. Second, CP nerve stumps were coapted three months after inserting 0-9 cross-bridges and the number of 1) CP neurons that regenerated their axons within three months or 2) CP motor nerves that reinnervated the extensor digitorum longus (EDL) muscle within five months was determined by counting and motor unit number estimation (MUNE), respectively. We found that three but not more cross-bridges promoted the regeneration of axons and reinnervation of EDL muscle by all the CP motoneurons as compared to only 33% regenerating their axons when no cross-bridges were inserted. The same 3-fold increase in sensory nerve regeneration was found. In conclusion, side-to-side cross-bridges ameliorate poor regeneration after delayed nerve repair possibly by sustaining the growth-permissive state of denervated nerve stumps. Such autografts may be used in human repair surgery to improve outcomes after unavoidable delays. PMID:26016986

  17. Musculocutaneous nerve injury after simulated freefall in a vertical wind-tunnel: a case report.

    PubMed

    Mautner, Kenneth; Keel, John C

    2007-03-01

    We report a case of a skydiver with isolated musculocutaneous nerve injury, which occurred after prolonged positioning of the arm during simulated freefall in a vertical wind-tunnel. Musculocutaneous nerve injury is rare, and the mechanism of isolated injury to this nerve is not entirely understood. Isolated peripheral nerve injuries such as this easily mimic other injuries and can be difficult to diagnose. The skydiver complained of right arm weakness and numbness that began after training in a vertical wind-tunnel. Exam revealed weakness in right elbow flexion and forearm supination, and diminished sensation in the right lateral forearm. Electrodiagnostic testing revealed a decreased amplitude in the right lateral antebrachial cutaneous nerve sensory nerve action potential, and fibrillations and positive sharp waves in the biceps and brachialis muscles. By 5 months, the subject reported complete sensory and motor recovery. Physical and electrodiagnostic findings corresponded to the distribution of the musculocutaneous nerve. The mechanism of injury was likely the prolonged abducted, extended, and externally rotated position of the shoulder during simulated freefall. Although isolated nerve injuries are uncommon, unusual activities and physiologic demands of athletes can result in such injuries. It is important to be aware of peripheral nerve injuries to facilitate proper diagnosis and management.

  18. Redoxins in peripheral neurons after sciatic nerve injury.

    PubMed

    Valek, Lucie; Kanngießer, Maike; Häussler, Annett; Agarwal, Nitin; Lillig, Christopher Horst; Tegeder, Irmgard

    2015-12-01

    Peripheral nerve injury causes redox stress in injured neurons by upregulations of pro-oxidative enzymes, but most neurons survive suggesting an activation of endogenous defense against the imbalance. As potential candidates we assessed thioredoxin-fold proteins, called redoxins, which maintain redox homeostasis by reduction of hydrogen peroxide or protein dithiol-disulfide exchange. Using a histologic approach, we show that the peroxiredoxins (Prdx1-6), the glutaredoxins (Glrx1, 2, 3 and 5), thioredoxin (Txn1 and 2) and their reductases (Txnrd1 and 2) are expressed in neurons, glial and/or vascular cells of the dorsal root ganglia (DRGs) and in the spinal cord. They show distinct cellular and subcellular locations in agreement with the GO terms for "cellular component". The expression and localization of Glrx, Txn and Txnrd proteins was not affected by sciatic nerve injury but peroxiredoxins were upregulated in the DRGs, Prdx1 and Prdx6 mainly in non-neuronal cells and Prdx4 and Prdx5 in DRG neurons, the latter associated with an increase of respective mRNAs and protein accumulation in peripheral and/or central fibers. The upregulation of Prdx4 and Prdx5 in DRG neurons was reduced in mice with a cre-loxP mediated deficiency of hypoxia inducible factor 1 alpha (HIF1α) in these neurons. The results identify Prdx4 and Prdx5 as endogenous HIF1α-dependent, transcriptionally regulated defenders of nerve injury evoked redox stress that may be important for neuronal survival and regeneration.

  19. Suprascapular nerve injury: A cause to consider in shoulder pain and dysfunction.

    PubMed

    Yao, Kaihan; Yew, Wei Ping

    2016-05-13

    Suprascapular nerve injury is increasingly being recognized as an important cause of shoulder dysfunction. The non-specific clinical features of suprascapular nerve injury can make diagnosis difficult. However, it is essential for clinicians to consider it as part of the differential diagnoses in patients with vague pain or sensory disturbances over the posterosuperior part of their shoulder or have unexplained atrophy and weakness of their supraspinatus or infraspinatus muscle. Electrodiagnostic studies are useful in confirming and localising the nerve injury, while MRIs can be employed to determine the cause of nerve injury and assess the integrity of the rotator cuff muscles. Isolated suprascapular nerve injury can be managed with a trial of conservative management for at least 6 months. Subsequently, decompression of the nerve through open or arthroscopic techniques can be considered - both are associated with high rates of pain relief and functional improvement.

  20. Mesenchymal Stem Cells Enhance Nerve Regeneration in a Rat Sciatic Nerve Repair and Hindlimb Transplant Model

    PubMed Central

    Cooney, Damon S.; Wimmers, Eric G.; Ibrahim, Zuhaib; Grahammer, Johanna; Christensen, Joani M.; Brat, Gabriel A.; Wu, Lehao W.; Sarhane, Karim A.; Lopez, Joseph; Wallner, Christoph; Furtmüller, Georg J.; Yuan, Nance; Pang, John; Sarkar, Kakali; Lee, W. P. Andrew; Brandacher, Gerald

    2016-01-01

    This study investigates the efficacy of local and intravenous mesenchymal stem cell (MSC) administration to augment neuroregeneration in both a sciatic nerve cut-and-repair and rat hindlimb transplant model. Bone marrow-derived MSCs were harvested and purified from Brown-Norway (BN) rats. Sciatic nerve transections and repairs were performed in three groups of Lewis (LEW) rats: negative controls (n = 4), local MSCs (epineural) injection (n = 4), and systemic MSCs (intravenous) injection (n = 4). Syngeneic (LEW-LEW) (n = 4) and allogeneic (BN-LEW) (n = 4) hindlimb transplants were performed and assessed for neuroregeneration after local or systemic MSC treatment. Rats undergoing sciatic nerve cut-and-repair and treated with either local or systemic injection of MSCs had significant improvement in the speed of recovery of compound muscle action potential amplitudes and axon counts when compared with negative controls. Similarly, rats undergoing allogeneic hindlimb transplants treated with local injection of MSCs exhibited significantly increased axon counts. Similarly, systemic MSC treatment resulted in improved nerve regeneration following allogeneic hindlimb transplants. Systemic administration had a more pronounced effect on electromotor recovery while local injection was more effective at increasing fiber counts, suggesting different targets of action. Local and systemic MSC injections significantly improve the pace and degree of nerve regeneration after nerve injury and hindlimb transplantation. PMID:27510321

  1. Rules to limp by: joint compensation conserves limb function after peripheral nerve injury.

    PubMed

    Bauman, Jay M; Chang, Young-Hui

    2013-10-23

    Locomotion persists across all manner of internal and external perturbations. The objective of this study was to identify locomotor compensation strategies in rodent models of peripheral nerve injury. We found that hip-to-toe limb length and limb angle was preferentially preserved over individual joint angles after permanent denervation of rat ankle extensor muscles. These findings promote further enquiry into the significance of limb-level function for neuromechanical control of legged locomotion.

  2. AlphaB-crystallin regulates remyelination after peripheral nerve injury

    PubMed Central

    Lim, Erin-Mai F.; Nakanishi, Stan T.; Hoghooghi, Vahid; Eaton, Shane E. A.; Palmer, Alexandra L.; Frederick, Ariana; Stratton, Jo A.; Stykel, Morgan G.; Zochodne, Douglas W.; Biernaskie, Jeffrey; Ousman, Shalina S.

    2017-01-01

    AlphaB-crystallin (αBC) is a small heat shock protein that is constitutively expressed by peripheral nervous system (PNS) axons and Schwann cells. To determine what role this crystallin plays after peripheral nerve damage, we found that loss of αBC impaired remyelination, which correlated with a reduced presence of myelinating Schwann cells and increased numbers of nonmyelinating Schwann cells. The heat shock protein also seems to regulate the cross-talk between Schwann cells and axons, because expected changes in neuregulin levels and ErbB2 receptor expression after PNS injury were disrupted in the absence of αBC. Such dysregulations led to defects in conduction velocity and motor and sensory functions that could be rescued with therapeutic application of the heat shock protein in vivo. Altogether, these findings show that αBC plays an important role in regulating Wallerian degeneration and remyelination after PNS injury. PMID:28137843

  3. Morphology of Donor and Recipient Nerves Utilised in Nerve Transfers to Restore Upper Limb Function in Cervical Spinal Cord Injury

    PubMed Central

    Messina, Aurora; Van Zyl, Natasha; Weymouth, Michael; Flood, Stephen; Nunn, Andrew; Cooper, Catherine; Hahn, Jodie; Galea, Mary P.

    2016-01-01

    Loss of hand function after cervical spinal cord injury (SCI) impacts heavily on independence. Multiple nerve transfer surgery has been applied successfully after cervical SCI to restore critical arm and hand functions, and the outcome depends on nerve integrity. Nerve integrity is assessed indirectly using muscle strength testing and intramuscular electromyography, but these measures cannot show the manifestation that SCI has on the peripheral nerves. We directly assessed the morphology of nerves biopsied at the time of surgery, from three patients within 18 months post injury. Our objective was to document their morphologic features. Donor nerves included teres minor, posterior axillary, brachialis, extensor carpi radialis brevis and supinator. Recipient nerves included triceps, posterior interosseus (PIN) and anterior interosseus nerves (AIN). They were fixed in glutaraldehyde, processed and embedded in Araldite Epon for light microscopy. Eighty percent of nerves showed abnormalities. Most common were myelin thickening and folding, demyelination, inflammation and a reduction of large myelinated axon density. Others were a thickened perineurium, oedematous endoneurium and Renaut bodies. Significantly, very thinly myelinated axons and groups of unmyelinated axons were observed indicating regenerative efforts. Abnormalities exist in both donor and recipient nerves and they differ in appearance and aetiology. The abnormalities observed may be preventable or reversible. PMID:27690115

  4. Human umbilical cord blood stem cells and brain-derived neurotrophic factor for optic nerve injury: a biomechanical evaluation

    PubMed Central

    Zhang, Zhong-jun; Li, Ya-jun; Liu, Xiao-guang; Huang, Feng-xiao; Liu, Tie-jun; Jiang, Dong-mei; Lv, Xue-man; Luo, Min

    2015-01-01

    Treatment for optic nerve injury by brain-derived neurotrophic factor or the transplantation of human umbilical cord blood stem cells has gained progress, but analysis by biomechanical indicators is rare. Rabbit models of optic nerve injury were established by a clamp. At 7 days after injury, the vitreous body received a one-time injection of 50 μg brain-derived neurotrophic factor or 1 × 106 human umbilical cord blood stem cells. After 30 days, the maximum load, maximum stress, maximum strain, elastic limit load, elastic limit stress, and elastic limit strain had clearly improved in rabbit models of optical nerve injury after treatment with brain-derived neurotrophic factor or human umbilical cord blood stem cells. The damage to the ultrastructure of the optic nerve had also been reduced. These findings suggest that human umbilical cord blood stem cells and brain-derived neurotrophic factor effectively repair the injured optical nerve, improve biomechanical properties, and contribute to the recovery after injury. PMID:26330839

  5. Peripheral nerve injuries in sports-related surgery: presentation, evaluation, and management: AAOS exhibit selection.

    PubMed

    Maak, Travis G; Osei, Daniel; Delos, Demetris; Taylor, Samuel; Warren, Russell F; Weiland, Andrew J

    2012-08-15

    Peripheral nerve injuries during sports-related operative interventions are rare complications, but the associated morbidity can be substantial. Early diagnosis, efficient and effective evaluation, and appropriate management are crucial to maximizing the prognosis, and a clear and structured algorithm is therefore required. We describe the surgical conditions and interventions that are commonly associated with intraoperative peripheral nerve injuries. In addition, we review the common postoperative presentations of patients with these injuries as well as the anatomic structures that are directly injured or associated with these injuries during the operation. Some examples of peripheral nerve injuries incurred during sports-related surgery include ulnar nerve injury during ulnar collateral ligament reconstruction of the elbow and elbow arthroscopy, median nerve injury during ulnar collateral ligament reconstruction of the elbow, axillary nerve injury during Bankart repair and the Bristow transfer, and peroneal nerve injury during posterolateral corner reconstruction of the knee and arthroscopic lateral meniscal repair. We also detail the clinical and radiographic evaluation of these patients, including the utility and timing of radiographs, magnetic resonance imaging (MRI), ultrasonography, electromyography (EMG), and nonoperative or operative management. The diagnosis, evaluation, and management of peripheral nerve injuries incurred during sports-related surgical interventions are critical to minimizing patient morbidity and maximizing postoperative function. Although these injuries occur during a variety of procedures, common themes exist regarding evaluation techniques and treatment algorithms. Nonoperative treatment includes physical therapy and medical management. Operative treatments include neurolysis, transposition, neurorrhaphy, nerve transfer, and tendon transfer. This article provides orthopaedic surgeons with a simplified, literature-based algorithm for

  6. Nicotine effects on muscarinic receptor-mediated free Ca[Formula: see text] level changes in the facial nucleus following facial nerve injury.

    PubMed

    Sun, Dawei; Zhou, Rui; Dong, Anbing; Sun, Wenhai; Zhang, Hongmei; Tang, Limin

    2016-06-01

    It was suggested that muscarinic, and nicotinic receptors increase free Ca[Formula: see text] levels in the facial nerve nucleus via various channels following facial nerve injury. However, intracellular Ca[Formula: see text] overload can trigger either necrotic or apoptotic cell death. It is assumed that, following facial nerve injury, the interactions of nicotinic and muscarinic acetylcholine receptors in facial nerve nucleus may negatively regulate free Ca[Formula: see text] concentrations in the facial nerve nucleus, which provide important information for the repair and regeneration of the facial nerve. The present study investigated the regulatory effects of nicotine on muscarinic receptor-mediated free calcium ion level changes in the facial nucleus in a rat model of facial nerve injury at 7, 30, and 90 days following facial nerve injury using laser confocal microscopy. The dose-dependent regulation of nicotine on muscarinic receptor-mediated free calcium ion level changes in the facial nucleus may decrease the range of free Ca[Formula: see text] increases following facial nerve injury, which is important for nerve cell regeneration. It is concluded that the negative effects of nicotine on muscarinic receptors are related to the [Formula: see text] subtype of nicotinic receptors.

  7. Retinal ganglion cell survival and axon regeneration after optic nerve injury in naked mole-rats.

    PubMed

    Park, Kevin K; Luo, Xueting; Mooney, Skyler J; Yungher, Benjamin J; Belin, Stephane; Wang, Chen; Holmes, Melissa M; He, Zhigang

    2017-02-01

    In the adult mammalian central nervous system (CNS), axonal damage often triggers neuronal cell death and glial activation, with very limited spontaneous axon regeneration. In this study, we performed optic nerve injury in adult naked mole-rats, the longest living rodent, with a maximum life span exceeding 30 years, and found that injury responses in this species are quite distinct from those in other mammalian species. In contrast to what is seen in other mammals, the majority of injured retinal ganglion cells (RGCs) survive with relatively high spontaneous axon regeneration. Furthermore, injured RGCs display activated signal transducer and activator of transcription-3 (STAT3), whereas astrocytes in the optic nerve robustly occupy and fill the lesion area days after injury. These neuron-intrinsic and -extrinsic injury responses are reminiscent of those in "cold-blooded" animals, such as fish and amphibians, suggesting that the naked mole-rat is a powerful model for exploring the mechanisms of neuronal injury responses and axon regeneration in mammals. J. Comp. Neurol. 525:380-388, 2017. © 2016 Wiley Periodicals, Inc.

  8. Treatment of Peroneal Nerve Injuries in the Multiligament Injured/Dislocated Knee.

    PubMed

    O'Malley, Michael P; Pareek, Ayoosh; Reardon, Patrick; Krych, Aaron; Stuart, Michael J; Levy, Bruce A

    2016-05-01

    Tibiofemoral knee dislocations are typically a consequence of high-energy mechanisms, causing significant damage to the soft tissue and osseous structures of the knee. Concomitant neurovascular injuries such as popliteal artery and peroneal nerve injuries are also common and can have significant long-term consequences. The mechanism typically involves a traction injury to the peroneal nerve subsequent to an extreme varus moment applied to the knee. Complete nerve injuries typically hold a worse prognosis than incomplete palsies. Rates of functional recovery in the setting of a complete palsy following a knee dislocation event have been dismal. A period of observation and nonoperative treatment is initially performed, utilizing orthotic devices to assist with lower extremity deficits. Surgical treatment options include neurolysis, nerve grafting, tendon transfer, arthrodesis, and direct motor nerve transfers. Motor nerve transfers continue to be explored with initial reports showing promising results.

  9. Debates to personal conclusion in peripheral nerve injury and reconstruction: A 30-year experience at Chang Gung Memorial Hospital.

    PubMed

    Chuang, David Chwei-Chin

    2016-01-01

    Significant progress has been achieved in the science and management of peripheral nerve injuries over the past 40 years. Yet there are many questions and few answers. The author, with 30 years of experience in treating them at the Chang Gung Memorial Hospital, addresses debates on various issues with personal conclusions. These include: (1) Degree of peripheral nerve injury, (2) Timing of nerve repair, (3)Technique of nerve repair, (4) Level of brachial plexus injury,(5) Level of radial nerve injury,(6) Traction avulsion amputation of major limb, (7) Proximal Vs distal nerve transfers in brachial plexus injuries and (8) Post paralysis facial synkinesis.

  10. Stress and IL-1β contribute to the development of depressive-like behavior following peripheral nerve injury

    PubMed Central

    Norman, GJ; Karelina, K; Zhang, N; Walton, JC; Morris, JS; DeVries, AC

    2016-01-01

    The physiological link between neuropathic pain and depression remains unknown despite a high comorbidity between these two disorders. A mouse model of spared nerve injury (SNI) was used to test the hypothesis that nerve injury precipitates depression through the induction of inflammation in the brain, and that prior exposure to stress exacerbates the behavioral and neuroinflammatory consequences of nerve injury. As compared with sham surgery, SNI induced mechanical allodynia, and significantly increased depressive-like behavior. Moreover, SNI animals displayed increased interleukin-1β (IL-1β) gene expression within the frontal cortex and concurrent increases in the expression of glial fibrillary acidic protein (GFAP) within the periaqueductal grey (PAG). Additionally, exposure to chronic restraint stress for 2 weeks before SNI exacerbated mechanical allodynia and depressive-like behavior, and resulted in an increase in IL-1β gene expression in the frontal cortex and brain-derived neurotrophic factor (BDNF) gene expression in PAG. Treatment with metyrapone (MET), a corticosteroid synthesis inhibitor, before stress eliminated deleterious effects of chronic stress on SNI. Finally, this study showed that interference with IL-1β signaling, through administration of IL-1 receptor antagonist (IL-1ra), ameliorated the effects of neuropathic pain on depressive-like behavior. Taken together, these data suggest that peripheral nerve injury leads to increased cytokine expression in the brain, which in turn, contributes to the development of depressive-like behavior. Furthermore, stress can facilitate the development of depressive-like behavior after nerve injury by promoting IL-1β expression. PMID:19773812

  11. Digital nerve injuries: epidemiology, results, costs, and impact on daily life.

    PubMed

    Thorsén, Frida; Rosberg, Hans-Eric; Steen Carlsson, Katarina; Dahlin, Lars B

    2012-09-01

    Epidemiology, results of treatment, impact on activity of daily living (ADL), and costs for treatment of digital nerve injuries have not been considered consistently. Case notes of patients of 0-99 years of age living in Malmö municipality, Sweden, who presented with a digital nerve injury and were referred to the Department of Hand Surgery in 1995-2005 were analysed retrospectively. The incidence was 6.2/100 000 inhabitants and year. Most commonly men (75%; median age 29 years) were injured. Isolated nerve injuries and concomitant tendon injuries were equally common. The direct costs (hospital stay, operation, outpatient visits, visits to a nurse and/or a hand therapist) for a concomitant tendon injury was almost double compared with an isolated digital nerve injury (6136 EUR [range, 744-29 689 EUR] vs 2653 EUR [range, 468-6949 EUR]). More than 50% of the patients who worked were injured at work and 79% lost time from work (median 59 days [range 3-337]). Permanent nerve dysfunction for the individual patient with ADL problems and subjective complaints of fumbleness, cold sensitivity, and pain occur in the patients despite surgery. It is concluded that digital nerve injuries, often considered as a minor injury and that affect young people at productive age, cause costs, and disability. Focus should be directed against prevention of the injury and to improve nerve regeneration from different aspects.

  12. Medial antebrachial cutaneous nerve injury after brachial plexus block: two case reports.

    PubMed

    Jung, Mi Jin; Byun, Ha Young; Lee, Chang Hee; Moon, Seung Won; Oh, Min-Kyun; Shin, Heesuk

    2013-12-01

    Medial antebrachial cutaneous (MABC) nerve injury associated with iatrogenic causes has been rarely reported. Local anesthesia may be implicated in the etiology of such injury, but has not been reported. Two patients with numbness and painful paresthesia over the medial aspect of the unilateral forearm were referred for electrodiagnostic study, which revealed MABC nerve lesion in each case. The highly selective nature of the MABC nerve injuries strongly suggested that they were the result of direct nerve injury by an injection needle during previous brachial plexus block procedures. Electrodiagnostic studies can be helpful in evaluating cases of sensory disturbance after local anesthesia. To our knowledge, these are the first documented cases of isolated MABC nerve injury following ultrasound-guided axillary brachial plexus block.

  13. GFAP immunoreactivity within the rat nucleus ambiguus after laryngeal nerve injury

    PubMed Central

    Berdugo-Vega, G; Arias-Gil, G; Rodriguez-Niedenführ, M; Davies, D C; Vázquez, T; Pascual-Font, A

    2014-01-01

    Changes that occur in astroglial populations of the nucleus ambiguus after recurrent (RLN) or superior (SLN) laryngeal nerve injury have hitherto not been fully characterised. In the present study, rat RLN and SLN were lesioned. After 3, 7, 14, 28 or 56 days of survival, the nucleus ambiguus was investigated by means of glial fibrillary acidic protein (GFAP) immunofluorescence or a combination of GFAP immunofluorescence and the application of retrograde tracers. GFAP immunoreactivity was significantly increased 3 days after RLN resection and it remained significantly elevated until after 28 days post injury (dpi). By 56 dpi it had returned to basal levels. In contrast, following RLN transection with repair, GFAP immunoreactivity was significantly elevated at 7 dpi and remained significantly elevated until 14 dpi. It had returned to basal levels by 28 dpi. Topographical analysis of the distribution of GFAP immunoreactivity revealed that after RLN injury, GFAP immunoreactivity was increased beyond the area of the nucleus ambiguus within which RLN motor neuron somata were located. GFAP immunoreactivity was also observed in the vicinity of neuronal somata that project into the uninjured SLN. Similarly, lesion of the SLN resulted in increased GFAP immunoreactivity around the neuronal somata projecting into it and also in the vicinity of the motor neuron somata projecting into the RLN. The increase in GFAP immunoreactivity outside of the region containing the motor neurons projecting into the injured nerve, may reflect the onset of a regenerative process attempting to compensate for impairment of one of the laryngeal nerves and may occur because of the dual innervation of the posterior cricoarytenoid muscle. This dual innervation of a very specialised muscle could provide a useful model system for studying the molecular mechanisms underlying axonal regeneration process and the results of the current study could provide the basis for studies into functional regeneration

  14. BDNF gene delivery mediated by neuron-targeted nanoparticles is neuroprotective in peripheral nerve injury.

    PubMed

    Lopes, Cátia D F; Gonçalves, Nádia P; Gomes, Carla P; Saraiva, Maria J; Pêgo, Ana P

    2017-03-01

    Neuron-targeted gene delivery is a promising strategy to treat peripheral neuropathies. Here we propose the use of polymeric nanoparticles based on thiolated trimethyl chitosan (TMCSH) to mediate targeted gene delivery to peripheral neurons upon a peripheral and minimally invasive intramuscular administration. Nanoparticles were grafted with the non-toxic carboxylic fragment of the tetanus neurotoxin (HC) to allow neuron targeting and were explored to deliver a plasmid DNA encoding for the brain-derived neurotrophic factor (BDNF) in a peripheral nerve injury model. The TMCSH-HC/BDNF nanoparticle treatment promoted the release and significant expression of BDNF in neural tissues, which resulted in an enhanced functional recovery after injury as compared to control treatments (vehicle and non-targeted nanoparticles), associated with an improvement in key pro-regenerative events, namely, the increased expression of neurofilament and growth-associated protein GAP-43 in the injured nerves. Moreover, the targeted nanoparticle treatment was correlated with a significantly higher density of myelinated axons in the distal stump of injured nerves, as well as with preservation of unmyelinated axon density as compared with controls and a protective role in injury-denervated muscles, preventing them from denervation. These results highlight the potential of TMCSH-HC nanoparticles as non-viral gene carriers to deliver therapeutic genes into the peripheral neurons and thus, pave the way for their use as an effective therapeutic intervention for peripheral neuropathies.

  15. Exacerbation of Charcot-Marie-Tooth type 2E neuropathy following traumatic nerve injury.

    PubMed

    Villalón, Eric; Dale, Jeffrey M; Jones, Maria; Shen, Hailian; Garcia, Michael L

    2015-11-19

    Charcot-Marie-Tooth disease (CMT) is the most commonly inherited peripheral neuropathy. CMT disease signs include distal limb neuropathy, abnormal gait, sensory defects, and deafness. We generated a novel line of CMT2E mice expressing hNF-L(E397K), which displayed muscle atrophy of the lower limbs without denervation, proximal reduction in large caliber axons, and decreased nerve conduction velocity. In this study, we challenged wild type, hNF-L and hNF-L(E397K) mice with crush injury to the sciatic nerve. We analyzed functional recovery by measuring toe spread and analyzed gait using the Catwalk system. hNF-L(E397K) mice demonstrated reduced recovery from nerve injury consistent with increased susceptibility to neuropathy observed in CMT patients. In addition, hNF-L(E397K) developed a permanent reduction in their ability to weight bear, increased mechanical allodynia, and premature gait shift in the injured limb, which led to increasingly disrupted interlimb coordination in hNF-L(E397K). Exacerbation of neuropathy after injury and identification of gait alterations in combination with previously described pathology suggests that hNF-L(E397K) mice recapitulate many of clinical signs associated with CMT2. Therefore, hNF-L(E397K) mice provide a model for determining the efficacy of novel therapies.

  16. Changes in microtubule-associated protein tau during peripheral nerve injury and regeneration

    PubMed Central

    Zha, Guang-bin; Shen, Mi; Gu, Xiao-song; Yi, Sheng

    2016-01-01

    Tau, a primary component of microtubule-associated protein, promotes microtubule assembly and/or disassembly and maintains the stability of the microtubule structure. Although the importance of tau in neurodegenerative diseases has been well demonstrated, whether tau is involved in peripheral nerve regeneration remains unknown. In the current study, we obtained sciatic nerve tissue from adult rats 0, 1, 4, 7, and 14 days after sciatic nerve crush and examined tau mRNA and protein expression levels and the location of tau in the sciatic nerve following peripheral nerve injury. The results from our quantitative reverse transcription polymerase chain reaction analysis showed that compared with the uninjured control sciatic nerve, mRNA expression levels for both tau and tau tubulin kinase 1, a serine/threonine kinase that regulates tau phosphorylation, were decreased following peripheral nerve injury. Our western blot assay results suggested that the protein expression levels of tau and phosphorylated tau initially decreased 1 day post nerve injury but then gradually increased. The results of our immunohistochemical labeling showed that the location of tau protein was not altered by nerve injury. Thus, these results showed that the expression of tau was changed following sciatic nerve crush, suggesting that tau may be involved in peripheral nerve repair and regeneration. PMID:27857758

  17. Beneficial Effect of Metformin on Nerve Regeneration and Functional Recovery After Sciatic Nerve Crush Injury in Diabetic Rats.

    PubMed

    Ma, Junxiong; Liu, Jun; Yu, Hailong; Chen, Yu; Wang, Qi; Xiang, Liangbi

    2016-05-01

    Neuroprotective effects of metformin have been increasingly recognized in both diabetic and non-diabetic conditions. Thus far, no information has been available on the potential beneficial effects of metformin on peripheral nerve regeneration in diabetes mellitus. The present study was designed to investigate such a possibility. Diabetes was established by a single injection of streptozotocin at 50 mg/kg in rats. After sciatic nerve crush injury, the diabetic rats were intraperitoneally administrated daily for 4 weeks with metformin (30, 200 and 500 mg/kg), or normal saline, respectively. The axonal regeneration was investigated by morphometric analysis and retrograde labeling. The functional recovery was evaluated by electrophysiological studies and behavioral analysis. It was found that metformin significantly enhanced axonal regeneration and functional recovery compared to saline after sciatic nerve injury in diabetic rats. In addition, metformin at 200 and 500 mg/kg showed better performance than that at 30 mg/kg. Taken together, metformin is capable of promoting nerve regeneration after sciatic nerve injuries in diabetes mellitus, highlighting its therapeutic values for peripheral nerve injury repair in diabetes mellitus.

  18. Different patterns of morphological changes in the hippocampus and dentate gyrus accompany the differential expression of disability following nerve injury

    PubMed Central

    Kalman, Eszter; Keay, Kevin A

    2014-01-01

    Physical and psychological trauma which results in mood disorders and the disruption of complex behaviours is associated with reductions in hippocampal volume. Clinical evaluation of neuropathic pain reveals mood and behavioural change in a significant number of patients. A rat model of neuropathic injury results in complex behavioural changes in a subpopulation (∼30%) of injured rats; these changes are co-morbid with a range of other ‘disabilities’. The specific objective of this study was to determine in rats the morphology of the hippocampus and dentate gyrus in individuals with and without complex behavioural disruptions following a constriction injury of the sciatic nerve, and to determine whether rats that develop disabilities following nerve injury have a reduced hippocampal volume compared with injured rats with no disabilities. The social behaviours of nerve-injured rats were evaluated before and after nerve injury. The morphology of the hippocampus of rats with and without behavioural disruptions was compared in serial histological sections. Single-housing and repeated social-interaction testing had no effect on the morphology of either the hippocampus or the dentate gyrus. Rats with transient or ongoing disability identified by behavioural disruption following sciatic nerve injury, show bilateral reductions in hippocampal volume, and lateralised reduction in the dentate gyrus (left side). Disabled rats display a combination of behavioural and physiological changes, which resemble many of the criteria used clinically to diagnose mood disorders. They also show reductions in the volume of the hippocampus similar to people with clinically diagnosed mood disorders. The sciatic nerve injury model reveals a similarity to the human neuropathic pain presentation presenting an anatomically specific focus for the investigation of the neural mechanisms underpinning the co-morbidity of chronic pain and mood disorder. PMID:25269883

  19. An approach to identify microRNAs involved in neuropathic pain following a peripheral nerve injury

    PubMed Central

    Norcini, Monica; Sideris, Alexandra; Martin Hernandez, Lourdes A.; Zhang, Jin; Blanck, Thomas J. J.; Recio-Pinto, Esperanza

    2014-01-01

    Peripheral nerve injury alters the expression of hundreds of proteins in dorsal root ganglia (DRG). Targeting some of these proteins has led to successful treatments for acute pain, but not for sustained post-operative neuropathic pain. The latter may require targeting multiple proteins. Since a single microRNA (miR) can affect the expression of multiple proteins, here, we describe an approach to identify chronic neuropathic pain-relevant miRs. We used two variants of the spared nerve injury (SNI): Sural-SNI and Tibial-SNI and found distinct pain phenotypes between the two. Both models induced strong mechanical allodynia, but only Sural-SNI rats maintained strong mechanical and cold allodynia, as previously reported. In contrast, we found that Tibial-SNI rats recovered from mechanical allodynia and never developed cold allodynia. Since both models involve nerve injury, we increased the probability of identifying differentially regulated miRs that correlated with the quality and magnitude of neuropathic pain and decreased the probability of detecting miRs that are solely involved in neuronal regeneration. We found seven such miRs in L3-L5 DRG. The expression of these miRs increased in Tibial-SNI. These miRs displayed a lower level of expression in Sural-SNI, with four having levels lower than those in sham animals. Bioinformatic analysis of how these miRs could affect the expression of some ion channels supports the view that, following a peripheral nerve injury, the increase of the seven miRs may contribute to the recovery from neuropathic pain while the decrease of four of them may contribute to the development of chronic neuropathic pain. The approach used resulted in the identification of a small number of potentially neuropathic pain relevant miRs. Additional studies are required to investigate whether manipulating the expression of the identified miRs in primary sensory neurons can prevent or ameliorate chronic neuropathic pain following peripheral nerve

  20. Peroneal nerve injuries as a complication of injection.

    PubMed

    Kirdi, N; Yakut, E; Meriç, A

    1998-01-01

    Ten children (8 males, 2 females) diagnosed with peroneal nerve injury as a complication of injection were included in this study. The age of the children ranged between four to seven years (mean 6.5 +/- 1.25 years). Physiotherapy and rehabilitation protocol included superficial heat, neuromuscular electrical stimulation (either galvanic or faradic current according to the response elicited), electromyographic biofeedback, exercises (passive, active-assistive and active), and orthotic support. Before treatment, foot-drop and steppage gait were observed in all the patients; both were remedied. The post-treatment muscle strength and electrodiagnostic test results showed statistically significant improvement when compared with pretreatment values (p < 0.05). We believe that our relatively favorable results in this study, manifested as shorter recovery time with no residual deficits, may be related to early intervention with an extensive physiotherapy program.

  1. Nerve injury-induced neuropathic pain causes disinhibition of the anterior cingulate cortex.

    PubMed

    Blom, Sigrid Marie; Pfister, Jean-Pascal; Santello, Mirko; Senn, Walter; Nevian, Thomas

    2014-04-23

    Neuropathic pain caused by peripheral nerve injury is a debilitating neurological condition of high clinical relevance. On the cellular level, the elevated pain sensitivity is induced by plasticity of neuronal function along the pain pathway. Changes in cortical areas involved in pain processing contribute to the development of neuropathic pain. Yet, it remains elusive which plasticity mechanisms occur in cortical circuits. We investigated the properties of neural networks in the anterior cingulate cortex (ACC), a brain region mediating affective responses to noxious stimuli. We performed multiple whole-cell recordings from neurons in layer 5 (L5) of the ACC of adult mice after chronic constriction injury of the sciatic nerve of the left hindpaw and observed a striking loss of connections between excitatory and inhibitory neurons in both directions. In contrast, no significant changes in synaptic efficacy in the remaining connected pairs were found. These changes were reflected on the network level by a decrease in the mEPSC and mIPSC frequency. Additionally, nerve injury resulted in a potentiation of the intrinsic excitability of pyramidal neurons, whereas the cellular properties of interneurons were unchanged. Our set of experimental parameters allowed constructing a neuronal network model of L5 in the ACC, revealing that the modification of inhibitory connectivity had the most profound effect on increased network activity. Thus, our combined experimental and modeling approach suggests that cortical disinhibition is a fundamental pathological modification associated with peripheral nerve damage. These changes at the cortical network level might therefore contribute to the neuropathic pain condition.

  2. Early treatment with UR13870, a novel inhibitor of p38α mitogenous activated protein kinase, prevents hyperreflexia and anxiety behaviors, in the spared nerve injury model of neuropathic pain.

    PubMed

    Galan-Arriero, Iriana; Avila-Martin, Gerardo; Ferrer-Donato, Agueda; Gomez-Soriano, Julio; Piazza, Stefano; Taylor, Julian

    2015-09-14

    Microglia cell activation plays a role in the development of neuropathic pain partly due to the activation of the p38α MAPK signaling pathway after nerve injury. In this study we assessed the effect of UR13870, a p38α MAPK inhibitor, in the "spared nerve injury" (SNI) model, to study its effects on modulation of spinal microglial activation and to test behavioral hyperreflexia responses and cerebral-mediated pain behavior. The effect of daily administration of UR13870 (10mg/kg p.o.) and Pregabalin (50mg/kg p.o.) on reflex hypersensitivity to mechanical and cold test stimuli and on affective related pain responses measured with the place escape avoidance paradigm and the open field-induced anxiety test, were evaluated after SNI in Sprague Dawley rats. Microglial reactivity in the ipsilateral lumbar laminae I/II dorsal horn was evaluated with OX-42 immunohistochemistry. UR13870 treatment significantly decreased hindlimb hyperreflexia to both mechanical and cold stimuli after SNI without loss of general motor function, in addition to a reduction in pain-related anxiety behavior at day 21 after SNI, accompanied by normalization of OX-42 immunoreactivity within the ipsilateral lumbar dorsal horn. Pregabalin treatment only reduced mechanical hyperreflexia and affected general motor function. Oral administration of the p38α MAPK inhibitor, UR13870, mediates antinociception to both mechanical and cold stimuli, and significantly restored inner-zone exploration in the open field test, accompanied by normalization in dorsal horn microglial activation in the SNI model.

  3. Peripheral nerve injury grading simplified on MR neurography: As referenced to Seddon and Sunderland classifications.

    PubMed

    Chhabra, Avneesh; Ahlawat, Shivani; Belzberg, Allan; Andreseik, Gustav

    2014-07-01

    The Seddon and Sunderland classifications have been used by physicians for peripheral nerve injury grading and treatment. While Seddon classification is simpler to follow and more relevant to electrophysiologists, the Sunderland grading is more often used by surgeons to decide when and how to intervene. With increasing availability of high-resolution and high soft-tissue contrast imaging provided by MR neurography, the surgical treatment can be guided following the above-described grading systems. The article discusses peripheral nerve anatomy, pathophysiology of nerve injury, traditional grading systems for classifying the severity of nerve injury, and the role of MR neurography in this domain, with respective clinical and surgical correlations, as one follows the anatomic paths of various nerve injury grading systems.

  4. Peripheral nerve injury grading simplified on MR neurography: As referenced to Seddon and Sunderland classifications

    PubMed Central

    Chhabra, Avneesh; Ahlawat, Shivani; Belzberg, Allan; Andreseik, Gustav

    2014-01-01

    The Seddon and Sunderland classifications have been used by physicians for peripheral nerve injury grading and treatment. While Seddon classification is simpler to follow and more relevant to electrophysiologists, the Sunderland grading is more often used by surgeons to decide when and how to intervene. With increasing availability of high-resolution and high soft-tissue contrast imaging provided by MR neurography, the surgical treatment can be guided following the above-described grading systems. The article discusses peripheral nerve anatomy, pathophysiology of nerve injury, traditional grading systems for classifying the severity of nerve injury, and the role of MR neurography in this domain, with respective clinical and surgical correlations, as one follows the anatomic paths of various nerve injury grading systems. PMID:25114384

  5. The radio-radial nerve transfer for elbow extension restoration in C5 to C7 nerve root injury.

    PubMed

    Flores, Leandro Pretto

    2012-01-01

    Extension of the elbow is required to oppose gravity; however, activation of the triceps brachii is frequently underestimated during the surgical planning for brachial plexus injuries. This report aims to describe a novel technique of distal nerve transfer designed for elbow extension reconstruction in patients sustaining a C5-C7 nerve root injury. We report a patient sustaining a brachial plexus injury with triceps palsy and preserved finger extension motion; after careful intraneural dissection of the radial nerve, a fascicle innervating the extensor digitorum communis muscle was sectioned, derouted and connected to a motor branch to the lateral head of the triceps. Eleven months after surgery, elbow extension strength scored MRC M4. No deficits on finger extension were observed.

  6. Regenerative effect of adipose tissue-derived stem cells transplantation using nerve conduit therapy on sciatic nerve injury in rats.

    PubMed

    Liu, Bai-Shuan; Yang, Yi-Chin; Shen, Chiung-Chyi

    2014-05-01

    This study proposed a biodegradable GGT nerve conduit containing genipin crosslinked gelatin annexed with tricalcium phosphate (TCP) ceramic particles for the regeneration of peripheral nerves. Cytotoxicity tests revealed that GGT-extracts were non-toxic and promoted proliferation and neuronal differentiation in the induction of stem cells (i-ASCs) derived from adipose tissue. Furthermore, the study confirmed the effectiveness of a GGT/i-ASCs nerve conduit as a guidance channel in the repair of a 10-mm gap in the sciatic nerve of rats. At eight weeks post-implantation, walking track analysis showed a significantly higher sciatic function index (SFI) (P < 0.05) in the GGT/i-ASC group than in the autograft group. Furthermore, the mean recovery index of compound muscle action potential (CMAP) differed significantly between GGT/i-ASCs and autograft groups (P < 0.05), both of which were significantly superior to the GGT group (P < 0.05). No severe inflammatory reaction in the peripheral nerve tissue at the site of implantation was observed in either group. Histological observation and immunohistochemistry revealed that the morphology and distribution patterns of nerve fibers in the GGT/i-ASCs nerve conduits were similar to those of the autografts. These promising results achieved through a combination of regenerative cells and GGT nerve conduits suggest the potential value in the future development of clinical applications for the treatment of peripheral nerve injury.

  7. Berberine Ameliorates Allodynia Induced by Chronic Constriction Injury of the Sciatic Nerve in Rats.

    PubMed

    Kim, Hyun Jee

    2015-08-01

    The objective of this study was to investigate whether berberine could ameliorate allodynia induced by chronic constriction injury (CCI) of the sciatic nerve in rats. After inducement of CCI, significant increases in the number of paw lifts from a cold plate test (cold allodynia) and decreased paw withdrawal threshold in the von Frey hair stimulation test (mechanical allodynia) were observed. However, these cold and mechanical allodynia were markedly alleviated by berberine administration in a dose-dependent manner. Sciatic nerve myeloperoxidase and malondialdehyde activities were also attenuated by berberine administration. Continuous injection for 7 days induced no development of tolerance. The antiallodynic effect of 20 mg/kg berberine was comparable to that of amitriptyline 10 mg/kg. This study demonstrated that berberine could mitigate allodynia induced by CCI, a neuropathic pain model, and it suggested that the anti-inflammatory and antioxidative properties of berberine contributed to the antiallodynic effect in the CCI model.

  8. Boric acid reduces axonal and myelin damage in experimental sciatic nerve injury.

    PubMed

    Kızılay, Zahir; Erken, Haydar Ali; Çetin, Nesibe Kahraman; Aktaş, Serdar; Abas, Burçin İrem; Yılmaz, Ali

    2016-10-01

    The aim of this study was to investigate the effects of boric acid in experimental acute sciatic nerve injury. Twenty-eight adult male rats were randomly divided into four equal groups (n = 7): control (C), boric acid (BA), sciatic nerve injury (I), and sciatic nerve injury + boric acid treatment (BAI). Sciatic nerve injury was generated using a Yasargil aneurysm clip in the groups I and BAI. Boric acid was given four times at 100 mg/kg to rats in the groups BA and BAI after injury (by gavage at 0, 24, 48 and 72 hours) but no injury was made in the group BA. In vivo electrophysiological tests were performed at the end of the day 4 and sciatic nerve tissue samples were taken for histopathological examination. The amplitude of compound action potential, the nerve conduction velocity and the number of axons were significantly lower and the myelin structure was found to be broken in group I compared with those in groups C and BA. However, the amplitude of the compound action potential, the nerve conduction velocity and the number of axons were significantly greater in group BAI than in group I. Moreover, myelin injury was significantly milder and the intensity of nuclear factor kappa B immunostaining was significantly weaker in group BAI than in group I. The results of this study show that administration of boric acid at 100 mg/kg after sciatic nerve injury in rats markedly reduces myelin and axonal injury and improves the electrophysiological function of injured sciatic nerve possibly through alleviating oxidative stress reactions.

  9. Boric acid reduces axonal and myelin damage in experimental sciatic nerve injury

    PubMed Central

    Kızılay, Zahir; Erken, Haydar Ali; Çetin, Nesibe Kahraman; Aktaş, Serdar; Abas, Burçin İrem; Yılmaz, Ali

    2016-01-01

    The aim of this study was to investigate the effects of boric acid in experimental acute sciatic nerve injury. Twenty-eight adult male rats were randomly divided into four equal groups (n = 7): control (C), boric acid (BA), sciatic nerve injury (I), and sciatic nerve injury + boric acid treatment (BAI). Sciatic nerve injury was generated using a Yasargil aneurysm clip in the groups I and BAI. Boric acid was given four times at 100 mg/kg to rats in the groups BA and BAI after injury (by gavage at 0, 24, 48 and 72 hours) but no injury was made in the group BA. In vivo electrophysiological tests were performed at the end of the day 4 and sciatic nerve tissue samples were taken for histopathological examination. The amplitude of compound action potential, the nerve conduction velocity and the number of axons were significantly lower and the myelin structure was found to be broken in group I compared with those in groups C and BA. However, the amplitude of the compound action potential, the nerve conduction velocity and the number of axons were significantly greater in group BAI than in group I. Moreover, myelin injury was significantly milder and the intensity of nuclear factor kappa B immunostaining was significantly weaker in group BAI than in group I. The results of this study show that administration of boric acid at 100 mg/kg after sciatic nerve injury in rats markedly reduces myelin and axonal injury and improves the electrophysiological function of injured sciatic nerve possibly through alleviating oxidative stress reactions. PMID:27904499

  10. Differentiation of Pre- and Postganglionic Nerve Injury Using MRI of the Spinal Cord

    PubMed Central

    Novikova, Liudmila N.; Orädd, Greger; Wiberg, Mikael; Novikov, Lev N.

    2016-01-01

    Brachial plexus injury (BPI) is a devastating type of nerve injury, potentially causing loss of motor and sensory function. Principally, BPI is either categorized as preganglionic or postganglionic, with the early establishment of injury level being crucial for choosing the correct treatment strategy. Despite diagnostic advances, the need for a reliable, non-invasive method for establishing the injury level remains. We studied the usefulness of in vivo magnetic resonance imaging (MRI) of the spinal cord for determination of injury level. The findings were related to neuronal and glial changes. Rats underwent unilateral L4 & L5 ventral roots avulsion or sciatic nerve axotomy. The injuries served as models for pre- and postganglionic BPI, respectively. MRI of the L4/L5 spinal cord segments 4 weeks after avulsion showed ventral horn (VH) shrinkage on the injured side compared to the uninjured side. Axotomy induced no change in the VH size on MRI. Following avulsion, histological sections of L4/L5 revealed shrinkage in the VH grey matter area occupied by NeuN-positive neurons, loss of microtubular-associated protein-2 positive dendritic branches (MAP2), pan-neurofilament positive axons (PanNF), synaptophysin-positive synapses (SYN) and increase in immunoreactivity for the microglial OX42 and astroglial GFAP markers. Axotomy induced no changes in NeuN-reactivity, modest decrease of MAP2 immunoreactivity, no changes in SYN and PanNF labelling, and a modest increase in OX42 and SYN labeling. Histological and radiological findings were congruent when assessing changes after axotomy, while MRI somewhat underestimated the shrinkage. This study indicates a potential diagnostic value of structural spinal cord MRI following BPI. PMID:28036395

  11. Common peroneal nerve dysfunction

    MedlinePlus

    Neuropathy - common peroneal nerve; Peroneal nerve injury; Peroneal nerve palsy ... type of peripheral neuropathy (damage to nerves outside the brain ... nerve injuries. Damage to the nerve disrupts the myelin sheath ...

  12. Collateral development and spinal motor reorganization after nerve injury and repair

    PubMed Central

    Yu, Youlai; Zhang, Peixun; Han, Na; Kou, Yuhui; Yin, Xiaofeng; Jiang, Baoguo

    2016-01-01

    Functional recovery is often unsatisfactory after severe extended nerve defects or proximal nerve trunks injuries repaired by traditional repair methods, as the long regeneration distance for the regenerated axons to reinnervate their original target end-organs. The proximal nerve stump can regenerate with many collaterals that reinnervate the distal stump after peripheral nerve injury, it may be possible to use nearby fewer nerve fibers to repair more nerve fibers at the distal end to shorten the regenerating distance. In this study, the proximal peroneal nerve was used to repair both the distal peroneal and tibial nerve. The number and location of motor neurons in spinal cord as well as functional and morphological recovery were assessed at 2 months, 4 months and 8 months after nerve repair, respectively. Projections from the intact peroneal and tibial nerves were also studied in normal animals. The changes of motor neurons were assessed using the retrograde neurotracers FG and DiI to backlabel motor neurons that regenerate axons into two different pathways. To evaluate the functional recovery, the muscle forces and sciatic function index were examined. The muscles and myelinated axons were assessed using electrophysiology and histology. The results showed that all labeled motor neurons after nerve repair were always confined within the normal peroneal nerve pool and nearly all the distribution of motor neurons labeled via distal different nerves was disorganized as compared to normal group. However, there was a significant decline in the number of double labeled motor neurons and an obvious improvement with respect to the functional and morphological recovery between 2 and 8 months. In addition, the tibial/peroneal motor neuron number ratio at different times was 2.11±0.05, 2.13±0.08, 2.09±0.12, respectively, and was close to normal group (2.21±0.09). Quantitative analysis showed no significant morphological differences between myelinated nerve fibers

  13. Collateral development and spinal motor reorganization after nerve injury and repair.

    PubMed

    Yu, Youlai; Zhang, Peixun; Han, Na; Kou, Yuhui; Yin, Xiaofeng; Jiang, Baoguo

    2016-01-01

    Functional recovery is often unsatisfactory after severe extended nerve defects or proximal nerve trunks injuries repaired by traditional repair methods, as the long regeneration distance for the regenerated axons to reinnervate their original target end-organs. The proximal nerve stump can regenerate with many collaterals that reinnervate the distal stump after peripheral nerve injury, it may be possible to use nearby fewer nerve fibers to repair more nerve fibers at the distal end to shorten the regenerating distance. In this study, the proximal peroneal nerve was used to repair both the distal peroneal and tibial nerve. The number and location of motor neurons in spinal cord as well as functional and morphological recovery were assessed at 2 months, 4 months and 8 months after nerve repair, respectively. Projections from the intact peroneal and tibial nerves were also studied in normal animals. The changes of motor neurons were assessed using the retrograde neurotracers FG and DiI to backlabel motor neurons that regenerate axons into two different pathways. To evaluate the functional recovery, the muscle forces and sciatic function index were examined. The muscles and myelinated axons were assessed using electrophysiology and histology. The results showed that all labeled motor neurons after nerve repair were always confined within the normal peroneal nerve pool and nearly all the distribution of motor neurons labeled via distal different nerves was disorganized as compared to normal group. However, there was a significant decline in the number of double labeled motor neurons and an obvious improvement with respect to the functional and morphological recovery between 2 and 8 months. In addition, the tibial/peroneal motor neuron number ratio at different times was 2.11±0.05, 2.13±0.08, 2.09±0.12, respectively, and was close to normal group (2.21±0.09). Quantitative analysis showed no significant morphological differences between myelinated nerve fibers

  14. Heritability of Nociception IV: Neuropathic pain assays are genetically distinct across methods of peripheral nerve injury

    PubMed Central

    Young, Erin E.; Costigan, Michael; Herbert, Teri A.; Lariviere, William R.

    2013-01-01

    Prior genetic correlation analysis of 22 heritable behavioral measures of nociception and hypersensitivity in the mouse identified five genetically distinct pain types. In the present study, we reanalyzed that dataset and included the results of an additional nine assays of nociception and hypersensitivity to: 1) replicate the previously identified five pain types; 2) test whether any of the newly added pain assays represent novel genetically distinct pain types; 3) test the level of genetic relatedness among nine commonly employed neuropathic pain assays. Multivariate analysis of pairwise correlations between assays shows that the newly added zymosan-induced heat hypersensitivity assay does not conform to the two previously identified groups of heat hypersensitivity assays and cyclophosphamide-induced cystitis, the first organ-specific visceral pain model examined, is genetically distinct from other inflammatory assays. The four included mechanical hypersensitivity assays are genetically distinct, and do not comprise a single pain type as previously reported. Among the nine neuropathic pain assays including autotomy, chemotherapy, nerve ligation and spared nerve injury assays, at least four genetically distinct types of neuropathic sensory abnormalities were identified, corresponding to differences in nerve injury method. In addition, two itch assays and Comt genotype were compared to the expanded set of nociception and hypersensitivity assays. Comt genotype was strongly related only to spontaneous inflammatory nociception assays. These results indicate the priority for continued investigation of genetic mechanisms in several assays newly identified to represent genetically distinct pain types. PMID:24071598

  15. Heritability of nociception IV: neuropathic pain assays are genetically distinct across methods of peripheral nerve injury.

    PubMed

    Young, Erin E; Costigan, Michael; Herbert, Teri A; Lariviere, William R

    2014-05-01

    Prior genetic correlation analysis of 22 heritable behavioral measures of nociception and hypersensitivity in the mouse identified 5 genetically distinct pain types. In the present study, we reanalyzed that dataset and included the results of an additional 9 assays of nociception and hypersensitivity, with the following goals: to replicate the previously identified 5 pain types; to test whether any of the newly added pain assays represent novel genetically distinct pain types; and to test the level of genetic relatedness among 9 commonly used neuropathic pain assays. Multivariate analysis of pairwise correlations between assays shows that the newly added zymosan-induced heat hypersensitivity assay does not conform to the 2 previously identified groups of heat hypersensitivity assays and cyclophosphamide-induced cystitis, the first organ-specific visceral pain model examined, is genetically distinct from other inflammatory assays. The 4 included mechanical hypersensitivity assays are genetically distinct and do not comprise a single pain type as previously reported. Among the 9 neuropathic pain assays including autotomy, chemotherapy, nerve ligation and spared nerve injury assays, at least 4 genetically distinct types of neuropathic sensory abnormalities were identified, corresponding to differences in nerve injury method. In addition, 2 itch assays and Comt genotype were compared to the expanded set of nociception and hypersensitivity assays. Comt genotype was strongly related only to spontaneous inflammatory nociception assays. These results indicate the priority for continued investigation of genetic mechanisms in several assays newly identified to represent genetically distinct pain types.

  16. Reconstruction of posterior interosseous nerve injury following biceps tendon repair: case report and cadaveric study.

    PubMed

    Mokhtee, David B; Brown, Justin M; Mackinnon, Susan E; Tung, Thomas H

    2009-06-01

    Surgical repair of distal biceps tendon rupture is a technically challenging procedure that has the potential for devastating and permanently disabling complications. We report two cases of posterior interosseous nerve (PIN) injury following successful biceps tendon repair utilizing both the single-incision and two-incision approaches. We also describe our technique of posterior interosseous nerve repair using a medial antebrachial cutaneous nerve graft (MABC) and a new approach to the terminal branches of the posterior interosseous nerve that makes this reconstruction possible. Finally, we advocate consideration for identification of the posterior interosseous nerve prior to reattachment of the biceps tendon to the radial tuberosity.

  17. Autotomy following nerve injury: genetic factors in the development of chronic pain.

    PubMed

    Inbal, R; Devor, M; Tuchendler, O; Lieblich, I

    1980-12-01

    Several weeks following transection and ligation of the hind limb nerves in rats, the animals often attack their anaesthetic foot ("autotomy"). This behaviour is thought to reflect a sensory pathology analogous to anaesthesia dolorosa. We report here that the extent of autotomy varies greatly in genetically different populations of rats. Rats of one population, LC2, showed high autotomy levels; rats of another, LC1, showed very low autotomy levels. The main genetic difference between these two populations is the presence of inbred Lewis rat stock in the LC1 population. Pure Lewis strain rats proved to have very low autotomy levels. Thus, constitutional differences between different rat populations effect the extent of autotomy. These data may bear on the fact that after seemingly identical nerve injuries, some humans develop chronic pain syndromes and others do not. Our rat strains may provide a model for investigating the physiological basis of constitutional susceptibility to chronic pain.

  18. Novel TRPM8 antagonist attenuates cold hypersensitivity after peripheral nerve injury in rats.

    PubMed

    Patel, Ryan; Gonçalves, Leonor; Newman, Robert; Jiang, Feng Li; Goldby, Anne; Reeve, Jennifer; Hendrick, Alan; Teall, Martin; Hannah, Duncan; Almond, Sarah; Brice, Nicola; Dickenson, Anthony H

    2014-04-01

    Abnormal cold sensitivity is a common feature of a range of neuropathies. In the murine somatosensory system, multiple aspects of cold sensitivity are dependent on TRPM8, both short term and in response to peripheral nerve injury. The specialized nature of cold-sensitive afferents and the restricted expression of TRPM8 render it an attractive target for the treatment of cold hypersensitivity. This current study examines the effect of a novel TRPM8 antagonist (M8-An) in naive and spinal nerve-ligated rats through behavioral and in vivo electrophysiological approaches. In vitro, M8-An inhibited icilin-evoked Ca(2+) currents in HEK293 cells stably expressing human TRPM8 with an IC(50) of 10.9 nM. In vivo, systemic M8-An transiently decreased core body temperature. Deep dorsal horn recordings were made in vivo from neurons innervating the hind paw. M8-An inhibited neuronal responses to innocuous and noxious cooling of the receptive field in spinal nerve-ligated rats but not in naive rats. No effect on neuronal responses to mechanical and heat stimulation was observed. In addition, M8-An also attenuated behavioral responses to cold but not mechanical stimulation after nerve ligation without affecting the uninjured contralateral response. The data presented here support a contribution of TRPM8 to the pathophysiology of cold hypersensitivity in this model and highlight the potential of the pharmacological block of TRPM8 in alleviating the associated symptoms.

  19. NERVE GROWTH FACTOR MAINTAINS POTASSIUM CONDUCTANCE AFTER NERVE INJURY IN ADULT CUTANEOUS AFFERENT DORSAL ROOT GANGLION NEURONS

    PubMed Central

    EVERILL, B.; KOCSIS, J. D.

    2008-01-01

    Whole-cell patch-clamp techniques were used to study the effects of nerve growth factor on voltage-dependent potassium conductance in normal and axotomized identified large cutaneous afferent dorsal root ganglion neurons (48–50 μm diameter) many of which probably give rise to myelinated Aβ fibers. K-currents were isolated by blocking Na- and Ca-currents with appropriate ion replacement and channel blockers. Separation of current components was achieved on the basis of response to variation in conditioning voltage. Cutaneous afferents were labeled by the retrograde marker hydroxy-stilbamide (FluoroGold) which was injected into the skin of the foot. The sciatic nerve was either ligated or crushed with fine forceps five to seven days later. Neurons were dissociated 14–17 days after injury. The cut ends of the sciatic nerves were positioned into polyethylene tubes, which were connected to mini-osmotic pumps filled with either nerve growth factor or sterile saline. Control neurons displayed a prominent sustained K-current and the transient potassium currents “A” and “D”. Nerve ligation, which blocks target reconnection resulted in near 50% reduction of total outward current; isolated sustained K-current and transient A-current were reduced by a comparable amount. Nerve crush, which allows regeneration to peripheral targets and exposure of the regenerating nerve to the distal nerve segment, resulted in a small reduction in sustained K-current but no reduction in transient A-current compared to controls. Levels of transient A-current and sustained K-current were maintained at control levels after nerve growth factor treatment. These results indicate that the large reduction in transient A-current, and in sustained K-current, observed in cutaneous afferent cell bodies after nerve ligation is prevented by application of nerve growth factor. PMID:11008179

  20. Role of neurotrophin in the taste system following gustatory nerve injury.

    PubMed

    Meng, Lingbin; Jiang, Xin; Ji, Rui

    2015-06-01

    Taste system is a perfect system to study degeneration and regeneration after nerve injury because the taste system is highly plastic and the regeneration is robust. Besides, degeneration and regeneration can be easily measured since taste buds arise in discrete locations, and nerves that innervate them can be accurately quantified. Neurotrophins are a family of proteins that regulate neural survival, function, and plasticity after nerve injury. Recent studies have shown that neurotrophins play an important role in the developmental and mature taste system, indicating neurtrophin might also regulate taste system following gustatory nerve injury. This review will summarize how taste system degenerates and regenerates after gustatory nerve cut and conclude potential roles of neurotrophin in regulating the process.

  1. Protective effect of intraoperative nerve monitoring against recurrent laryngeal nerve injury during re-exploration of the thyroid

    PubMed Central

    2013-01-01

    Background Previous thyroid or parathyroid surgery induces scarring or distorts anatomy, and increases the risk of recurrent laryngeal nerve (RLN) injury for a reoperation. The benefit of intraoperative nerve monitoring (IONM) for re-exploration (a second nerve exploration) and reoperation has not been established. Methods Two hundred and ten patients were given a thyroid or parathyroid reoperation at our hospital between 2001 and 2010. Using IONM, we re-explored 56 patients who had been operated on before June 2007. The injury rate in these patients was compared with that of the 15 patients re-explored without IONM between 2001 and 2006. Results Of the 70 nerves that were re-explored using IONM, only one was incidentally injured, significantly fewer than the three injured in the 15 nerves re-explored without using IONM (1.43% vs. 20%, P = 0.0164). Conclusions IONM helped prevent RLN damage when re-exploring nerves during thyroid and parathyroid surgery. We recommend the routine use of IONM in thyroid and parathyroid reoperations. PMID:23618223

  2. Association of Electroencephalography (EEG) Power Spectra with Corneal Nerve Fiber Injury in Retinoblastoma Patients.

    PubMed

    Liu, Jianliang; Sun, Juanjuan; Diao, Yumei; Deng, Aijun

    2016-09-04

    BACKGROUND In our clinical experience we discovered that EEG band power may be correlated with corneal nerve injury in retinoblastoma patients. This study aimed to investigate biomarkers obtained from electroencephalography (EEG) recordings to reflect corneal nerve injury in retinoblastoma patients. MATERIAL AND METHODS Our study included 20 retinoblastoma patients treated at the Department of Ophthalmology, Affiliated Hospital of Weifang Medical University between 2010 and 2014. Twenty normal individuals were included in the control group. EEG activity was recorded continuously with 32 electrodes using standard EEG electrode placement for detecting EEG power. A cornea confocal microscope was used to examine corneal nerve injury in retinoblastoma patients and normal individuals. Spearman rank correlation analysis was used to analyze the correlation between corneal nerve injury and EEG power changes. The sensitivity and specificity of changed EEG power in diagnosis of corneal nerve injury were also analyzed. RESULTS The predominantly slow EEG oscillations changed gradually into faster waves in retinoblastoma patients. The EEG pattern in retinoblastoma patients was characterized by a distinct increase of delta (P<0.01) and significant decrease of theta power P<0.05). Corneal nerves were damaged in corneas of retinoblastoma patients. Corneal nerve injury was positively correlated with delta EEG spectra power and negatively correlated with theta EEG spectra power. The diagnostic sensitivity and specificity by compounding in the series were 60% and 67%, respectively. CONCLUSIONS Changes in delta and theta of EEG appear to be associated with occurrence of corneal nerve injury. Useful information can be provided for evaluating corneal nerve damage in retinoblastoma patients through analyzing EEG power bands.

  3. Chapter 23: Manual stimulation of target muscles has different impact on functional recovery after injury of pure motor or mixed nerves.

    PubMed

    Sinis, Nektarios; Manoli, Thodora; Werdin, Frank; Kraus, Armin; Schaller, Hans E; Guntinas-Lichius, Orlando; Grosheva, Maria; Irintchev, Andrey; Skouras, Emanouil; Dunlop, Sarah; Angelov, Doychin N

    2009-01-01

    Direct coaptation and interpositional nerve grafting (IPNG) of an injured peripheral nerve is still associated with poor functional recovery. Main reasons for that are thought to be an extensive collateral axonal branching at the site of transection and the polyinnervation of motor endplates due to terminal axonal and intramuscular sprouting. Moreover, severe changes occurring within the muscle after long-term denervation, like loss of muscle bulk and circulation as well as progressive fibrosis, have a negative effect on the quality of functional recovery after reinnervation. We have recently shown that manual stimulation (MS) of paralyzed vibrissal muscles in rat promotes full recovery after facial nerve coaptation. Furthermore, MS improved functional recovery after hypoglossal nerve repair, hypoglossal-facial IPNG of the facial nerve in rat. In contrary, MS did not improve recovery after injury of the median nerve in rat, which is however a mixed peripheral nerve comparing to the facial nerve. It is speculated that manually stimulated recovery of motor function requires an intact sensory input, which is affected in case of mixed peripheral nerves but not in case of pure motor nerves. In this article, we summarize our results of MS in several peripheral nerve injury models in order to illustrate the application potential of this method and to give insights into further investigations on that field.

  4. Intra-articular peroneal nerve incarceration following multi-ligament knee injury.

    PubMed

    Alhoukail, Amro; Panu, Anukul; Olson, Jaret; Jomha, Nadr M

    2015-10-01

    Knee dislocation with a common peroneal nerve injury is a serious problem. A case of multi-ligamentous knee injury with the unusual and interesting finding of a common peroneal nerve rupture incarcerated within the knee joint is presented. MRI and arthroscopic images are used to document this occurrence. To date, there are no published reports of a similar finding in the English orthopaedic literature. Level of evidence IV.

  5. A single trial of transcutaneous electrical nerve stimulation reduces chronic neuropathic pain following median nerve injury in rats.

    PubMed

    Cho, Hwi-Young; Suh, Hye Rim; Han, Hee Chul

    2014-01-01

    Neuropathic pain is a devastating chronic condition and is often induced in the upper limb following nerve injury or damage. Various drugs or surgical methods have been used to manage neuropathic pain; however, these are frequently accompanied by undesirable side effects. Transcutaneous electrical nerve stimulation (TENS) is a safe and non-invasive intervention that has been used to alleviate different types of pain in the clinic, but it is unclear whether TENS can improve chronic neuropathic pain in the upper limb. Thus, the aim of this study was to investigate the effects of a single trial of TENS on chronic neuropathic pain following median nerve injury. Male rats weighing 200-250 g received median nerve-ligation of the right forearm, while the control group received only skin-incision without nerve-ligation. Neuropathic pain-behaviors, including mechanical, cold, and thermal allodynia, were measured for 4 weeks. After the development of chronic neuropathic pain, TENS (100 Hz, 200 µs, sub-motor threshold) or placebo-TENS (sham stimulation) was applied for 20 min to the ipsilateral or contralateral side. Neuropathic pain behavior was assessed before and after intervention. Median nerve-ligation significantly induced and maintained neuropathic pain in the ipsilateral side. TENS application to the ipsilateral side effectively attenuated the three forms of chronic neuropathic pain in the ipsilateral side compared to sham-treated rats (peripheral and central effects), while TENS application to contralateral side only reduced mechanical allodynia in the ipsilateral side (central effect). Our findings demonstrate that TENS can alleviate chronic neuropathic pain following median nerve injury.

  6. Treatment of Combined Injuries of the Axillary and Suprascapular Nerves with Scapulothoracic Dissociation.

    PubMed

    Sano, Kazufumi; Ozeki, Satoru

    2015-12-01

    A 20-year-old man suffered the combined axillary and suprascapular nerve palsies associated with scapulothoracic dissociation by motorcycle accident. The dislocated shoulder girdle was reduced and stabilized with osteosynthesis of the fractured clavicle and reattachment of the trapezius avulsed from the scapular spine for removal of continuous traction force to these damaged nerves. Because of no evidence of recovery on manual muscle test and electromyogram, exploration for these nerves was administered 6 weeks after injury. Although neurolysis of both nerves revealed neural continuity, excessive tension still existed on the suprascapular nerve. It was thought that previous operation in which the shoulder girdle had been reduced and stabilized as much as possible could not achieve complete anatomical reduction of the scapula. As an additional treatment, medial walls of the suprascapular and spinoglenoid notches were shaven to relax the suprascapular nerve. After a year, complete recovery of both the axillary and suprascapular nerve was identified. Although scapulothoracic dissociation is commonly recognized as massive injury of the shoulder girdle with poor prognosis because of existence of accompanied severe neurovascular injuries, there are more than a few cases in which partial damage on the infraclavicular brachial plexus is only accompanied. In case of them, there is the possibility of lesions in continuity of the nerves in which good prognosis might be expected with surgical intervention including early reduction of the shoulder girdle for removal of excessive tension to the damaged nerve.

  7. Results of nerve grafting in radial nerve injuries occurring proximal to the humerus, including those within the posterior cord.

    PubMed

    Bertelli, Jayme Augusto; Ghizoni, Marcos Flávio

    2016-01-01

    OBJECT Results of radial nerve grafting are largely unknown for lesions of the radial nerve that occur proximal to the humerus, including those within the posterior cord. METHODS The authors describe 13 patients with proximal radial nerve injuries who were surgically treated and then followed for at least 24 months. The patients' average age was 26 years and the average time between accident and surgery was 6 months. Sural nerve graft length averaged 12 cm. Recovery was scored according to the British Medical Research Council (BMRC) scale, which ranges from M0 to M5 (normal muscle strength). RESULTS After grafting, all 7 patients with an elbow extension palsy recovered elbow extension, scoring M4. Six of the 13 recovered M4 wrist extension, 6 had M3, and 1 had M2. Thumb and finger extension was scored M4 in 3 patients, M3 in 2, M2 in 2, and M0 in 6. CONCLUSIONS The authors consider levels of strength of M4 for elbow and wrist extension and M3 for thumb and finger extension to be good results. Based on these criteria, overall good results were obtained in only 5 of the 13 patients. In proximal radial nerve lesions, the authors now advocate combining nerve grafts with nerve or tendon transfers to reconstruct wrist, thumb, and finger extension.

  8. Nerve Regeneration in the Peripheral Nervous System versus the Central Nervous System and the Relevance to Speech and Hearing after Nerve Injuries

    ERIC Educational Resources Information Center

    Gordon, Tessa; Gordon, Karen

    2010-01-01

    Schwann cells normally form myelin sheaths around axons in the peripheral nervous system (PNS) and support nerve regeneration after nerve injury. In contrast, nerve regeneration in the central nervous system (CNS) is not supported by the myelinating cells known as oligodendrocytes. We have found that: 1) low frequency electrical stimulation can be…

  9. Acceleration of Regeneration of Large-Gap Peripheral Nerve Injuries Using Accellular Nerve Allografts Plus Amniotic Fluid Derived Stem Cells (AFS)

    DTIC Science & Technology

    2015-09-01

    Nerve Allografts plus amniotic Fluid Derived Stem Cells (AFS). PRINCIPAL INVESTIGATOR: Li, Zhongyu CONTRACTING ORGANIZATION: Wake Forest...Gap Peripheral Nerve Injuries Using 5a. CONTRACT NUMBER Acellular Nerve Allografts plus amniotic Fluid Derived Stem Cells (AFS). 5b. GRANT NUMBER...Major accomplishments this year include successful seeding of AFS into ANA. This accomplishment also documented that these cells remained viable up

  10. Lingual nerve injury after third molar removal: Unilateral atrophy of fungiform papillae

    PubMed Central

    de-Pablo-Garcia-Cuenca, Alba; Bescós-Atín, Maria S.

    2014-01-01

    Background: Pain and sensory changes due to lingual nerve injury are one of the most common alterations that follow surgical removal of third molar. They are usually transient but other less common complications, such as the atrophy of fungiform papillae, have an uncertain prognosis. Case Description: We report a case of a 34-year-old woman who presented a unilateral lingual atrophy of fungiform papillae after third molar extraction accompanied by severe dysesthesia that altered her daily life significantly during the following months and how this complication evolved over time. We conducted a literature review on the different factors that can lead to a lingual nerve injury. Clinical Implications: The clinical evolution of temporary and permanent somatosensitve injuries is an important fact to take into consideration during the postoperative management because it will indicate the lesion prognosis. Key words:Lingual nerve, third molar removal, somatosensitive alteration, papillae atrophy, permanent injury, temporary injury. PMID:24790723

  11. A Novel Cytokine Pathway Suppresses Glial Cell Melanogenesis after Injury to Adult Nerve

    PubMed Central

    Rizvi, Tilat A.; Huang, Yuan; Sidani, Amer; Atit, Radhika; Largaespada, David A.; Boissy, Raymond E.; Ratner, Nancy

    2006-01-01

    The neural crest gives rise to numerous cell types, including Schwann cells, neurons, and melanocytes. The extent to which adult neural crest-derived cells retain plasticity has not been tested previously. We report that cutting adult mouse sciatic nerve induces pigmentation around nerve fascicles, among muscle bundles, and in the hypodermis. Pigmented cells are derived from adult nerve, because pigmentation occurs even when nerve fragments are grafted into tyrosinase null albino mice. Pigmentation defects are pervasive in patients with neurofibromatosis type 1 (NF1). Mice hemizygous for Nf1 mutations show enhanced pigmentation after nerve lesion and occasionally form pigmented and unpigmented tumors. The Nf1 nerve and the Nf1 host environment both contribute to enhanced pigmentation. Grafted purified Nf1 mutant glial cells [S100+–p75NGFR+–GFAP+–EGFR+ or S100+–p75NGFR+–GFAP+–EGFR−] mimic nerve-derived pigmentation. The NF1 protein, neurofibromin, is a Ras-GAP that acts downstream of a few defined receptor tyrosine kinases, including [β-common (βc)] the shared common receptor for granulocyte and monocyte colony-stimulating factor, interleukin-3 (IL3), and IL5. Cytokines in the environment have the potential to suppress pigmentation as shown by nerve injury experiments in null mice; when is βc absent or Nf1 is mutant, melanogenesis is increased. Thus, the adult nerve glial cell phenotype is maintained after nerve injury by response to cytokines, through neurofibromin. PMID:12427839

  12. Inferior Alveolar Nerve Injury after Mandibular Third Molar Extraction: a Literature Review

    PubMed Central

    Juodzbalys, Gintaras

    2014-01-01

    ABSTRACT Objectives The purpose of this study was to systematically review the comprehensive overview of literature data about injury to the inferior alveolar nerve after lower third molar extraction to discover the prevalence of injury, the risk factors, recovery rates, and alternative methods of treatment. Material and Methods Literature was selected through a search of PubMed electronic databases. Articles from January 2009 to June 2014 were searched. English language articles with a minimum of 6 months patient follow-up and injury analysis by patient’s reporting, radiographic, and neurosensory testing were selected. Results In total, 84 literature sources were reviewed, and 14 of the most relevant articles that are suitable to the criteria were selected. Articles were analyzed on men and women. The influence of lower third molar extraction (especially impacted) on the inferior alveolar nerve was clearly seen. Conclusions The incidence of injury to the inferior alveolar nerve after lower third molar extraction was about 0.35 - 8.4%. The injury of the inferior alveolar nerve can be predicted by various radiological signs. There are few risk factors that may increase the risk of injury to the nerve such as patients over the age of 24 years old, with horizontal impactions, and extraction by trainee surgeons. Recovery is preferable and permanent injury is very rare. PMID:25635208

  13. Reciprocal regulation of nuclear factor kappa B and its inhibitor ZAS3 after peripheral nerve injury

    PubMed Central

    Wu, Lai-Chu; Goettl, Virginia M; Madiai, Francesca; Hackshaw, Kevin V; Hussain, Syed-Rehan A

    2006-01-01

    Background NF-κB binds to the κB motif to regulate transcription of genes involved in growth, immunity and inflammation, and plays a pivotal role in the production of pro-inflammatory cytokines after nerve injuries. The zinc finger protein ZAS3 also binds to the κB or similar motif. In addition to competition for common DNA sites, in vitro experiments have shown that ZAS3 can inhibit NF-κB via the association with TRAF2 to inhibit the nuclear translocation of NF-κB. However, the physiological significance of the ZAS3-mediated inhibition of NF-κB has not been demonstrated. The purpose of this study is to characterize ZAS3 proteins in nervous tissues and to use spinal nerve ligation, a neuropathic pain model, to demonstrate a functional relationship between ZAS3 and NF-κB. Results Immunohistochemical experiments show that ZAS3 is expressed in specific regions of the central and peripheral nervous system. Abundant ZAS3 expression is found in the trigeminal ganglion, hippocampal formation, dorsal root ganglia, and motoneurons. Low levels of ZAS3 expressions are also found in the cerebral cortex and in the grey matter of the spinal cord. In those nervous tissues, ZAS3 is expressed mainly in the cell bodies of neurons and astrocytes. Together with results of Western blot analyses, the data suggest that ZAS3 protein isoforms with differential cellular distribution are produced in a cell-specific manner. Further, neuropathic pain confirmed by persistent mechanical allodynia was manifested in rats seven days after L5 and L6 lumbar spinal nerve ligation. Changes in gene expression, including a decrease in ZAS3 and an increase in the p65 subunit of NF-κB were observed in dorsal root ganglion ipsilateral to the ligation when compared to the contralateral side. Conclusion ZAS3 is expressed in nervous tissues involved in cognitive function and pain modulation. The down-regulation of ZAS3 after peripheral nerve injury may lead to activation of NF-κB, allowing Wallerian

  14. Connexin 43 contributes to ectopic orofacial pain following inferior alveolar nerve injury

    PubMed Central

    Shinoda, Masamichi; Honda, Kuniya; Unno, Syumpei; Shimizu, Noriyoshi; Iwata, Koichi

    2016-01-01

    Background Clinically, it is well known that injury of mandibular nerve fiber induces persistent ectopic pain which can spread to a wide area of the orofacial region innervated by the uninjured trigeminal nerve branches. However, the exact mechanism of such persistent ectopic orofacial pain is not still known. The present study was undertaken to determine the role of connexin 43 in the trigeminal ganglion on mechanical hypersensitivity in rat whisker pad skin induced by inferior alveolar nerve injury. Here, we examined changes in orofacial mechanical sensitivity following inferior alveolar nerve injury. Furthermore, changes in connexin 43 expression in the trigeminal ganglion and its localization in the trigeminal ganglion were also examined. In addition, we investigated the functional significance of connexin 43 in relation to mechanical allodynia by using a selective gap junction blocker (Gap27). Results Long-lasting mechanical allodynia in the whisker pad skin and the upper eyelid skin, and activation of satellite glial cells in the trigeminal ganglion, were induced after inferior alveolar nerve injury. Connexin 43 was expressed in the activated satellite glial cells encircling trigeminal ganglion neurons innervating the whisker pad skin, and the connexin 43 protein expression was significantly increased after inferior alveolar nerve injury. Administration of Gap27 in the trigeminal ganglion significantly reduced satellite glial cell activation and mechanical hypersensitivity in the whisker pad skin. Moreover, the marked activation of satellite glial cells encircling trigeminal ganglion neurons innervating the whisker pad skin following inferior alveolar nerve injury implies that the satellite glial cell activation exerts a major influence on the excitability of nociceptive trigeminal ganglion neurons. Conclusions These findings indicate that the propagation of satellite glial cell activation throughout the trigeminal ganglion via gap junctions, which are

  15. A Romanian therapeutic approach to peripheral nerve injury.

    PubMed

    Zegrea, I; Chivu, Laura Ioana; Albu, Mădălina Georgiana; Zamfirescu, D; Chivu, R D; Ion, Daniela Adriana; Lascăr, I

    2012-01-01

    The study of nerve regeneration and functional recovery of the injured peripheral nerves represents a worldwide subject of clinical and scientific research. Our team aimed to obtain the first guide for nerve regeneration, bioartificial and biodegradable, using exclusively Romanian resources and having the advantages of price and quality, over the imported nerve conduits already used in clinical practice. First steps of this project consisted in obtaining the prototype of nerve guide conduit and its' testing in vitro and in vivo. Tests of physicochemical characterization, FTIR (Fourier Transform Infrared) spectrometry, thermal analysis (differential calorimetry, thermo-gravimetry), electron microscopy, water absorption and enzymatic degradation of the obtained prototype were followed by in vivo testing. The first results, obtained on a group of Brown Norway rats who suffered experimental lesions of 1 cm at the level of left sciatic nerve, which have then been repaired using the Romanian conduit prototype, are favorable in terms of biocompatibility, biodegradable capacity and support of nerve regeneration.

  16. Possible role of alpha-lipoic acid in the treatment of peripheral nerve injuries

    PubMed Central

    2010-01-01

    Recent findings on the antioxidant effects of pretreatment with α-lipoic acid (α-LA) on the crush injury of rat sciatic nerve confirm the possible usefulness of α-LA administration in humans with peripheral nerve injuries. We discussed this issue in relation with our recent results in which the combined employment of α-LA and γ-linolenic acid with a rehabilitation program for six weeks reduced sensory symptoms and neuropathic pain in patients with compressive radiculopathy syndrome from disc-nerve root conflict in comparison with patients submitted to rehabilitation program alone for six weeks. PMID:20807428

  17. Experimental study on the effect of electrostimulation on neural regeneration after oculomotor nerve injury.

    PubMed

    Zhu, Ningxi; Zhang, Chunmei; Li, Zhen; Meng, Youqiang; Feng, Baohui; Wang, Xuhui; Yang, Min; Wan, Liang; Ning, Bo; Li, Shiting

    2014-12-01

    The oculomotor nerve can regenerate anatomically and histologically after injury; however, the degree of functional recovery of extraocular muscles and the pupil sphincter muscle was not satisfactory. Electrostimulation was one potential intervention that was increasingly being studied for use in nerve injury settings. However, the effect of electrostimulation on regeneration of the injured oculomotor nerve was still obscure. In this study, we studied the effects of electrostimulation on neural regeneration in terms of neurofunction, myoelectrophysiology, neuroanatomy, and neurohistology after oculomotor nerve injury and found that electrostimulation on the injured oculomotor nerve enhanced the speed and final level of its functional and electrophysiological recovery, promoted neural regeneration, and enhanced the selectivity and specificity of reinnervation of the regenerated neuron, the conformity among the electrophysiological and functional recovery of extraocular muscles, and neural regeneration, and that the function of extraocular muscles recovered slower than electrophysiology. Thus, we speculated that electrostimulation on the injured oculomotor nerve produced a marked effect on all phases of neural regeneration including neuronal survival, sprout formation, axonal elongation, target reconnection, and synaptogenesis. We think that neural electrostimulation can be used in oculomotor nerve injury.

  18. Mrpl10 and Tbp Are Suitable Reference Genes for Peripheral Nerve Crush Injury

    PubMed Central

    Wang, Yaxian; Shan, Qianqian; Meng, Yali; Pan, Jiacheng; Yi, Sheng

    2017-01-01

    Peripheral nerve injury triggers the dysregulation of a large number of genes at multiple sites, including neurons, peripheral nerve stump, and the target organ. Housekeeping genes were frequently used as reference genes to normalize the expression values of target genes. Suitable selection of housekeeping genes that are stably expressed after nerve injury minimizes bias elicited by reference genes and thus helps to better and more sensitively reflect gene expression changes. However, many housekeeping genes have been used as reference genes without testing the expression patterns of themselves. In the current study, we calculated the expression stability of nine commonly used housekeeping genes, such as 18S (18S ribosomal RNA), Actb (β-actin), CypA (cyclophilin A), Gapdh (glyceraldehydes-3-phosphate dehydrogenase), Hprt (hypoxanthine guanine phosphoribosyl transferase), Pgk1 (phosphoglycerate kinase 1), Tbp (TATA box binding protein), Ubc (ubiquitin C), YwhaZ (tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation), and four newly identified housekeeping genes, including Ankrd27 (Ankyrin repeat domain 27), Mrpl10 (mitochondrial ribosomal protein L10), Rictor (rapamycin-insensitive companion of mTOR, Complex 2), and Ubxn 11 (UBX domain protein 11), in both distal sciatic nerve samples and dorsal root ganglion (DRG) samples after sciatic nerve injury. Our results suggested that following peripheral nerve injury, Mrpl10 and Tbp might be used as suitable reference genes for sciatic nerve stump and DRGs, respectively. PMID:28134789

  19. Soluble complement receptor 1 protects the peripheral nerve from early axon loss after injury.

    PubMed

    Ramaglia, Valeria; Wolterman, Ruud; de Kok, Maryla; Vigar, Miriam Ann; Wagenaar-Bos, Ineke; King, Rosalind Helen Mary; Morgan, Brian Paul; Baas, Frank

    2008-04-01

    Complement activation is a crucial early event in Wallerian degeneration. In this study we show that treatment of rats with soluble complement receptor 1 (sCR1), an inhibitor of all complement pathways, blocked both systemic and local complement activation after crush injury of the sciatic nerve. Deposition of membrane attack complex (MAC) in the nerve was inhibited, the nerve was protected from axonal and myelin breakdown at 3 days after injury, and macrophage infiltration and activation was strongly reduced. We show that both classical and alternative complement pathways are activated after acute nerve trauma. Inhibition of the classical pathway by C1 inhibitor (Cetor) diminished, but did not completely block, MAC deposition in the injured nerve, blocked myelin breakdown, inhibited macrophage infiltration, and prevented macrophage activation at 3 days after injury. However, in contrast to sCR1 treatment, early signs of axonal degradation were visible in the nerve, linking MAC deposition to axonal damage. We conclude that sCR1 protects the nerve from early axon loss after injury and propose complement inhibition as a potential therapy for the treatment of diseases in which axon loss is the main cause of disabilities.

  20. Profiling of the dynamically alteredgene expression in peripheral nerve injury using NGS RNA sequencing technique

    PubMed Central

    Han, Duanyang; Chen, Yixun; Kou, Yuhui; Weng, Jian; Chen, Bo; Yu, Youlai; Zhang, Peixun; Jiang, Baoguo

    2016-01-01

    Functional recovery of peripheral nerve injuries is of major demand in clinical practice worldwide. Although, to some extent, peripheral nervous system can spontaneously regenerate, post-injury recovery is often associated with poor functional outcome. The molecular mechanism controlling the peripheral nerve repair process is still majorly unclear. In this study, by utilizing the Next Generation Sequencing (NGS) RNA sequencing technique, we aim to profile the gene expression spectrum of the peripheral nerve repair. In total, we detected 2847 were differentially expressed at day 7 post crush nerve injury. The GO, Panther, IPA and GSEA analysis was performed to decipher the biological processes involving the differentially expressed genes. Collectively, our results highlighted the inflammatory response and related signaling pathway (NFkB and TNFa signaling) play key role in peripheral nerve repair regulation. Furthermore, Network analysis illustrated that the IL10, IL18, IFN-γ and PDCD1 were four key regulators with multiple participations in peripheral nerve repair and potentially exert influence to the repair process. The expression changes of IL10, IL18, IFN-γ, PDCD1 and TNFSF14 (LIGHT) were further validated by western blot analysis. Hopefully, the present study may provide useful platform to further reveal the molecular mechanism of peripheral nerve repair and discover promising treatment target to enhance peripheral nerve regeneration. PMID:27158375

  1. The superior laryngeal nerve injury of a famous soprano, Amelita Galli-Curci.

    PubMed

    Marchese-Ragona, R; Restivo, D A; Mylonakis, I; Ottaviano, G; Martini, A; Sataloff, R T; Staffieri, A

    2013-02-01

    The superior laryngeal nerve (SLN) has been attributed much less clinical significance than the recurrent laryngeal nerve. It has sometimes been described as the 'neglected' nerve in thyroid surgery, although injury to this nerve can cause significant disability. The external branch of the SLN is the only motor supply to the cricothyroid muscle, which increases the tension of the ipsilateral vocal fold during highfrequency phonation, particularly in women and voice professionals. Damage to this nerve can manifest as ipsilateral cricothyroid muscle paralysis, and clinical symptoms may include a hoarse, breathy voice, frequent throat clearing, vocal fatigue or diminished vocal frequency range, especially when rising pitch. SLN paralysis can be a significant issue for those whose careers depend largely on a full range of voice. The famous opera soprano, Amelita Galli-Curci, suffered SLN injury during thyroid surgery with distressing consequences.

  2. In vitro models for peripheral nerve regeneration.

    PubMed

    Geuna, S; Raimondo, S; Fregnan, F; Haastert-Talini, K; Grothe, C

    2016-02-01

    The study of peripheral nerve repair and regeneration is particularly relevant in the light of the high clinical incidence of nerve lesions. However, the clinical outcome after nerve lesions is often far from satisfactory and the functional recovery is almost never complete. Therefore, a number of therapeutic approaches are being investigated, ranging from local delivery of trophic factors and other molecules to bioactive biomaterials and complex nerve prostheses. Translation of the new therapeutic approaches to the patient always requires a final pre-clinical step using in vivo animal models. The need to limit as much as possible animal use in biomedical research, however, makes the preliminary use of in vitro models mandatory from an ethical point of view. In this article, the different types of in vitro models available today for the study of peripheral nerve regeneration have been ranked by adopting a three-step stair model based on their increasing ethical impact: (i) cell line-based models, which raise no ethical concern; (ii) primary cell-based models, which have low ethical impact as animal use, although necessary, is limited; and (iii) organotypic ex vivo-based models, which raise moderate ethical concerns as the use of laboratory animals is required although with much lower impact on animal wellbeing in comparison to in vivo models of peripheral nerve regeneration. This article aims to help researchers in selecting the best experimental approach for their scientific goals driven by the 'Three Rs' (3Rs) rules (Replacement, Reduction or Refinement of animal use in research) for scientific research.

  3. Whole limb kinematics are preferentially conserved over individual joint kinematics after peripheral nerve injury.

    PubMed

    Chang, Young-Hui; Auyang, Arick G; Scholz, John P; Nichols, T Richard

    2009-11-01

    Biomechanics and neurophysiology studies suggest whole limb function to be an important locomotor control parameter. Inverted pendulum and mass-spring models greatly reduce the complexity of the legs and predict the dynamics of locomotion, but do not address how numerous limb elements are coordinated to achieve such simple behavior. As a first step, we hypothesized whole limb kinematics were of primary importance and would be preferentially conserved over individual joint kinematics after neuromuscular injury. We used a well-established peripheral nerve injury model of cat ankle extensor muscles to generate two experimental injury groups with a predictable time course of temporary paralysis followed by complete muscle self-reinnervation. Mean trajectories of individual joint kinematics were altered as a result of deficits after injury. By contrast, mean trajectories of limb orientation and limb length remained largely invariant across all animals, even with paralyzed ankle extensor muscles, suggesting changes in mean joint angles were coordinated as part of a long-term compensation strategy to minimize change in whole limb kinematics. Furthermore, at each measurement stage (pre-injury, paralytic and self-reinnervated) step-by-step variance of individual joint kinematics was always significantly greater than that of limb orientation. Our results suggest joint angle combinations are coordinated and selected to stabilize whole limb kinematics against short-term natural step-by-step deviations as well as long-term, pathological deviations created by injury. This may represent a fundamental compensation principle allowing animals to adapt to changing conditions with minimal effect on overall locomotor function.

  4. Polylactic-co-glycolic acid microspheres containing three neurotrophic factors promote sciatic nerve repair after injury.

    PubMed

    Zhao, Qun; Li, Zhi-Yue; Zhang, Ze-Peng; Mo, Zhou-Yun; Chen, Shi-Jie; Xiang, Si-Yu; Zhang, Qing-Shan; Xue, Min

    2015-09-01

    A variety of neurotrophic factors have been shown to repair the damaged peripheral nerve. However, in clinical practice, nerve growth factor, neurotrophin-3 and brain-derived neurotrophic factor are all peptides or proteins that may be rapidly deactivated at the focal injury site; their local effective concentration time following a single medication cannot meet the required time for spinal axons to regenerate and cross the glial scar. In this study, we produced polymer sustained-release microspheres based on the polylactic-co-glycolic acid copolymer; the microspheres at 300-μm diameter contained nerve growth factor, neurotrophin-3 and brain-derived neurotrophic factor. Six microspheres were longitudinally implanted into the sciatic nerve at the anastomosis site, serving as the experimental group; while the sciatic nerve in the control group was subjected to the end-to-end anastomosis using 10/0 suture thread. At 6 weeks after implantation, the lower limb activity, weight of triceps surae muscle, sciatic nerve conduction velocity and the maximum amplitude were obviously better in the experimental group than in the control group. Compared with the control group, more regenerating nerve fibers were observed and distributed in a dense and ordered manner with thicker myelin sheaths in the experimental group. More angiogenesis was also visible. Experimental findings indicate that polylactic-co-glycolic acid composite microspheres containing nerve growth factor, neurotrophin-3 and brain-derived neurotrophic factor can promote the restoration of sciatic nerve in rats after injury.

  5. Polylactic-co-glycolic acid microspheres containing three neurotrophic factors promote sciatic nerve repair after injury

    PubMed Central

    Zhao, Qun; Li, Zhi-yue; Zhang, Ze-peng; Mo, Zhou-yun; Chen, Shi-jie; Xiang, Si-yu; Zhang, Qing-shan; Xue, Min

    2015-01-01

    A variety of neurotrophic factors have been shown to repair the damaged peripheral nerve. However, in clinical practice, nerve growth factor, neurotrophin-3 and brain-derived neurotrophic factor are all peptides or proteins that may be rapidly deactivated at the focal injury site; their local effective concentration time following a single medication cannot meet the required time for spinal axons to regenerate and cross the glial scar. In this study, we produced polymer sustained-release microspheres based on the polylactic-co-glycolic acid copolymer; the microspheres at 300-μm diameter contained nerve growth factor, neurotrophin-3 and brain-derived neurotrophic factor. Six microspheres were longitudinally implanted into the sciatic nerve at the anastomosis site, serving as the experimental group; while the sciatic nerve in the control group was subjected to the end-to-end anastomosis using 10/0 suture thread. At 6 weeks after implantation, the lower limb activity, weight of triceps surae muscle, sciatic nerve conduction velocity and the maximum amplitude were obviously better in the experimental group than in the control group. Compared with the control group, more regenerating nerve fibers were observed and distributed in a dense and ordered manner with thicker myelin sheaths in the experimental group. More angiogenesis was also visible. Experimental findings indicate that polylactic-co-glycolic acid composite microspheres containing nerve growth factor, neurotrophin-3 and brain-derived neurotrophic factor can promote the restoration of sciatic nerve in rats after injury. PMID:26604912

  6. Mesenchymal stem cells in a polycaprolactone conduit promote sciatic nerve regeneration and sensory neuron survival after nerve injury.

    PubMed

    Frattini, Flávia; Lopes, Fatima Rosalina Pereira; Almeida, Fernanda Martins; Rodrigues, Rafaela Fintelman; Boldrini, Leonardo Cunha; Tomaz, Marcelo A; Baptista, Abrahão Fontes; Melo, Paulo A; Martinez, Ana Maria Blanco

    2012-10-01

    Despite the fact that the peripheral nervous system is able to regenerate after traumatic injury, the functional outcomes following damage are limited and poor. Bone marrow mesenchymal stem cells (MSCs) are multipotent cells that have been used in studies of peripheral nerve regeneration and have yielded promising results. The aim of this study was to evaluate sciatic nerve regeneration and neuronal survival in mice after nerve transection followed by MSC treatment into a polycaprolactone (PCL) nerve guide. The left sciatic nerve of C57BL/6 mice was transected and the nerve stumps were placed into a biodegradable PCL tube leaving a 3-mm gap between them; the tube was filled with MSCs obtained from GFP+ animals (MSC-treated group) or with a culture medium (Dulbecco's modified Eagle's medium group). Motor function was analyzed according to the sciatic functional index (SFI). After 6 weeks, animals were euthanized, and the regenerated sciatic nerve, the dorsal root ganglion (DRG), the spinal cord, and the gastrocnemius muscle were collected and processed for light and electron microscopy. A quantitative analysis of regenerated nerves showed a significant increase in the number of myelinated fibers in the group that received, within the nerve guide, stem cells. The number of neurons in the DRG was significantly higher in the MSC-treated group, while there was no difference in the number of motor neurons in the spinal cord. We also found higher values of trophic factors expression in MSC-treated groups, especially a nerve growth factor. The SFI revealed a significant improvement in the MSC-treated group. The gastrocnemius muscle showed an increase in weight and in the levels of creatine phosphokinase enzyme, suggesting an improvement of reinnervation and activity in animals that received MSCs. Immunohistochemistry documented that some GFP+ -transplanted cells assumed a Schwann-cell-like phenotype, as evidenced by their expression of the S-100 protein, a Schwann cell

  7. Sciatic nerve injury caused by a stretching exercise in a trained dancer.

    PubMed

    Shim, Ho Yong; Lim, Oh Kyung; Bae, Keun Hwan; Park, Seok Min; Lee, Ju Kang; Park, Ki Deok

    2013-12-01

    Sciatic nerve injury after stretching exercise is uncommon. We report a case of an 18-year-old female trained dancer who developed sciatic neuropathy primarily involving the tibial division after routine stretching exercise. The patient presented with dysesthesia and weakness of the right foot during dorsiflexion and plantarflexion. The mechanism of sciatic nerve injury could be thought as hyperstretching alone, not caused by both hyperstretching and compression. Electrodiagnostic tests and magnetic resonance imaging revealed evidence of the right sciatic neuropathy from the gluteal fold to the distal tibial area, and partial tear of the left hamstring origin and fluid collection between the left hamstring and ischium without left sciatic nerve injury. Recovery of motor weakness was obtained by continuous rehabilitation therapy and some evidence of axonal regeneration was obtained by follow-up electrodiagnostic testing performed at 3, 5, and 12 months after injury.

  8. Instability of spatial encoding by CA1 hippocampal place cells after peripheral nerve injury.

    PubMed

    Cardoso-Cruz, Helder; Lima, Deolinda; Galhardo, Vasco

    2011-06-01

    Several authors have shown that the hippocampus responds to painful stimulation and suggested that prolonged painful conditions could lead to abnormal hippocampal functioning. The aim of the present study was to evaluate whether the induction of persistent peripheral neuropathic pain would affect basic hippocampal processing such as the spatial encoding performed by CA1 place cells. These place cells fire preferentially in a certain spatial position in the environment, and this spatial mapping remains stable across multiple experimental sessions even when the animal is removed from the testing environment. To address the effect of prolonged pain on the stability of place cell encoding, we chronically implanted arrays of electrodes in the CA1 hippocampal region of adult rats and recorded the multichannel neuronal activity during a simple food-reinforced alternation task in a U-shaped runway. The activity of place cells was followed over a 3-week period before and after the establishment of an animal model of neuropathy, spared nerve injury. Our results show that the nerve injury increased the number of place fields encoded per cell and the mapping size of the place fields. In addition, there was an increase in in-field coherence while the amount of spatial information content that a single spike conveyed about the animal location decreased over time. Other measures of spatial tuning (in-field firing rate, firing peak and number of spikes) were unchanged between the experimental groups. These results demonstrate that the functioning of spatial place cells is altered during neuropathic pain conditions.

  9. Upregulation of EMMPRIN (OX47) in Rat Dorsal Root Ganglion Contributes to the Development of Mechanical Allodynia after Nerve Injury.

    PubMed

    Wang, Qun; Sun, Yanyuan; Ren, Yingna; Gao, Yandong; Tian, Li; Liu, Yang; Pu, Yanan; Gou, Xingchun; Chen, Yanke; Lu, Yan

    2015-01-01

    Matrix metalloproteinases (MMPs) are widely implicated in inflammation and tissue remodeling associated with various neurodegenerative diseases and play an important role in nociception and allodynia. Extracellular Matrix Metalloproteinase Inducer (EMMPRIN) plays a key regulatory role for MMP activities. However, the role of EMMPRIN in the development of neuropathic pain is not clear. Western blotting, real-time quantitative RT-PCR (qRT-PCR), and immunofluorescence were performed to determine the changes of messenger RNA and protein of EMMPRIN/OX47 and their cellular localization in the rat dorsal root ganglion (DRG) after nerve injury. Paw withdrawal threshold test was examined to evaluate the pain behavior in spinal nerve ligation (SNL) model. The lentivirus containing OX47 shRNA was injected into the DRG one day before SNL. The expression level of both mRNA and protein of OX47 was markedly upregulated in ipsilateral DRG after SNL. OX47 was mainly expressed in the extracellular matrix of DRG. Administration of shRNA targeted against OX47 in vivo remarkably attenuated mechanical allodynia induced by SNL. In conclusion, peripheral nerve injury induced upregulation of OX47 in the extracellular matrix of DRG. RNA interference against OX47 significantly suppressed the expression of OX47 mRNA and the development of mechanical allodynia. The altered expression of OX47 may contribute to the development of neuropathic pain after nerve injury.

  10. Mobile zinc increases rapidly in the retina after optic nerve injury and regulates ganglion cell survival and optic nerve regeneration.

    PubMed

    Li, Yiqing; Andereggen, Lukas; Yuki, Kenya; Omura, Kumiko; Yin, Yuqin; Gilbert, Hui-Ya; Erdogan, Burcu; Asdourian, Maria S; Shrock, Christine; de Lima, Silmara; Apfel, Ulf-Peter; Zhuo, Yehong; Hershfinkel, Michal; Lippard, Stephen J; Rosenberg, Paul A; Benowitz, Larry

    2017-01-10

    Retinal ganglion cells (RGCs), the projection neurons of the eye, cannot regenerate their axons once the optic nerve has been injured and soon begin to die. Whereas RGC death and regenerative failure are widely viewed as being cell-autonomous or influenced by various types of glia, we report here that the dysregulation of mobile zinc (Zn(2+)) in retinal interneurons is a primary factor. Within an hour after the optic nerve is injured, Zn(2+) increases several-fold in retinal amacrine cell processes and continues to rise over the first day, then transfers slowly to RGCs via vesicular release. Zn(2+) accumulation in amacrine cell processes involves the Zn(2+) transporter protein ZnT-3, and deletion of slc30a3, the gene encoding ZnT-3, promotes RGC survival and axon regeneration. Intravitreal injection of Zn(2+) chelators enables many RGCs to survive for months after nerve injury and regenerate axons, and enhances the prosurvival and regenerative effects of deleting the gene for phosphatase and tensin homolog (pten). Importantly, the therapeutic window for Zn(2+) chelation extends for several days after nerve injury. These results show that retinal Zn(2+) dysregulation is a major factor limiting the survival and regenerative capacity of injured RGCs, and point to Zn(2+) chelation as a strategy to promote long-term RGC protection and enhance axon regeneration.

  11. Rehabilitation, Using Guided Cerebral Plasticity, of a Brachial Plexus Injury Treated with Intercostal and Phrenic Nerve Transfers

    PubMed Central

    Dahlin, Lars B.; Andersson, Gert; Backman, Clas; Svensson, Hampus; Björkman, Anders

    2017-01-01

    Recovery after surgical reconstruction of a brachial plexus injury using nerve grafting and nerve transfer procedures is a function of peripheral nerve regeneration and cerebral reorganization. A 15-year-old boy, with traumatic avulsion of nerve roots C5–C7 and a non-rupture of C8–T1, was operated 3 weeks after the injury with nerve transfers: (a) terminal part of the accessory nerve to the suprascapular nerve, (b) the second and third intercostal nerves to the axillary nerve, and (c) the fourth to sixth intercostal nerves to the musculocutaneous nerve. A second operation—free contralateral gracilis muscle transfer directly innervated by the phrenic nerve—was done after 2 years due to insufficient recovery of the biceps muscle function. One year later, electromyography showed activation of the biceps muscle essentially with coughing through the intercostal nerves, and of the transferred gracilis muscle by deep breathing through the phrenic nerve. Voluntary flexion of the elbow elicited clear activity in the biceps/gracilis muscles with decreasing activity in intercostal muscles distal to the transferred intercostal nerves (i.e., corresponding to eighth intercostal), indicating cerebral plasticity, where neural control of elbow flexion is gradually separated from control of breathing. To restore voluntary elbow function after nerve transfers, the rehabilitation of patients operated with intercostal nerve transfers should concentrate on transferring coughing function, while patients with phrenic nerve transfers should focus on transferring deep breathing function. PMID:28316590

  12. Time-course of Changes in Activation Among Facial Nerve Injury

    PubMed Central

    Xiao, Fu-Long; Gao, Pei-Yi; Sui, Bin-Bin; Wan, Hong; Lin, Yan; Xue, Jing; Zhou, Jian; Qian, Tian-Yi; Wang, Shiwei; Li, Dezhi; Liu, Song

    2015-01-01

    Abstract Patients suffering different intervals of facial nerve injury were investigated by functional magnetic resonance imaging to study changes in activation within cortex. Forty-five patients were divided into 3 groups based on intervals of facial nerve injury. Another 16 age and sex-matched healthy participants were included as a control group. Patients and healthy participants underwent task functional magnetic resonance imaging (eye blinking and lip pursing) examination. Functional reorganization after facial nerve injury is dynamic and time-dependent. Correlation between activation in sensorimotor area and intervals of facial nerve injury was significant, with a Pearson correlation coefficient of −0.951 (P < 0.001) in the left sensorimotor area and a Pearson correlation coefficient of 0.333 (P = 0.025) in the right sensorimotor area. Increased activation in integration areas, such as supramarginal gyrus and precunes lobe, could be detected in the early-middle stage of facial dysfunction compared with normal individuals. Decreased activation in sensorimotor area contralateral to facial nerve injury could be found in late stage of facial dysfunction compared with normal individuals. Dysfunction in the facial nerve has devastating effects on the activity of sensorimotor areas, whereas enhanced intensity in the sensorimotor area ipsilateral to the facial nerve injury in middle stage of facial dysfunction suggests the possible involvement of interhemispheric reorganization. Behavioral or brain stimulation technique treatment in this stage could be applied to alter reorganization within sensorimotor area in the rehabilitation of facial function, monitoring of therapeutic efficacy, and improvement in therapeutic intervention along the course of recovery. PMID:26512554

  13. Traumatic Neuroma in Continuity Injury Model in Rodents

    PubMed Central

    Kemp, Stephen William Peter; Khu, Kathleen Joy Ong Lopez; Kumar, Ranjan; Webb, Aubrey A.; Midha, Rajiv

    2012-01-01

    Abstract Traumatic neuroma in continuity (NIC) results in profound neurological deficits, and its management poses the most challenging problem to peripheral nerve surgeons today. The absence of a clinically relevant experimental model continues to handicap our ability to investigate ways of better diagnosis and treatment for these disabling injuries. Various injury techniques were tested on Lewis rat sciatic nerves. Optimal experimental injuries that consistently resulted in NIC combined both intense focal compression and traction forces. Nerves were harvested at 0, 5, 13, 21, and 65 days for histological examination. Skilled locomotion and ground reaction force (GRF) analysis were performed up to 9 weeks on the experimental (n=6) and crush-control injuries (n=5). Focal widening, disruption of endoneurium and perineurium with aberrant intra- and extrafascicular axonal regeneration and progressive fibrosis was consistently demonstrated in 14 of 14 nerves with refined experimental injuries. At 8 weeks, experimental animals displayed a significantly greater slip ratio in both skilled locomotor assessments, compared to nerve crush animals (p<0.01). GRFs of the crush- injured animals showed earlier improvement compared to the experimental animals, whose overall GRF patterns failed to recover as well as the crush group. We have demonstrated histological features and poor functional recovery consistent with NIC formation in a rat model. The injury mechanism employed combines traction and compression forces akin to the physical forces at play in clinical nerve injuries. This model may serve as a tool to help diagnose this injury earlier and to develop intervention strategies to improve patient outcomes. PMID:22011082

  14. Treatment of transected peripheral nerves with artemin improved motor neuron regeneration, but did not reduce nerve injury-induced pain behaviour.

    PubMed

    Widenfalk, Johan; Wu, Weiping; Hao, Jingxia; Person, Jonas K E; Wiesenfeldt-Hallin, Zsuzsanna; Risling, Mårten

    2009-01-01

    Incomplete recovery of function and neuropathic pain are common problems after peripheral nerve injury. To develop new treatment strategies for peripheral nerve injuries we investigated whether the neurotrophic factor artemin could improve outcome after sciatic nerve injuries in rats. Artemin is a member of the glial cell line-derived neurotrophic factor (GDNF) family and exerts neuroprotective effects on sensory neurons as well as influencing behavioural thermal sensitivity. We additionally evaluated if fibrin sealant, which is sometimes used as a nerve glue, had any effects on neuropathic pain-related behaviour. After the sciatic nerve had been transected, 30 animals were randomised to one of three groups: treatment with a fibrin sealant that contained artemin in conjunction with sutures; fibrin sealant with no artemin (sham) in conjunction with sutures; or sutures alone (n=10 in each group). Motor function, sensory function, and autotomy were evaluated from 1 to 12 weeks after injury. Retrograde flourogold tracing 12 weeks after injury showed that the addition of artemin increased the number of regenerating motor neurons. However, it did not improve their performance, as measured by the Sciatic Function Index, compared with sham or suture alone. Animals treated with artemin had a non-significant increase in motor nerve conduction velocity compared with sham. However, artemin did not reverse nerve injury-induced pain behaviour such as cold or heat hypersensitivity. Fibrin sealant in itself did not ameliorate motor performance, or regeneration of motor neurons, or give rise to nerve injury-induced pain behaviour. The results indicate that artemin is of value as a treatment for peripheral nerve injuries, although the effects were limited. As the artemin high-affinity receptor GFRalpha-3 is present in Schwann cells and not in motor neurons, the effect on motor neuron axon regeneration may result from an indirect effect through Schwann cells in the injured nerve.

  15. Inferior Alveolar Nerve Injuries Following Implant Placement - Importance of Early Diagnosis and Treatment: a Systematic Review

    PubMed Central

    Juodzbalys, Gintaras

    2014-01-01

    ABSTRACT Objectives The purpose of this article is to systematically review diagnostic procedures and risk factors associated with inferior alveolar nerve injury following implant placement, to identify the time interval between inferior alveolar nerve injury and its diagnosis after surgical dental implant placement and compare between outcomes of early and delayed diagnosis and treatment given based on case series recorded throughout a period of 10 years. Material and Methods We performed literature investigation through MEDLINE (PubMed) electronic database and manual search through dental journals to find articles concerning inferior alveolar nerve injury following implant placement. The search was restricted to English language articles published during the last 10 years, from December 2004 to March 2014. Results In total, we found 33 articles related to the topic, of which 27 were excluded due to incompatibility with established inclusion criteria. Six articles were eventually chosen to be suitable. The studies presented diagnostic methods of inferior alveolar nerve sensory deficit, and we carried out an assessment of the proportion of patients diagnosed within different time intervals from the time the injury occurred. Conclusions Various diagnostic methods have been developed throughout the years for dealing with 1 quite frequent complication in the implantology field - inferior alveolar nerve injury. Concurrently, the importance of early diagnosis and treatment was proved repeatedly. According to the results of the data analysis, a relatively high percentage of the practitioners successfully accomplished this target and achieved good treatment outcomes. PMID:25635209

  16. Localized and sustained delivery of erythropoietin from PLGA microspheres promotes functional recovery and nerve regeneration in peripheral nerve injury.

    PubMed

    Zhang, Wei; Gao, Yuan; Zhou, Yan; Liu, Jianheng; Zhang, Licheng; Long, Anhua; Zhang, Lihai; Tang, Peifu

    2015-01-01

    Erythropoietin (EPO) has been demonstrated to exert neuroprotective effects on peripheral nerve injury recovery. Though daily intraperitoneal injection of EPO during a long period of time was effective, it was a tedious procedure. In addition, only limited amount of EPO could reach the injury sites by general administration, and free EPO is easily degraded in vivo. In this study, we encapsulated EPO in poly(lactide-co-glycolide) (PLGA) microspheres. Both in vitro and in vivo release assays showed that the EPO-PLGA microspheres allowed sustained release of EPO within a period of two weeks. After administration of such EPO-PLGA microspheres, the peripheral nerve injured rats had significantly better recovery compared with those which received daily intraperitoneal injection of EPO, empty PLGA microspheres, or saline treatments. This was supported by the functional, electrophysiological, and histological evaluations of the recovery done at week 8 postoperatively. We conclude that sustained delivery of EPO could be achieved by using EPO-PLGA microspheres, and such delivery method could further enhance the recovery function of EPO in nerve injury recovery.

  17. More nerve root injuries occur with minimally invasive lumbar surgery: Let's tell someone

    PubMed Central

    Epstein, Nancy E.

    2016-01-01

    Background: In a recent study entitled: “More nerve root injuries occur with minimally invasive lumbar surgery, especially extreme lateral interbody fusion (XLIF): A review”, Epstein documented that more nerve root injuries occurred utilizing minimally invasive surgery (MIS) versus open lumbar surgery for diskectomy, decompression of stenosis (laminectomy), and/or fusion for instability. Methods: In large multicenter Spine Patient Outcomes Research Trial reviews performed by Desai et al., nerve root injury with open diskectomy occurred in 0.13–0.25% of cases, occurred in 0% of laminectomy/stenosis with/without fusion cases, and just 2% for open laminectomy/stenosis/degenerative spondylolisthesis with/without fusion. Results: In another MIS series performed largely for disc disease (often contained nonsurgical disc herniations, therefore unnecessary procedures) or spondylolisthesis, the risk of root injury was 2% for transforaminal lumbar interbody fusion (TLIF) versus 7.8% for posterior lumbar interbody fusion (PLIF). Furthermore, the high frequencies of radiculitis/nerve root/plexus injuries incurring during anterior lumbar interbody fusions (ALIF: 15.8%) versus extreme lumbar interbody fusions (XLIF: 23.8%), addressing disc disease, failed back surgery, and spondylolisthesis, were far from acceptable. Conclusions: The incidence of nerve root injuries following any of the multiple MIS lumbar surgical techniques (TLIF/PLIF/ALIF/XLIF) resulted in more nerve root injuries when compared with open conventional lumbar surgical techniques. Considering the majority of these procedures are unnecessarily being performed for degenerative disc disease alone, spine surgeons should be increasingly asked why they are offering these operations to their patients? PMID:26904373

  18. Avoiding injury to the inferior alveolar nerve by routine use of intraoperative radiographs during implant placement.

    PubMed

    Burstein, Jeffrey; Mastin, Chris; Le, Bach

    2008-01-01

    Injury to the inferior alveolar nerve during implant placement in the posterior atrophic mandible is a rare but serious complication. Although a preoperative computerized tomography scan can help determine the distance from the alveolar ridge to the nerve canal, variables such as magnification errors, ridge anatomy, and operator technique can increase the chance for complications. The routine use of intraoperative periapical radiographs during the drilling sequence is an inexpensive and reliable tool, allowing the operator to confidently adjust the direction and depth of the implant during placement. Most important, it helps avoid the risk of injury to the inferior alveolar nerve in cases in which there is limited vertical alveolar bone. Using this technique for 21 implants placed in the posterior atrophic mandible, with less than 10 mm of vertical bone to the inferior alveolar nerve canal, the authors observed no incidents of postoperative paresthesia.

  19. The pathogenesis of non-freezing cold nerve injury. Observations in the rat.

    PubMed

    Jia, J; Pollock, M

    1997-04-01

    Non-freezing cold nerve injury is uncommon in civilian practice, but may reach epidemic proportions in war zones. Studied since the time of Hippocrates, its aetiology has remained elusive. We sought to replicate experimentally, a peripheral nerve cold temperature gradient, since this has been emphasized in clinical descriptions. Our observations, in the rat, of the vasa nervorum show that cold-induced intravascular aggregation is followed by a 'no-reflow' phenomenon which culminates in endothelial damage and delayed thrombotic occlusion.

  20. Sciatic nerve injury repair: a visualized analysis of research fronts and development trends.

    PubMed

    Liu, Guangyao; Jiang, Rui; Jin, Yan

    2014-09-15

    A total of 3,446 publications regarding sciatic nerve injury repair and protection indexed by Web of Science during 2000-2004 were used for a detailed analysis of temporal-spatial distribution characteristics. Reference co-citation networks of the 100 top-cited publications as per the number of total citations were created using the Web of Science database and the information visualization tool, CiteSpaceIII. The key words that showed high frequency in these publications were included for analyzing the research fronts and development trends for sciatic nerve injury repair and protection. Through word frequency trend analysis, studies on bone marrow mesenchymal stem cells, adipose-derived stem cells, and skeletal muscle-derived multipotent stem cells combined with tissue-engineered scaffold material will become the forefronts in the field of sciatic nerve injury repair and protection in the near future.

  1. Optic Nerve Injury Secondary to Endoscopic Sinus Surgery: an Analysis of Three Cases

    PubMed Central

    Kim, Jin Young; Kim, Hyun Jun; Kim, Chang-Hoon; Lee, Jeung-Gweon

    2005-01-01

    Major orbital complications after the endoscopic sinus surgeries are rare and of these, optic nerve injury is one of the most serious. This study was to undertaken to analyze 3 cases of optic nerve injury after endoscopic sinus surgery. The three cases included one patient with a loss of visual acuity and visual field defect, and two patients with total blindness. In all cases, no improvement of visual acuity was observed despite treatment. It is important to frequently check the location and direction of the endoscope during surgery to avoid optic nerve injury. In addition, surgeons must have a precise knowledge of the detailed anatomy through cadaver dissections, an ability to interpret the PNS CT scan and experienced procedural surgical skills. PMID:15861507

  2. Cytidine 5′-diphosphocholine administration prevents peripheral neuropathic pain after sciatic nerve crush injury in rats

    PubMed Central

    Emril, Dessy R; Wibowo, Samekto; Meliala, Lucas; Susilowati, Rina

    2016-01-01

    Background Cytidine 5′-diphosphocholine (citicoline) has been shown to have beneficial effects in central nervous system injury as well as in motoric functional recovery after peripheral nerve injury. This study aimed to examine the effect of citicoline on prevention of neuropathic pain in a rat model of sciatic nerve crush injury. Methods Forty experimental rats were divided into four groups. In three groups, the right sciatic nerves were crushed in the mid-thigh region, and a gelatin sponge moistened with 0.4 or 0.8 mL of 100 µmol/L citicoline, or saline 0.4 mL in the control group, was applied. The fourth group of rats was sham-operated, ie the sciatic nerve was exposed with no crush. Functional assessments were performed 4 weeks after crush injury. von Frey filaments (100 g threshold) were used to assess neuropathic pain. In addition, the sciatic functional index and extensor postural thrust (EPT) tests were used to assess motoric function. Results The crush/citicoline 0.4 mL group had a lower percentage of pain (23.53%, n=17) compared with the crush/saline group (53.33%, n=15, P<0.005). The crush/citicoline 0.4 mL group also showed better motoric recovery, as seen in stronger EPT results (P<0.001). However, the sciatic functional index analysis did not show significant differences between groups (P=0.35). The crush/citicoline 0.8 mL group showed a higher percentage of pain (66.67%, n=18) and less EPT recovery. These results may be explained by more severe nerve injury due to compression with a larger administered volume. Conclusion In situ administration of 0.4 mL of 100 µmol/L citicoline prevents the occurrence of neuropathic pain and induces motoric recovery, evaluated by EPT test, 4 weeks after sciatic nerve injury. PMID:27284264

  3. Delayed Presentation of Sciatic Nerve Injury after Total Hip Arthroplasty: Neurosurgical Considerations, Diagnosis, and Management

    PubMed Central

    Xu, Linda W.; Veeravagu, Anand; Azad, Tej D.; Harraher, Ciara; Ratliff, John K.

    2016-01-01

    Background  Total hip arthroplasty (THA) is an established treatment for end-stage arthritis, congenital deformity, and trauma with good long-term clinical and functional outcomes. Delayed sciatic nerve injury is a rare complication after THA that requires prompt diagnosis and management. Methods  We present a case of sciatic nerve motor and sensory deficit in a 52-year-old patient 2 years after index left THA. Electromyography (EMG) results and imaging with radiographs and CT of the affected hip demonstrated an aberrant acetabular cup screw in the posterior-inferior quadrant adjacent to the sciatic nerve. Case Description  The patient underwent surgical exploration that revealed injury to the peroneal division of the sciatic nerve due to direct injury from screw impingement. A literature review identified 11 patients with late-onset neuropathy after THA. Ten patients underwent surgical exploration and pain often resolved after surgery with 56% of patients recovering sensory function and 25% experiencing full recovery of motor function. Conclusions  Delayed neuropathy of the sciatic nerve is a rare complication after THA that is most often due to hardware irritation, component failure, or wear-related pseudotumor formation. Operative intervention is often pursued to explore and directly visualize the nerve with limited results in the literature showing modest relief of pain and sensory symptoms and poor restoration of motor function. PMID:27602309

  4. A Review of Bioactive Release from Nerve Conduits as a Neurotherapeutic Strategy for Neuronal Growth in Peripheral Nerve Injury

    PubMed Central

    Choonara, Yahya E.; Bijukumar, Divya; du Toit, Lisa C.

    2014-01-01

    Peripheral nerve regeneration strategies employ the use of polymeric engineered nerve conduits encompassed with components of a delivery system. This allows for the controlled and sustained release of neurotrophic growth factors for the enhancement of the innate regenerative capacity of the injured nerves. This review article focuses on the delivery of neurotrophic factors (NTFs) and the importance of the parameters that control release kinetics in the delivery of optimal quantities of NTFs for improved therapeutic effect and prevention of dose dumping. Studies utilizing various controlled-release strategies, in attempt to obtain ideal release kinetics, have been reviewed in this paper. Release strategies discussed include affinity-based models, crosslinking techniques, and layer-by-layer technologies. Currently available synthetic hollow nerve conduits, an alternative to the nerve autografts, have proven to be successful in the bridging and regeneration of primarily the short transected nerve gaps in several patient cases. However, current research emphasizes on the development of more advanced nerve conduits able to simulate the effectiveness of the autograft which includes, in particular, the ability to deliver growth factors. PMID:25143934

  5. Inferior alveolar nerve injury following orthognathic surgery: a review of assessment issues

    PubMed Central

    PHILLIPS, C.; ESSICK, G.

    2011-01-01

    SUMMARY The sensory branches of the trigeminal nerve encode information about facial expressions, speaking and chewing movements, and stimuli that come into contact with the orofacial tissues. Whatever the cause, damage to the inferior alveolar nerve negatively affects the quality of facial sensibility as well as the patient's ability to translate patterns of altered nerve activity into functionally meaningful motor behaviours. There is no generally accepted, standard method of estimating sensory disturbances in the distribution of the inferior alveolar nerve following injury. Assessment of sensory alterations can be conducted using three types of measures: (i) objective electrophysiological measures of nerve conduction, (ii) sensory testing (stimulus) measures and (iii) patient report. Each type of measure with advantages and disadvantages for use are reviewed. PMID:21058973

  6. Early extraction: a silver bullet to avoid nerve injury in lower third molar removal?

    PubMed

    Zhang, Q-B; Zhang, Z-Q

    2012-10-01

    This retrospective study evaluated the effects of early extraction of immature lower third molar on preventing complications, particularly nerve injury following lower third molar removal. Patients were grouped according to age and radiographic results: group A (518 patients, ≤23 years, immature teeth with apical foramen not closed); group B (532 patients, >23 years, mature teeth with closed apical foramen). Group A included 230 males and 288 females (average age 17 years). In group A, 808 lower mandibular third molars were extracted bilaterally in 290 and unilaterally in 228 patients; the incidence of complications was 2.48% (20/808) (all were temporary), the incidence of nerve injury was 0%. Group B included 250 males and 282 females (average age 39 years). In group B, 810 lower third molars were extracted bilaterally in 278 and unilaterally in 254 patients; the incidence of complications was 10% (81/810), the incidence of nerve injury was 1.6% (13/810). All complications were temporary, except two removals of permanent inferior alveolar nerve numbness (>6 months). In this study, early removal of the lower third molar was effective in avoiding some postoperative complications, especially nerve injury. Early extraction of lower third molar in youngsters is recommended following a team consultation.

  7. Functional recovery guided by an electrospun silk fibroin conduit after sciatic nerve injury in rats.

    PubMed

    Park, Sook Young; Ki, Chang Seok; Park, Young Hwan; Lee, Kwang Gill; Kang, Seok Woo; Kweon, Hae Yong; Kim, Hyun Jeong

    2015-01-01

    The aim of this study was to evaluate the regenerative capacity of a newly developed nerve guidance conduit using electrospun silk fibroin (SFNC) implanted in a 10-mm defect of the sciatic nerve in rats. After evaluating the physical properties and cytocompatibility of SFNC in vitro, rats were randomly allocated into three groups: defect only, autograft and SFNC. To compare motor function and abnormal sensation among groups, ankle stance angle (ASA) and severity of autotomy were observed for 10 weeks after injury. Immunostaining with axonal neurofilament (NF) and myelin basic protein (MBP) antibodies were performed to investigate regenerated nerve fibres inside SFNC. ASA increased significantly in the SFNC group at 1, 7 and 10 weeks after injury compared to the defect only group (p<0.05). At one week, mean ASA of the SFNC group was significantly higher than that of the autograft group (p<0.05). Onset and severity of autotomy decreased significantly in the SFNC group compared to other groups (p<0.05). Autotomy in the SFNC group started at 4 weeks and maximally reached toe level. However, the defect only and autograft groups first showed autotomy at 2 and 1 weeks following injury, respectively, and then reached the sole level. Well myelinated nerve fibres stained with NF and MBP were found inside SFNC. In conclusion, SFNC could be helpful in restoring motor function and preventing abnormal sensations after nerve injury.

  8. Laparoscopic injury of the obturator nerve during fertility-sparing procedure for cervical cancer

    PubMed Central

    2012-01-01

    Background Intraoperative injury of the obturator nerve has rarely been reported in patients with gynecological malignancies undergoing extensive radical surgeries. Irreversible damage of this nerve causes thigh paresthesia and claudication. Intraoperative repair may be done by end-to-end anastomosis or grafting when achieving tension-free anastomosis is not possible. Case presentation A 28-year-old woman with stage IB cervical cancer underwent fertility–sparing surgery, including conization and bilateral pelvic lymphadenectomy. The left obturator nerve was damaged intraoperatively during pelvic dissection. Conclusion Immediate laparoscopic repair was successful and there was no functional deficit in the left thigh for six months postoperatively. PMID:22931409

  9. Impacts of Rho kinase inhibitor Fasudil on Rho/ROCK signaling pathway in rabbits with optic nerve injury

    PubMed Central

    Yu, Jianglong; Lin, Lin; Luan, Xinping; Jing, Xiepan; Maierab

    2015-01-01

    Objective: The aim of this study was to study the impacts of Rho kinase inhibitor Fasudil on expressions of Rho/ROCK signaling pathway associated genes in rabbits with optic nerve injury (ONI), and to explore the therapeutic mechanisms towards ONI. Methods: The rabbit ONI model was established, then the rabbits were divided into model group (treated with saline), control group (treated with dexamethasone, Dex), and intervention group (treated with Fasudil, Fas). The eyeball and optic nerve were sampled at 3, 7, 14 and 21 days after injury. The morphological changes of retina and optic nerve were observed. The expressions of RhoA, Caspase-3, Rock 2 and Nogo-A gene were determined by immunohistochemistry and real-time polymerase chain reaction (RT-PCR) methods. Results: At different time after injury, there were significant differences of RhoA, Caspase-3, Rock 2 and Nogo-A gene expression among three groups (P < 0.05). Conclusions: After ONI, Fas can decrease the expression of Caspase-3 gene, and down-regulate the expressions of Nogo-A and Rock 2 gene. Therefore, it can treat ONI through affecting the Rho/ROCK signaling pathway. PMID:26823796

  10. Vagus nerve stimulation mediates protection from kidney ischemia-reperfusion injury through α7nAChR+ splenocytes

    PubMed Central

    Inoue, Tsuyoshi; Abe, Chikara; Sung, Sun-sang J.; Moscalu, Stefan; Jankowski, Jakub; Huang, Liping; Ye, Hong; Guyenet, Patrice G.

    2016-01-01

    The nervous and immune systems interact in complex ways to maintain homeostasis and respond to stress or injury, and rapid nerve conduction can provide instantaneous input for modulating inflammation. The inflammatory reflex referred to as the cholinergic antiinflammatory pathway regulates innate and adaptive immunity, and modulation of this reflex by vagus nerve stimulation (VNS) is effective in various inflammatory disease models, such as rheumatoid arthritis and inflammatory bowel disease. Effectiveness of VNS in these models necessitates the integration of neural signals and α7 nicotinic acetylcholine receptors (α7nAChRs) on splenic macrophages. Here, we sought to determine whether electrical stimulation of the vagus nerve attenuates kidney ischemia-reperfusion injury (IRI), which promotes the release of proinflammatory molecules. Stimulation of vagal afferents or efferents in mice 24 hours before IRI markedly attenuated acute kidney injury (AKI) and decreased plasma TNF. Furthermore, this protection was abolished in animals in which splenectomy was performed 7 days before VNS and IRI. In mice lacking α7nAChR, prior VNS did not prevent IRI. Conversely, adoptive transfer of VNS-conditioned α7nAChR splenocytes conferred protection to recipient mice subjected to IRI. Together, these results demonstrate that VNS-mediated attenuation of AKI and systemic inflammation depends on α7nAChR-positive splenocytes. PMID:27088805

  11. Misdirection and guidance of regenerating axons after experimental nerve injury and repair.

    PubMed

    de Ruiter, Godard C W; Spinner, Robert J; Verhaagen, Joost; Malessy, Martijn J A

    2014-02-01

    Misdirection of regenerating axons is one of the factors that can explain the limited results often found after nerve injury and repair. In the repair of mixed nerves innervating different distal targets (skin and muscle), misdirection may, for example, lead to motor axons projecting toward skin, and vice versa-that is, sensory axons projecting toward muscle. In the repair of motor nerves innervating different distal targets, misdirection may result in reinnervation of the wrong target muscle, which might function antagonistically. In sensory nerve repair, misdirection might give an increased perceptual territory. After median nerve repair, for example, this might lead to a dysfunctional hand. Different factors may be involved in the misdirection of regenerating axons, and there may be various mechanisms that can later correct for misdirection. In this review the authors discuss these different factors and mechanisms that act along the pathway of the regenerating axon. The authors review recently developed evaluation methods that can be used to investigate the accuracy of regeneration after nerve injury and repair (including the use of transgenic fluorescent mice, retrograde tracing techniques, and motion analysis). In addition, the authors discuss new strategies that can improve in vivo guidance of regenerating axons (including physical guidance with multichannel nerve tubes and biological guidance accomplished using gene therapy).

  12. Recovery of nerve injury-induced alexia for Braille using forearm anaesthesia.

    PubMed

    Björkman, Anders; Rosén, Birgitta; Lundborg, Göran

    2008-04-16

    Nerve injuries in the upper extremity may severely affect hand function. Cutaneous forearm anaesthesia has been shown to improve hand sensation in nerve-injured patients. A blind man who lost his Braille reading capability after an axillary plexus injury was treated with temporary cutaneous forearm anaesthesia. After treatment sensory functions of the hand improved and the patient regained his Braille reading capability. The mechanism behind the improvement is likely unmasking of inhibited or silent neurons, but after repeated treatment sessions at increasing intervals the improvement has remained at 1-year follow-up, implying a structural change in the somatosensory cortex.

  13. Histone deacetylase inhibitors relieve morphine resistance in neuropathic pain after peripheral nerve injury.

    PubMed

    Uchida, Hitoshi; Matsushita, Yosuke; Araki, Kohei; Mukae, Takehiro; Ueda, Hiroshi

    2015-08-01

    Neuropathic pain is often insensitive to morphine. Our previous study has demonstrated that neuron-restrictive silencer factor represses mu opioid receptor (MOP) gene expression in the dorsal root ganglion (DRG) via histone hypoacetylation-mediated mechanisms after peripheral nerve injury, thereby causing loss of peripheral morphine analgesia. Here, we showed that histone deacetylase (HDAC) inhibitors, such as trichostatin A and valproic acid, restored peripheral and systemic morphine analgesia in neuropathic pain. Also, these agents blocked nerve injury-induced MOP down-regulation in the DRG. These results suggest that HDAC inhibitors could serve as adjuvant analgesics to morphine for the management of neuropathic pain.

  14. Role of macrophages in Wallerian degeneration and axonal regeneration after peripheral nerve injury.

    PubMed

    Chen, Peiwen; Piao, Xianhua; Bonaldo, Paolo

    2015-11-01

    The peripheral nervous system (PNS) has remarkable regenerative abilities after injury. Successful PNS regeneration relies on both injured axons and non-neuronal cells, including Schwann cells and immune cells. Macrophages are the most notable immune cells that play key roles in PNS injury and repair. Upon peripheral nerve injury, a large number of macrophages are accumulated at the injury sites, where they not only contribute to Wallerian degeneration, but also are educated by the local microenvironment and polarized to an anti-inflammatory phenotype (M2), thus contributing to axonal regeneration. Significant progress has been made in understanding how macrophages are educated and polarized in the injured microenvironment as well as how they contribute to axonal regeneration. Following the discussion on the main properties of macrophages and their phenotypes, in this review, we will summarize the current knowledge regarding the mechanisms of macrophage infiltration after PNS injury. Moreover, we will discuss the recent findings elucidating how macrophages are polarized to M2 phenotype in the injured PNS microenvironment, as well as the role and underlying mechanisms of macrophages in peripheral nerve injury, Wallerian degeneration and regeneration. Furthermore, we will highlight the potential application by targeting macrophages in treating peripheral nerve injury and peripheral neuropathies.

  15. Analgesic effect of sinomenine in rodents after inflammation and nerve injury.

    PubMed

    Gao, Tianle; Hao, Jingxia; Wiesenfeld-Hallin, Zsuzsanna; Wang, Dan-Qiao; Xu, Xiao-Jun

    2013-12-05

    Sinomenine is an alkaloid originally isolated from the root of the plant Sinomenium acutum. It is used in traditional medicine in China to treat rheumatic arthritis. In the present study, we evaluated the potential antinociceptive effects of sinomenine in rodents with nociceptive, inflammatory and neuropathic pain. In normal rats and mice, systemic sinomenine produced moderate antinociceptive effect in the hot plate and tail flick tests. Sinomenine also exerted analgesic effects on mechanical and heat hypersensitivity in mice after carrageenan induced inflammation. Finally, sinomenine effectively alleviated mechanical and cold allodynia in rats and mice after injury to peripheral nerve or spinal cord. The analgesic effect of sinomenine is not associated with side effects and is not reversed by the opioid receptor antagonist naloxone. Our results showed that sinomenine has a wide spectrum analgesic effect in rodent models of nociceptive, inflammatory and neuropathic pain.

  16. Bone marrow-derived cells in the population of spinal microglia after peripheral nerve injury

    PubMed Central

    Tashima, Ryoichi; Mikuriya, Satsuki; Tomiyama, Daisuke; Shiratori-Hayashi, Miho; Yamashita, Tomohiro; Kohro, Yuta; Tozaki-Saitoh, Hidetoshi; Inoue, Kazuhide; Tsuda, Makoto

    2016-01-01

    Accumulating evidence indicates that peripheral nerve injury (PNI) activates spinal microglia that are necessary for neuropathic pain. Recent studies using bone marrow (BM) chimeric mice have reported that after PNI, circulating BM-derived cells infiltrate into the spinal cord and differentiate into microglia-like cells. This raises the possibility that the population of spinal microglia after PNI may be heterogeneous. However, the infiltration of BM cells in the spinal cord remains controversial because of experimental adverse effects of strong irradiation used for generating BM chimeric mice. In this study, we evaluated the PNI-induced spinal infiltration of BM-derived cells not only by irradiation-induced myeloablation with various conditioning regimens, but also by parabiosis and mice with genetically labelled microglia, models without irradiation and BM transplantation. Results obtained from these independent approaches provide compelling evidence indicating little contribution of circulating BM-derived cells to the population of spinal microglia after PNI. PMID:27005516

  17. Downregulation of ClC-3 in dorsal root ganglia neurons contributes to mechanical hypersensitivity following peripheral nerve injury.

    PubMed

    Pang, Rui-Ping; Xie, Man-Xiu; Yang, Jie; Shen, Kai-Feng; Chen, Xi; Su, Ying-Xue; Yang, Chao; Tao, Jing; Liang, Si-Jia; Zhou, Jia-Guo; Zhu, He-Quan; Wei, Xu-Hong; Li, Yong-Yong; Qin, Zhi-Hai; Liu, Xian-Guo

    2016-11-01

    ClC-3 chloride channel/antiporter has been demonstrated to play an important role in synaptic transmission in central nervous system. However, its expression and function in sensory neurons is poorly understood. In present work, we found that ClC-3 is expressed at high levels in dorsal root ganglia (DRG). Co-immunofluorescent data showed that ClC-3 is mainly distributed in A- and C-type nociceptive neurons. ClC-3 expression in DRG is decreased in the spared nerve injury (SNI) model of neuropathic pain. Knockdown of local ClC-3 in DRG neurons with siRNA increased mechanical sensitivity in naïve rats, while overexpression of ClC-3 reversed the hypersensitivity to mechanical stimuli after peripheral nerve injury. In addition, genetic deletion of ClC-3 enhances mouse mechanical sensitivity but did not affect thermal and cold threshold. Restoration of ClC-3 expression in ClC-3 deficient mice reversed the mechanical sensitivity. Mechanistically, loss of ClC-3 enhanced mechanical sensitivity through increasing the excitability of DRG neurons. These data indicate that ClC-3 is an endogenous inhibitor of neuropathic pain development. Downregulation of ClC-3 by peripheral nerve injury is critical for mechanical hypersensitivity. Our findings suggest that ClC-3 is a novel therapeutic target for treating neuropathic pain.

  18. Permanent reorganization of Ia afferent synapses on motoneurons after peripheral nerve injuries

    PubMed Central

    Alvarez, Francisco J.; Bullinger, Katie L.; Titus, Haley E.; Nardelli, Paul; Cope, Timothy C.

    2010-01-01

    After peripheral nerve injuries to a motor nerve the axons of motoneurons and proprioceptors are disconnected from the periphery and monosynaptic connections from group I afferents and motoneurons become diminished in the spinal cord. Following successful reinnervation in the periphery, motor strength, proprioceptive sensory encoding, and Ia afferent synaptic transmission on motoneurons partially recover. Muscle stretch reflexes, however, never recover and motor behaviors remain uncoordinated. In this review, we summarize recent findings that suggest that lingering motor dysfunction might be in part related to decreased connectivity of Ia afferents centrally. First, sensory afferent synapses retract from lamina IX causing a permanent relocation of the inputs to more distal locations and significant disconnection from motoneurons. Second, peripheral reconnection between proprioceptive afferents and muscle spindles is imperfect. As a result, a proportion of sensory afferents that retain central connections with motoneurons might not reconnect appropriately in the periphery. A hypothetical model is proposed in which the combined effect of peripheral and central reconnection deficits might explain the failure of muscle stretch to initiate or modulate firing of many homonymous motoneurons. PMID:20536938

  19. Results of ulnar nerve neurotization to biceps brachii muscle in brachial plexus injury

    PubMed Central

    Rezende, Marcelo Rosa De; Rabelo, Neylor Teofilo Araújo; Silveira, Clóvis Castanho; Petersen, Pedro Araújo; Paula, Emygdio José Leomil De; Mattar, Rames

    2012-01-01

    OBJECTIVE: To evaluate the factors influencing the results of ulnar nerve neurotization at the motor branch of the brachii biceps muscle, aiming at the restoration of elbow flexion in patients with brachial plexus injury. METHODS: 19 patients, with 18 men and 1 woman, mean age 28.7 years. Eight patients had injury to roots C5-C6 and 11, to roots C5-C6-C7. The average time interval between injury and surgery was 7.5 months. Four patients had cervical fractures associated with brachial plexus injury. The postoperative follow-up was 15.7 months. RESULTS: Eight patients recovered elbow flexion strength MRC grade 4; two, MRC grade 3 and nine, MRC <3. There was no impairment of the previous ulnar nerve function. CONCLUSION: The surgical results of ulnar nerve neurotization at the motor branch of brachii biceps muscle are dependent on the interval between brachial plexus injury and surgical treatment, the presence of associated fractures of the cervical spine and occipital condyle, residual function of the C8-T1 roots after the injury and the involvement of the C7 root. Signs of reinnervation manifested up to 3 months after surgery showed better results in the long term. Level of Evidence: IV, Case Series. PMID:24453624

  20. Diffuse noxious inhibitory controls and nerve injury: restoring an imbalance between descending monoamine inhibitions and facilitations.

    PubMed

    Bannister, Kirsty; Patel, Ryan; Goncalves, Leonor; Townson, Louisa; Dickenson, Anthony H

    2015-09-01

    Diffuse noxious inhibitory controls (DNICs) utilize descending inhibitory controls through poorly understood brain stem pathways. The human counterpart, conditioned pain modulation, is reduced in patients with neuropathy aligned with animal data showing a loss of descending inhibitory noradrenaline controls together with a gain of 5-HT3 receptor-mediated facilitations after neuropathy. We investigated the pharmacological basis of DNIC and whether it can be restored after neuropathy. Deep dorsal horn neurons were activated by von Frey filaments applied to the hind paw, and DNIC was induced by a pinch applied to the ear in isoflurane-anaesthetized animals. Spinal nerve ligation was the model of neuropathy. Diffuse noxious inhibitory control was present in control rats but abolished after neuropathy. α2 adrenoceptor mechanisms underlie DNIC because the antagonists, yohimbine and atipamezole, markedly attenuated this descending inhibition. We restored DNIC in spinal nerve ligated animals by blocking 5-HT3 descending facilitations with the antagonist ondansetron or by enhancing norepinephrine modulation through the use of reboxetine (a norepinephrine reuptake inhibitor, NRI) or tapentadol (μ-opioid receptor agonist and NRI). Additionally, ondansetron enhanced DNIC in normal animals. Diffuse noxious inhibitory controls are reduced after peripheral nerve injury illustrating the central impact of neuropathy, leading to an imbalance in descending excitations and inhibitions. Underlying noradrenergic mechanisms explain the relationship between conditioned pain modulation and the use of tapentadol and duloxetine (a serotonin, NRI) in patients. We suggest that pharmacological strategies through manipulation of the monoamine system could be used to enhance DNIC in patients by blocking descending facilitations with ondansetron or enhancing norepinephrine inhibitions, so possibly reducing chronic pain.

  1. G9a participates in nerve injury-induced Kcna2 downregulation in primary sensory neurons

    PubMed Central

    Liang, Lingli; Gu, Xiyao; Zhao, Jian-Yuan; Wu, Shaogen; Miao, Xuerong; Xiao, Jifang; Mo, Kai; Zhang, Jun; Lutz, Brianna Marie; Bekker, Alex; Tao, Yuan-Xiang

    2016-01-01

    Nerve injury-induced downregulation of voltage-gated potassium channel subunit Kcna2 in the dorsal root ganglion (DRG) is critical for DRG neuronal excitability and neuropathic pain genesis. However, how nerve injury causes this downregulation is still elusive. Euchromatic histone-lysine N-methyltransferase 2, also known as G9a, methylates histone H3 on lysine residue 9 to predominantly produce a dynamic histone dimethylation, resulting in condensed chromatin and gene transcriptional repression. We showed here that blocking nerve injury-induced increase in G9a rescued Kcna2 mRNA and protein expression in the axotomized DRG and attenuated the development of nerve injury-induced pain hypersensitivity. Mimicking this increase decreased Kcna2 mRNA and protein expression, reduced Kv current, and increased excitability in the DRG neurons and led to spinal cord central sensitization and neuropathic pain-like symptoms. G9a mRNA is co-localized with Kcna2 mRNA in the DRG neurons. These findings indicate that G9a contributes to neuropathic pain development through epigenetic silencing of Kcna2 in the axotomized DRG. PMID:27874088

  2. Painful Nerve Injury Upregulates Thrombospondin-4 Expression in Dorsal Root Ganglia

    PubMed Central

    Pan, Bin; Yu, Hongwei; Park, John; Yu, Yanhui Peter; Luo, Z. David; Hogan, Quinn H.

    2014-01-01

    Thrombospondin-4 (TSP4) belongs to a family of large oligomeric, extracellular matrix glycoproteins that mediate interactions between cells and interactions of cells with underlying matrix components. Recent evidence shows that TSP4 may contribute to the generation of neuropathic pain. However, there is no systematic examination of TSP4 expression in the DRGs after injury. We therefore investigated whether TSP4 protein level is changed in DRGs after injury following spinal nerve ligation (SNL) and spared nerve injury (SNI) in rats using western blot, immunohistochemistry, and immunocytochemistry. After nerve ligation, TSP4 protein level is up-regulated in the axotomized somata of the L5 DRG. There is substantial additional TSP4 in the non-neuronal compartment of the L5 DRG that does not co-stain for markers of satellite glia, microglia, or Schwann cells and appears to be in the interstitial space. Evidence of intracellular overexpression of TSP4 persists in neurons dissociated from the L5 DRG after SNL. These findings indicate that following peripheral nerve injury, TSP4 protein expression is elevated in the cytoplasm of axotomized sensory neurons and in the surrounding interstitial space. PMID:25327416

  3. Hypoesthesia after IAN block anesthesia with lidocaine: management of mild to moderate nerve injury

    PubMed Central

    Moon, Sungjoo; Lee, Seung-Jong; Kim, Euiseong

    2012-01-01

    Hypoesthesia after an inferior alveolar nerve (IAN) block does not commonly occur, but some cases are reported. The causes of hypoesthesia include a needle injury or toxicity of local anesthetic agents, and the incidence itself can cause stress to both dentists and patients. This case presents a hypoesthesia on mental nerve area followed by IAN block anesthesia with 2% lidocaine. Prescription of steroids for a week was performed and periodic follow up was done. After 1 wk, the symptoms got much better and after 4 mon, hypoesthesia completely disappeared. During this healing period, only early steroid medication was prescribed. In most cases, hypoesthesia is resolved within 6 mon, but being aware of etiology and the treatment options of hypoesthesia is important. Because the hypoesthesia caused by IAN block anesthesia is a mild to moderate nerve injury, early detection of symptom and prescription of steroids could be helpful for improvement of the hypoesthesia. PMID:23430216

  4. Nerve injury enhances rat neuronal glutamate transporter expression: identification by differential display PCR.

    PubMed

    Kiryu, S; Yao, G L; Morita, N; Kato, H; Kiyama, H

    1995-12-01

    An increase in neuronal glutamate transporter expression after nerve injury was demonstrated by means of differential display PCR (DD-PCR) coupled with in situ hybridization. DD-PCR was carried out to compare differences in expression of mRNAs between axotomized and normal hypoglossal motoneurons in the rat. The expression of several gene fragments were found to be increased following nerve injury; the full length cDNA corresponding to one fragment was cloned by subsequent rat cDNA library screening. The close homology of glutamate transporters with our rat cDNA led us to conclude that this clone corresponds to the rat neuronal glutamate transporter (rat EAAC1). We speculate that the upregulation of this glutamate uptake system may increase the resistance of these cells against neurotoxic glutamate accumulation during the process of nerve regeneration.

  5. Evaluation of trigeminal nerve injuries in relation to third molar surgery in a prospective patient cohort. Recommendations for prevention.

    PubMed

    Renton, T; Yilmaz, Z; Gaballah, K

    2012-12-01

    Trigeminal nerve injury is the most problematic consequence of dental surgical procedures with major medico-legal implications. This study reports the signs and symptoms that are the features of trigeminal nerve injuries caused by mandibular third molar (M3M) surgery. 120 patients with nerve injury following M3M surgery were assessed. All data were analysed using the SPSS statistical programme and Microsoft Excel. 53 (44.2%) inferior alveolar nerve (IAN) injury cases and 67 (55.8%) lingual nerve injury (LNI) cases were caused by third molar surgery (TMS). Neuropathy was demonstrable in all patients with varying degrees of paraesthesia, dysaesthesia (in the form of burning pain), allodynia and hyperalgesia. Pain was one of the presenting signs and symptoms in 70% of all cases. Significantly more females had IAN injuries and LNIs (p<0.05). The mean ages of the two groups of patients were similar. Speech and eating were significantly more problematic for patients with LNIs. In conclusion, chronic pain is often a symptom after TMS-related nerve injury, resulting in significant functional problems. Better dissemination of good practice in TMS will significantly minimize these complex nerve injuries and prevent unnecessary suffering.

  6. Nerve Growth Factor Inhibits Sympathetic Neurons' Response to an Injury Cytokine

    NASA Astrophysics Data System (ADS)

    Shadiack, Annette M.; Vaccariello, Stacey A.; Sun, Yi; Zigmond, Richard E.

    1998-06-01

    Axonal damage to adult peripheral neurons causes changes in neuronal gene expression. For example, axotomized sympathetic, sensory, and motor neurons begin to express galanin mRNA and protein, and recent evidence suggests that galanin plays a role in peripheral nerve regeneration. Previous studies in sympathetic and sensory neurons have established that galanin expression is triggered by two consequences of nerve transection: the induction of leukemia inhibitory factor (LIF) and the reduction in the availability of the target-derived factor, nerve growth factor. It is shown in the present study that no stimulation of galanin expression occurs following direct application of LIF to intact neurons in the superior cervical sympathetic ganglion. Injection of animals with an antiserum to nerve growth factor concomitant with the application of LIF, on the other hand, does stimulate galanin expression. The data suggest that the response of neurons to an injury factor, LIF, is affected by whether the neurons still receive trophic signals from their targets.

  7. The response of spinal microglia to chemotherapy-evoked painful peripheral neuropathies is distinct from that evoked by traumatic nerve injuries

    PubMed Central

    Zheng, F. Y.; Xiao, W.-H.; Bennett, G. J.

    2011-01-01

    Painful peripheral neuropathies produced by nerve trauma are accompanied by substantial axonal degeneration and by a response in spinal cord microglia that is characterized by hypertrophy and increased expression of several intracellular and cell-surface markers, including ionizing calcium-binding adapter molecule 1 (Iba1) and Cd11b (a complement receptor 3 antigen recognized by the OX42 antibody). The microglia response has been hypothesized to be essential for the pathogenesis of the neuropathic pain state. In contrast, the painful peripheral neuropathies produced by low doses of cancer chemotherapeutics do not produce degeneration of axons in the peripheral nerve, although they do cause partial degeneration of the sensory axons’ distal-most tips, i.e. the intraepidermal nerve fibers that form the axons’ terminal receptor arbors. The question thus arises as to whether the relatively minor and distal axonal injury characterizing the chemotherapy-evoked neuropathies is sufficient to evoke the microglial response that is seen after traumatic nerve injury. We examined the lumbar spinal cord of rats with painful peripheral neuropathies due to the anti-neoplastic agents, paclitaxel, vincristine, and oxaliplatin, and the anti-retroviral agent, 2′,3′-dideoxycytidine (ddC), and compared them to rats with a complete sciatic nerve transection and the partial sciatic nerve injury produced in the chronic constriction injury model (CCI). As expected, microglia hypertrophy and increased expression of Iba1 were pronounced in the nerve transection and CCI animals. However, there was no microglia hypertrophy or increased Iba1 staining in the animals treated with paclitaxel, vincristine, oxaliplatin, or ddC. These results suggest that the mechanisms that produce neuropathic pain after exposure to chemotherapeutics may be fundamentally different than those operating after nerve trauma. PMID:21195745

  8. Injury signals cooperate with Nf1 loss to relieve the tumor-suppressive environment of adult peripheral nerve.

    PubMed

    Ribeiro, Sara; Napoli, Ilaria; White, Ian J; Parrinello, Simona; Flanagan, Adrienne M; Suter, Ueli; Parada, Luis F; Lloyd, Alison C

    2013-10-17

    Schwann cells are highly plastic cells that dedifferentiate to a progenitor-like state following injury. However, deregulation of this plasticity, may be involved in the formation of neurofibromas, mixed-cell tumors of Schwann cell (SC) origin that arise upon loss of NF1. Here, we show that adult myelinating SCs (mSCs) are refractory to Nf1 loss. However, in the context of injury, Nf1-deficient cells display opposing behaviors along the wounded nerve; distal to the injury, Nf1(-/-) mSCs redifferentiate normally, whereas at the wound site Nf1(-/-) mSCs give rise to neurofibromas in both Nf1(+/+) and Nf1(+/-) backgrounds. Tracing experiments showed that distinct cell types within the tumor derive from Nf1-deficient SCs. This model of neurofibroma formation demonstrates that neurofibromas can originate from adult SCs and that the nerve environment can switch from tumor suppressive to tumor promoting at a site of injury. These findings have implications for both the characterization and treatment of neurofibromas.

  9. Escalated regeneration in sciatic nerve crush injury by the combined therapy of human amniotic fluid mesenchymal stem cells and fermented soybean extracts, Natto

    PubMed Central

    Pan, Hung-Chuan; Yang, Dar-Yu; Ho, Shu-Peng; Sheu, Meei-Ling; Chen, Chung-Jung; Hwang, Shiaw-Min; Chang, Ming-Hong; Cheng, Fu-Chou

    2009-01-01

    Attenuation of inflammatory cell deposits and associated cytokines prevented the apoptosis of transplanted stem cells in a sciatic nerve crush injury model. Suppression of inflammatory cytokines by fermented soybean extracts (Natto) was also beneficial to nerve regeneration. In this study, the effect of Natto on transplanted human amniotic fluid mesenchymal stem cells (AFS) was evaluated. Peripheral nerve injury was induced in SD rats by crushing a sciatic nerve using a vessel clamp. Animals were categorized into four groups: Group I: no treatment; Group II: fed with Natto (16 mg/day for 7 consecutive days); Group III: AFS embedded in fibrin glue; Group IV: Combination of group II and III therapy. Transplanted AFS and Schwann cell apoptosis, inflammatory cell deposits and associated cytokines, motor function, and nerve regeneration were evaluated 7 or 28 days after injury. The deterioration of neurological function was attenuated by AFS, Natto, or the combined therapy. The combined therapy caused the most significantly beneficial effects. Administration of Natto suppressed the inflammatory responses and correlated with decreased AFS and Schwann cell apoptosis. The decreased AFS apoptosis was in line with neurological improvement such as expression of early regeneration marker of neurofilament and late markers of S-100 and decreased vacuole formation. Administration of either AFS, or Natto, or combined therapy augmented the nerve regeneration. In conclusion, administration of Natto may rescue the AFS and Schwann cells from apoptosis by suppressing the macrophage deposits, associated inflammatory cytokines, and fibrin deposits. PMID:19698158

  10. Anterior shoulder dislocation with axillary artery and nerve injury.

    PubMed

    Razif, M A Mohamed; Rajasingam, V

    2002-12-01

    We report a rare case of left axillary artery injury associated with anterior dislocation of the left shoulder in a 25 yrs old male as a result of a road traffic accident. The shoulder dislocation was reduced. A left upper limb angiogram showed an obstructed left axillary artery. The obstructed segment was surgically reconstructed with a Dacron graft. Six months post operation in follow up, he was found to have good left shoulder function and no neurovascular deficit. This is an injury that could have been easily missed without a simple clinical examination.

  11. Expression and regulation of redoxins at nociceptive signaling sites after sciatic nerve injury in mice

    PubMed Central

    Valek, Lucie; Kanngießer, Maike; Tegeder, Irmgard

    2015-01-01

    Injury of the sciatic nerve results in regulations of pro- and anti-oxidative enzymes at sites of nociceptive signaling including the injured nerve, dorsal root ganglia (DRGs), dorsal horn of the spinal cord, thalamus and somatosensory cortex (Valek et al., 2015) [1]. The present DiB paper shows immunohistochemistry of redoxins including peroxiredoxins (Prdx1–6), glutaredoxins (Glrx1, 2, 3, 5), thioredoxins (Txn1, 2) and thioredoxin reductases (Txnrd1, 2) in the DRGs, spinal cord and sciatic nerve and thalamus in naïve mice and 7 days after Spared sciatic Nerve Injury (SNI) in control mice (Hif1α-flfl) and in mice with a specific deletion of hypoxia inducible factor 1 alpha (SNS-HIF1α−/−) in DRG neurons. The sciatic nerves were immunostained for the respective redoxins and counterstained with hematoxylin. The redoxin immunoreactivity was quantified with ImageJ. For the DRGs and spinal cord the data show the quantitative assessment of the intensity of redoxin immunoreactivity transformed to rainbow pseudocolors. In addition, some redoxin examples of the ipsi and contralateral dorsal and ventral horns of the lumbar spinal cord and some redoxin examples of the thalamus are presented. PMID:26693520

  12. Long-term subjective and objective outcome after primary repair of traumatic facial nerve injuries.

    PubMed

    Frijters, Erik; Hofer, Stefan O P; Mureau, Marc A M

    2008-08-01

    Although traumatic facial nerve paralysis is a severe handicap, there are no follow-up studies evaluating outcome after primary repair of traumatic facial nerve injuries. From May 1988 to August 2005, 27 patients (mean age, 27 years) were operated for traumatic facial nerve lesions (mean number of affected branches, 2.2). End-to-end facial nerve repair was always performed. All patients were invited to our outpatient clinic for standardized questionnaires (Facial Disability Index, Short Form-36 Health Survey), physical examination (Sunnybrook Facial Grading System), and clinical photographs. Sixteen patients participated in the follow-up study (mean, 9.2 years). Mean Facial Disability Index Physical and Social scores were 86 and 81, respectively, indicating good subjective facial functioning. The mean Sunnybrook Facial Grading System score was 74 indicating adequate facial functioning. Mean physical and mental health scores (Short Form-36 Health Survey) were comparable with normative data. Primary end-to-end repair of traumatic facial nerve injuries results in good long-term objective and subjective functional and emotional outcome.

  13. Transplantation of Embryonic Spinal Cord Derived Cells Helps to Prevent Muscle Atrophy after Peripheral Nerve Injury

    PubMed Central

    Ruven, Carolin; Li, Wen; Li, Heng; Wong, Wai-Man; Wu, Wutian

    2017-01-01

    Injuries to peripheral nerves are frequent in serious traumas and spinal cord injuries. In addition to surgical approaches, other interventions, such as cell transplantation, should be considered to keep the muscles in good condition until the axons regenerate. In this study, E14.5 rat embryonic spinal cord fetal cells and cultured neural progenitor cells from different spinal cord segments were injected into transected musculocutaneous nerve of 200–300 g female Sprague Dawley (SD) rats, and atrophy in biceps brachii was assessed. Both kinds of cells were able to survive, extend their axons towards the muscle and form neuromuscular junctions that were functional in electromyographic studies. As a result, muscle endplates were preserved and atrophy was reduced. Furthermore, we observed that the fetal cells had a better effect in reducing the muscle atrophy compared to the pure neural progenitor cells, whereas lumbar cells were more beneficial compared to thoracic and cervical cells. In addition, fetal lumbar cells were used to supplement six weeks delayed surgical repair after the nerve transection. Cell transplantation helped to preserve the muscle endplates, which in turn lead to earlier functional recovery seen in behavioral test and electromyography. In conclusion, we were able to show that embryonic spinal cord derived cells, especially the lumbar fetal cells, are beneficial in the treatment of peripheral nerve injuries due to their ability to prevent the muscle atrophy. PMID:28264437

  14. Transplantation of Embryonic Spinal Cord Derived Cells Helps to Prevent Muscle Atrophy after Peripheral Nerve Injury.

    PubMed

    Ruven, Carolin; Li, Wen; Li, Heng; Wong, Wai-Man; Wu, Wutian

    2017-02-27

    Injuries to peripheral nerves are frequent in serious traumas and spinal cord injuries. In addition to surgical approaches, other interventions, such as cell transplantation, should be considered to keep the muscles in good condition until the axons regenerate. In this study, E14.5 rat embryonic spinal cord fetal cells and cultured neural progenitor cells from different spinal cord segments were injected into transected musculocutaneous nerve of 200-300 g female Sprague Dawley (SD) rats, and atrophy in biceps brachii was assessed. Both kinds of cells were able to survive, extend their axons towards the muscle and form neuromuscular junctions that were functional in electromyographic studies. As a result, muscle endplates were preserved and atrophy was reduced. Furthermore, we observed that the fetal cells had a better effect in reducing the muscle atrophy compared to the pure neural progenitor cells, whereas lumbar cells were more beneficial compared to thoracic and cervical cells. In addition, fetal lumbar cells were used to supplement six weeks delayed surgical repair after the nerve transection. Cell transplantation helped to preserve the muscle endplates, which in turn lead to earlier functional recovery seen in behavioral test and electromyography. In conclusion, we were able to show that embryonic spinal cord derived cells, especially the lumbar fetal cells, are beneficial in the treatment of peripheral nerve injuries due to their ability to prevent the muscle atrophy.

  15. Single session of brief electrical stimulation immediately following crush injury enhances functional recovery of rat facial nerve.

    PubMed

    Foecking, Eileen M; Fargo, Keith N; Coughlin, Lisa M; Kim, James T; Marzo, Sam J; Jones, Kathryn J

    2012-01-01

    Peripheral nerve injuries lead to a variety of pathological conditions, including paresis or paralysis when the injury involves motor axons. We have been studying ways to enhance the regeneration of peripheral nerves using daily electrical stimulation (ES) following a facial nerve crush injury. In our previous studies, ES was not initiated until 24 h after injury. The current experiment tested whether ES administered immediately following the crush injury would further decrease the time for complete recovery from facial paralysis. Rats received a unilateral facial nerve crush injury and an electrode was positioned on the nerve proximal to the crush site. Animals received daily 30 min sessions of ES for 1 d (day of injury only), 2 d, 4 d, 7 d, or daily until complete functional recovery. Untreated animals received no ES. Animals were observed daily for the return of facial function. Our findings demonstrated that one session of ES was as effective as daily stimulation at enhancing the recovery of most functional parameters. Therefore, the use of a single 30 min session of ES as a possible treatment strategy should be studied in human patients with paralysis as a result of acute nerve injuries.

  16. Sigma-1 receptors regulate activity-induced spinal sensitization and neuropathic pain after peripheral nerve injury.

    PubMed

    de la Puente, Beatriz; Nadal, Xavier; Portillo-Salido, Enrique; Sánchez-Arroyos, Ricard; Ovalle, Sergio; Palacios, Gabriel; Muro, Asunción; Romero, Luz; Entrena, José Manuel; Baeyens, José Manuel; López-García, José Antonio; Maldonado, Rafael; Zamanillo, Daniel; Vela, José Miguel

    2009-10-01

    Sigma-1 receptor (sigma(1)R) is expressed in key CNS areas involved in nociceptive processing but only limited information is available about its functional role. In the present study we investigated the relevance of sigma(1)R in modulating nerve injury-evoked pain. For this purpose, wild-type mice and mice lacking the sigma(1)R gene were exposed to partial sciatic nerve ligation and neuropathic pain-related behaviors were investigated. To explore underlying mechanisms, spinal processing of repetitive nociceptive stimulation and expression of extracellular signal-regulated kinase (ERK) were also investigated. Sensitivity to noxious heat of homozygous sigma(1)R knockout mice did not differ from wild-type mice. Baseline values obtained in sigma(1)R knockout mice before nerve injury in the plantar, cold-plate and von Frey tests were also indistinguishable from those obtained in wild-type mice. However, cold and mechanical allodynia did not develop in sigma(1)R null mice exposed to partial sciatic nerve injury. Using isolated spinal cords we found that mice lacking sigma(1)R showed reduced wind-up responses respect to wild-type mice, as evidenced by a reduced number of action potentials induced by trains of C-fiber intensity stimuli. In addition, in contrast to wild-type mice, sigma(1)R knockout mice did not show increased phosphorylation of ERK in the spinal cord after sciatic nerve injury. Both wind-up and ERK activation have been related to mechanisms of spinal cord sensitization. Our findings identify sigma(1)R as a constituent of the mechanisms modulating activity-induced sensitization in pain pathways and point to sigma(1)R as a new potential target for drugs designed to alleviate neuropathic pain.

  17. Nitrogen Substituent Polarity Influences Dithiocarbamate-Mediated Lipid Oxidation, Nerve Copper Accumulation, and Myelin Injury

    PubMed Central

    Valentine, Holly L.; Viquez, Olga M.; Amarnath, Kalyani; Amarnath, Venkataraman; Zyskowski, Justin; Kassa, Endalkachew N.; Valentine, William M.

    2009-01-01

    Dithiocarbamates have a wide spectrum of applications in industry, agriculture, and medicine, with new applications being investigated. Past studies have suggested that the neurotoxicity of some dithiocarbamates may result from copper accumulation, protein oxidative damage, and lipid oxidation. The polarity of a dithiocarbamate’s nitrogen substituents influences the lipophilicity of the copper complexes it generates and thus potentially determines its ability to promote copper accumulation within nerve and induce myelin injury. In the current study, a series of dithiocarbamate-copper complexes differing in their lipophilicity were evaluated for their relative abilities to promote lipid peroxidation determined by malondialdehyde levels generated in an ethyl arachidonate oil-in-water emulsion. In a second component of this study, rats were exposed to either N,N-diethyldithiocarbamate or sarcosine dithiocarbamate; both generate dithiocarbamate-copper complexes that are lipid and water soluble, respectively. Following the exposures, brain, tibial nerve, spinal cord and liver tissue copper levels were measured by inductively coupled mass spectroscopy to assess the relative abilities of these two dithiocarbamates to promote copper accumulation. Peripheral nerve injury was evaluated using grip strengths, nerve conduction velocities and morphologic changes at the light microscope level. Additionally, the protein expression levels of glutathione transferase alpha and heme-oxygenase-1 in nerve were determined and the quantity of protein carbonyls measured to assess levels of oxidative stress and injury. The data provide evidence that dithiocarbamate-copper complexes are redox active; and that the ability of dithiocarbamate complexes to promote lipid peroxidation is correlated to the lipophilicity of the complex. Consistent with neurotoxicity requiring the formation of a lipid soluble copper complex, significant increases in copper accumulation, oxidative stress and myelin

  18. Nitrogen substituent polarity influences dithiocarbamate-mediated lipid oxidation, nerve copper accumulation, and myelin injury.

    PubMed

    Valentine, Holly L; Viquez, Olga M; Amarnath, Kalyani; Amarnath, Venkataraman; Zyskowski, Justin; Kassa, Endalkachew N; Valentine, William M

    2009-01-01

    Dithiocarbamates have a wide spectrum of applications in industry, agriculture, and medicine, with new applications being investigated. Past studies have suggested that the neurotoxicity of some dithiocarbamates may result from copper accumulation, protein oxidative damage, and lipid oxidation. The polarity of a dithiocarbamate's nitrogen substituents influences the lipophilicity of the copper complexes that it generates and thus potentially determines its ability to promote copper accumulation within nerve and induce myelin injury. In the current study, a series of dithiocarbamate-copper complexes differing in their lipophilicity were evaluated for their relative abilities to promote lipid peroxidation determined by malondialdehyde levels generated in an ethyl arachidonate oil-in-water emulsion. In a second component of this study, rats were exposed to either N,N-diethyldithiocarbamate or sarcosine dithiocarbamate; both generated dithiocarbamate-copper complexes that were lipid- and water-soluble, respectively. Following the exposures, brain, tibial nerve, spinal cord, and liver tissue copper levels were measured by inductively coupled mass spectroscopy to assess the relative abilities of these two dithiocarbamates to promote copper accumulation. Peripheral nerve injury was evaluated using grip strengths, nerve conduction velocities, and morphologic changes at the light microscope level. Additionally, the protein expression levels of glutathione transferase alpha and heme-oxygenase-1 in nerve were determined, and the quantity of protein carbonyls was measured to assess levels of oxidative stress and injury. The data provided evidence that dithiocarbamate-copper complexes are redox active and that the ability of dithiocarbamate complexes to promote lipid peroxidation is correlated to the lipophilicity of the complex. Consistent with neurotoxicity requiring the formation of a lipid-soluble copper complex, significant increases in copper accumulation, oxidative

  19. Temporal changes in MrgC expression after spinal nerve injury

    PubMed Central

    He, Shao-Qiu; Han, Liang; Li, Zhe; Xu, Qian; Tiwari, Vinod; Yang, Fei; Guan, Xiaowei; Wang, Yun; Raja, Srinivasa N.; Dong, Xinzhong; Guan, Yun

    2014-01-01

    Mas-related G-protein-coupled receptor subtype C (MrgC) may play an important role in pain sensation. However, the distribution of MrgC receptors in different subpopulations of rodent dorsal root ganglion (DRG) neurons has not been clearly demonstrated owing to a lack of MrgC-selectively antibody. It is also unclear whether peripheral nerve injury induces different time-dependent changes in MrgC expression in injured and uninjured DRG neurons. Here we showed that MrgC immunoreactivity is distributed in both IB4-positive (non-peptidergic) and calcitonin gene-related peptide-positive (peptidergic) DRG neurons in mice and rats. Importantly, the MrgC mRNA level and MrgC immunoreactivity were both decreased in the injured L5 DRG compared to corresponding levels in the contralateral (uninjured) DRG in rats on days 14 and 30 after an L5 spinal nerve ligation. In contrast, mRNA and protein levels of MrgC were increased in the adjacent uninjured L4 DRG. Thus, nerve injury may induce temporal changes in MrgC expression that differ between injured and uninjured DRG neurons. In animal behavior tests, chronic constriction injury of the sciatic nerve induced mechanical pain hypersensitivity in wild-type mice and Mrg-clusterΔ−/− mice (Mrg KO). However, the duration of mechanical hypersensitivity was longer in the Mrg KO mice than in their wild-type littermates, indicating that activation of Mrgs may constitute an endogenous mechanism that inhibits the maintenance of neuropathic pain. These findings extend our knowledge about the distribution of MrgC in rodent DRG neurons and the regulation of its expression by nerve injury. PMID:24374082

  20. Microencapsulation improves inhibitory effects of transplanted olfactory ensheathing cells on pain after sciatic nerve injury

    PubMed Central

    Zhao, Hao; Yang, Bao-lin; Liu, Zeng-xu; Yu, Qing; Zhang, Wen-jun; Yuan, Keng; Zeng, Hui-hong; Zhu, Gao-chun; Liu, De-ming; Li, Qing

    2015-01-01

    Olfactory bulb tissue transplantation inhibits P2X2/3 receptor-mediated neuropathic pain. However, the olfactory bulb has a complex cellular composition, and the mechanism underlying the action of purified transplanted olfactory ensheathing cells (OECs) remains unclear. In the present study, we microencapsulated OECs in alginic acid, and transplanted free and microencapsulated OECs into the region surrounding the injured sciatic nerve in rat models of chronic constriction injury. We assessed mechanical nociception in the rat models 7 and 14 days after surgery by measuring paw withdrawal threshold, and examined P2X2/3 receptor expression in L4–5 dorsal root ganglia using immunohistochemistry. Rats that received free and microencapsulated OEC transplants showed greater withdrawal thresholds than untreated model rats, and weaker P2X2/3 receptor immunoreactivity in dorsal root ganglia. At 14 days, paw withdrawal threshold was much higher in the microencapsulated OEC-treated animals. Our results confirm that microencapsulated OEC transplantation suppresses P2X2/3 receptor expression in L4–5 dorsal root ganglia in rat models of neuropathic pain and reduces allodynia, and also suggest that transplantation of microencapsulated OECs is more effective than transplantation of free OECs for the treatment of neuropathic pain. PMID:26487865

  1. Dorsal root ganglion transcriptome analysis following peripheral nerve injury in mice

    PubMed Central

    Wu, Shaogen; Marie Lutz, Brianna; Miao, Xuerong; Liang, Lingli; Mo, Kai; Chang, Yun-Juan; Du, Peicheng; Soteropoulos, Patricia; Tian, Bin; Kaufman, Andrew G.; Bekker, Alex; Hu, Yali

    2016-01-01

    Background Peripheral nerve injury leads to changes in gene expression in primary sensory neurons of the injured dorsal root ganglia. These changes are believed to be involved in neuropathic pain genesis. Previously, these changes have been identified using gene microarrays or next generation RNA sequencing with poly-A tail selection, but these approaches cannot provide a more thorough analysis of gene expression alterations after nerve injury. Methods The present study chose to eliminate mRNA poly-A tail selection and perform strand-specific next generation RNA sequencing to analyze whole transcriptomes in the injured dorsal root ganglia following spinal nerve ligation. Quantitative real-time reverse transcriptase polymerase chain reaction assay was carried out to verify the changes of some differentially expressed RNAs in the injured dorsal root ganglia after spinal nerve ligation. Results Our results showed that more than 50 million (M) paired mapped sequences with strand information were yielded in each group (51.87 M–56.12 M in sham vs. 51.08 M–57.99 M in spinal nerve ligation). Six days after spinal nerve ligation, expression levels of 11,163 out of a total of 27,463 identified genes in the injured dorsal root ganglia significantly changed, of which 52.14% were upregulated and 47.86% downregulated. The largest transcriptional changes were observed in protein-coding genes (91.5%) followed by noncoding RNAs. Within 944 differentially expressed noncoding RNAs, the most significant changes were seen in long interspersed noncoding RNAs followed by antisense RNAs, processed transcripts, and pseudogenes. We observed a notable proportion of reads aligning to intronic regions in both groups (44.0% in sham vs. 49.6% in spinal nerve ligation). Using quantitative real-time polymerase chain reaction, we confirmed consistent differential expression of selected genes including Kcna2, Oprm1 as well as lncRNAs Gm21781 and 4732491K20Rik following spinal nerve

  2. Traumatic peripheral nerve injuries: epidemiological findings, neuropathic pain and quality of life in 158 patients.

    PubMed

    Ciaramitaro, Palma; Mondelli, Mauro; Logullo, Francesco; Grimaldi, Serena; Battiston, Bruno; Sard, Arman; Scarinzi, Cecilia; Migliaretti, Giuseppe; Faccani, Giuliano; Cocito, Dario

    2010-06-01

    The objectives of this study were (1) epidemiological analysis of traumatic peripheral nerve injuries; (2) assessment of neuropathic pain and quality of life in patients affected by traumatic neuropathies. All consecutive patients with a diagnosis of traumatic neuropathies from four Italian centres were enrolled. Electromyography confirmed clinical level and site diagnosis of peripheral nerve injury. All patients were evaluated by disability scales, pain screening tools, and quality of life tests. 158 consecutive patients for a total of 211 traumatic neuropathies were analysed. The brachial plexus was a frequent site of traumatic injury (36%) and the radial, ulnar, and peroneal were the most commonly involved nerves with 15% of iatrogenic injuries. Seventy-two percent of the traumatic neuropathies were painful. Pain was present in 66% and neuropathic pain in 50% of all patients. Patients had worse quality of life scores than did the healthy Italian population. Moreover, there was a strong correlation between the quality of life and the severity of the pain, particularly neuropathic pain (Short Form-36 [SF-36] p < 0.005; Beck Depression Inventory [BDI] p < 0.0001). Traumatic neuropathies were more frequent in young males after road accidents, mainly in the upper limbs. Severe neuropathic pain and not only disability contributed to worsening the quality of life in patients with traumatic neuropathies.

  3. Differential Effects of 670 and 830 nm Red near Infrared Irradiation Therapy: A Comparative Study of Optic Nerve Injury, Retinal Degeneration, Traumatic Brain and Spinal Cord Injury

    PubMed Central

    Giacci, Marcus K.; Wheeler, Lachlan; Lovett, Sarah; Dishington, Emma; Majda, Bernadette; Bartlett, Carole A.; Thornton, Emma; Harford-Wright, Elizabeth; Leonard, Anna; Vink, Robert; Harvey, Alan R.; Provis, Jan; Dunlop, Sarah A.; Fitzgerald, Melinda

    2014-01-01

    Red/near-infrared irradiation therapy (R/NIR-IT) delivered by laser or light-emitting diode (LED) has improved functional outcomes in a range of CNS injuries. However, translation of R/NIR-IT to the clinic for treatment of neurotrauma has been hampered by lack of comparative information regarding the degree of penetration of the delivered irradiation to the injury site and the optimal treatment parameters for different CNS injuries. We compared the treatment efficacy of R/NIR-IT at 670 nm and 830 nm, provided by narrow-band LED arrays adjusted to produce equal irradiance, in four in vivo rat models of CNS injury: partial optic nerve transection, light-induced retinal degeneration, traumatic brain injury (TBI) and spinal cord injury (SCI). The number of photons of 670 nm or 830 nm light reaching the SCI injury site was 6.6% and 11.3% of emitted light respectively. Treatment of rats with 670 nm R/NIR-IT following partial optic nerve transection significantly increased the number of visual responses at 7 days after injury (P≤0.05); 830 nm R/NIR-IT was partially effective. 670 nm R/NIR-IT also significantly reduced reactive species and both 670 nm and 830 nm R/NIR-IT reduced hydroxynonenal immunoreactivity (P≤0.05) in this model. Pre-treatment of light-induced retinal degeneration with 670 nm R/NIR-IT significantly reduced the number of Tunel+ cells and 8-hydroxyguanosine immunoreactivity (P≤0.05); outcomes in 830 nm R/NIR-IT treated animals were not significantly different to controls. Treatment of fluid-percussion TBI with 670 nm or 830 nm R/NIR-IT did not result in improvements in motor or sensory function or lesion size at 7 days (P>0.05). Similarly, treatment of contusive SCI with 670 nm or 830 nm R/NIR-IT did not result in significant improvements in functional recovery or reduced cyst size at 28 days (P>0.05). Outcomes from this comparative study indicate that it will be necessary to optimise delivery devices, wavelength, intensity and duration of R

  4. Normal distribution of VGLUT1 synapses on spinal motoneuron dendrites and their reorganization after nerve injury.

    PubMed

    Rotterman, Travis M; Nardelli, Paul; Cope, Timothy C; Alvarez, Francisco J

    2014-03-05

    Peripheral nerve injury induces permanent alterations in spinal cord circuitries that are not reversed by regeneration. Nerve injury provokes the loss of many proprioceptive IA afferent synapses (VGLUT1-IR boutons) from motoneurons, the reduction of IA EPSPs in motoneurons, and the disappearance of stretch reflexes. After motor and sensory axons successfully reinnervate muscle, lost IA VGLUT1 synapses are not re-established and the stretch reflex does not recover; however, electrically evoked EPSPs do recover. The reasons why remaining IA synapses can evoke EPSPs on motoneurons, but fail to transmit useful stretch signals are unknown. To better understand changes in the organization of VGLUT1 IA synapses that might influence their input strength, we analyzed their distribution over the entire dendritic arbor of motoneurons before and after nerve injury. Adult rats underwent complete tibial nerve transection followed by microsurgical reattachment and 1 year later motoneurons were intracellularly recorded and filled with neurobiotin to map the distribution of VGLUT1 synapses along their dendrites. We found in control motoneurons an average of 911 VGLUT1 synapses; ~62% of them were lost after injury. In controls, VGLUT1 synapses were focused to proximal dendrites where they were grouped in tight clusters. After injury, most synaptic loses occurred in the proximal dendrites and remaining synapses were declustered, smaller, and uniformly distributed throughout the dendritic arbor. We conclude that this loss and reorganization renders IA afferent synapses incompetent for efficient motoneuron synaptic depolarization in response to natural stretch, while still capable of eliciting EPSPs when synchronously fired by electrical volleys.

  5. Developing Extracellular Matrix Technology to Treat Retinal or Optic Nerve Injury

    PubMed Central

    van der Merwe, Yolandi

    2015-01-01

    Abstract Adult mammalian CNS neurons often degenerate after injury, leading to lost neurologic functions. In the visual system, retinal or optic nerve injury often leads to retinal ganglion cell axon degeneration and irreversible vision loss. CNS axon degeneration is increasingly linked to the innate immune response to injury, which leads to tissue-destructive inflammation and scarring. Extracellular matrix (ECM) technology can reduce inflammation, while increasing functional tissue remodeling, over scarring, in various tissues and organs, including the peripheral nervous system. However, applying ECM technology to CNS injuries has been limited and virtually unstudied in the visual system. Here we discuss advances in deriving fetal CNS-specific ECMs, like fetal porcine brain, retina, and optic nerve, and fetal non-CNS-specific ECMs, like fetal urinary bladder, and the potential for using tissue-specific ECMs to treat retinal or optic nerve injuries in two platforms. The first platform is an ECM hydrogel that can be administered as a retrobulbar, periocular, or even intraocular injection. The second platform is an ECM hydrogel and polymer “biohybrid” sheet that can be readily shaped and wrapped around a nerve. Both platforms can be tuned mechanically and biochemically to deliver factors like neurotrophins, immunotherapeutics, or stem cells. Since clinical CNS therapies often use general anti-inflammatory agents, which can reduce tissue-destructive inflammation but also suppress tissue-reparative immune system functions, tissue-specific, ECM-based devices may fill an important need by providing naturally derived, biocompatible, and highly translatable platforms that can modulate the innate immune response to promote a positive functional outcome. PMID:26478910

  6. Cathepsin B-dependent motor neuron death after nerve injury in the adult mouse

    SciTech Connect

    Sun, Li; Wu, Zhou; Baba, Masashi; Peters, Christoph; Uchiyama, Yasuo; Nakanishi, Hiroshi

    2010-08-27

    Research highlights: {yields} Cathepsin B (CB), a lysosomal cysteine protease, is expressed in neuron and glia. {yields} CB increased in hypogrossal nucleus neurons after nerve injury in adult mice. {yields} CB-deficiency significantly increased the mean survival ratio of injured neurons. {yields} Thus, CB plays a critical role in axotomy-induced neuronal death in adult mice. -- Abstract: There are significant differences in the rate of neuronal death after peripheral nerve injury between species. The rate of neuronal death of motor neurons after nerve injury in the adult rats is very low, whereas that in adult mice is relatively high. However, the understanding of the mechanism underlying axotomy-induced motor neuron death in adult mice is limited. Cathepsin B (CB), a typical cysteine lysosomal protease, has been implicated in three major morphologically distinct pathways of cell death; apoptosis, necrosis and autophagic cell death. The possible involvement of CB in the neuronal death of hypogrossal nucleus (HGN) neurons after nerve injury in adult mice was thus examined. Quantitative analyses showed the mean survival ratio of HGN neurons in CB-deficient (CB-/-) adult mice after nerve injury was significantly greater than that in the wild-type mice. At the same time, proliferation of microglia in the injured side of the HGN of CB-/- adult mice was markedly reduced compared with that in the wild-type mice. On the injured side of the HGN in the wild-type adult mice, both pro- and mature forms of CB markedly increased in accordance with the increase in the membrane-bound form of LC3 (LC3-II), a marker protein of autophagy. Furthermore, the increase in CB preceded an increase in the expression of Noxa, a major executor for axotomy-induced motor neuron death in the adult mouse. Conversely, expression of neither Noxa or LC3-II was observed in the HGN of adult CB-/- mice after nerve injury. These observations strongly suggest that CB plays a critical role in axotomy

  7. Sympathetic modulation of sensory nerve activity with age: human and rodent skin models.

    PubMed

    Khalil, Z; LeVasseur, S; Merhi, M; Helme, R D

    1997-11-01

    1. Sensory nerves serve an afferent role and mediate neurogenic components of inflammation and tissue repair via an axon reflex release of sensory peptides at sites of injury. Dysfunction of these nerves with age could contribute to delayed tissue healing. 2. Complementary animal and human skin models were used in the present studies to investigate changes in the modulation of sensory nerve function by sympathetic efferents during ageing. Laser Doppler flowmetry was used to monitor neurogenic skin vascular responses. 3. The animal model used skin of the hind footpad of anaesthetized rats combined with electrical stimulation of the sciatic nerve, while the human model comprised capsaicin electrophoresis to the volar surface of the forearm. Sympathetic modulation was effected by systemic phentolamine pretreatment in animals and local application in the human model. 4. The results obtained from the human model confirmed the reported decline in sensory nerve function and showed no change in sympathetic modulation with age. The results from the animal model confirm and expand results obtained from the human model. 5. The use of low (5 Hz) and high (15 Hz) frequency electrical stimulation (20 V, 2 ms for 1 min) revealed a preferential response of aged sensory nerves to low-frequency electrical stimulation parameters with differential sympathetic modulation that is dependent on the frequency of stimulation.

  8. In vivo detection of nerve injury in familial amyloid polyneuropathy by magnetic resonance neurography

    PubMed Central

    Hund, Ernst; Hornung, Benjamin; Hegenbart, Ute; Schönland, Stefan O.; Kimmich, Christoph; Kristen, Arnt V.; Purrucker, Jan; Röcken, Christoph; Heiland, Sabine; Bendszus, Martin; Pham, Mirko

    2015-01-01

    Transthyretin familial amyloid polyneuropathy is a rare, autosomal-dominant inherited multisystem disorder usually manifesting with a rapidly progressive, axonal, distally-symmetric polyneuropathy. The detection of nerve injury by nerve conduction studies is limited, due to preferential involvement of small-fibres in early stages. We investigated whether lower limb nerve-injury can be detected, localized and quantified in vivo by high-resolution magnetic resonance neurography. We prospectively included 20 patients (12 male and eight female patients, mean age 47.9 years, range 26–66) with confirmed mutation in the transthyretin gene: 13 with symptomatic polyneuropathy and seven asymptomatic gene carriers. A large age- and sex-matched cohort of healthy volunteers served as controls (20 male and 20 female, mean age 48.1 years, range 30–73). All patients received detailed neurological and electrophysiological examinations and were scored using the Neuropathy Impairment Score–Lower Limbs, Neuropathy Deficit and Neuropathy Symptom Score. Magnetic resonance neurography (3 T) was performed with large longitudinal coverage from proximal thigh to ankle-level and separately for each leg (140 axial slices/leg) by using axial T2-weighted (repetition time/echo time = 5970/55 ms) and dual echo (repetition time 5210 ms, echo times 12 and 73 ms) turbo spin echo 2D sequences with spectral fat saturation. A 3D T2-weighted inversion-recovery sequence (repetition time/echo time 3000/202 ms) was acquired for imaging of the spinal nerves and lumbar plexus (50 axial slice reformations). Precise manual segmentation of the spinal/sciatic/tibial/common peroneal nerves was performed on each slice. Histogram-based normalization of nerve–voxel signal intensities was performed using the age- and sex-matched control group as normative reference. Nerve-voxels were subsequently classified as lesion-voxels if a threshold of >1.2 (normalized signal-intensity) was exceeded. At distal thigh

  9. Role of the Excitability Brake Potassium Current IKD in Cold Allodynia Induced by Chronic Peripheral Nerve Injury.

    PubMed

    González, Alejandro; Ugarte, Gonzalo; Restrepo, Carlos; Herrera, Gaspar; Piña, Ricardo; Gómez-Sánchez, José Antonio; Pertusa, María; Orio, Patricio; Madrid, Rodolfo

    2017-03-22

    Cold allodynia is a common symptom of neuropathic and inflammatory pain following peripheral nerve injury. The mechanisms underlying this disabling sensory alteration are not entirely understood. In primary somatosensory neurons, cold sensitivity is mainly determined by a functional counterbalance between cold-activated TRPM8 channels and Shaker-like Kv1.1-1.2 channels underlying the excitability brake current IKD Here we studied the role of IKD in damage-triggered painful hypersensitivity to innocuous cold. We found that cold allodynia induced by chronic constriction injury (CCI) of the sciatic nerve in mice, was related to both an increase in the proportion of cold-sensitive neurons (CSNs) in DRGs contributing to the sciatic nerve, and a decrease in their cold temperature threshold. IKD density was reduced in high-threshold CSNs from CCI mice compared with sham animals, with no differences in cold-induced TRPM8-dependent current density. The electrophysiological properties and neurochemical profile of CSNs revealed an increase of nociceptive-like phenotype among neurons from CCI animals compared with sham mice. These results were validated using a mathematical model of CSNs, including IKD and TRPM8, showing that a reduction in IKD current density shifts the thermal threshold to higher temperatures and that the reduction of this current induces cold sensitivity in former cold-insensitive neurons expressing low levels of TRPM8-like current. Together, our results suggest that cold allodynia is largely due to a functional downregulation of IKD in both high-threshold CSNs and in a subpopulation of polymodal nociceptors expressing TRPM8, providing a general molecular and neural mechanism for this sensory alteration.SIGNIFICANCE STATEMENT This paper unveils the critical role of the brake potassium current IKD in damage-triggered cold allodynia. Using a well-known form of nerve injury and combining behavioral analysis, calcium imaging, patch clamping, and pharmacological

  10. Abeta-afferents activate neurokinin-1 receptor in dorsal horn neurons after nerve injury.

    PubMed

    Zheng, Ji-Hong; Song, Xue-Jun

    2005-05-12

    We provide new evidence demonstrating that peripheral nerve injury produces profound alterations in synaptic input to dorsal horn neurons mediated by non-nociceptive sensory neurons, and activation of neurokinin-1 receptor may be involved in the enhanced synaptic response and thus contribute to the tactile allodynia. Our results show that Abeta-fiber-evoked field potential significantly increased in the first postoperative week and decreased thereafter while maximal mechanical allodynia was exhibited. The neurokinin-1 receptor antagonist L703,606 significantly reduced Abeta-fiber-evoked field potential in nerve-injured but not in sham-operated animals. The non-N-methyl-D-aspartate receptor antagonist CNQX inhibited Abeta-fiber-evoked field potential in both nerve-injured and sham-operated rats, while the N-methyl-D-aspartate receptor antagonist MK-801 did not affect Abeta-fiber-evoked field potential in either CCI or sham-operated animals.

  11. Neuromuscular rehabilitation by treadmill running or electrical stimulation after peripheral nerve injury and repair.

    PubMed

    Marqueste, Tanguy; Alliez, Jean-Roch; Alluin, Olivier; Jammes, Yves; Decherchi, Patrick

    2004-05-01

    Numerous studies have been devoted to the regeneration of the motor pathway toward a denervated muscle after nerve injury. However, the regeneration of sensory muscle endings after repair by self-anastomosis are little studied. In previous electrophysiological studies, our laboratory showed that the functional characteristics of tibialis anterior muscle afferents are differentially affected after injury and repair of the peroneal nerve with and without chronic electrostimulation. The present study focuses on the axonal regeneration of mechano- (fibers I and II) and metabosensitive (fibers III and IV) muscle afferents by evaluating the recovery of their response to different test agents after nerve injury and repair by self-anastomosis during 10 wk of treadmill running (LSR). Data were compared with control animals (C), animals with nerve lesion and suture (LS), and animals with lesion, suture, and chronic muscle rehabilitation by electrostimulation (LSE) with a biphasic current modulated in pulse duration and frequency, eliciting a pattern mimicking the activity delivered by the nerve to the muscle. Compared with the C group, results indicated that 1) muscle weight was smaller in LS and LSR groups, 2) the fatigue index was greater in the LS group and smaller in the LSE group, 3) metabosensibility remained altered in the LS and LSE groups, and 4) mechanosensitivity presented a large increase of the activation pattern in the LS and LSE groups. Our data indicated that chronic muscle electrostimulation partially favors the recovery of muscle properties (i.e., muscle weight and twitch response were close to the C group) and that rehabilitation by treadmill running also efficiently induced a better functional muscle afferent recovery (i.e., the discharge pattern was similar to the C group). The effectiveness of the chronic electromyostimulation and the treadmill exercise on afferent recovery is discussed with regard to parameters listed above.

  12. [Application of direct long-standing electrostimulation in consequences of the sciatic nerve injury].

    PubMed

    Tsymbaliuk, Iu V

    2013-04-01

    The results of surgical treatment of 57 patients, suffering consequences of the sciatic nerve injury, using the system for long-lasting electrostimulation "Naysi 3M", were presented. The domestically manufactured system is individual and gives possibility to conduct the direct electrostimulation procedures in the home conditions, several times a day, for a long time. Positive results, consisting of the various degree enhancement of the lower extremities movements volume and strength, the sensitivity restoration and the pain severity reduction or disappearance, were achieved in 46 (81%) patients. In inefficacy of conservative treatment and presence of indications for the operation in patients with sciatic nerve injury the long-lasting electrostimulation secures restoration of the lower extremities lost functions, the pain syndrome and the vegetative-trophic disorders regress.

  13. Choroidal rupture and optic nerve injury with equipment designated as 'child-safe'.

    PubMed

    Petrarca, Robert; Saldana, Manuel

    2012-08-27

    Blunt ocular trauma from a child's plastic foam-covered toy baseball bat caused traumatic optic neuropathy and choroidal rupture in a 9-year-old child. The examination revealed a visual acuity of 6/60, a relative afferent pupillary defect, optic nerve swelling, commotio retinae and retinal haemorrhages. There was no orbital fracture or intraorbital haematoma on CT scanning. Optical coherence tomography showed macular oedema and disruption of the retinal pigment epithelium and Bruch's membrane. The child was admitted for intravenous methylprednisolone and discharged on topical steroid treatment. At 1 month follow-up, visual acuity had improved to 6/12. Optic nerve swelling had resolved and the fundus had two crescent-shaped choroidal rupture scars. Choroidal rupture and optic neuropathy can be secondary to indirect trauma, and even when the mechanism of injury is with a piece of equipment designated as suitable for children, serious ocular injury can occur.

  14. Increase of transcription factor EB (TFEB) and lysosomes in rat DRG neurons and their transportation to the central nerve terminal in dorsal horn after nerve injury.

    PubMed

    Jung, J; Uesugi, N; Jeong, N Y; Park, B S; Konishi, H; Kiyama, H

    2016-01-28

    In the spinal dorsal horn (DH), nerve injury activates microglia and induces neuropathic pain. Several studies clarified an involvement of adenosine triphosphate (ATP) in the microglial activation. However, the origin of ATP together with the release mechanism is unclear. Recent in vitro study revealed that an ATP marker, quinacrine, in lysosomes was released from neurite terminal of dorsal root ganglion (DRG) neurons to extracellular space via lysosomal exocytosis. Here, we demonstrate a possibility that the lysosomal ingredient including ATP released from DRG neurons by lysosomal-exocytosis is an additional source of the glial activation in DH after nerve injury. After rat L5 spinal nerve ligation (SNL), mRNA for transcription factor EB (TFEB), a transcription factor controlling lysosomal activation and exocytosis, was induced in the DRG. Simultaneously both lysosomal protein, LAMP1- and vesicular nuclear transporter (VNUT)-positive vesicles were increased in L5 DRG neurons and ipsilateral DH. The quinacrine staining in DH was increased and co-localized with LAMP1 immunoreactivity after nerve injury. In DH, LAMP1-positive vesicles were also co-localized with a peripheral nerve marker, Isolectin B4 (IB4) lectin. Injection of the adenovirus encoding mCherry-LAMP1 into DRG showed that mCherry-positive lysosomes are transported to the central nerve terminal in DH. These findings suggest that activation of lysosome synthesis including ATP packaging in DRG, the central transportation of the lysosome, and subsequent its exocytosis from the central nerve terminal of DRG neurons in response to nerve injury could be a partial mechanism for activation of microglia in DH. This lysosome-mediated microglia activation mechanism may provide another clue to control nociception and pain.

  15. Interlimb Reflexes Induced by Electrical Stimulation of Cutaneous Nerves after Spinal Cord Injury.

    PubMed

    Butler, Jane E; Godfrey, Sharlene; Thomas, Christine K

    2016-01-01

    Whether interlimb reflexes emerge only after a severe insult to the human spinal cord is controversial. Here the aim was to examine interlimb reflexes at rest in participants with chronic (>1 year) spinal cord injury (SCI, n = 17) and able-bodied control participants (n = 5). Cutaneous reflexes were evoked by delivering up to 30 trains of stimuli to either the superficial peroneal nerve on the dorsum of the foot or the radial nerve at the wrist (5 pulses, 300 Hz, approximately every 30 s). Participants were instructed to relax the test muscles prior to the delivery of the stimuli. Electromyographic activity was recorded bilaterally in proximal and distal arm and leg muscles. Superficial peroneal nerve stimulation evoked interlimb reflexes in ipsilateral and contralateral arm and contralateral leg muscles of SCI and control participants. Radial nerve stimulation evoked interlimb reflexes in the ipsilateral leg and contralateral arm muscles of control and SCI participants but only contralateral leg muscles of control participants. Interlimb reflexes evoked by superficial peroneal nerve stimulation were longer in latency and duration, and larger in magnitude in SCI participants. Interlimb reflex properties were similar for both SCI and control groups for radial nerve stimulation. Ascending interlimb reflexes tended to occur with a higher incidence in participants with SCI, while descending interlimb reflexes occurred with a higher incidence in able-bodied participants. However, the overall incidence of interlimb reflexes in SCI and neurologically intact participants was similar which suggests that the neural circuitry underlying these reflexes does not necessarily develop after central nervous system injury.

  16. Interlimb Reflexes Induced by Electrical Stimulation of Cutaneous Nerves after Spinal Cord Injury

    PubMed Central

    Butler, Jane E.; Godfrey, Sharlene; Thomas, Christine K.

    2016-01-01

    Whether interlimb reflexes emerge only after a severe insult to the human spinal cord is controversial. Here the aim was to examine interlimb reflexes at rest in participants with chronic (>1 year) spinal cord injury (SCI, n = 17) and able-bodied control participants (n = 5). Cutaneous reflexes were evoked by delivering up to 30 trains of stimuli to either the superficial peroneal nerve on the dorsum of the foot or the radial nerve at the wrist (5 pulses, 300 Hz, approximately every 30 s). Participants were instructed to relax the test muscles prior to the delivery of the stimuli. Electromyographic activity was recorded bilaterally in proximal and distal arm and leg muscles. Superficial peroneal nerve stimulation evoked interlimb reflexes in ipsilateral and contralateral arm and contralateral leg muscles of SCI and control participants. Radial nerve stimulation evoked interlimb reflexes in the ipsilateral leg and contralateral arm muscles of control and SCI participants but only contralateral leg muscles of control participants. Interlimb reflexes evoked by superficial peroneal nerve stimulation were longer in latency and duration, and larger in magnitude in SCI participants. Interlimb reflex properties were similar for both SCI and control groups for radial nerve stimulation. Ascending interlimb reflexes tended to occur with a higher incidence in participants with SCI, while descending interlimb reflexes occurred with a higher incidence in able-bodied participants. However, the overall incidence of interlimb reflexes in SCI and neurologically intact participants was similar which suggests that the neural circuitry underlying these reflexes does not necessarily develop after central nervous system injury. PMID:27049521

  17. A psychophysical study of the mechanisms of sensory recovery following nerve injury in humans.

    PubMed

    Van Boven, R W; Johnson, K O

    1994-02-01

    Twenty-four subjects were studied before and up to 1 year after surgery that produced injury to a major sensory branch of the trigeminal nerve. We employed a battery of 11 psychophysical tests, in which the neural mechanisms underlying performance are understood, to study the basis of recovery following nerve injury. Immediately after nerve injury, sensation was profoundly impaired in all subjects. In the following weeks and months, the recovery of performance proceeded in an orderly fashion. Although the rates of recovery varied between subjects, the order of recovery between tasks did not. The recovery rates fell into three distinct categories. Recovery in one task, brush-stroke directional discrimination, was most rapid. Two weeks after nerve injury, 52% of subjects could discriminate brush-stroke direction; by 3 months only one subject could not perform this task. The second category comprised recovery rates for pain thresholds for noxious heat, cold and mechanical stimuli, and to preinjury performance in tasks assessing touch and vibration detection, two-point discrimination, cooling detection and subjective magnitude estimation of mechanical force. The third, slowest group included recovery rates for warming detection and grating orientation discrimination. Early recovery to preinjury performance levels in the brush-stroke direction and one-point versus two-point discrimination tasks was correlated with later recovery to near normal performance in the grating orientation task. The grating orientation task was unique in providing a measure that corresponded consistently with the subjects' reports of sensory deficits. Our psychophysical findings are consistent with neurophysiological data showing that the major primary afferent fibre classes reinnervate the skin at a similar rate. A hypothesis that accounts for the psychophysical findings in this study is that differences in recovery rates between tasks is determined largely by their relative dependencies on

  18. Third-Degree Hindpaw Burn Injury Induced Apoptosis of Lumbar Spinal Cord Ventral Horn Motor Neurons and Sciatic Nerve and Muscle Atrophy in Rats

    PubMed Central

    Wu, Sheng-Hua; Cheng, Kuang-I; Chai, Chee-Yin; Yeh, Jwu-Lai; Wu, Tai-Cheng; Kwan, Aij-Lie

    2015-01-01

    Background. Severe burns result in hypercatabolic state and concomitant muscle atrophy that persists for several months, thereby limiting patient recovery. However, the effects of burns on the corresponding spinal dermatome remain unknown. This study aimed to investigate whether burns induce apoptosis of spinal cord ventral horn motor neurons (VHMNs) and consequently cause skeletal muscle wasting. Methods. Third-degree hindpaw burn injury with 1% total body surface area (TBSA) rats were euthanized 4 and 8 weeks after burn injury. The apoptosis profiles in the ventral horns of the lumbar spinal cords, sciatic nerves, and gastrocnemius muscles were examined. The Schwann cells in the sciatic nerve were marked with S100. The gastrocnemius muscles were harvested to measure the denervation atrophy. Result. The VHMNs apoptosis in the spinal cord was observed after inducing third-degree burns in the hindpaw. The S100 and TUNEL double-positive cells in the sciatic nerve increased significantly after the burn injury. Gastrocnemius muscle apoptosis and denervation atrophy area increased significantly after the burn injury. Conclusion. Local hindpaw burn induces apoptosis in VHMNs and Schwann cells in sciatic nerve, which causes corresponding gastrocnemius muscle denervation atrophy. Our results provided an animal model to evaluate burn-induced muscle wasting, and elucidate the underlying mechanisms. PMID:25695065

  19. Neonatal sensory nerve injury-induced synaptic plasticity in the trigeminal principal sensory nucleus.

    PubMed

    Lo, Fu-Sun; Erzurumlu, Reha S

    2016-01-01

    Sensory deprivation studies in neonatal mammals, such as monocular eye closure, whisker trimming, and chemical blockade of the olfactory epithelium have revealed the importance of sensory inputs in brain wiring during distinct critical periods. But very few studies have paid attention to the effects of neonatal peripheral sensory nerve damage on synaptic wiring of the central nervous system (CNS) circuits. Peripheral somatosensory nerves differ from other special sensory afferents in that they are more prone to crush or severance because of their locations in the body. Unlike the visual and auditory afferents, these nerves show regenerative capabilities after damage. Uniquely, damage to a somatosensory peripheral nerve does not only block activity incoming from the sensory receptors but also mediates injury-induced neuro- and glial chemical signals to the brain through the uninjured central axons of the primary sensory neurons. These chemical signals can have both far more and longer lasting effects than sensory blockade alone. Here we review studies which focus on the consequences of neonatal peripheral sensory nerve damage in the principal sensory nucleus of the brainstem trigeminal complex.

  20. Effects of Taxol on Regeneration in a Rat Sciatic Nerve Transection Model

    PubMed Central

    Hsu, Shih-Tien; Yao, Chun-Hsu; Hsu, Yuan-Man; Lin, Jia-Horng; Chen, Yung-Hsiang; Chen, Yueh-Sheng

    2017-01-01

    Recent studies describe taxol as a candidate treatment for promoting central nerve regeneration. However, taxol has serious side effects including peripheral neurotoxicity, and little information is known about the effect of taxol on peripheral nerve regeneration. We investigated the effects of taxol on regeneration in a rat sciatic nerve transection model. Rats were divided into four groups (n = 10): normal saline (i.p.) as the control, Cremophor EL vehicle, and 2 or 6 mg/kg of taxol in the Cremophor EL solution (four times in day-2, 4, 6, and 8), respectively. We evaluated neuronal electrophysiology, animal behaviour, neuronal connectivity, macrophage infiltration, location and expression levels of calcitonin gene-related peptide (CGRP), and expression levels of both nerve growth factors and immunoregulatory factors. In the high-dose taxol group (6 mg/kg), neuronal electrophysiological function was significantly impaired. Licking latencies were significantly changed while motor coordination was unaffected. Neuronal connectivity, macrophage density, and expression levels of CGRP was dramatically reduced. Expression levels of nerve growth factors and immunoregulatory factors was also reduced, while it was increased in the low-dose taxol group (2 mg/kg). These results indicate that taxol can modulate local inflammatory conditions, impair nerve regeneration, and impede recovery of a severe peripheral nerve injury. PMID:28181572

  1. N,N-diethyldithiocarbamate produces copper accumulation, lipid peroxidation, and myelin injury in rat peripheral nerve.

    PubMed

    Tonkin, Elizabeth G; Valentine, Holly L; Milatovic, Dejan M; Valentine, William M

    2004-09-01

    Previous studies have demonstrated the ability of the dithiocarbamate, disulfiram, to produce a peripheral neuropathy in humans and experimental animals and have also provided evidence that N,N-diethyldithiocarbamate (DEDC) is a proximate toxic species of disulfiram. The ability of DEDC to elevate copper levels in the brain suggests that it may also elevate levels of copper in peripheral nerve, possibly leading to oxidative stress and lipid peroxidation from redox cycling of copper. The study presented here investigates the potential of DEDC to promote copper accumulation and lipid peroxidation in peripheral nerve. Rats were administered either DEDC or deionized water by ip osmotic pumps and fed a normal diet or diet containing elevated copper, and the levels of metals, isoprostanes, and the severity of lesions in peripheral nerve and brain were assessed by ICP-AES/AAS, GC/MS, and light microscopy, respectively. Copper was the only metal that demonstrated any significant compound-related elevations relative to controls, and total copper was increased in both brain and peripheral nerve in animals administered DEDC on both diets. In contrast, lesions and elevated F2-isoprostanes were significantly increased only in peripheral nerve for the rats administered DEDC on both diets. Autometallography staining of peripheral nerve was consistent with increased metal content along the myelin sheath, but in brain, focal densities were observed, and a periportal distribution occurred in liver. These data are consistent with the peripheral nervous system being more sensitive to DEDC-mediated demyelination and demonstrate the ability of DEDC to elevate copper levels in peripheral nerve. Additionally lipid peroxidation appears to either be a contributing event in the development of demyelination, possibly through an increase of redox active copper, or a consequence of the myelin injury.

  2. Indirect optic nerve injury in two-wheeler riders in northeast India

    PubMed Central

    Bhattacharjee, Kasturi; Jain, Lokesh; Sarma, Gitumoni; Sarma, Angshuman Sen; Medhi, Jnanankar; Das, Dipankar; Buragohain, Sanjoy Kr

    2008-01-01

    Purpose: To investigate the association of posterior indirect traumatic optic neuropathy and superior temporal orbital rim injury in two-wheeler riders and documentation of the clinical profile of such cases. Design: Retrospective observational study. Materials and Methods: Records of all patients reporting with cranio-orbital injury and vision loss following road traffic accidents between October 1994 and April 2006 were reviewed and from them cases with vision loss solely from indirect optic nerve injury were taken up for study. The prognostic significance of different presenting features, role of intravenous methyl prednisolone (IVMP) and relative risk of superior orbital rim injury to posterior indirect traumatic optic neuropathy (at 95% confidence interval) was calculated. Results: Out of 129 consecutive cases of cranio-orbital injury, 35 had posterior indirect traumatic optic neuropathy with minor ipsilateral superior temporal orbital rim trauma and none used any protective headwear. Presenting clinical features like relative afferent pupillary defect (P= 0.365), optic disc status (P= 0.518) and visual evoked potential (VEP) (P= 0.366) were disproportionate to visual loss. Only VEP had prognostic significance. The IVMP did not provide any added therapeutic benefit. The remaining 94 cases sustained direct blinding ocular trauma and 28 of them had associated intracranial pathology. The relative risk of superior temporal orbital rim injury to posterior indirect optic nerve trauma was 2.25. Conclusion: Superior temporal orbital rim injury, even when minor, carries a potential risk for development of blindness from indirect posterior indirect traumatic optic neuropathy in two-wheeler drivers. Presenting signs do not correlate with visual status. Only VEP has prognostic significance and the condition is untreatable. PMID:18974518

  3. Neuroglial ATP release through innexin channels controls microglial cell movement to a nerve injury

    PubMed Central

    Lipitz, Jeffrey B.; Dahl, Gerhard

    2010-01-01

    Microglia, the immune cells of the central nervous system, are attracted to sites of injury. The injury releases adenosine triphosphate (ATP) into the extracellular space, activating the microglia, but the full mechanism of release is not known. In glial cells, a family of physiologically regulated unpaired gap junction channels called innexons (invertebrates) or pannexons (vertebrates) located in the cell membrane is permeable to ATP. Innexons, but not pannexons, also pair to make gap junctions. Glial calcium waves, triggered by injury or mechanical stimulation, open pannexon/innexon channels and cause the release of ATP. It has been hypothesized that a glial calcium wave that triggers the release of ATP causes rapid microglial migration to distant lesions. In the present study in the leech, in which a single giant glial cell ensheathes each connective, hydrolysis of ATP with 10 U/ml apyrase or block of innexons with 10 µM carbenoxolone (CBX), which decreased injury-induced ATP release, reduced both movement of microglia and their accumulation at lesions. Directed movement and accumulation were restored in CBX by adding ATP, consistent with separate actions of ATP and nitric oxide, which is required for directed movement but does not activate glia. Injection of glia with innexin2 (Hminx2) RNAi inhibited release of carboxyfluorescein dye and microglial migration, whereas injection of innexin1 (Hminx1) RNAi did not when measured 2 days after injection, indicating that glial cells’ ATP release through innexons was required for microglial migration after nerve injury. Focal stimulation either mechanically or with ATP generated a calcium wave in the glial cell; injury caused a large, persistent intracellular calcium response. Neither the calcium wave nor the persistent response required ATP or its release. Thus, in the leech, innexin membrane channels releasing ATP from glia are required for migration and accumulation of microglia after nerve injury. PMID:20876360

  4. Sciatic nerve injury in adult rats causes distinct changes in the central projections of sensory neurons expressing different glial cell line-derived neurotrophic factor family receptors

    PubMed Central

    Keast, Janet R.; Forrest, Shelley L.; Osborne, Peregrine B.

    2010-01-01

    Most small unmyelinated neurons in adult rat dorsal ganglia (DRG) express one or more of the co-receptors targeted by glial cell line-derived neurotrophic factor (GDNF), neurturin and artemin (GFRα1, GFRα2 and GFRα3 respectively). The function of these GDNF family ligands (GFLs) is not fully elucidated but recent evidence suggests GFLs could function in sensory neuron regeneration after nerve injury and peripheral nociceptor sensitisation. In this study, we used immunohistochemistry to determine if the DRG neurons targeted by each GFL change after sciatic nerve injury. We compared complete sciatic nerve transection and the chronic constriction model and found the pattern of changes incurred by each injury was broadly similar. In lumbar spinal cord, there was a widespread increase in neuronal GFRα1 immunoreactivity (IR) in the L1-6 dorsal horn. GFRα3-IR also increased but in a more restricted area. In contrast, GFRα2-IR decreased in patches of superficial dorsal horn and this loss was more extensive after transection injury. No change in calcitonin gene-related peptide-IR was detected after either injury. Analysis of double-immunolabelled L5 DRG sections suggested the main effect of injury on GFRα1- and GFRα3-IR was to increase expression in both myelinated and unmyelinated neurons. In contrast, no change in basal expression of GFRα2-IR was detected in DRG by analysis of fluorescence intensity and there was a small but significant reduction in GFRα2-IR neurons. Our results suggest the DRG neuronal populations targeted by GDNF, neurturin or artemin, and the effect of exogenous GFLs could change significantly after a peripheral nerve injury. PMID:20533358

  5. NERVE AS MODEL TEMPERATURE END ORGAN

    PubMed Central

    Bernhard, C. G.; Granit, Ragnar

    1946-01-01

    Rapid local cooling of mammalian nerve sets up a discharge which is preceded by a local temperature potential, the cooled region being electronegative relative to a normal portion of the nerve. Heating the nerve locally above its normal temperature similarly makes the heated region electronegative relative to a region at normal temperature, and again a discharge is set up from the heated region. These local temperature potentials, set up by the nerve itself, are held to serve as "generator potentials" and the mechanism found is regarded as the prototype for temperature end organs. PMID:19873460

  6. Interhemispheric plasticity protects the deafferented somatosensory cortex from functional takeover after nerve injury.

    PubMed

    Yu, Xin; Koretsky, Alan P

    2014-11-01

    Functional changes across brain hemispheres have been reported after unilateral cortical or peripheral nerve injury. Interhemispheric callosal connections usually underlie this cortico-cortical plasticity. However, the effect of the altered callosal inputs on local cortical plasticity in the adult brain is not well studied. Ipsilateral functional magnetic resonance imaging (fMRI) activation has been reliably detected in the deafferented barrel cortex (BC) at 2 weeks after unilateral infraorbital denervation (IO) in adult rats. The ipsilateral fMRI signal relies on callosal-mediated interhemispheric plasticity. This form of interhemispheric plasticity provides a good chronic model to study the interaction between callosal inputs and local cortical plasticity. The receptive field of forepaw in the primary somatosensory cortex (S1), which is adjacent to the BC, was mapped with fMRI. The S1 receptive field expanded to take over a portion of the BC in 2 weeks after both ascending inputs and callosal inputs were removed in IO rats with ablated contralateral BC (IO+ablation). This expansion, estimated specifically by fMRI mapping, is significantly larger than what has been observed in the IO rats with intact callosal connectivity, as well as in the rats with sham surgery. This work indicates that altered callosal inputs prevent the functional takeover of the deafferented BC from adjacent cortices and may help preserve the functional identity of the BC.

  7. Interhemispheric Plasticity Protects the Deafferented Somatosensory Cortex from Functional Takeover After Nerve Injury

    PubMed Central

    Koretsky, Alan P.

    2014-01-01

    Abstract Functional changes across brain hemispheres have been reported after unilateral cortical or peripheral nerve injury. Interhemispheric callosal connections usually underlie this cortico-cortical plasticity. However, the effect of the altered callosal inputs on local cortical plasticity in the adult brain is not well studied. Ipsilateral functional magnetic resonance imaging (fMRI) activation has been reliably detected in the deafferented barrel cortex (BC) at 2 weeks after unilateral infraorbital denervation (IO) in adult rats. The ipsilateral fMRI signal relies on callosal-mediated interhemispheric plasticity. This form of interhemispheric plasticity provides a good chronic model to study the interaction between callosal inputs and local cortical plasticity. The receptive field of forepaw in the primary somatosensory cortex (S1), which is adjacent to the BC, was mapped with fMRI. The S1 receptive field expanded to take over a portion of the BC in 2 weeks after both ascending inputs and callosal inputs were removed in IO rats with ablated contralateral BC (IO+ablation). This expansion, estimated specifically by fMRI mapping, is significantly larger than what has been observed in the IO rats with intact callosal connectivity, as well as in the rats with sham surgery. This work indicates that altered callosal inputs prevent the functional takeover of the deafferented BC from adjacent cortices and may help preserve the functional identity of the BC. PMID:25117691

  8. Peripheral nerve injury modulates neurotrophin signaling in the peripheral and central nervous system.

    PubMed

    Richner, Mette; Ulrichsen, Maj; Elmegaard, Siri Lander; Dieu, Ruthe; Pallesen, Lone Tjener; Vaegter, Christian Bjerggaard

    2014-12-01

    Peripheral nerve injury disrupts the normal functions of sensory and motor neurons by damaging the integrity of axons and Schwann cells. In contrast to the central nervous system, the peripheral nervous system possesses a considerable capacity for regrowth, but regeneration is far from complete and functional recovery rarely returns to pre-injury levels. During development, the peripheral nervous system strongly depends upon trophic stimulation for neuronal differentiation, growth and maturation. The perhaps most important group of trophic substances in this context is the neurotrophins (NGF, BDNF, NT-3 and NT-4/5), which signal in a complex spatial and timely manner via the two structurally unrelated p75(NTR) and tropomyosin receptor kinase (TrkA, Trk-B and Trk-C) receptors. Damage to the adult peripheral nerves induces cellular mechanisms resembling those active during development, resulting in a rapid and robust increase in the synthesis of neurotrophins in neurons and Schwann cells, guiding and supporting regeneration. Furthermore, the injury induces neurotrophin-mediated changes in the dorsal root ganglia and in the spinal cord, which affect the modulation of afferent sensory signaling and eventually may contribute to the development of neuropathic pain. The focus of this review is on the expression patterns of neurotrophins and their receptors in neurons and glial cells of the peripheral nervous system and the spinal cord. Furthermore, injury-induced changes of expression patterns and the functional consequences in relation to axonal growth and remyelination as well as to neuropathic pain development will be reviewed.

  9. The efficacy of a scaffold-free Bio 3D conduit developed from human fibroblasts on peripheral nerve regeneration in a rat sciatic nerve model

    PubMed Central

    Yurie, Hirofumi; Ikeguchi, Ryosuke; Aoyama, Tomoki; Kaizawa, Yukitoshi; Tajino, Junichi; Ito, Akira; Ohta, Souichi; Oda, Hiroki; Takeuchi, Hisataka; Akieda, Shizuka; Tsuji, Manami; Nakayama, Koichi; Matsuda, Shuichi

    2017-01-01

    Background Although autologous nerve grafting is the gold standard treatment of peripheral nerve injuries, several alternative methods have been developed, including nerve conduits that use supportive cells. However, the seeding efficacy and viability of supportive cells injected in nerve grafts remain unclear. Here, we focused on a novel completely biological, tissue-engineered, scaffold-free conduit. Methods We developed six scaffold-free conduits from human normal dermal fibroblasts using a Bio 3D Printer. Twelve adult male rats with immune deficiency underwent mid-thigh-level transection of the right sciatic nerve. The resulting 5-mm nerve gap was bridged using 8-mm Bio 3D conduits (Bio 3D group, n = 6) and silicone tube (silicone group, n = 6). Several assessments were conducted to examine nerve regeneration eight weeks post-surgery. Results Kinematic analysis revealed that the toe angle to the metatarsal bone at the final segment of the swing phase was significantly higher in the Bio 3D group than the silicone group (-35.78 ± 10.68 versus -62.48 ± 6.15, respectively; p < 0.01). Electrophysiological studies revealed significantly higher compound muscle action potential in the Bio 3D group than the silicone group (53.60 ± 26.36% versus 2.93 ± 1.84%; p < 0.01). Histological and morphological studies revealed neural cell expression in all regions of the regenerated nerves and the presence of many well-myelinated axons in the Bio 3D group. The wet muscle weight of the tibialis anterior muscle was significantly higher in the Bio 3D group than the silicone group (0.544 ± 0.063 versus 0.396 ± 0.031, respectively; p < 0.01). Conclusions We confirmed that scaffold-free Bio 3D conduits composed entirely of fibroblast cells promote nerve regeneration in a rat sciatic nerve model. PMID:28192527

  10. Nerve injury induces a new profile of tactile and mechanical nociceptor input from undamaged peripheral afferents.

    PubMed

    Boada, M Danilo; Gutierrez, Silvia; Aschenbrenner, Carol A; Houle, Timothy T; Hayashida, Ken-Ichiro; Ririe, Douglas G; Eisenach, James C

    2015-01-01

    Chronic pain after nerve injury is often accompanied by hypersensitivity to mechanical stimuli, yet whether this reflects altered input, altered processing, or both remains unclear. Spinal nerve ligation or transection results in hypersensitivity to mechanical stimuli in skin innervated by adjacent dorsal root ganglia, but no previous study has quantified the changes in receptive field properties of these neurons in vivo. To address this, we recorded intracellularly from L4 dorsal root ganglion neurons of anesthetized young adult rats, 1 wk after L5 partial spinal nerve ligation (pSNL) or sham surgery. One week after pSNL, hindpaw mechanical withdrawal threshold in awake, freely behaving animals was decreased in the L4 distribution on the nerve-injured side compared with sham controls. Electrophysiology revealed that high-threshold mechanoreceptive cells of A-fiber conduction velocity in L4 were sensitized, with a seven-fold reduction in mechanical threshold, a seven-fold increase in receptive field area, and doubling of maximum instantaneous frequency in response to peripheral stimuli, accompanied by reductions in after-hyperpolarization amplitude and duration. Only a reduction in mechanical threshold (minimum von Frey hair producing neuronal activity) was observed in C-fiber conduction velocity high-threshold mechanoreceptive cells. In contrast, low-threshold mechanoreceptive cells were desensitized, with a 13-fold increase in mechanical threshold, a 60% reduction in receptive field area, and a 40% reduction in instantaneous frequency to stimulation. No spontaneous activity was observed in L4 ganglia, and the likelihood of recording from neurons without a mechanical receptive field was increased after pSNL. These data suggest massively altered input from undamaged sensory afferents innervating areas of hypersensitivity after nerve injury, with reduced tactile and increased nociceptive afferent response. These findings differ importantly from previous preclinical

  11. Nerve injury induces a new profile of tactile and mechanical nociceptor input from undamaged peripheral afferents

    PubMed Central

    Gutierrez, Silvia; Aschenbrenner, Carol A.; Houle, Timothy T.; Hayashida, Ken-ichiro; Ririe, Douglas G.; Eisenach, James C.

    2014-01-01

    Chronic pain after nerve injury is often accompanied by hypersensitivity to mechanical stimuli, yet whether this reflects altered input, altered processing, or both remains unclear. Spinal nerve ligation or transection results in hypersensitivity to mechanical stimuli in skin innervated by adjacent dorsal root ganglia, but no previous study has quantified the changes in receptive field properties of these neurons in vivo. To address this, we recorded intracellularly from L4 dorsal root ganglion neurons of anesthetized young adult rats, 1 wk after L5 partial spinal nerve ligation (pSNL) or sham surgery. One week after pSNL, hindpaw mechanical withdrawal threshold in awake, freely behaving animals was decreased in the L4 distribution on the nerve-injured side compared with sham controls. Electrophysiology revealed that high-threshold mechanoreceptive cells of A-fiber conduction velocity in L4 were sensitized, with a seven-fold reduction in mechanical threshold, a seven-fold increase in receptive field area, and doubling of maximum instantaneous frequency in response to peripheral stimuli, accompanied by reductions in after-hyperpolarization amplitude and duration. Only a reduction in mechanical threshold (minimum von Frey hair producing neuronal activity) was observed in C-fiber conduction velocity high-threshold mechanoreceptive cells. In contrast, low-threshold mechanoreceptive cells were desensitized, with a 13-fold increase in mechanical threshold, a 60% reduction in receptive field area, and a 40% reduction in instantaneous frequency to stimulation. No spontaneous activity was observed in L4 ganglia, and the likelihood of recording from neurons without a mechanical receptive field was increased after pSNL. These data suggest massively altered input from undamaged sensory afferents innervating areas of hypersensitivity after nerve injury, with reduced tactile and increased nociceptive afferent response. These findings differ importantly from previous preclinical

  12. Ischemic injury leads to extracellular matrix alterations in retina and optic nerve

    PubMed Central

    Reinhard, Jacqueline; Renner, Marina; Wiemann, Susanne; Shakoor, Daniel A.; Stute, Gesa; Dick, H. Burkhard; Faissner, Andreas; Joachim, Stephanie C.

    2017-01-01

    Retinal ischemia occurs in a variety of eye diseases. Restrained blood flow induces retinal damage, which leads to progressive optic nerve degeneration and vision loss. Previous studies indicate that extracellular matrix (ECM) constituents play an important role in complex tissues, such as retina and optic nerve. They have great impact on de- and regeneration processes and represent major candidates of central nervous system glial scar formation. Nevertheless, the importance of the ECM during ischemic retina and optic nerve neurodegeneration is not fully understood yet. In this study, we analyzed remodeling of the extracellular glycoproteins fibronectin, laminin, tenascin-C and tenascin-R and the chondroitin sulfate proteoglycans (CSPGs) aggrecan, brevican and phosphacan/RPTPβ/ζ in retinae and optic nerves of an ischemia/reperfusion rat model via quantitative real-time PCR, immunohistochemistry and Western blot. A variety of ECM constituents were dysregulated in the retina and optic nerve after ischemia. Regarding fibronectin, significantly elevated mRNA and protein levels were observed in the retina following ischemia, while laminin and tenascin-C showed enhanced immunoreactivity in the optic nerve after ischemia. Interestingly, CSPGs displayed significantly increased expression levels in the optic nerve. Our study demonstrates a dynamic expression of ECM molecules following retinal ischemia, which strengthens their regulatory role during neurodegeneration. PMID:28262779

  13. Delaying histone deacetylase response to injury accelerates conversion into repair Schwann cells and nerve regeneration

    PubMed Central

    Brügger, Valérie; Duman, Mert; Bochud, Maëlle; Münger, Emmanuelle; Heller, Manfred; Ruff, Sophie; Jacob, Claire

    2017-01-01

    The peripheral nervous system (PNS) regenerates after injury. However, regeneration is often compromised in the case of large lesions, and the speed of axon reconnection to their target is critical for successful functional recovery. After injury, mature Schwann cells (SCs) convert into repair cells that foster axonal regrowth, and redifferentiate to rebuild myelin. These processes require the regulation of several transcription factors, but the driving mechanisms remain partially understood. Here we identify an early response to nerve injury controlled by histone deacetylase 2 (HDAC2), which coordinates the action of other chromatin-remodelling enzymes to induce the upregulation of Oct6, a key transcription factor for SC development. Inactivating this mechanism using mouse genetics allows earlier conversion into repair cells and leads to faster axonal regrowth, but impairs remyelination. Consistently, short-term HDAC1/2 inhibitor treatment early after lesion accelerates functional recovery and enhances regeneration, thereby identifying a new therapeutic strategy to improve PNS regeneration after lesion. PMID:28139683

  14. Qualitative effect on mRNAs of injury-associated proteins by cell phone like radiation in rat facial nerves.

    PubMed

    Yan, Ji-Geng; Agresti, Michael; Zhang, Lin-Ling; Yan, Yuhui; Matloub, Hani S

    2009-01-01

    Rats were exposed to cell phone radiation for 6 hours per day for 18 weeks. The buccal and mandibular branches of the facial nerve were evaluated for this study. The mRNA levels of four proteins that are usually up regulated when an injury has occurred were investigated; included were Calcium ATP-ase, Endothelin, Neural Cell Adhesion Molecule, and Neural Growth Factor. These isolated mRNAs were subjected to RT-PCR and all four were up regulated. The mandibular nerve showed a higher and broader level of up regulation than the buccal nerve. All four mRNA up regulations for the mandibular nerve and two for the buccal nerve were also statistically significant. These specific injury-related findings were mild. As the use of these cell phones continues, there most likely will be permanent damage to these tissues over the years and the likelihood of tumors, cancers, and system failures will potentially increase.

  15. [Monitoring of recurrent laryngeal nerve injury using an electromyographic endotracheal tube in thyroid and parathyroid surgery. Anesthetic aspects].

    PubMed

    Martín Jaramago, J; Tamarit Conejeros, M; Escudero Torrella, M; Solaz Roldán, C

    2013-12-01

    Recurrent laryngeal nerve injury remains one of the main complications in thyroid and parathyroid surgery. When this injury is bilateral, an acute upper airway obstruction may occur, leading to a potentially life-threatening situation for the patient. The visual identification of the nerve during surgery is the best way to preserve its integrity. However identification of the nerves by means of electromyographic stimuli through electrodes attached to endotracheal tubes could help in decreasing nerve injury. In these cases the experience and role of the anesthetist is essential to correctly place the electromyographic endotracheal tube and ensure that the electrodes are in touch with the vocal cords during the surgery. Moreover, the results of the electromyography can be affected by the neuromuscular blocking agents. Therefore, the choice and dose must be adapted, in order to ensure a suitable anesthetic depth, and adequate response.

  16. Enhanced synthesis and secretion of apolipoprotein E from sciatic nerves of streptozotocin-induced diabetic rats after injury

    SciTech Connect

    Ishibashi, S.; Yamada, N.; Oka, Y.; Shimano, H.; Mori, N.; Yoon, T.H.; Shimada, M.; Kanazawa, Y.; Akanuma, Y.; Murase, T.

    1988-08-30

    To elucidate the pathogenesis of diabetic neuropathy, synthesis and secretion of apolipoprotein E (apo E) from sciatic nerves after injury was studied in normal and streptozotocin-induced diabetic rats. Seven, 14, 28, 45 and 59 days after making crush injury on sciatic nerves with concomitant administration of streptozotocin (50 mg/kg body weight), the nerves were taken out and incubated with (/sup 35/S)methionine. The (/sup 35/S)labeled apo E was precipitated with specific antiserum. The amounts of apo E secreted into medium by nerves of diabetic rats were 7 times greater than those of non-diabetic rats 7 days after injury. This enhanced secretion of apo E was relatively selective for this protein, since the ratio of the immunoprecipitable apo E to the TCA preciptitable protein in the medium increased in diabetic rats. Intriguing possibility deduced from these results is that the secretion of apo E is involved in the development of diabetic neuropathy.

  17. RNA editing enzyme ADAR2 is a mediator of neuropathic pain after peripheral nerve injury.

    PubMed

    Uchida, Hitoshi; Matsumura, Shinji; Okada, Shunpei; Suzuki, Tsutomu; Minami, Toshiaki; Ito, Seiji

    2017-01-26

    Transcriptional and post-translational regulations are important in peripheral nerve injury-induced neuropathic pain, but little is known about the role of post-transcriptional modification. Our objective was to determine the possible effect of adenosine deaminase acting on RNA (ADAR) enzymes, which catalyze post-transcriptional RNA editing, in tactile allodynia, a hallmark of neuropathic pain. Seven days after L5 spinal nerve transection (SNT) in adult mice, we found an increase in ADAR2 expression and a decrease in ADAR3 expression in the injured, but not in the uninjured, dorsal root ganglions (DRGs). These changes were accompanied by elevated levels of editing at the D site of the serotonin 2C receptor (5-HT2CR), at the I/V site of coatomer protein complex subunit α (COPA), and at the R/G site of AMPA receptor subunit GluA2 in the injured DRG. Compared to Adar2(+/+)/Gria2(R/R) littermate controls, Adar2(-/-)/Gria2(R/R) mice completely lacked the increased editing of 5-HT2CR, COPA, and GluA2 transcripts in the injured DRG and showed attenuated tactile allodynia after SNT. Furthermore, the antidepressant fluoxetine inhibited neuropathic allodynia after injury and reduced the COPA I/V site editing in the injured DRG. These findings suggest that ADAR2 is a mediator of injury-induced tactile allodynia and thus a potential therapeutic target for the treatment of neuropathic pain.-Uchida, H., Matsumura, S., Okada, S., Suzuki, T., Minami, T., Ito, S. RNA editing enzyme ADAR2 is a mediator of neuropathic pain after peripheral nerve injury.

  18. Calpain 3 Expression Pattern during Gastrocnemius Muscle Atrophy and Regeneration Following Sciatic Nerve Injury in Rats

    PubMed Central

    Wu, Ronghua; Yan, Yingying; Yao, Jian; Liu, Yan; Zhao, Jianmei; Liu, Mei

    2015-01-01

    Calpain 3 (CAPN3), also known as p94, is a skeletal muscle-specific member of the calpain family that is involved in muscular dystrophy; however, the roles of CAPN3 in muscular atrophy and regeneration are yet to be understood. In the present study, we attempted to explain the effect of CAPN3 in muscle atrophy by evaluating CAPN3 expression in rat gastrocnemius muscle following reversible sciatic nerve injury. After nerve injury, the wet weight ratio and cross sectional area (CSA) of gastrocnemius muscle were decreased gradually from 1–14 days and then recovery from 14–28 days. The active form of CAPN3 (~62 kDa) protein decreased slightly on day 3 and then increased from day 7 to 14 before a decrease from day 14 to 28. The result of linear correlation analysis showed that expression of the active CAPN3 protein level was negatively correlated with muscle wet weight ratio. CAPN3 knockdown by short interfering RNA (siRNA) injection improved muscle recovery on days 7 and 14 after injury as compared to that observed with control siRNA treatment. Depletion of CAPN3 gene expression could promote myoblast differentiation in L6 cells. Based on these findings, we conclude that the expression pattern of the active CAPN3 protein is linked to muscle atrophy and regeneration following denervation: its upregulation during early stages may promote satellite cell renewal by inhibiting differentiation, whereas in later stages, CAPN3 expression may be downregulated to stimulate myogenic differentiation and enhance recovery. These results provide a novel mechanistic insight into the role of CAPN3 protein in muscle regeneration after peripheral nerve injury. PMID:26569227

  19. A novel electrical model of nerve and muscle using Pspice

    NASA Astrophysics Data System (ADS)

    Peasgood, W.; Dissado, L. A.; Lam, C. K.; Armstrong, A.; Wood, W.

    2003-02-01

    In this work, a model is developed to simulate the biological processes involved in nerve fibre transmission and subsequent muscle contraction. The model has been based on approximating biological structure and function to electrical circuits and as such was implemented on an electronics simulation software package called Pspice. Models of nerve, the nerve-muscle interface and muscle fibre have been implemented. The time dependent ionic properties of the nerve and muscle membranes have been simulated using the Hodgkin-Huxley equations and for the muscle fibre, the implementation of the Huxley sliding filament theory for muscular contraction. The results show that nerve may be considered as a fractal transmission line and that the amplitude of the nerve membrane depolarization is dependent on the dimensions of the fibre. Additionally, simulation of the nerve-muscle interface allows the fractal nerve model to be connected to the muscle fibre model and it is shown that a two sarcomere molecular simulation can produce realistic macroscopic muscle force profiles.

  20. Comparison of immunohistochemical and functional reinnervation of skin and muscle after peripheral nerve injury.

    PubMed

    Verdu, E; Navarro, X

    1997-07-01

    In order to investigate the usefulness of immunohistochemical detection of regenerating axons as a correlate of functional recovery, reinnervation of mouse foot pads, hairy skin, and muscle were studied at several intervals along 3 months after sciatic nerve crush using immunohistochemical markers PGP 9.5 and CGRP. These histological results were compared with functional recovery of sweat glands (SGs), plantar muscles, and pain sensibility. One week after nerve injury all neural functions were abolished in the operated hindpaw of all mice, no CGRP-immunoreactive (-ir) fibers were seen in the samples studied, while PGP 9.5 immunofluorescence remained at dim levels within nerve trunks, but disappeared from terminal innervation. The first PGP 9.5- and CGRP-ir regenerating fibers were seen at 15-16 days postoperation (dpo) in dermal nerve trunks of dorsal hairy skin and some days later in dermal trunks of foot pads. Regenerating nerve fibers progressed along the periphery of the dermis reinnervating the different dermal appendages. At 25 dpo all target organs were reinnervated. The first SGs activated by pilocarpine reappeared by 16 dpo and increased in number to 88% of control counts. Nociceptive responses reappeared at 17 dpo and reached 100% of control values. The first PGP immunofluorescence in neuromuscular junctions was seen at 16 dpo, while the first muscle action potentials were recorded at 19 dpo, and the potentials amplitude increased to 66% of controls. Good correlations were found between morphological and functional results of reinnervation. However, the density and distribution of nerve profiles in the tissues studied did not reach normal levels, while neural functions conveyed by small fibers reached levels similar to controls.

  1. Radial nerve injury associated with humeral shaft fracture: a retrospective study

    PubMed Central

    Ricci, Flávia Pessoni Faleiros Macêdo; Barbosa, Rafael Inácio; Elui, Valéria Meirelles Carril; Barbieri, Cláudio Henrique; Mazzer, Nilton; Fonseca, Marisa de Cássia Registro

    2015-01-01

    Objective: To determine the profile of patients with humeral diaphyseal fractures in a tertiary hospital. Methods: We conducted a survey from January 2010 to July 2012, including data from patients classified under humeral diaphyseal fracture (S42.3) according to the International Classification of Diseases (ICD-10). The variables analyzed were: age, gender, presence of radial nerve injury, causal agent and the type of treatment carried out. Results: The main causes of trauma were car accidents. The radial nerve lesion was present in some cases and was caused by the same trauma that caused the fracture or iatrogenic injury. Most of these fractures occurred in the middle third of humeral diaphysis and was treated conservatively. Conclusion: The profile of patients with fracture of humeral shaft, in this specific sample, was composed mainly of adult men involved in traffic accidents; the associated radial nerve lesion was present in most of these fractures and its cause was strongly related to the trauma mechanism. Level of Evidence II, Retrospective Study. PMID:26327789

  2. Nerve injury induces robust allodynia and ectopic discharges in Nav1.3 null mutant mice

    PubMed Central

    Nassar, Mohammed A; Baker, Mark D; Levato, Alessandra; Ingram, Rachel; Mallucci, Giovanna; McMahon, Stephen B; Wood, John N

    2006-01-01

    Changes in sodium channel activity and neuronal hyperexcitability contribute to neuropathic pain, a major clinical problem. There is strong evidence that the re-expression of the embryonic voltage-gated sodium channel subunit Nav1.3 underlies neuronal hyperexcitability and neuropathic pain. Here we show that acute and inflammatory pain behaviour is unchanged in global Nav1.3 mutant mice. Surprisingly, neuropathic pain also developed normally in the Nav1.3 mutant mouse. To rule out any genetic compensation mechanisms that may have masked the phenotype, we investigated neuropathic pain in two conditional Nav1.3 mutant mouse lines. We used Nav1.8-Cre mice to delete Nav1.3 in nociceptors at E14 and NFH-Cre mice to delete Nav1.3 throughout the nervous system postnatally. Again normal levels of neuropathic pain developed after nerve injury in both lines. Furthermore, ectopic discharges from damaged nerves were unaffected by the absence of Nav1.3 in global knock-out mice. Our data demonstrate that Nav1.3 is neither necessary nor sufficient for the development of nerve-injury related pain. PMID:17052333

  3. Does Pulsed Magnetic Field Therapy Influence Nerve Regeneration in the Median Nerve Model of the Rat?

    PubMed Central

    Beck-Broichsitter, Benedicta E.; Lamia, Androniki; Fregnan, Federica; Smeets, Ralf; Becker, Stephan T.; Sinis, Nektarios

    2014-01-01

    The aim of this study was to evaluate the impact of pulsed magnetic field therapy on peripheral nerve regeneration after median nerve injury and primary coaptation in the rat. Both median nerves were surgically exposed and denervated in 24 female Wistar rats. A microsurgical coaptation was performed on the right side, whereas on the left side a spontaneous healing was prevented. The study group underwent a daily pulsed magnetic field therapy; the other group served as a control group. The grasping force was recorded 2 weeks after the surgical intervention for a period of 12 weeks. The right median nerve was excised and histologically examined. The histomorphometric data and the functional assessments were analyzed by t-test statistics and one-way ANOVA. One-way ANOVA indicated a statistically significant influence of group affiliation and grasping force (P = 0.0078). Grasping strength was higher on a significant level in the experimental group compared to the control group permanently from the 9th week to the end of the study. T-test statistics revealed a significantly higher weight of the flexor digitorum sublimis muscle (P = 0.0385) in the experimental group. The histological evaluation did not reveal any statistically significant differences concerning the histomorphometric parameters. Our results suggest that the pulsed magnetic field therapy has a positive influence on the functional aspects of neural regeneration. More studies are needed to precisely evaluate and optimize the intensity and duration of the application. PMID:25143937

  4. Blast injury research models

    PubMed Central

    Kirkman, E.; Watts, S.; Cooper, G.

    2011-01-01

    Blast injuries are an increasing problem in both military and civilian practice. Primary blast injury to the lungs (blast lung) is found in a clinically significant proportion of casualties from explosions even in an open environment, and in a high proportion of severely injured casualties following explosions in confined spaces. Blast casualties also commonly suffer secondary and tertiary blast injuries resulting in significant blood loss. The presence of hypoxaemia owing to blast lung complicates the process of fluid resuscitation. Consequently, prolonged hypotensive resuscitation was found to be incompatible with survival after combined blast lung and haemorrhage. This article describes studies addressing new forward resuscitation strategies involving a hybrid blood pressure profile (initially hypotensive followed later by normotensive resuscitation) and the use of supplemental oxygen to increase survival and reduce physiological deterioration during prolonged resuscitation. Surprisingly, hypertonic saline dextran was found to be inferior to normal saline after combined blast injury and haemorrhage. New strategies have therefore been developed to address the needs of blast-injured casualties and are likely to be particularly useful under circumstances of enforced delayed evacuation to surgical care. PMID:21149352

  5. Structure and function of myelinated nerve fibers in the rabbit eye following ischemia/reperfusion injury.

    PubMed

    Guo, Wenyi; Cringle, Stephen J; Su, Er-Ning; Yu, Paula K; Yu, Xiao-Bo; Sun, Xinghuai; Morgan, William; Yu, Dao-Yi

    2006-02-01

    The rabbit eye presents a valuable model to study the effects of vascular occlusion on the function and structure of myelinated nerve fibers. The rabbit eye has a band of myelinated nerve fibers within the intraocular compartment that are supplied by a narrow band of retinal vasculature. These vessels were transiently occluded ( approximately 8 hours) using laser photocoagulation and the transmission of electrical signals along the nerve fibers was assessed by recording the visual evoked response (VER). Morphological damage was assessed by histological techniques. The ischemic insult produced no permanent change in retinal function as assessed by electroretinography, but the VER was suppressed, indicating failure of nerve fiber transmission. Histologically, the visible damage to the region supported by the retinal vasculature worsened following reperfusion, showing evidence of demyelination and necrosis followed by macrophage responses and gliosis. This rabbit model of ischemia/reperfusion of the retinal vasculature offers a rare opportunity to reliably study the response of myelinated nerve fibers to ischemia/reperfusion insults and has demonstrated the susceptibility of myelinated nerve fibers to such insults.

  6. An Apolipoprotein E-Mimetic Stimulates Axonal Regeneration and Remyelination after Peripheral Nerve Injury

    PubMed Central

    Fowler, Kenneth A.; Neil, Jessica E.; Colton, Carol A.; Vitek, Michael P.

    2010-01-01

    Elevated apolipoprotein E (apoE) synthesis within crushed sciatic nerves advocates that apoE could benefit axonal repair and reconstruction of axonal and myelin membranes. We created an apoE-mimetic peptide, COG112 (acetyl-RQIKIWFQNRRMKWKKCLRVRLASHLRKLRKRLL-amide), and found that postinjury treatment with COG112 significantly improved recovery of motor and sensory function following sciatic nerve crush in C57BL/6 mice. Morphometric analysis of injured sciatic nerves revealed that COG112 promoted axonal regrowth after 2 weeks of treatment. More strikingly, the thickness of myelin sheaths was increased by COG112 treatment. Consistent with these histological findings, COG112 potently elevated growth associated protein 43 (GAP-43) and peripheral myelin protein zero (P0), which are markers of axon regeneration and remyelination, respectively. Electron microscopic examination further suggested that the apoE-mimetic COG112 may increase clearance of myelin debris. Schwann cell uptake of cholesterol-containing low-density lipoprotein particles was selectively enhanced by COG112 treatment in a Schwann cell line S16. Moreover, COG112 significantly promoted axon elongation in primary dorsal root ganglion cultures from rat pups. Considering that cholesterol and lipids are needed for reconstructing myelin sheaths and axon extension, these data support a hypothesis where supplementation with exogenous apoE-mimetics such as COG112 may be a promising strategy for restoring lost functional and structural elements following nerve injury. PMID:20406857

  7. An apolipoprotein E-mimetic stimulates axonal regeneration and remyelination after peripheral nerve injury.

    PubMed

    Li, Feng-Qiao; Fowler, Kenneth A; Neil, Jessica E; Colton, Carol A; Vitek, Michael P

    2010-07-01

    Elevated apolipoprotein E (apoE) synthesis within crushed sciatic nerves advocates that apoE could benefit axonal repair and reconstruction of axonal and myelin membranes. We created an apoE-mimetic peptide, COG112 (acetyl-RQIKIWFQNRRMKWKKCLRVRLASHLRKLRKRLL-amide), and found that postinjury treatment with COG112 significantly improved recovery of motor and sensory function following sciatic nerve crush in C57BL/6 mice. Morphometric analysis of injured sciatic nerves revealed that COG112 promoted axonal regrowth after 2 weeks of treatment. More strikingly, the thickness of myelin sheaths was increased by COG112 treatment. Consistent with these histological findings, COG112 potently elevated growth associated protein 43 (GAP-43) and peripheral myelin protein zero (P0), which are markers of axon regeneration and remyelination, respectively. Electron microscopic examination further suggested that the apoE-mimetic COG112 may increase clearance of myelin debris. Schwann cell uptake of cholesterol-containing low-density lipoprotein particles was selectively enhanced by COG112 treatment in a Schwann cell line S16. Moreover, COG112 significantly promoted axon elongation in primary dorsal root ganglion cultures from rat pups. Considering that cholesterol and lipids are needed for reconstructing myelin sheaths and axon extension, these data support a hypothesis where supplementation with exogenous apoE-mimetics such as COG112 may be a promising strategy for restoring lost functional and structural elements following nerve injury.

  8. Repeated activation of delta opioid receptors counteracts nerve injury-induced TNF-α up-regulation in the sciatic nerve of rats with neuropathic pain

    PubMed Central

    Vicario, Nunzio; Parenti, Rosalba; Aricò, Giuseppina; Turnaturi, Rita; Scoto, Giovanna Maria; Chiechio, Santina

    2016-01-01

    Despite mu opioid receptor agonists are the cornerstones of moderate-to-severe acute pain treatment, their effectiveness in chronic pain conditions is controversial. In contrast to mu opioid receptor agonists, a number of studies have reported the effectiveness of delta opioid receptor agonists on neuropathic pain strengthening the idea that delta opioid receptors gain importance when chronic pain develops. Among other effects, it has been shown that delta opioid receptor activation in optic nerve astrocytes inhibits tumor necrosis factor-α-mediated inflammation in response to severe hypoxia. Considering the involvement of tumor necrosis factor-α in the development and maintenance of neuropathic pain, with this study we sought to correlate the effect of delta opioid receptor agonist on the development of mechanical allodynia to tumor necrosis factor-α expression at the site of nerve injury in rats subjected to chronic constriction injury of the sciatic nerve. To this aim, we measured the levels of tumor necrosis factor-α in the sciatic nerve of rats with neuropathic pain after repeated injections with a delta opioid receptor agonist. Results obtained demonstrated that repeated administrations of the delta opioid receptor agonist SNC80 (10 mg/kg, i.p. for seven consecutive days) significantly inhibited the development of mechanical allodynia in rats with neuropathic pain and that the improvement of neuropathic symptom was timely related to the reduced expression of tumor necrosis factor-α in the rat sciatic nerve. We demonstrated also that when treatment with the delta opioid receptor agonist was suspended both allodynia and tumor necrosis factor-α up-regulation in the sciatic nerve of rats with neuropathic pain were restored. These results show that persistent delta opioid receptor activation significantly attenuates neuropathic pain and negatively regulates sciatic nerve tumor necrosis factor-α expression in chronic constriction injury rats. PMID:27590071

  9. Morphological assessment of early axonal regeneration in end-to-side nerve coaptation models.

    PubMed

    Oyamatsu, Hiroshi; Koga, Daisuke; Igarashi, Michihiro; Shibata, Minoru; Ushiki, Tatsuo

    2012-10-01

    Histological changes were observed in peripheral nerves following end-to-side nerve coaptation to determine the effects of perineurial opening and deliberate donor nerve injury during surgery. Twenty rats were randomised into four groups as follows: group 1, end-to-side nerve coaptation without perineurial opening; group 2, end-to-side nerve coaptation with simple perineurial opening; group 3, end-to-side nerve coaptation with partial crush injury after perineurial opening; group 4, end-to-side nerve coaptation with partial neurotomy after perineurial opening. Seven days after coaptation of the musculocutaneous (recipient) nerve to the ulnar (donor) nerve, the nerves were immunohistochemically analysed using antibodies against neurofilament-H (RT97) and phosphorylated GAP-43 (p-GAP-43). The former labels all axons, including regenerating axons and degenerated axonal debris, while the latter only labels regenerating axons. Results demonstrated no regenerating nerves in the recipient nerve of group 1. In group 2, because nerve herniation from the perineurial opening partially injured donor nerve fibres, some regenerating axons extended proximally and distally along the partially injured fibres in the donor nerve; some of these regenerating axons also extended into the recipient nerve via the perineurial opening. In groups 3 and 4, thin regenerating axons were more prominent in recipient and donor nerves compared with group 2. Statistical evaluation revealed increased efficacy of perineurial opening and deliberate donor nerve injury in end-to-side nerve coaptation, suggesting that partial nerve fibre herniation with partial axonotmesis or neurotomesis was important for effective axonal regeneration in end-to-side nerve coaptation.

  10. Modulation of NMDA receptor expression in the rat spinal cord by peripheral nerve injury and adrenal medullary grafting.

    PubMed

    Hama, A T; Unnerstall, J R; Siegan, J B; Sagen, J

    1995-07-31

    Excessive activation of N-methyl-D-aspartate (NMDA) receptors in the spinal cord consequent to peripheral injury has been implicated in the initiation of neuropathologic events leading to a state of chronic hyperexcitability and persistence of exaggerated sensory processing. In other CNS disease or injury states, NMDA-mediated neurotoxic damage is associated with a loss of NMDA receptors, and outcome may be improved by agents reducing NMDA activation. Previous findings in our laboratory have demonstrated that the transplantation of adrenal medullary tissue into the spinal subarachnoid space can alleviate sensory abnormalities and reduce the induction of a putative nitric oxide synthase consequent to peripheral nerve injury. In order to determine changes in NMDA receptor expression in the spinal cord following peripheral nerve injury and adrenal medullary grafting, NMDA receptor binding using a high-affinity competitive NMDA receptor antagonist, CGP-39653, and NMDAR1 subunit distribution using immunocytochemistry were investigated. Two weeks following peripheral nerve injury by loose ligation of the right sciatic nerve, either adrenal medullary or striated muscle (control) tissue pieces were implanted in the spinal subarachnoid space. Binding studies revealed a marked reduction in [3H]CGP-39653 binding at L4-L5 levels ipsilateral to peripheral nerve injury in control transplanted animals. In contrast, NMDA binding was normalized in adrenal medullary grafted animals. In addition, NMDAR1 immunoreactivity was reduced in both the dorsal horn neuropil and motor neurons of the ventral horn in animals with peripheral nerve injury, while levels in adrenal medullary grafted animals appeared similar to intact controls. These results suggest that adrenal medullary transplants reduce abnormal sensory processing resulting from peripheral injury by intervening in the spinal NMDA-excitotoxicity cascade.

  11. Linear Ordered Collagen Scaffolds Loaded with Collagen-Binding Basic Fibroblast Growth Factor Facilitate Recovery of Sciatic Nerve Injury in Rats

    PubMed Central

    Ma, Fukai; Xiao, Zhifeng; Chen, Bing; Hou, Xianglin

    2014-01-01

    Natural biological functional scaffolds, consisting of biological materials filled with promoting elements, provide a promising strategy for the regeneration of peripheral nerve defects. Collagen conduits have been used widely due to their excellent biological properties. Linear ordered collagen scaffold (LOCS) fibers are good lumen fillers that can guide nerve regeneration in an ordered direction. In addition, basic fibroblast growth factor (bFGF) is important in the recovery of nerve injury. However, the traditional method for delivering bFGF to the lesion site has no long-term effect because of its short half-life and rapid diffusion. Therefore, we fused a specific collagen-binding domain (CBD) peptide to the N-terminal of native basic fibroblast growth factor (NAT-bFGF) to retain bFGF on the collagen scaffolds. In this study, a natural biological functional scaffold was constructed using collagen tubes filled with collagen-binding bFGF (CBD-bFGF)-loaded LOCS to promote regeneration in a 5-mm rat sciatic nerve transection model. Functional evaluation, histological investigation, and morphometric analysis indicated that the natural biological functional scaffold retained more bFGF at the injury site, guided axon growth, and promoted nerve regeneration as well as functional restoration. PMID:24188561

  12. The change of HCN1/HCN2 mRNA expression in peripheral nerve after chronic constriction injury induced neuropathy followed by pulsed electromagnetic field therapy

    PubMed Central

    Liu, Hui; Zhou, Jun; Gu, Lianbing; Zuo, Yunxia

    2017-01-01

    Neuropathic pain is usually defined as a chronic pain state caused by peripheral or central nerve injury as a result of acute damage or systemic diseases. It remains a difficult disease to treat. Recent studies showed that the frequency of action potentials in nociceptive afferents is affected by the activity of hyperpolarization-activated cyclic nucleotide-gated cation channels (HCN) family. In the current study, we used a neuropathy rat model induced by chronic constriction injury (CCI) of sciatic nerve to evaluate the change of expression of HCN1/HCN2 mRNA in peripheral nerve and spinal cord. Rats were subjected to CCI with or without pulsed electromagnetic field (PEMF) therapy. It was found that CCI induced neural cell degeneration while PEMF promoted nerve regeneration as documented by Nissl staining. CCI shortened the hind paw withdrawal latency (PWL) and hind paw withdrawal threshold (PWT) and PEMF prolonged the PWL and PWT. In addition, CCI lowers the expression of HCN1 and HCN2 mRNA and PEMF cannot restore the expression of HCN1 and HCN2 mRNA. Our results indicated that PEMF can promote nerve regeneration and could be used for the treatment of neuropathic pain. PMID:27901476

  13. Fifth lumbar spinal nerve injury causes neurochemical changes in corresponding as well as adjacent spinal segments: a possible mechanism underlying neuropathic pain.

    PubMed

    Shehab, Safa Al-Deen Saudi

    2014-01-01

    Previous investigations of the anatomical basis of the neuropathic-like manifestations in the spinal nerve ligation animal model have shown that the central terminations of the unmyelinated primary afferents of L5 spinal nerve are not restricted to the corresponding L5 spinal segment, and rather extend to two spinal segments rostrally and one segment caudally where they intermingle with primary afferents of the adjacent L4 spinal nerve. The aim of the present study was to investigate the neurochemical changes in the dorsal horn of the spinal cord and DRGs after L5 nerve injury in rats. In the first experiment, the right L5 nerve was ligated and sectioned for 14 days, and isolectin B4 (IB4, a tracer for unmyelinated primary afferents) was injected into the left L5 nerve. The results showed that the vasoactive intestinal peptide (VIP) was up-regulated in laminae I-II of L3-L6 spinal segments on the right side in exactly the same areas where IB4 labelled terminals were revealed on the left side. In the second experiment, L5 was ligated and sectioned and the spinal cord and DRGs were stained immunocytochemically with antibodies raised against various peptides known to be involved in pain transmission and hyperalgesia. The results showed that L5 nerve lesion caused down-regulation of substance P, calcitonin-gene related peptide and IB4 binding and up-regulation of neuropeptide Y and neurokinin-1 receptor in the dorsal horn of L4 and L5 spinal segments. Similar neurochemical changes were observed only in the corresponding L5 DRG with minimal effects observed in L3, L4 and L6 DRGs. Although, L5 nerve injury caused an up-regulation in NPY, no change in SP and CGRP immunoreactivity was observed in ipsilateral garcile nucleus. These neuroplastic changes in the dorsal horn of the spinal cord, in the adjacent uninjured territories of the central terminations of the adjacent uninjured nerves, might explain the mechanism of hyperalgesia after peripheral nerve injury.

  14. Characterization of intrinsic properties of cingulate pyramidal neurons in adult mice after nerve injury

    PubMed Central

    2009-01-01

    The anterior cingulate cortex (ACC) is important for cognitive and sensory functions including memory and chronic pain. Glutamatergic excitatory synaptic transmission undergo long-term potentiation in ACC pyramidal cells after peripheral injury. Less information is available for the possible long-term changes in neuronal action potentials or intrinsic properties. In the present study, we characterized cingulate pyramidal cells in the layer II/III of the ACC in adult mice. We then examined possible long-term changes in intrinsic properties of the ACC pyramidal cells after peripheral nerve injury. In the control mice, we found that there are three major types of pyramidal cells according to their action potential firing pattern: (i) regular spiking (RS) cells (24.7%), intrinsic bursting (IB) cells (30.9%), and intermediate (IM) cells (44.4%). In a state of neuropathic pain, the population distribution (RS: 21.3%; IB: 31.2%; IM: 47.5%) and the single action potential properties of these three groups were indistinguishable from those in control mice. However, for repetitive action potentials, IM cells from neuropathic pain animals showed higher initial firing frequency with no change for the properties of RS and IB neurons from neuropathic pain mice. The present results provide the first evidence that, in addition to synaptic potentiation reported previously, peripheral nerve injury produces long-term plastic changes in the action potentials of cingulate pyramidal neurons in a cell type-specific manner. PMID:20015370

  15. Peripheral Nerve Injury in Developing Rats Reorganizes Representation Pattern in Motor Cortex

    NASA Astrophysics Data System (ADS)

    Donoghue, John P.; Sanes, Jerome N.

    1987-02-01

    We investigated the effect of neonatal nerve lesions on cerebral motor cortex organization by comparing the cortical motor representation of normal adult rats with adult rats that had one forelimb removed on the day of birth. Mapping of cerebral neocortex with electrical stimulation revealed an altered relationship between the motor cortex and the remaining muscles. Whereas distal forelimb movements are normally elicited at the lowest threshold in the motor cortex forelimb area, the same stimuli activated shoulder and trunk muscles in experimental animals. In addition, an expanded cortical representation of intact body parts was present and there was an absence of a distinct portion of motor cortex. These data demonstrate that representation patterns in motor cortex can be altered by peripheral nerve injury during development.

  16. Immune system augmentation by glatiramer acetate of peripheral nerve regeneration-crush versus transection models of rat sciatic nerve.

    PubMed

    Luria, Shai; Cohen, Avraham; Safran, Ori; Firman, Shimon; Liebergall, Meir

    2013-10-01

    Immune system augmentation, using the antigen glatiramer acetate (GA), which is known to affect cellular immunity, has been shown to have a positive effect on peripheral nerve regeneration. We aimed to compare the effect of GA on the regeneration of crushed versus transected nerves. Wild-type rats underwent crush or transection and repair of the sciatic nerve. They were examined 3 weeks postinjury histologically (axon count) and functionally (tibialis anterior muscle weight and footprint analysis). GA was found to augment regeneration both histologically and functionally. In the transected nerve, a significant increase in axon count distal to the injury site was seen in the GA group versus control. A similar yet statistically insignificant trend was found in the crushed nerve. Improvement was found in the footprint analysis between the GA and control groups in both crush and transected nerve groups. We found improvement in the footprint analysis in the crush versus transection group. GA was found to improve the regeneration of the peripheral nerve. Histologically, this was more pronounced in the transection injury. The discrepancy between the different functional measures examined may be explained by the distance of the reinnervated muscles evaluated from the injury site.

  17. Association of overactive bladder and stress urinary incontinence in rats with pudendal nerve ligation injury.

    PubMed

    Furuta, Akira; Kita, Masafumi; Suzuki, Yasuyuki; Egawa, Shin; Chancellor, Michael B; de Groat, William C; Yoshimura, Naoki

    2008-05-01

    Approximately one-third of patients with stress urinary incontinence (SUI) also suffer from urgency incontinence, which is one of the major symptoms of overactive bladder (OAB) syndrome. Pudendal nerve injury has been recognized as a possible cause for both SUI and OAB. Therefore, we investigated the effects of pudendal nerve ligation (PNL) on bladder function and urinary continence in female Sprague-Dawley rats. Conscious cystometry with or without capsaicin pretreatment (125 mg/kg sc), leak point pressures (LPPs), contractile responses of bladder muscle strips to carbachol or phenylephrine, and levels of nerve growth factor (NGF) protein and mRNA in the bladder were compared in sham and PNL rats 4 wk after the injury. Urinary frequency detected by a reduction in intercontraction intervals and voided volume was observed in PNL rats compared with sham rats, but it was not seen in PNL rats with capsaicin pretreatment that desensitizes C-fiber-afferent pathways. LPPs in PNL rats were significantly decreased compared with sham rats. The contractile responses of detrusor muscle strips to phenylephrine, but not to carbachol, were significantly increased in PNL rats. The levels of NGF protein and mRNA in the bladder of PNL rats were significantly increased compared with sham rats. These results suggest that pudendal nerve neuropathy induced by PNL may be one of the potential risk factors for OAB, as well as SUI. Somato-visceral cross sensitization between somatic (pudendal) and visceral (bladder) sensory pathways that increases NGF expression and alpha(1)-adrenoceptor-mediated contractility in the bladder may be involved in this pathophysiological mechanism.

  18. Histological observation of RGCs and optic nerve injury in acute ocular hypertension rats

    PubMed Central

    Li, Shuang; Fang, Jia-Hua; Jiang, Fa-Gang

    2010-01-01

    AIM To explore the injury of retinal ganglion cells (RGCs) and optic nerves in acute ocular hypertension (OHT) rats. METHODS We retrogradely labeled RGCs and optic nerves of Sprague-Dawley rats by injecting 20g/L fluorogold (FG) into bilateral superior colliculi. Twenty-four hours after the injection, the right eyes were performed physiological saline anterior chamber perfusion with intraocular pressure maintained at 100mmHg for 60 minutes, while the contralateral eyes were performed sham procedure as control group without elevation of the saline bottle. Retinal hematoxylin and eosin (HE) sections, retinal whole mounts and frozen sections were made 14 days later to observe the morphology and survival of RGCs. Frozen sections and transmission electron microscopy were utilized to investigate the histological manifestations of optic nerves at the same time. RESULTS A larger number of RGCs presented in control group. It had an average density of 1995±125/mm2 and distributed uniformly, while RGCs in OHT eyes reduced significantly to 1505±43/mm2 compared with control group (P<0.05). The optic nerves in control group showed stronger and more uniform fluorescence on the frozen sections, and the auxiliary fibers as well as myelin sheaths were in even and intact organization by transmission electron microscopy. However, exiguous fluorescence signals, vesicular dissociation and disintegration of myelin sheaths were found in OHT group. CONCLUSION The present study suggested that fluorogold retrograde tracing is a feasible, convenient method for quantitative and qualitative study of neuronal populations and axonal injury in acute ocular hypertension rats. PMID:22553581

  19. Autotaxin and lysophosphatidic acid1 receptor-mediated demyelination of dorsal root fibers by sciatic nerve injury and intrathecal lysophosphatidylcholine

    PubMed Central

    2010-01-01

    Background Although neuropathic pain is frequently observed in demyelinating diseases such as Guillain-Barré syndrome and multiple sclerosis, the molecular basis for the relationship between demyelination and neuropathic pain behaviors is poorly understood. Previously, we found that lysophosphatidic acid receptor (LPA1) signaling initiates sciatic nerve injury-induced neuropathic pain and demyelination. Results In the present study, we have demonstrated that sciatic nerve injury induces marked demyelination accompanied by myelin-associated glycoprotein (MAG) down-regulation and damage of Schwann cell partitioning of C-fiber-containing Remak bundles in the sciatic nerve and dorsal root, but not in the spinal nerve. Demyelination, MAG down-regulation and Remak bundle damage in the dorsal root were abolished in LPA1 receptor-deficient (Lpar1-/-) mice, but these alterations were not observed in sciatic nerve. However, LPA-induced demyelination in ex vivo experiments was observed in the sciatic nerve, spinal nerve and dorsal root, all which express LPA1 transcript and protein. Nerve injury-induced dorsal root demyelination was markedly attenuated in mice heterozygous for autotaxin (atx+/-), which converts lysophosphatidylcholine (LPC) to LPA. Although the addition of LPC to ex vivo cultures of dorsal root fibers in the presence of recombinant ATX caused potent demyelination, it had no significant effect in the absence of ATX. On the other hand, intrathecal injection of LPC caused potent dorsal root demyelination, which was markedly attenuated or abolished in atx+/- or Lpar1-/- mice. Conclusions These results suggest that LPA, which is converted from LPC by ATX, activates LPA1 receptors and induces dorsal root demyelination following nerve injury, which causes neuropathic pain. PMID:21062487

  20. Increased response to glutamate in small diameter dorsal root ganglion neurons after sciatic nerve injury.

    PubMed

    Gong, Kerui; Kung, Ling-Hsuan; Magni, Giulia; Bhargava, Aditi; Jasmin, Luc

    2014-01-01

    Glutamate in the peripheral nervous system is involved in neuropathic pain, yet we know little how nerve injury alters responses to this neurotransmitter in primary sensory neurons. We recorded neuronal responses from the ex-vivo preparations of the dorsal root ganglia (DRG) one week following a chronic constriction injury (CCI) of the sciatic nerve in adult rats. We found that small diameter DRG neurons (<30 µm) exhibited increased excitability that was associated with decreased membrane threshold and rheobase, whereas responses in large diameter neurons (>30 µm) were unaffected. Puff application of either glutamate, or the selective ionotropic glutamate receptor agonists alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) and kainic acid (KA), or the group I metabotropic receptor (mGluR) agonist (S)-3,5-dihydroxyphenylglycine (DHPG), induced larger inward currents in CCI DRGs compared to those from uninjured rats. N-methyl-D-aspartate (NMDA)-induced currents were unchanged. In addition to larger inward currents following CCI, a greater number of neurons responded to glutamate, AMPA, NMDA, and DHPG, but not to KA. Western blot analysis of the DRGs revealed that CCI resulted in a 35% increase in GluA1 and a 60% decrease in GluA2, the AMPA receptor subunits, compared to uninjured controls. mGluR1 receptor expression increased by 60% in the membrane fraction, whereas mGluR5 receptor subunit expression remained unchanged after CCI. These results show that following nerve injury, small diameter DRG neurons, many of which are nociceptive, have increased excitability and an increased response to glutamate that is associated with changes in receptor expression at the neuronal membrane. Our findings provide further evidence that glutamatergic transmission in the periphery plays a role in nociception.

  1. Efferent vagal nerve stimulation attenuates acute lung injury following burn: The importance of the gut-lung axis

    PubMed Central

    Krzyzaniak, Michael J.; Peterson, Carrie Y.; Cheadle, Gerald; Loomis, William; Wolf, Paul; Kennedy, Vince; Putnam, James G.; Bansal, Vishal; Eliceiri, Brian; Baird, Andrew; Coimbra, Raul

    2014-01-01

    Background The purpose of this study was to assess acute lung injury when protection to the gut mucosal barrier offered by vagus nerve stimulation is eliminated by an abdominal vagotomy. Methods Male balb/c mice were subjected to 30% total body surface area steam burn with and without electrical stimulation to the right cervical vagus nerve. A cohort of animals were subjected to abdominal vagotomy. Lung histology, myeloperoxidase and ICAM-1 immune staining, myeloperoxidase enzymatic assay, and tissue KC levels were analyzed 24 hours after burn. Additionally, lung IkB-α, NF-kB immunoblots, and NF-kB-DNA binding measured by photon emission analysis using NF-kB-luc transgenic mice were performed. Results Six hours post burn, phosphorylation of both NF-kB p65 and IkB-α were observed. Increased photon emission signal was seen in the lungs of NF-kB-luc transgenic animals. Vagal nerve stimulation blunted NF-kB activation similar to sham animals whereas abdominal vagotomy eliminated the anti-inflammatory effect. After burn, MPO positive cells and ICAM-1 expression in the lung endothelium was increased, and lung histology demonstrated significant injury at 24 hours. Vagal nerve stimulation markedly decreased neutrophil infiltration as demonstrated by MPO immune staining and enzyme activity. Vagal stimulation also markedly attenuated acute lung injury at 24 hours. The protective effects of vagal nerve stimulation were reversed by performing an abdominal vagotomy. Conclusion Vagal nerve stimulation is an effective strategy to protect against acute lung injury following burn. Moreover, the protective effects of vagal nerve stimulation in the prevention of acute lung injury are eliminated by performing an abdominal vagotomy. These results establish the importance of the gut-lung axis after burn in the genesis of acute lung injury. PMID:21783215

  2. Injury-Dependent and Disability-Specific Lumbar Spinal Gene Regulation following Sciatic Nerve Injury in the Rat

    PubMed Central

    Denyer, Gareth S.; Keay, Kevin A.

    2015-01-01

    Allodynia, hyperalgesia and spontaneous pain are cardinal sensory signs of neuropathic pain. Clinically, many neuropathic pain patients experience affective-motivational state changes, including reduced familial and social interactions, decreased motivation, anhedonia and depression which are severely debilitating. In earlier studies we have shown that sciatic nerve chronic constriction injury (CCI) disrupts social interactions, sleep-wake-cycle and endocrine function in one third of rats, a subgroup reliably identified six days after injury. CCI consistently produces allodynia and hyperalgesia, the intensity of which was unrelated either to the altered social interactions, sleep-wake-cycle or endocrine changes. This decoupling of the sensory consequences of nerve injury from the affective-motivational changes is reported in both animal experiments and human clinical data. The sensory changes triggered by CCI are mediated primarily by functional changes in the lumbar dorsal horn, however, whether lumbar spinal changes may drive different affective-motivational states has never been considered. In these studies, we used microarrays to identify the unique transcriptomes of rats with altered social behaviours following sciatic CCI to determine whether specific patterns of lumbar spinal adaptations characterised this subgroup. Rats underwent CCI and on the basis of reductions in dominance behaviour in resident-intruder social interactions were categorised as having Pain & Disability, Pain & Transient Disability or Pain alone. We examined the lumbar spinal transcriptomes two and six days after CCI. Fifty-four ‘disability-specific’ genes were identified. Sixty-five percent were unique to Pain & Disability rats, two-thirds of which were associated with neurotransmission, inflammation and/or cellular stress. In contrast, 40% of genes differentially regulated in rats without disabilities were involved with more general homeostatic processes (cellular structure

  3. Nociceptive and Neuronal Evaluation of the Sciatic Nerve of Wistar Rats Subjected to Compression Injury and Treated with Resistive Exercise

    PubMed Central

    Antunes, Juliana Sobral; Lovison, Keli; Karvat, Jhenifer; Peretti, Ana Luiza; Vieira, Lizyana; Higuchi, Guilherme Hideaki; Ribeiro, Lucinéia de Fátima Chasko

    2016-01-01

    Background. To investigate the climb stairs resistance exercise on nociception and axonal regeneration in the sciatic nerve of rats. Methods. 24 Wistar rats were divided: control group (CG—no injury), exercise group (EG—no injury with physical exercise), lesion group (LG—injury, but without exercise), and treated group (LEG—injury and physical exercise). LG and LEG were subjected to sciatic nerve compression with hemostat. From the 3rd day after injury began treatment with exercise, and after 22 days occurs the removal of a nerve fragment for morphological analysis. Results. Regarding allodynia, CG obtained values less than EG (p = 0.012) and larger than LG and LEG (p < 0.001). Histological results showed that CG and EG had normal appearance, as LG and LEG showed up with large amounts of inflammatory infiltration, degeneration and disruption of nerve fibers, and reduction of the myelin sheath; however LEG presented some regenerated fibers. From the morphometric data there were significant differences, for nerve fiber diameter, comparing CG with LG and LEG and comparing axon diameter and the thickness of the myelin of the CG to others. Conclusion. Climb stairs resistance exercise was not effective to speed up the regenerative process of axons. PMID:27594795

  4. Muscle-targeted hydrodynamic gene introduction of insulin-like growth factor-1 using polyplex nanomicelle to treat peripheral nerve injury.

    PubMed

    Nagata, Kazuya; Itaka, Keiji; Baba, Miyuki; Uchida, Satoshi; Ishii, Takehiko; Kataoka, Kazunori

    2014-06-10

    The recovery of neurologic function after peripheral nerve injury often remains incomplete because of the prolonged reinnervation process, which leads to skeletal muscle atrophy and articular contracture from disuse over time. To rescue the skeletal muscle and promote functional recovery, insulin-like growth factor-1 (IGF-1), a potent myogenic factor, was introduced into the muscle by hydrodynamic injection of IGF-1-expressing plasmid DNA using a biocompatible nonviral gene carrier, a polyplex nanomicelle. In a mouse model of sciatic nerve injury, the introduction of IGF-1 into the skeletal muscle of the paralyzed limb effectively alleviated a decrease in muscle weight compared with that in untreated control mice. Histologic analysis of the muscle revealed the IGF-1-expressing plasmid DNA (pDNA) to have a myogenic effect, inducing muscle hypertrophy with the upregulation of the myogenic regulatory factors, myogenin and MyoD. The evaluation of motor function by walking track analysis revealed that the group that received the hydrodynamic injection of IGF-1-expressing pDNA using the polyplex nanomicelle had significantly early recovery of motor function compared with groups receiving negative control pDNA and untreated controls. Early recovery of sensation in the distal area of sciatic nerve injury was also induced by the introduction of IGF-1-expressing pDNA, presumably because of the effect of secreted IGF-1 protein in the vicinity of the injured sciatic nerve exerting a synergistic effect with muscle hypertrophy, inducing a more favorable prognosis. This approach of introducing IGF-1 into skeletal muscle is promising for the treatment of peripheral nerve injury by promoting early motor function recovery.

  5. [The ultrasound assessment of neuro-muscular apparatus by the radial nerve injuries].

    PubMed

    Golubev, V G; Kkhir Bek, M; Iulov, V V; Goncharov, N G

    2011-01-01

    The use of ultrasound (US) scanning to assess the muscular function during the reinnervation is a new concept in medicine. The US signs of muscle denervation were thoroughly described in the article. The US muscle monitoring was performed by the complete and partial radial nerve injury in various follow-up periods. Absolute and relative indications for surgery were determined. The comparative characteristics of structural muscular changes, together with the US test for the assessment of the treatment efficacy and nerval and muscular recovery were suggested.

  6. Foot drop after ethanol embolization of calf vascular malformation: a lesson on nerve injury.

    PubMed

    Tay, Vincent Khwee-Soon; Mohan, P Chandra; Liew, Wendy Kein Meng; Mahadev, Arjandas; Tay, Kiang Hiong

    2013-08-01

    Ethanol is often used in sclerotherapy to treat vascular malformations. Nerve injury is a known complication of this procedure. However, the management of this complication is not well described in literature. This case describes a 10-year-old boy with a slow flow vascular malformation in the right calf who underwent transarterial ethanol embolization following prior unsuccessful direct percutaneous sclerotherapy. The development of a dense foot drop that subsequently recovered is described, and the management of this uncommon but distressful complication is discussed.

  7. Foot Drop after Ethanol Embolization of Calf Vascular Malformation: A Lesson on Nerve Injury

    SciTech Connect

    Tay, Vincent Khwee-Soon; Mohan, P. Chandra; Liew, Wendy Kein Meng; Mahadev, Arjandas; Tay, Kiang Hiong

    2013-08-01

    Ethanol is often used in sclerotherapy to treat vascular malformations. Nerve injury is a known complication of this procedure. However, the management of this complication is not well described in literature. This case describes a 10-year-old boy with a slow flow vascular malformation in the right calf who underwent transarterial ethanol embolization following prior unsuccessful direct percutaneous sclerotherapy. The development of a dense foot drop that subsequently recovered is described, and the management of this uncommon but distressful complication is discussed.

  8. Bilateral Cranial IX and X Nerve Palsies After Mild Traumatic Brain Injury

    PubMed Central

    Yoo, Seung Don; Kim, Dong Hwan; Lee, Seung Ah; Joo, Hye In; Yeo, Jin Ah

    2016-01-01

    We report a 57-year-old man with bilateral cranial nerve IX and X palsies who presented with severe dysphagia. After a mild head injury, the patient complained of difficult swallowing. Physical examination revealed normal tongue motion and no uvular deviation. Cervical X-ray findings were negative, but a brain computed tomography revealed a skull fracture involving bilateral jugular foramen. Laryngoscopy indicated bilateral vocal cord palsy. In a videofluoroscopic swallowing study, food residue remained in the vallecula and pyriform sinus, and there was reduced motion of the pharynx and larynx. Electromyography confirmed bilateral superior and recurrent laryngeal neuropathy. PMID:26949684

  9. Median Nerve Trauma in a Rat Model of Work-Related Musculoskeletal Disorder

    PubMed Central

    CLARK, BRIAN D.; BARR, ANN E.; SAFADI, FAYEZ F.; BEITMAN, LISA; AL-SHATTI, TALAL; AMIN, MAMTA; GAUGHAN, JOHN P.; BARBE, MARY F.

    2006-01-01

    Anatomical and physiological changes were evaluated in the median nerves of rats trained to perform repetitive reaching. Motor degradation was evident after 4 weeks. ED1-immunoreactive macrophages were seen in the transcarpal region of the median nerve of both forelimbs by 5–6 weeks. Fibrosis, characterized by increased immunoexpression of collagen type I by 8 weeks and connective tissue growth factor by 12 weeks, was evident. The conduction velocity (NCV) within the carpal tunnel showed a modest but significant decline after 9–12 weeks. The lowest NCV values were found in animals that refused to participate in the task for the full time available. Thus, both anatomical and physiological signs of progressive tissue damage were present in this model. These results, together with other recent findings indicate that work-related carpal tunnel syndrome develops through mechanisms that include injury, inflammation, fibrosis and subsequent nerve compression. PMID:12908929

  10. Efficacy of low level laser therapy on neurosensory recovery after injury to the inferior alveolar nerve

    PubMed Central

    Ozen, Tuncer; Orhan, Kaan; Gorur, Ilker; Ozturk, Adnan

    2006-01-01

    Background The most severe complication after the removal of mandibular third molars is injury to the inferior alveolar nerve or the lingual nerve. These complications are rather uncommon (0.4% to 8.4%) and most of them are transient. However, some of them persist for longer than 6 months, which can leave various degrees of long-term permanent disability. While several methods such as pharmacologic therapy, microneurosurgery, autogenous and alloplastic grafting can be used for the treatment of long-standing sensory aberrations in the inferior alveolar nerve, there are few reports regarding low level laser treatment. This paper reports the effects of low level laser therapy in 4 patients with longstanding sensory nerve impairment following mandibular third molar surgery. Methods Four female patients had complaints of paresthesia and dysesthesia of the lip, chin and gingiva, and buccal regions. Each patient had undergone mandibular third molar surgery at least 1 year before. All patients were treated with low level laser therapy. Clinical neurosensory tests (the brush stroke directional discrimination test, 2-point discrimination test, and a subjective assessment of neurosensory function using a visual analog scale) were used before and after treatment, and the responses were plotted over time. Results When the neurosensory assessment scores after treatment with LLL therapy were compared with the baseline values prior to treatment, there was a significant acceleration in the time course, as well as in the magnitude, of neurosensory return. The VAS analysis revealed progressive improvement over time. Conclusion Low level laser therapy seemed to be conducive to the reduction of long-standing sensory nerve impairment following third molar surgery. Further studies are worthwhile regarding the clinical application of this treatment modality. PMID:16480503

  11. Electrical properties of rat muscle after sciatic nerve injury: Impact on surface impedance measurements assessed via finite element analysis

    NASA Astrophysics Data System (ADS)

    Ahad, M. A.; Rutkove, S. B.

    2010-04-01

    Tetrapolar surface electrical impedance methods are sensitive to changes in muscle status and can therefore provide a means for studying neuromuscular disease noninvasively. In order to better understand the relationship between surface impedance measurements and the actual muscle electrical properties, we performed measurements on 20 adult Wistar rats, 8 of which underwent sciatic nerve crush. Surface impedance measurements were performed on the left hind limb both before injury and out to 2 weeks after injury. In addition, both normal and sciatic crush animals were sacrificed and the dielectric properties of the extracted gastrocnemius muscle measured. We found that 50 kHz conductivities were greater in the animals that underwent crush than in the animals that did not. The permittivities in both directions, however, showed non-significant differences. In order to analyze the effect of these changes as well as the accompanying reduction in muscle volume, a finite element model of the hind limb was developed based on computerized tomographic imaging. The model successfully predicted the surface impedance values in the animals after crush injury and, by its inverse application, may be used to help determine the underlying electrical properties of muscle in various neuromuscular diseases based on surface impedance data.

  12. Adenoviral-Mediated Glial Cell Line–Derived Neurotrophic Factor Gene Transfer Has a Protective Effect on Sciatic Nerve Following Constriction-Induced Spinal Cord Injury

    PubMed Central

    Chou, An-Kuo; Yang, Ming-Chang; Tsai, Hung-Pei; Chai, Chee-Yin; Tai, Ming-Hong; Kwan, Aij-Li; Hong, Yi-Ren

    2014-01-01

    Neuropathic pain due to peripheral nerve injury may be associated with abnormal central nerve activity. Glial cell-line-derived neurotrophic factor (GDNF) can help attenuate neuropathic pain in different animal models of nerve injury. However, whether GDNF can ameliorate neuropathic pain in the spinal cord dorsal horn (SCDH) in constriction-induced peripheral nerve injury remains unknown. We investigated the therapeutic effects of adenoviral-mediated GDNF on neuropathic pain behaviors, microglial activation, pro-inflammatory cytokine expression and programmed cell death in a chronic constriction injury (CCI) nerve injury animal model. In this study, neuropathic pain was produced by CCI on the ipsilateral SCDH. Mechanical allodynia was examined with von Frey filaments and thermal sensitivity was tested using a plantar test apparatus post-operatively. Target proteins GDNF-1, GDNFRa-1, MMP2, MMP9, p38, phospho-p38, ED1, IL6, IL1β, AIF, caspase-9, cleaved caspase-9, caspase-3, cleaved caspase-3, PARP, cleaved PARP, SPECTRIN, cleaved SPECTRIN, Beclin-1, PKCσ, PKCγ, iNOS, eNOS and nNOS were detected. Microglial activity was measured by observing changes in immunoreactivity with OX-42. NeuN and TUNEL staining were used to reveal whether apoptosis was attenuated by GDNF. Results showed that administrating GDNF began to attenuate both allodynia and thermal hyperalgesia at day 7. CCI-rats were found to have lower GDNF and GDNFRa-1 expression compared to controls, and GDNF re-activated their expression. Also, GDNF significantly down-regulated CCI-induced protein expression except for MMP2, eNOS and nNOS, indicating that the protective action of GDNF might be associated with anti-inflammation and prohibition of microglia activation. Immunocytochemistry staining showed that GDNF reduced CCI-induced neuronal apoptosis. In sum, GDNF enhanced the neurotrophic effect by inhibiting microglia activation and cytokine production via p38 and PKC signaling. GDNF could be a good

  13. Effects of locally applied nerve growth factor to the inferior alveolar nerve histology in a rabbit model of mandibular distraction osteogenesis.

    PubMed

    Wang, L; Zhao, Y; Cheng, X; Yang, Y; Liu, G; Ma, Q; Shang, H; Tian, L; Lei, D

    2009-01-01

    Distraction osteogenesis (DO) is widely used in deformities and defects of the craniofacial bone. Accelerating inferior alveolar nerve (IAN) recovery would aid the process. Nerve growth factor (NGF) plays a vital role in peripheral nerve regeneration. In this study, the ability of locally applied human NGF beta (hNGFbeta) to enhance the morphological recovery of the IAN in a rabbit model of mandibular DO was studied. Rabbits underwent bilateral DO with a rate of 0.5mm per 12h. Two doses of 40 microg hNGFbeta in buffer were injected into callus at the beginning the of consolidation time. The contralateral side received injections of placebo. Rabbits were killed at 14 and 28 days. IAN specimens were subjected to histological and histomorphometric analysis. In both 14 and 28 days consolidation experiments, nerve histological analysis showed less degeneration and more regeneration in nerve fibers on the hNGFbeta treated side than the control side. Histomorphometric analysis showed that the myelinated fiber density on the hNGFbeta treated side was significantly higher than on the control side (p<0.01). The data indicate that locally applied hNGFbeta can accelerate the morphological recovery of the IAN and may play a role in reducing nerve injury in mandibular DO clinically.

  14. Type III Monteggia fracture with posterior interosseous nerve injury in a child

    PubMed Central

    Wang, Jing; Chen, Min; Du, Jiang

    2017-01-01

    Abstract Rationale: Elbow injury in children by improper treatment or a delay of more than 3 weeks could lead to old unreduced Monteggia fracture, which are difficult to manage. Conservative or normal surgical methods usually fail. Patient concerns: Herein, we present a 6-year-old boy with sustaining injury approximately 1 month to his left elbow. Activity in his elbow was restricted, and his ability to extend his wrist and fingers was impaired. Diagnoses: Type III Monteggia elbow fracture-dislocation consisting of radial head dislocation and malunion of the ulna associated with posterior interosseous nerve palsy were confirmed, which requiring surgical treatment. Interventions: A closed reduction was performed with hyperplastic scar tissues erased and the radial head relocated. Outcomes: Follow-up 4 months later showed satisfactory recovery of function. Lessons: Forearm fractures in children may be misjudged, and that early anatomical reduction rather than conservative treatment may be required. PMID:28296780

  15. Chaperone Proteins in the Central Nervous System and Peripheral Nervous System after Nerve Injury.

    PubMed

    Ousman, Shalina S; Frederick, Ariana; Lim, Erin-Mai F

    2017-01-01

    Injury to axons of the central nervous system (CNS) and the peripheral nervous system (PNS) is accompanied by the upregulation and downregulation of numerous molecules that are involved in mediating nerve repair, or in augmentation of the original damage. Promoting the functions of beneficial factors while reducing the properties of injurious agents determines whether regeneration and functional recovery ensues. A number of chaperone proteins display reduced or increased expression following CNS and PNS damage (crush, transection, contusion) where their roles have generally been found to be protective. For example, chaperones are involved in mediating survival of damaged neurons, promoting axon regeneration and remyelination and, improving behavioral outcomes. We review here the various chaperone proteins that are involved after nervous system axonal damage, the functions that they impact in the CNS and PNS, and the possible mechanisms by which they act.

  16. SIP30 Is Regulated by ERK in Peripheral Nerve Injury-induced Neuropathic Pain*

    PubMed Central

    Peng, Guangdun; Han, Mei; Du, Yimin; Lin, Anning; Yu, Lei; Zhang, Yuqiu; Jing, Naihe

    2009-01-01

    ERK plays an important role in chronic neuropathic pain. However, the underlying mechanism is largely unknown. Here we show that in chronic constriction injury-treated rat spinal cords, up-regulation of SIP30 (SNAP25-interacting protein 30), which is involved in the development and maintenance of chronic constriction injury-induced neuropathic pain, correlates with ERK activation and that the up-regulation of SIP30 is suppressed by intrathecal delivery of the MEK inhibitor U0126. In PC12 cells, up-regulation of SIP30 by nerve growth factor is also dependent on ERK activation. We found that there is an ERK-responsive region in the rat sip30 promoter. Activation of ERK promotes the recruitment of the transcription factor cyclic AMP-response element-binding protein to the sip30 gene promoter. Taken together, our results provide a potential downstream target of ERK activation-mediated neuropathic pain. PMID:19723624

  17. Chaperone Proteins in the Central Nervous System and Peripheral Nervous System after Nerve Injury

    PubMed Central

    Ousman, Shalina S.; Frederick, Ariana; Lim, Erin-Mai F.

    2017-01-01

    Injury to axons of the central nervous system (CNS) and the peripheral nervous system (PNS) is accompanied by the upregulation and downregulation of numerous molecules that are involved in mediating nerve repair, or in augmentation of the original damage. Promoting the functions of beneficial factors while reducing the properties of injurious agents determines whether regeneration and functional recovery ensues. A number of chaperone proteins display reduced or increased expression following CNS and PNS damage (crush, transection, contusion) where their roles have generally been found to be protective. For example, chaperones are involved in mediating survival of damaged neurons, promoting axon regeneration and remyelination and, improving behavioral outcomes. We review here the various chaperone proteins that are involved after nervous system axonal damage, the functions that they impact in the CNS and PNS, and the possible mechanisms by which they act. PMID:28270745

  18. Vitamin D3 potentiates myelination and recovery after facial nerve injury.

    PubMed

    Montava, Marion; Garcia, Stéphane; Mancini, Julien; Jammes, Yves; Courageot, Joël; Lavieille, Jean-Pierre; Feron, François

    2015-10-01

    Roles of vitamin D on the immune and nervous systems are increasingly recognized. Two previous studies demonstrated that ergocalciferol (vitamin D2) or cholecalciferol (vitamin D3) induced functional recovery and increased myelination in a rat model of peroneal nerve transection. The current report assessed whether cholecalciferol was efficient in repairing transected rabbit facial nerves. Animals were randomized into two groups of rabbits with an unilateral facial nerve surgery: the vitamin D group included animals receiving a weekly oral bolus of vitamin D3 (200 IU/kg/day), from day 1 post-surgery; the control group included animals receiving a weekly oral bolus of vehicle (triglycerides). Contralateral unsectioned facial nerves from all experimental animals were used as controls for the histological study. The facial functional index was measured every week while the inner diameter of myelin sheath and the G ratio were quantified at the end of the 3 month experiment. The current report indicates that cholecalciferol significantly increases functional recovery and myelination, after 12 weeks of treatment. To the best of our knowledge, this is the first study investigating the therapeutic benefit of vitamin D supplementation in an animal model of facial paralysis. It paves further the way for clinical trials based on the administration of this steroid in individuals with injured facial nerves.

  19. Phenotypic switching of nonpeptidergic cutaneous sensory neurons following peripheral nerve injury.

    PubMed

    Wang, Ting; Molliver, Derek C; Jing, Xiaotang; Schwartz, Erica S; Yang, Fu-Chia; Samad, Omar Abdel; Ma, Qiufu; Davis, Brian M

    2011-01-01

    In adult mammals, the phenotype of half of all pain-sensing (nociceptive) sensory neurons is tonically modulated by growth factors in the glial cell line-derived neurotrophic factor (GDNF) family that includes GDNF, artemin (ARTN) and neurturin (NRTN). Each family member binds a distinct GFRα family co-receptor, such that GDNF, NRTN and ARTN bind GFRα1, -α2, and -α3, respectively. Previous studies revealed transcriptional regulation of all three receptors in following axotomy, possibly in response to changes in growth factor availability. Here, we examined changes in the expression of GFRα1-3 in response to injury in vivo and in vitro. We found that after dissociation of adult sensory ganglia, up to 27% of neurons die within 4 days (d) in culture and this can be prevented by nerve growth factor (NGF), GDNF and ARTN, but not NRTN. Moreover, up-regulation of ATF3 (a marker of neuronal injury) in vitro could be prevented by NGF and ARTN, but not by GDNF or NRTN. The lack of NRTN efficacy was correlated with rapid and near-complete loss of GFRα2 immunoreactivity. By retrogradely-labeling cutaneous afferents in vivo prior to nerve cut, we demonstrated that GFRα2-positive neurons switch phenotype following injury and begin to express GFRα3 as well as the capsaicin receptor, transient receptor potential vanilloid 1(TRPV1), an important transducer of noxious stimuli. This switch was correlated with down-regulation of Runt-related transcription factor 1 (Runx1), a transcription factor that controls expression of GFRα2 and TRPV1 during development. These studies show that NRTN-responsive neurons are unique with respect to their plasticity and response to injury, and suggest that Runx1 plays an ongoing modulatory role in the adult.

  20. Single injection of a novel nerve growth factor coacervate improves structural and functional regeneration after sciatic nerve injury in adult rats.

    PubMed

    Li, Rui; Wu, Jiang; Lin, Zhenkun; Nangle, Matthew R; Li, Yi; Cai, Pingtao; Liu, Dan; Ye, Libin; Xiao, Zecong; He, Chaochao; Ye, Jingjing; Zhang, Hongyu; Zhao, Yingzheng; Wang, Jian; Li, Xiaokun; He, Yan; Ye, Qingsong; Xiao, Jian

    2017-02-01

    The prototypical neurotrophin, nerve growth factor (NGF), plays an important role in the development and maintenance of many neurons in both the central and peripheral nervous systems, and can promote functional recovery after peripheral nerve injury in adulthood. However, repair of peripheral nerve defects is hampered by the short half-life of NGF in vivo, and treatment with either NGF alone or NGF contained in synthetic nerve conduits is inferior to the use of nerve autografts, the current gold standard. We tested the reparative ability of a single local injection of a polyvalent coacervate containing polycation-poly(ethylene argininylaspartate diglyceride; PEAD), heparin, and NGF, in adult rats following sciatic nerve crush injury, using molecular, histological and behavioral approaches. In vitro assays demonstrated that NGF was loaded into the coacervate at nearly 100% efficiency, and was protected from proteolytic degradation. In vivo, the coacervate enhanced NGF bioavailability, leading to a notable improvement in motor function (track walking analysis) after 30days. The NGF coacervate treatment was also associated with better weight gain and reduction in atrophy of the gastrocnemius muscle. Furthermore, light and electron microscopy showed that the number of myelinated axons and axon-to-fiber ratio (G-ratio) were significantly higher in NGF coacervate-treated rats compared with control groups. Expression of markers of neural tissue regeneration (MAP-2, S-100β, MBP and GAP-43), as well as proliferating Schwann cells and myelin-axon relationships (GFAP and NF200), were also increased. These observations suggest that even a single administration of NGF coacervate could have therapeutic value for peripheral nerve regeneration and functional recovery.

  1. Evaluation of spinal cord injury animal models

    PubMed Central

    Zhang, Ning; Fang, Marong; Chen, Haohao; Gou, Fangming; Ding, Mingxing

    2014-01-01

    Because there is no curative treatment for spinal cord injury, establishing an ideal animal model is important to identify injury mechanisms and develop therapies for individuals suffering from spinal cord injuries. In this article, we systematically review and analyze various kinds of animal models of spinal cord injury and assess their advantages and disadvantages for further studies. PMID:25598784

  2. Inferior Alveolar Nerve Injuries Associated with Mandibular Fractures at Risk: A Two-Center Retrospective Study

    PubMed Central

    Boffano, Paolo; Roccia, Fabio; Gallesio, Cesare; Karagozoglu, K.; Forouzanfar, Tymour

    2014-01-01

    The aim of the study was to investigate the incidence of the inferior alveolar nerve (IAN) injury in mandibular fractures. This study is based on two databases that have continuously recorded patients hospitalized with maxillofacial fractures in two departments—Department of Maxillofacial Surgery, Vrije Universiteit University Medical Center, Amsterdam, the Netherlands, and Division of Maxillofacial Surgery, San Giovanni Battista Hospital, Turin, Italy. Demographic, anatomic, and etiology variables were considered for each patient and statistically assessed in relation to the neurosensory IAN impairment. Statistically significant associations were found between IAN injury and fracture displacement (p = 0.03), isolated mandibular fractures (p = 0.01), and angle fractures (p = 0.004). A statistically significant association was also found between IAN injury and assaults (p = 0.03). Displaced isolated mandibular angle fractures could be considered at risk for increased incidence of IAN injury. Assaults seem to be the most important etiological factor that is responsible for IAN lesions. PMID:25383147

  3. Biepicondylar fracture dislocation of the elbow joint concomitant with ulnar nerve injury

    PubMed Central

    Konya, M Nuri; Aslan, Ahmet; Sofu, Hakan; Yıldırım, Timur

    2013-01-01

    In this article, we present a case of humeral biepicondylar fracture dislocation concomitant with ulnar nerve injury in a seventeen year-old male patient. Physical examination of our patient in the emergency room revealed a painful, edematous and deformed-looking left elbow joint. Hypoesthesia of the little finger was also diagnosed on the left hand. Radiological assessment ended up with a posterior fracture dislocation of the elbow joint accompanied by intra-articular loose bodies. Open reduction-Internal fixation of the fracture dislocation and ulnar nerve exploration were performed under general anesthesia at the same session as surgical treatment of our patient. Physical therapy and rehabilitation protocol was implemented at the end of two weeks post-operatively. Union of the fracture lines, as well as the olecranon osteotomy site, was achieved at the end of four months post-operatively. Ulnar nerve function was fully restored without any sensory or motor loss. Range of motion at the elbow joint was 20-120 degrees at the latest follow-up. PMID:23610759

  4. Biepicondylar fracture dislocation of the elbow joint concomitant with ulnar nerve injury.

    PubMed

    Konya, M Nuri; Aslan, Ahmet; Sofu, Hakan; Yıldırım, Timur

    2013-04-18

    In this article, we present a case of humeral biepicondylar fracture dislocation concomitant with ulnar nerve injury in a seventeen year-old male patient. Physical examination of our patient in the emergency room revealed a painful, edematous and deformed-looking left elbow joint. Hypoesthesia of the little finger was also diagnosed on the left hand. Radiological assessment ended up with a posterior fracture dislocation of the elbow joint accompanied by intra-articular loose bodies. Open reduction-Internal fixation of the fracture dislocation and ulnar nerve exploration were performed under general anesthesia at the same session as surgical treatment of our patient. Physical therapy and rehabilitation protocol was implemented at the end of two weeks post-operatively. Union of the fracture lines, as well as the olecranon osteotomy site, was achieved at the end of four months post-operatively. Ulnar nerve function was fully restored without any sensory or motor loss. Range of motion at the elbow joint was 20-120 degrees at the latest follow-up.

  5. A novel therapeutic target for peripheral nerve injury-related diseases: aminoacyl-tRNA synthetases

    PubMed Central

    Park, Byung Sun; Yeo, Seung Geun; Jung, Junyang; Jeong, Na Young

    2015-01-01

    Aminoacyl-tRNA synthetases (AminoARSs) are essential enzymes that perform the first step of protein synthesis. Beyond their original roles, AminoARSs possess non-canonical functions, such as cell cycle regulation and signal transduction. Therefore, AminoARSs represent a powerful pharmaceutical target if their non-canonical functions can be controlled. Using AminoARSs-specific primers, we screened mRNA expression in the spinal cord dorsal horn of rats with peripheral nerve injury created by sciatic nerve axotomy. Of 20 AminoARSs, we found that phenylalanyl-tRNA synthetase beta chain (FARSB), isoleucyl-tRNA synthetase (IARS) and methionyl-tRNA synthetase (MARS) mRNA expression was increased in spinal dorsal horn neurons on the injured side, but not in glial cells. These findings suggest the possibility that FARSB, IARS and MARS, as a neurotransmitter, may transfer abnormal sensory signals after peripheral nerve damage and become a new target for drug treatment. PMID:26692865

  6. Radiosurgical Ablation of the Renal Nerve in a Porcine Model: A Minimally Invasive Therapeutic Approach to Treat Refractory Hypertension

    PubMed Central

    Long, Sarah A; Gardner, Edward A; Tay, Jonathan; Ladich, Elena; Chamberlain, David; Fogarty, Thomas J.; Maguire, Patrick J

    2017-01-01

    Background Hypertension is strongly associated with cardiovascular diseases such as heart failure, stroke, kidney disease, and has been correlated with an increased risk for heart attack. Current treatment regimens for hypertension are highly inadequate, with reports indicating that only 50.1% of the clinical population with the disease has their blood pressure under control. Objective To study the feasibility of using minimally invasive radiosurgery to ablate the renal nerves as a novel treatment for refractory hypertension, and to assess the safety and efficacy of such an approach. Methods A Hanford porcine (miniswine) model (N = 6) was used to investigate the feasibility of using the CyberHeart radiosurgical platform (CyberHeart Inc., Mountain View, CA, USA) to create safe renal nerve ablations. Norepinephrine (NE) levels were measured pre and post treatment. Additionally, renal nerve and arterial histology were studied to examine effect. Results Plasma norepinephrine levels showed a decrease over the six-month time point. Urea, nitrogen, and creatinine levels showed no changes post procedure. Histology documented no significant arterial injury in targeted areas. Renal nerves documented histologic change consistent with nerve ablation. Conclusion CyberHeart radiosurgery of the renal nerve is feasible and resulted in norepinephrine reduction and renal nerve injury consistent with radiosurgical targeted ablation. PMID:28367392

  7. Effects of Nerve Injury and Segmental Regeneration on the Cellular Correlates of Neural Morphallaxis

    PubMed Central

    Martinez, Veronica G.; Manson, Josiah M.B.; Zoran, Mark J.

    2009-01-01

    Functional recovery of neural networks after injury requires a series of signaling events similar to the embryonic processes that governed initial network construction. Neural morphallaxis, a form of nervous system regeneration, involves reorganization of adult neural connectivity patterns. Neural morphallaxis in the worm, Lumbriculus variegatus, occurs during asexual reproduction and segmental regeneration, as body fragments acquire new positional identities along the anterior–posterior axis. Ectopic head (EH) formation, induced by ventral nerve cord lesion, generated morphallactic plasticity including the reorganization of interneuronal sensory fields and the induction of a molecular marker of neural morphallaxis. Morphallactic changes occurred only in segments posterior to an EH. Neither EH formation, nor neural morphallaxis was observed after dorsal body lesions, indicating a role for nerve cord injury in morphallaxis induction. Furthermore, a hierarchical system of neurobehavioral control was observed, where anterior heads were dominant and an EH controlled body movements only in the absence of the anterior head. Both suppression of segmental regeneration and blockade of asexual fission, after treatment with boric acid, disrupted the maintenance of neural morphallaxis, but did not block its induction. Therefore, segmental regeneration (i.e., epimorphosis) may not be required for the induction of morphallactic remodeling of neural networks. However, on-going epimorphosis appears necessary for the long-term consolidation of cellular and molecular mechanisms underlying the morphallaxis of neural circuitry. PMID:18561185

  8. Neuroprotective activity of thioctic acid in central nervous system lesions consequent to peripheral nerve injury.

    PubMed

    Tomassoni, Daniele; Amenta, Francesco; Di Cesare Mannelli, Lorenzo; Ghelardini, Carla; Nwankwo, Innocent E; Pacini, Alessandra; Tayebati, Seyed Khosrow

    2013-01-01

    Peripheral neuropathies are heterogeneous disorders presenting often with hyperalgesia and allodynia. This study has assessed if chronic constriction injury (CCI) of sciatic nerve is accompanied by increased oxidative stress and central nervous system (CNS) changes and if these changes are sensitive to treatment with thioctic acid. Thioctic acid is a naturally occurring antioxidant existing in two optical isomers (+)- and (-)-thioctic acid and in the racemic form. It has been proposed for treating disorders associated with increased oxidative stress. Sciatic nerve CCI was made in spontaneously hypertensive rats (SHRs) and in normotensive reference cohorts. Rats were untreated or treated intraperitoneally for 14 days with (+/-)-, (+)-, or (-)-thioctic acid. Oxidative stress, astrogliosis, myelin sheets status, and neuronal injury in motor and sensory cerebrocortical areas were assessed. Increase of oxidative stress markers, astrogliosis, and neuronal damage accompanied by a decreased expression of neurofilament were observed in SHR. This phenomenon was more pronounced after CCI. Thioctic acid countered astrogliosis and neuronal damage, (+)-thioctic acid being more active than (+/-)- or (-)-enantiomers. These findings suggest a neuroprotective activity of thioctic acid on CNS lesions consequent to CCI and that the compound may represent a therapeutic option for entrapment neuropathies.

  9. Postsynaptic potentiation of corticospinal projecting neurons in the anterior cingulate cortex after nerve injury

    PubMed Central

    2014-01-01

    Long-term potentiation (LTP) is the key cellular mechanism for physiological learning and pathological chronic pain. In the anterior cingulate cortex (ACC), postsynaptic recruitment or modification of AMPA receptor (AMPAR) GluA1 contribute to the expression of LTP. Here we report that pyramidal cells in the deep layers of the ACC send direct descending projecting terminals to the dorsal horn of the spinal cord (lamina I-III). After peripheral nerve injury, these projection cells are activated, and postsynaptic excitatory responses of these descending projecting neurons were significantly enhanced. Newly recruited AMPARs contribute to the potentiated synaptic transmission of cingulate neurons. PKA-dependent phosphorylation of GluA1 is important, since enhanced synaptic transmission was abolished in GluA1 phosphorylation site serine-845 mutant mice. Our findings provide strong evidence that peripheral nerve injury induce long-term enhancement of cortical-spinal projecting cells in the ACC. Direct top-down projection system provides rapid and profound modulation of spinal sensory transmission, including painful information. Inhibiting cortical top-down descending facilitation may serve as a novel target for treating neuropathic pain. PMID:24890933

  10. The development of military medical care for peripheral nerve injuries during World War I.

    PubMed

    Hanigan, William

    2010-05-01

    Although the clinical and electrical diagnoses and treatments of peripheral nerve injuries (PNIs) had been described prior to World War I, many reports were fragmented and incomplete. Individual physicians' experiences were not extensive, and in 1914 the patient with a PNI remained a subject of medical curiosity, and was hardly a focus of comprehensive care. World War I altered these conditions; casualties with septic wounds and PNIs swamped the general hospitals. By 1915, specialized hospitals or wards were developed to care for neurological injuries. In the United Kingdom, Sir Robert Jones developed the concept of Military Orthopedic Centres, with coordinated specialized care and rehabilitation. Military appointments of neurologists and electrotherapists sharpened clinical diagnoses and examinations. Surgical techniques were introduced, then discarded or accepted as surgeons developed skills to meet the new conditions. The US Surgeon General, William Gorgas, and his consultant in neurosurgery, Charles Frazier, went a step further, with the organization of a research laboratory as well as the establishment of a Peripheral Nerve Commission and Registry. Despite these developments and good intentions, postwar follow-up for PNIs remained incomplete at best. Records were lost, personnel transferred, and patients discharged from the system. The lack of a standardized grading system seriously impaired the ability to record clinical changes and compare outcomes. Nevertheless, specialized treatment of a large number of PNIs during World War I established a foundation for comprehensive care that influenced military medical services in the next world war.

  11. Neuroprotective Activity of Thioctic Acid in Central Nervous System Lesions Consequent to Peripheral Nerve Injury

    PubMed Central

    Ghelardini, Carla; Nwankwo, Innocent E.; Pacini, Alessandra

    2013-01-01

    Peripheral neuropathies are heterogeneous disorders presenting often with hyperalgesia and allodynia. This study has assessed if chronic constriction injury (CCI) of sciatic nerve is accompanied by increased oxidative stress and central nervous system (CNS) changes and if these changes are sensitive to treatment with thioctic acid. Thioctic acid is a naturally occurring antioxidant existing in two optical isomers (+)- and (−)-thioctic acid and in the racemic form. It has been proposed for treating disorders associated with increased oxidative stress. Sciatic nerve CCI was made in spontaneously hypertensive rats (SHRs) and in normotensive reference cohorts. Rats were untreated or treated intraperitoneally for 14 days with (+/−)-, (+)-, or (−)-thioctic acid. Oxidative stress, astrogliosis, myelin sheets status, and neuronal injury in motor and sensory cerebrocortical areas were assessed. Increase of oxidative stress markers, astrogliosis, and neuronal damage accompanied by a decreased expression of neurofilament were observed in SHR. This phenomenon was more pronounced after CCI. Thioctic acid countered astrogliosis and neuronal damage, (+)-thioctic acid being more active than (+/−)- or (−)-enantiomers. These findings suggest a neuroprotective activity of thioctic acid on CNS lesions consequent to CCI and that the compound may represent a therapeutic option for entrapment neuropathies. PMID:24527432

  12. Interleukin-1β overproduction is a common cause for neuropathic pain, memory deficit, and depression following peripheral nerve injury in rodents

    PubMed Central

    Gui, Wen-Shan; Wei, Xiao; Mai, Chun-Lin; Murugan, Madhuvika; Wu, Long-Jun; Xin, Wen-Jun; Zhou, Li-Jun

    2016-01-01

    Background Chronic pain is often accompanied by short-term memory deficit and depression. Currently, it is believed that short-term memory deficit and depression are consequences of chronic pain. Here, we test the hypothesis that the symptoms might be caused by overproduction of interleukin-1beta (IL-1β) in the injured nerve independent of neuropathic pain following spared nerve injury in rats and mice. Results Mechanical allodynia, a behavioral sign of neuropathic pain, was not correlated with short-term memory deficit and depressive behavior in spared nerve injury rats. Spared nerve injury upregulated IL-1β in the injured sciatic nerve, plasma, and the regions in central nervous system closely associated with pain, memory and emotion, including spinal dorsal horn, hippocampus, prefrontal cortex, nucleus accumbens, and amygdala. Importantly, the spared nerve injury-induced memory deficits, depressive, and pain behaviors were substantially prevented by peri-sciatic administration of IL-1β neutralizing antibody in rats or deletion of IL-1 receptor type 1 in mice. Furthermore, the behavioral abnormalities induced by spared nerve injury were mimicked in naïve rats by repetitive intravenous injection of re combinant rat IL-1β (rrIL-1β) at a pathological concentration as determined from spared nerve injury rats. In addition, microglia were activated by both spared nerve injury and intravenous injection of rrIL-1β and the effect of spared nerve injury was substantially reversed by peri-sciatic administration of anti-IL-1β. Conclusions Neuropathic pain was not necessary for the development of cognitive and emotional disorders, while the overproduction of IL-1β in the injured sciatic nerve following peripheral nerve injury may be a common mechanism underlying the generation of neuropathic pain, memory deficit, and depression. PMID:27175012

  13. Pharmacological activation of 5-HT7 receptors reduces nerve injury-induced mechanical and thermal hypersensitivity.

    PubMed

    Brenchat, Alex; Nadal, Xavier; Romero, Luz; Ovalle, Sergio; Muro, Asunción; Sánchez-Arroyos, Ricard; Portillo-Salido, Enrique; Pujol, Marta; Montero, Ana; Codony, Xavier; Burgueño, Javier; Zamanillo, Daniel; Hamon, Michel; Maldonado, Rafael; Vela, José Miguel

    2010-06-01

    The involvement of the 5-HT(7) receptor in nociception and pain, particularly chronic pain (i.e., neuropathic pain), has been poorly investigated. In the present study, we examined whether the 5-HT(7) receptor participates in some modulatory control of nerve injury-evoked mechanical hypersensitivity and thermal (heat) hyperalgesia in mice. Activation of 5-HT(7) receptors by systemic administration of the selective 5-HT(7) receptor agonist AS-19 (1 and 10mg/kg) exerted a clear-cut reduction of mechanical and thermal hypersensitivities that were reversed by co-administering the selective 5-HT(7) receptor antagonist SB-258719. Interestingly, blocking of 5-HT(7) receptors with SB-258719 (2.5 and 10mg/kg) enhanced mechanical (but not thermal) hypersensitivity in nerve-injured mice and induced mechanical hypersensitivity in sham-operated mice. Effectiveness of the treatment with a 5-HT(7) receptor agonist was maintained after repeated systemic administration: no tolerance to the antiallodynic and antihyperalgesic effects was developed following treatment with the selective 5-HT(7) receptor agonist E-57431 (10mg/kg) twice daily for 11 days. The 5-HT(7) receptor co-localized with GABAergic cells in the dorsal horn of the spinal cord, suggesting that the activation of spinal inhibitory GABAergic interneurons could contribute to the analgesic effects of 5-HT(7) receptor agonists. In addition, a significant increase of 5-HT(7) receptors was found by immunohistochemistry in the ipsilateral dorsal horn of the spinal cord after nerve injury, suggesting a "pain"-triggered regulation of receptor expression. These results support the idea that the 5-HT(7) receptor subtype is involved in the control of pain and point to a new potential use of 5-HT(7) receptor agonists for the treatment of neuropathic pain.

  14. Bulbocavernosus Reflex Test for Diagnosis of Pudendal Nerve Injury in Female Patients with Diabetic Neurogenic Bladder

    PubMed Central

    Niu, Xiaoting; Wang, Xun; Huang, Huanjie; Ni, Peiqi; Lin, Yuanshao; Shao, Bei

    2016-01-01

    The study was designed to investigate the clinical application and significance of the bulbocavernosus reflex (BCR) test for diagnosing diabetic neurogenic bladder (DNB) in female subjects. In this study, 68 female patients with DNB and 40 female normal controls were subjected to a nerve conduction study (NCS) of all four limbs and the BCR test. The data were analyzed and compared, and the corresponding diagnostic sensitivities were discussed. Mean BCR latency for female DNB patients was significantly prolonged, compared to that of the control group, suggesting pudendal nerve injuries in female DNB patients. Moreover, DNB patients were categorized according to the diabetes course. Compared to that of Group A (diabetes course < 5 y), the mean BCR latency was significantly prolonged in Group B (diabetes course between 5 and 10 y) and then further prolonged in Group C (diabetes course > 10 y), which were all longer than the control group. Furthermore, compared with that of the controls, the mean BCR latency was prolonged in DNB patients with or without NCS abnormalities in limbs. Nevertheless, no significant difference was observed in BCR latency between DNB patients with and without NCS abnormalities. Significantly increasing trends were also observed in the NCS and BCR abnormality rates along with increased diabetes course. Most importantly, compared with the NCS of limbs, the BCR test was more sensitive in diagnosing DNB in the female subjects. Overall, our findings suggest that the BCR test would help to assess the pudendal nerve injury in female DNB patients, which might be a potential diagnostic tool in the clinic. PMID:28053822

  15. Absence of galectin-3 promotes neuroprotection in retinal ganglion cells after optic nerve injury.

    PubMed

    Abreu, Carla Andreia; De Lima, Silmara Veline; Mendonça, Henrique Rocha; Goulart, Camila de Oliveira; Martinez, Ana Maria Blanco

    2017-03-01

    A trauma to the mature central nervous system (CNS) often leads to persistent deficits, due to the inability of axons to regenerate after being injured. Increasing evidence suggests that pro-inflammatory and pro-apoptotic genes can present a major obstacle to promoting neuroprotection of retinal ganglion cells and consequently succeed in axonal regeneration. This study evaluated the effect of the absence of galectin-3 (Gal-3) on retinal ganglion cells (RGC) survival and axonal regeneration/degeneration after optic nerve crush injury. Two weeks after crush there was a 2.6 fold increase in the rate of cell survival in Gal-3-/- mice (1283±79.15) compared to WT animals (495.4±53.96). However, no regeneration was observed in the Gal-3-/- mice two weeks after lesion. Furthermore, axonal degeneration presented a particular pattern on those mice; Electron Microscopy (EM) analysis showed incomplete axon degeneration while the WT mice presented an advanced stage of degeneration. This suggests that the removal of the nerve fibers in the Gal 3-/- mice could be deficient and this would cause a delay in the process of Wallerian degeneration once there is a decrease in the number of macrophages/microglia in the nerve. This study demonstrates how the absence of Gal-3 can affect RGC survival and optic nerve regeneration/degeneration after lesion. Our results suggest that the absence of Gal-3 plays an important role in the survival of RGC and thus can be a potential target for therapeutic intervention in RGC neuroprotection.

  16. TRESK channel contribution to nociceptive sensory neurons excitability: modulation by nerve injury

    PubMed Central

    2011-01-01

    Background Neuronal hyperexcitability is a crucial phenomenon underlying spontaneous and evoked pain. In invertebrate nociceptors, the S-type leak K+ channel (analogous to TREK-1 in mammals) plays a critical role of in determining neuronal excitability following nerve injury. Few data are available on the role of leak K2P channels after peripheral axotomy in mammals. Results Here we describe that rat sciatic nerve axotomy induces hyperexcitability of L4-L5 DRG sensory neurons and decreases TRESK (K2P18.1) expression, a channel with a major contribution to total leak current in DRGs. While the expression of other channels from the same family did not significantly change, injury markers ATF3 and Cacna2d1 were highly upregulated. Similarly, acute sensory neuron dissociation (in vitro axotomy) produced marked hyperexcitability and similar total background currents compared with neurons injured in vivo. In addition, the sanshool derivative IBA, which blocked TRESK currents in transfected HEK293 cells and DRGs, increased intracellular calcium in 49% of DRG neurons in culture. Most IBA-responding neurons (71%) also responded to the TRPV1 agonist capsaicin, indicating that they were nociceptors. Additional evidence of a biological role of TRESK channels was provided by behavioral evidence of pain (flinching and licking), in vivo electrophysiological evidence of C-nociceptor activation following IBA injection in the rat hindpaw, and increased sensitivity to painful pressure after TRESK knockdown in vivo. Conclusions In summary, our results clearly support an important role of TRESK channels in determining neuronal excitability in specific DRG neurons subpopulations, and show that axonal injury down-regulates TRESK channels, therefore contributing to neuronal hyperexcitability. PMID:21527011

  17. Cavernous nerve injury elicits GAP-43 mRNA expression but not regeneration of injured pelvic ganglion neurons.

    PubMed

    Kato, Ryuichi; Kiryu-Seo, Sumiko; Sato, Yoshikazu; Hisasue, Shinichi; Tsukamoto, Taiji; Kiyama, Hiroshi

    2003-10-03

    Recovery of erectile dysfunction after cavernous nerve injury takes a long period. To elucidate this mechanism, unilateral cavernous nerve of male rat was cut, and the expression level of a nerve regeneration marker, the growth associated protein-43 (GAP-43) mRNA was evaluated by in situ hybridization and RT-PCR. While GAP-43 mRNA expression was transiently increased in the injured neurons of the major pelvic ganglion (MPG) at 7 days after nerve injury, continuous increase of GAP-43 mRNA was observed in the contralateral MPG from 7 days to 6 months after the nerve injury. Histochemical double-labeling studies for either neuronal NOS (nNOS) or tyrosine hydroxylase (TH) and the GAP-43 mRNA expression demonstrated that in injured MPG the transient up-regulation of GAP-43 mRNA was mainly seen in nNOS negative and/or TH positive neurons, suggesting non-parasympathetic post-ganglionic neurons, and also demonstrated that in contralateral MPG GAP-43 mRNA positive neurons were gradually increased in nNOS positive but TH negative neurons, suggesting parasympathetic post-ganglionic neurons. When a retrograde tracer Fluorogold (FG) was injected into the penile crus 7 days before histological experiments, FG-positive neurons were, if any, hardly seen in nNOS-positive neurons of the injured MPG for at least 6 months, whereas numerous FG-positive cells were seen in nNOS-positive neurons of the contralateral MPG. These results suggest that post-ganglionic projecting neurons of the intact side, which express increased GAP-43 mRNA, would be most likely to contribute to the recovery of the erectile function after unilateral cavernous nerve injury possibly by a plastic change such as nerve sprouting.

  18. Acceleration of Regeneration of Large-Gap Peripheral Nerve Injuries Using Acellular Nerve Allografts Plus Amniotic Fluid Derived Stem Cells (AFS)

    DTIC Science & Technology

    2014-09-01

    505. 2. Ma J, Smith BP, Smith TL, Walker FO, Rosencrance E, Koman LA. Juvenile and adult rat neuromuscular junctions: density, distribution, and...occur in neuromuscular junctions following delayed nerve injury/repair will be studied. If successful, the potential for the denervated muscle to...2002, 2007). In addition, axon morphology will be assessed and compared between treatment groups. Analysis of neuromuscular junction (NMJ) density

  19. Mandibular Branch of the Facial Nerve in Wistar Rats: New Experimental Model to Assess Facial Nerve Regeneration

    PubMed Central

    Bento, Ricardo Ferreira; Salomone, Raquel; Nascimento, Silvia Bona do; Ferreira, Ricardo Jose Rodriguez; Silva, Ciro Ferreira da; Costa, Heloisa Juliana Zabeu Rossi

    2014-01-01

    Introduction The ideal animal model for nerve regeneration studies is the object of controversy, because all models described by the literature have advantages and disadvantages. Objective To describe the histologic and functional patterns of the mandibular branch of the facial nerve of Wistar rats to create a new experimental model of facial nerve regeneration. Methods Forty-two male rats were submitted to a nerve conduction test of the mandibular branch to obtain the compound muscle action potential. Twelve of these rats had the mandibular branch surgically removed and submitted to histologic analysis (number, partial density, and axonal diameter) of the proximal and distal segments. Results There was no statistically significant difference in the functional and histologic variables studied. Conclusion These new histologic and functional standards of the mandibular branch of the facial nerve of rats establish an objective, easy, and greatly reproducible model for future facial nerve regeneration studies. PMID:25992106

  20. Mandibular branch of the facial nerve in wistar rats: new experimental model to assess facial nerve regeneration.

    PubMed

    Bento, Ricardo Ferreira; Salomone, Raquel; Nascimento, Silvia Bona do; Ferreira, Ricardo Jose Rodriguez; Silva, Ciro Ferreira da; Costa, Heloisa Juliana Zabeu Rossi

    2014-07-01

    Introduction The ideal animal model for nerve regeneration studies is the object of controversy, because all models described by the literature have advantages and disadvantages. Objective To describe the histologic and functional patterns of the mandibular branch of the facial nerve of Wistar rats to create a new experimental model of facial nerve regeneration. Methods Forty-two male rats were submitted to a nerve conduction test of the mandibular branch to obtain the compound muscle action potential. Twelve of these rats had the mandibular branch surgically removed and submitted to histologic analysis (number, partial density, and axonal diameter) of the proximal and distal segments. Results There was no statistically significant difference in the functional and histologic variables studied. Conclusion These new histologic and functional standards of the mandibular branch of the facial nerve of rats establish an objective, easy, and greatly reproducible model for future facial nerve regeneration studies.

  1. Evaluation of Tookad-mediated photodynamic effect on peripheral nerve and pelvic nerve in a canine model

    NASA Astrophysics Data System (ADS)

    Hetzel, Fred W.; Chen, Qun; Dole, Kenneth C.; Blanc, Dominique; Whalen, Lawrence R.; Gould, Daniel H.; Huang, Zheng

    2006-02-01

    Photodynamic therapy (PDT) mediated with a novel vascular targeting photosensitizer pd-bacteriopheophorbide (Tookad) has been investigated as an alternative modality for the treatment of prostate cancer and other diseases. This study investigated, for the first time, the vascular photodynamic effects of Tookad-PDT on nerve tissues. We established an in situ canine model using the cutaneous branches of the saphenous nerve to evaluate the effect of Tookad-PDT secondary to vascular damage on compound-action potentials. With Tookad dose of 2 mg/kg, treatment with 50 J/cm2 induced little change in nerve conduction. However, treatment with 100 J/cm2 resulted in decreases in nerve conduction velocities, and treatment with 200 J/cm2 caused a total loss of nerve conduction. Vasculature surrounding the saphenous nerve appeared irritated. The nerve itself looked swollen and individual fibers were not as distinct as they were before PDT treatment. Epineurium had mild hemorrhage, leukocyte infiltration, fibroplasias and vascular hypertrophy. However, the nerve fascicles and nerve fibers were free of lesions. We also studied the effect of Tookad-PDT secondary to vascular damage on the pelvic nerve in the immediate vicinity of the prostate gland. The pelvic nerve and saphenous nerve showed different sensitivity and histopathological responses to Tookad-PDT. Degeneration nerve fibers and necrotic neurons were seen in the pelvic nerve at a dose level of 1 mg/kg and 50 J/cm2. Adjacent connective tissue showed areas of hemorrhage, fibrosis and inflammation. Our preliminary results suggest that possible side effects of interstitial PDT on prostate nerve tissues need to be further investigated.

  2. Reorganization of laryngeal motoneurons after crush injury in the recurrent laryngeal nerve of the rat

    PubMed Central

    Hernández-Morato, Ignacio; Valderrama-Canales, Francisco J; Berdugo, Gabriel; Arias, Gonzalo; McHanwell, Stephen; Sañudo, José; Vázquez, Teresa; Pascual-Font, Arán

    2013-01-01

    Motoneurons innervating laryngeal muscles are located in the nucleus ambiguus (Amb), but there is no general agreement on the somatotopic representation and even less is known on how an injury in the recurrent laryngeal nerve (RLN) affects this pattern. This study analyzes the normal somatotopy of those motoneurons and describes its changes over time after a crush injury to the RLN. In the control group (control group 1, n = 9 rats), the posterior cricoarytenoid (PCA) and thyroarytenoid (TA) muscles were injected with cholera toxin-B. In the experimental groups the left RLN of each animal was crushed with a fine tip forceps and, after several survival periods (1, 2, 4, 8, 12 weeks; minimum six rats per time), the PCA and TA muscles were injected as described above. After each surgery, the motility of the vocal folds was evaluated. Additional control experiments were performed; the second control experiment (control group 2, n = 6 rats) was performed labeling the TA and PCA immediately prior to the section of the superior laryngeal nerve (SLN), in order to eliminate the possibility of accidental labeling of the cricothyroid (CT) muscle by spread from the injection site. The third control group (control group 3, n = 5 rats) was included to determine if there is some sprouting from the SLN into the territories of the RLN after a crush of this last nerve. One week after the crush injury of the RLN, the PCA and TA muscles were injected immediately before the section of the SLN. The results show that a single population of neurons represents each muscle with the PCA in the most rostral position followed caudalwards by the TA. One week post-RLN injury, both the somatotopy and the number of labeled motoneurons changed, where the labeled neurons were distributed randomly; in addition, an area of topographical overlap of the two populations was observed and vocal fold mobility was lost. In the rest of the survival periods, the overlapping area is larger, but the movement of

  3. Reorganization of laryngeal motoneurons after crush injury in the recurrent laryngeal nerve of the rat.

    PubMed

    Hernández-Morato, Ignacio; Valderrama-Canales, Francisco J; Berdugo, Gabriel; Arias, Gonzalo; McHanwell, Stephen; Sañudo, José; Vázquez, Teresa; Pascual-Font, Arán

    2013-04-01

    Motoneurons innervating laryngeal muscles are located in the nucleus ambiguus (Amb), but there is no general agreement on the somatotopic representation and even less is known on how an injury in the recurrent laryngeal nerve (RLN) affects this pattern. This study analyzes the normal somatotopy of those motoneurons and describes its changes over time after a crush injury to the RLN. In the control group (control group 1, n = 9 rats), the posterior cricoarytenoid (PCA) and thyroarytenoid (TA) muscles were injected with cholera toxin-B. In the experimental groups the left RLN of each animal was crushed with a fine tip forceps and, after several survival periods (1, 2, 4, 8, 12 weeks; minimum six rats per time), the PCA and TA muscles were injected as described above. After each surgery, the motility of the vocal folds was evaluated. Additional control experiments were performed; the second control experiment (control group 2, n = 6 rats) was performed labeling the TA and PCA immediately prior to the section of the superior laryngeal nerve (SLN), in order to eliminate the possibility of accidental labeling of the cricothyroid (CT) muscle by spread from the injection site. The third control group (control group 3, n = 5 rats) was included to determine if there is some sprouting from the SLN into the territories of the RLN after a crush of this last nerve. One week after the crush injury of the RLN, the PCA and TA muscles were injected immediately before the section of the SLN. The results show that a single population of neurons represents each muscle with the PCA in the most rostral position followed caudalwards by the TA. One week post-RLN injury, both the somatotopy and the number of labeled motoneurons changed, where the labeled neurons were distributed randomly; in addition, an area of topographical overlap of the two populations was observed and vocal fold mobility was lost. In the rest of the survival periods, the overlapping area is larger, but

  4. Slit-Robo GTPase-activating proteins are differentially expressed in murine dorsal root ganglia: modulation by peripheral nerve injury.

    PubMed

    Chen, Zhi-Bing; Zhang, Hai-Ying; Zhao, Jiu-Hong; Zhao, Wei; Zhao, Dan; Zheng, Lin-Feng; Zhang, Xian-Fang; Liao, Xiao-Ping; Yi, Xi-Nan

    2012-04-01

    The Slit-Robo GTPase-activating proteins (srGAPs) play an important role in neurite outgrowth and axon guidance; however, little is known about its role in nerve regeneration after injury. Here, we studied the expression of srGAPs in mouse dorsal root ganglia (DRG) following sciatic nerve transection (SNT) using morphometric and immunohistochemical techniques. Reverse transcriptase polymerase chain reaction and Western blot analysis indicated that srGAP1 and srGAP3, but not srGAP2, were expressed in normal adult DRG. Following unilateral SNT, elevated mRNA and protein levels of srGAP1 and srGAP3 were detected in the ipsilateral relative to contralateral L(3-4) DRGs from day 3 to day 14. Immunohistochemical results showed that srGAP1 and srGAP3 were largely expressed in subpopulations of DRG neurons in naïve DRGs. However, after SNT, srGAP3 in neurons was significantly increased in the ipsilateral relative to contralateral DRGs, which peaked at day 7 to day 14. Interestingly, DRG neurons with strong srGAP3 labeling also coexpressed Robo2 after peripheral nerve injury. These results suggest that srGAPs are differentially expressed in murine DRG and srGAP3 are the predominant form. Moreover, srGAP3 may participate in Slit-Robo signaling in response to peripheral nerve injury or the course of nerve regeneration.

  5. Nerve growth factor delivery by ultrasound-mediated nanobubble destruction as a treatment for acute spinal cord injury in rats

    PubMed Central

    Song, Zhaojun; Wang, Zhigang; Shen, Jieliang; Xu, Shengxi; Hu, Zhenming

    2017-01-01

    Background Spinal cord injuries (SCIs) can cause severe disability or death. Treatment options include surgical intervention, drug therapy, and stem cell transplantation. However, the efficacy of these methods for functional recovery remains unsatisfactory. Purpose This study was conducted to explore the effect of ultrasound (US)-mediated destruction of poly(lactic-co-glycolic acid) (PLGA) nanobubbles (NBs) expressing nerve growth factor (NGF) (NGF/PLGA NBs) on nerve regeneration in rats following SCI. Materials and methods Adult male Sprague Dawley rats were randomly divided into four treatment groups after Allen hit models of SCI were established. The groups were normal saline (NS) group, NGF and NBs group, NGF and US group, and NGF/PLGA NBs and US group. Histological changes after SCI were observed by hematoxylin and eosin staining. Neuron viability was determined by Nissl staining. Terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling staining was used to examine cell apoptosis. NGF gene and protein expressions were detected by quantitative reverse transcription polymerase chain reaction and Western blotting. Green fluorescent protein expression in the spinal cord was examined using an inverted fluorescence microscope. The recovery of neural function was determined using the Basso, Beattie, and Bresnahan test. Results NGF therapy using US-mediated NGF/PLGA NBs destruction significantly increased NGF expression, attenuated histological injury, decreased neuron loss, inhibited neuronal apoptosis in injured spinal cords, and increased BBB scores in rats with SCI. Conclusion US-mediated NGF/PLGA NBs destruction effectively transfects the NGF gene into target tissues and has a significant effect on the injured spinal cord. The combination of US irradiation and gene therapy through NGF/PLGA NBs holds great promise for the future of nanomedicine and the development of noninvasive treatment options for SCI and other diseases. PMID:28280337

  6. Involvement of Brain-Enriched Guanylate Kinase-Associated Protein (BEGAIN) in Chronic Pain after Peripheral Nerve Injury

    PubMed Central

    Fukuda, Masafumi; Furue, Hidemasa; Abe, Manabu; Nishida, Kazuhiko; Yao, Ikuko; Yamada, Akihiro; Okumura, Nobuaki; Nakazawa, Takanobu; Yamamoto, Tadashi; Sakimura, Kenji; Takao, Toshifumi; Ito, Seiji

    2016-01-01

    Maintenance of neuropathic pain caused by peripheral nerve injury crucially depends on the phosphorylation of GluN2B, a subunit of the N-methyl-d-aspartate (NMDA) receptor, at Tyr1472 (Y1472) and subsequent formation of a postsynaptic density (PSD) complex of superficial spinal dorsal horn neurons. Here we took advantage of comparative proteomic analysis based on isobaric stable isotope tags (iTRAQ) between wild-type and knock-in mice with a mutation of Y1472 to Phe of GluN2B (Y1472F-KI) to search for PSD proteins in the spinal dorsal horn that mediate the signaling downstream of phosphorylated Y1472 GluN2B. Among several candidate proteins, we focused on brain-enriched guanylate kinase-associated protein (BEGAIN), which was specifically up-regulated in wild-type mice after spared nerve injury (SNI). Immunohistochemical analysis using the generated antibody demonstrated that BEGAIN was highly localized at the synapse of inner lamina II in the spinal dorsal horn and that its expression was up-regulated after SNI in wild-type, but not in Y1472F-KI, mice. In addition, alteration of the kinetics of evoked excitatory postsynaptic currents for NMDA but not those for α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors in spinal lamina II was demonstrated by BEGAIN deletion. We demonstrated that mechanical allodynia, a condition of abnormal pain induced by innocuous stimuli, in the SNI model was significantly attenuated in BEGAIN-deficient mice. However, there was no significant difference between naive wild-type and BEGAIN-knockout mice in terms of physiological threshold for mechanical stimuli. These results suggest that BEGAIN was involved in pathological pain transmission through NMDA receptor activation by the phosphorylation of GluN2B at Y1472 in spinal inner lamina II. PMID:27785460

  7. Involvement of Brain-Enriched Guanylate Kinase-Associated Protein (BEGAIN) in Chronic Pain after Peripheral Nerve Injury.

    PubMed

    Katano, Tayo; Fukuda, Masafumi; Furue, Hidemasa; Yamazaki, Maya; Abe, Manabu; Watanabe, Masahiko; Nishida, Kazuhiko; Yao, Ikuko; Yamada, Akihiro; Hata, Yutaka; Okumura, Nobuaki; Nakazawa, Takanobu; Yamamoto, Tadashi; Sakimura, Kenji; Takao, Toshifumi; Ito, Seiji

    2016-01-01

    Maintenance of neuropathic pain caused by peripheral nerve injury crucially depends on the phosphorylation of GluN2B, a subunit of the N-methyl-d-aspartate (NMDA) receptor, at Tyr1472 (Y1472) and subsequent formation of a postsynaptic density (PSD) complex of superficial spinal dorsal horn neurons. Here we took advantage of comparative proteomic analysis based on isobaric stable isotope tags (iTRAQ) between wild-type and knock-in mice with a mutation of Y1472 to Phe of GluN2B (Y1472F-KI) to search for PSD proteins in the spinal dorsal horn that mediate the signaling downstream of phosphorylated Y1472 GluN2B. Among several candidate proteins, we focused on brain-enriched guanylate kinase-associated protein (BEGAIN), which was specifically up-regulated in wild-type mice after spared nerve injury (SNI). Immunohistochemical analysis using the generated antibody demonstrated that BEGAIN was highly localized at the synapse of inner lamina II in the spinal dorsal horn and that its expression was up-regulated after SNI in wild-type, but not in Y1472F-KI, mice. In addition, alteration of the kinetics of evoked excitatory postsynaptic currents for NMDA but not those for α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors in spinal lamina II was demonstrated by BEGAIN deletion. We demonstrated that mechanical allodynia, a condition of abnormal pain induced by innocuous stimuli, in the SNI model was significantly attenuated in BEGAIN-deficient mice. However, there was no significant difference between naive wild-type and BEGAIN-knockout mice in terms of physiological threshold for mechanical stimuli. These results suggest that BEGAIN was involved in pathological pain transmission through NMDA receptor activation by the phosphorylation of GluN2B at Y1472 in spinal inner lamina II.

  8. Post-evaluation of the neurophaties treatment post-trauma with therapeutic laser. Model in sciatic nerve of frog

    NASA Astrophysics Data System (ADS)

    Escobar, Antonio S.; Ocampo, Arcelia F. M.; Hernández, María G. H.; Jasso, José L. C.; Lira, Maricela O. F.; Flores, Mariana A.; Balderrama, Vicente L.

    2010-05-01

    The purpose of this study was to evaluate the compound nerve action potential amplitude and latency measured to determine the degree of myelination and the number of fibers stimulated in a model of stimulated frog sciatic nerve laser at 810 nm as perioperative treatment after injury. It used 30 bullfrogs (Rana catesbeiana) to obtain 60 sciatic nerves forming four groups, groups 1 and 2 worked with nerves in vitro, were dissected in humid chambers for placing isolated organ, was recorded on compound nerve action potential, the second group laser was applied at 24, 48, 72, 96 and 120 hours and at the same time were placed in 10% formalin. Groups 3 and 4 are worked in vivo localizing the nerve and causing damage through compression, occurred over the compound nerve action potential to assess the degree of myelination and the number of fibers stimulated, the group 4 was applied to 810 nm laser (500 Hz, 10 J, 200 mW) after injury, after 48 hours, three frogs were sacrificed by introducing the nerves in 10% formalin. The latency recorded by stimulating the sciatic nerve of frog to 0.5 mA and 100 ms in groups 1 and 2 show significant differences (p<0.001 and p<000) as in the amplitude (p<000 and p<000). Groups 3 and 4, which was stimulated at 100 mA and 100 ms latency showed no statistically significant difference (p>000), as to the extent, if any statistically significant difference. (p<0.001 and p<0.000). The laser produces a favorable response in the treatment of paresthesia (post-traumatic neuropathy).

  9. Post-evaluation of the neurophaties treatment post-trauma with therapeutic laser. Model in sciatic nerve of frog

    SciTech Connect

    Escobar, Antonio S.; Ocampo, Arcelia F. M.; Hernandez, Maria G. H.; Jasso, Jose L. C.

    2010-05-31

    The purpose of this study was to evaluate the compound nerve action potential amplitude and latency measured to determine the degree of myelination and the number of fibers stimulated in a model of stimulated frog sciatic nerve laser at 810 nm as perioperative treatment after injury. It used 30 bullfrogs (Rana catesbeiana) to obtain 60 sciatic nerves forming four groups, groups 1 and 2 worked with nerves in vitro, were dissected in humid chambers for placing isolated organ, was recorded on compound nerve action potential, the second group laser was applied at 24, 48, 72, 96 and 120 hours and at the same time were placed in 10% formalin. Groups 3 and 4 are worked in vivo localizing the nerve and causing damage through compression, occurred over the compound nerve action potential to assess the degree of myelination and the number of fibers stimulated, the group 4 was applied to 810 nm laser (500 Hz, 10 J, 200 mW) after injury, after 48 hours, three frogs were sacrificed by introducing the nerves in 10% formalin. The latency recorded by stimulating the sciatic nerve of frog to 0.5 mA and 100 ms in groups 1 and 2 show significant differences (p<0.001 and p<000) as in the amplitude (p<000 and p<000). Groups 3 and 4, which was stimulated at 100 mA and 100 ms latency showed no statistically significant difference (p>000), as to the extent, if any statistically significant difference. (p<0.001 and p<0.000). The laser produces a favorable response in the treatment of paresthesia (post-traumatic neuropathy).

  10. Peripheral nerve injury is associated with chronic, reversible changes in global DNA methylation in the mouse prefrontal cortex.

    PubMed

    Tajerian, Maral; Alvarado, Sebastian; Millecamps, Magali; Vachon, Pascal; Crosby, Cecilia; Bushnell, M Catherine; Szyf, Moshe; Stone, Laura S

    2013-01-01

    Changes in brain structure and cortical function are associated with many chronic pain conditions including low back pain and fibromyalgia. The magnitude of these changes correlates with the duration and/or the intensity of chronic pain. Most studies report changes in common areas involved in pain modulation, including the prefrontal cortex (PFC), and pain-related pathological changes in the PFC can be reversed with effective treatment. While the mechanisms underlying these changes are unknown, they must be dynamically regulated. Epigenetic modulation of gene expression in response to experience and environment is reversible and dynamic. Epigenetic modulation by DNA methylation is associated with abnormal behavior and pathological gene expression in the central nervous system. DNA methylation might also be involved in mediating the pathologies associated with chronic pain in the brain. We therefore tested a) whether alterations in DNA methylation are found in the brain long after chronic neuropathic pain is induced in the periphery using the spared nerve injury modal and b) whether these injury-associated changes are reversible by interventions that reverse the pathologies associated with chronic pain. Six months following peripheral nerve injury, abnormal sensory thresholds and increased anxiety were accompanied by decreased global methylation in the PFC and the amygdala but not in the visual cortex or the thalamus. Environmental enrichment attenuated nerve injury-induced hypersensitivity and reversed the changes in global PFC methylation. Furthermore, global PFC methylation correlated with mechanical and thermal sensitivity in neuropathic mice. In summary, induction of chronic pain by peripheral nerve injury is associated with epigenetic changes in the brain. These changes are detected long after the original injury, at a long distance from the site of injury and are reversible with environmental manipulation. Changes in brain structure and cortical function that

  11. More nerve root injuries occur with minimally invasive lumbar surgery, especially extreme lateral interbody fusion: A review

    PubMed Central

    Epstein, Nancy E.

    2016-01-01

    Background: In the lumbar spine, do more nerve root injuries occur utilizing minimally invasive surgery (MIS) techniques versus open lumbar procedures? To answer this question, we compared the frequency of nerve root injuries for multiple open versus MIS operations including diskectomy, laminectomy with/without fusion addressing degenerative disc disease, stenosis, and/or degenerative spondylolisthesis. Methods: Several of Desai et al. large Spine Patient Outcomes Research Trial studies showed the frequency for nerve root injury following an open diskectomy ranged from 0.13% to 0.25%, for open laminectomy/stenosis with/without fusion it was 0%, and for open laminectomy/stenosis/degenerative spondylolisthesis with/without fusion it was 2%. Results: Alternatively, one study compared the incidence of root injuries utilizing MIS transforaminal lumbar interbody fusion (TLIF) versus posterior lumbar interbody fusion (PLIF) techniques; 7.8% of PLIF versus 2% of TLIF patients sustained root injuries. Furthermore, even higher frequencies of radiculitis and nerve root injuries occurred during anterior lumbar interbody fusions (ALIFs) versus extreme lateral interbody fusions (XLIFs). These high frequencies were far from acceptable; 15.8% following ALIF experienced postoperative radiculitis, while 23.8% undergoing XLIF sustained root/plexus deficits. Conclusions: This review indicates that MIS (TLIF/PLIF/ALIF/XLIF) lumbar surgery resulted in a higher incidence of root injuries, radiculitis, or plexopathy versus open lumbar surgical techniques. Furthermore, even a cursory look at the XLIF data demonstrated the greater danger posed to neural tissue by this newest addition to the MIS lumbar surgical armamentariu. The latter should prompt us as spine surgeons to question why the XLIF procedure is still being offered to our patients? PMID:26904372

  12. Cannabinoid 1 receptor knockout mice display cold allodynia, but enhanced recovery from spared-nerve injury-induced mechanical hypersensitivity

    PubMed Central

    Piskoun, Boris; Russo, Lori; Norcini, Monica; Blanck, Thomas; Recio-Pinto, Esperanza

    2016-01-01

    Background The function of the Cannabinoid 1 receptor (CB1R) in the development of neuropathic pain is not clear. Mounting evidence suggest that CB1R expression and activation may contribute to pain. Cannabinoid 1 receptor knockout mice (CB1R−/−) generated on a C57Bl/6 background exhibit hypoalgesia in the hotplate assay and formalin test. These findings suggest that Cannabinoid 1 receptor expression mediates the responses to at least some types of painful stimuli. By using this mouse line, we sought to determine if the lack of Cannabinoid 1 receptor unveils a general hypoalgesic phenotype, including protection against the development of neuropathic pain. The acetone test was used to measure cold sensitivity, the electronic von Frey was used to measure mechanical thresholds before and after spared-nerve injury, and analysis of footprint patterns was conducted to determine if motor function is differentially affected after nerve-injury in mice with varying levels of Cannabinoid 1 receptor. Results At baseline, CB1R−/− mice were hypersensitive in the acetone test, and this phenotype was maintained after spared-nerve injury. Using calcium imaging of lumbar dorsal root ganglion (DRG) cultures, a higher percentage of neurons isolated from CB1R−/− mice were menthol sensitive relative to DRG isolated from wild-type (CB1R+/+) mice. Baseline mechanical thresholds did not differ among genotypes, and mechanical hypersensitivity developed similarly in the first two weeks following spared-nerve injury (SNI). At two weeks post-SNI, CB1R−/− mice recovered significantly from mechanical hypersensitivity, while the CB1R+/+ mice did not. Heterozygous knockouts (CB1R+/−) transiently developed cold allodynia only after injury, but recovered mechanical thresholds to a similar extent as the CB1R−/− mice. Sciatic functional indices, which reflect overall nerve health, and alternation coefficients, which indicate uniformity of strides, were not significantly different

  13. NR2B Expression in Rat DRG Is Differentially Regulated Following Peripheral Nerve Injuries That Lead to Transient or Sustained Stimuli-Evoked Hypersensitivity

    PubMed Central

    Norcini, Monica; Sideris, Alexandra; Adler, Samantha M.; Hernandez, Lourdes A. M.; Zhang, Jin; Blanck, Thomas J. J.; Recio-Pinto, Esperanza

    2016-01-01

    Following injury, primary sensory neurons undergo changes that drive central sensitization and contribute to the maintenance of persistent hypersensitivity. NR2B expression in the dorsal root ganglia (DRG) has not been previously examined in neuropathic pain models. Here, we investigated if changes in NR2B expression within the DRG are associated with hypersensitivities that result from peripheral nerve injuries. This was done by comparing the NR2B expression in the DRG derived from two modalities of the spared nerve injury (SNI) model, since each variant produces different neuropathic pain phenotypes. Using the electronic von Frey to stimulate the spared and non-spared regions of the hindpaws, we demonstrated that sural-SNI animals develop sustained neuropathic pain in both regions while the tibial-SNI animals recover. NR2B expression was measured at Day 23 and Day 86 post-injury. At Day 23 and 86 post-injury, sural-SNI animals display strong hypersensitivity, whereas tibial-SNI animals display 50 and 100% recovery from post-injury-induced hypersensitivity, respectively. In tibial-SNI at Day 86, but not at Day 23 the perinuclear region of the neuronal somata displayed an increase in NR2B protein. This retention of NR2B protein within the perinuclear region, which will render them non-functional, correlates with the recovery observed in tibial-SNI. In sural-SNI at Day 86, DRG displayed an increase in NR2B mRNA which correlates with the development of sustained hypersensitivity in this model. The increase in NR2B mRNA was not associated with an increase in NR2B protein within the neuronal somata. The latter may result from a decrease in kinesin Kif17, since Kif17 mediates NR2B transport to the soma’s plasma membrane. In both SNIs, microglia/macrophages showed a transient increase in NR2B protein detected at Day 23 but not at Day 86, which correlates with the initial post-injury induced hypersensitivity in both SNIs. In tibial-SNI at Day 86, but not at Day 23

  14. NR2B Expression in Rat DRG Is Differentially Regulated Following Peripheral Nerve Injuries That Lead to Transient or Sustained Stimuli-Evoked Hypersensitivity.

    PubMed

    Norcini, Monica; Sideris, Alexandra; Adler, Samantha M; Hernandez, Lourdes A M; Zhang, Jin; Blanck, Thomas J J; Recio-Pinto, Esperanza

    2016-01-01

    Following injury, primary sensory neurons undergo changes that drive central sensitization and contribute to the maintenance of persistent hypersensitivity. NR2B expression in the dorsal root ganglia (DRG) has not been previously examined in neuropathic pain models. Here, we investigated if changes in NR2B expression within the DRG are associated with hypersensitivities that result from peripheral nerve injuries. This was done by comparing the NR2B expression in the DRG derived from two modalities of the spared nerve injury (SNI) model, since each variant produces different neuropathic pain phenotypes. Using the electronic von Frey to stimulate the spared and non-spared regions of the hindpaws, we demonstrated that sural-SNI animals develop sustained neuropathic pain in both regions while the tibial-SNI animals recover. NR2B expression was measured at Day 23 and Day 86 post-injury. At Day 23 and 86 post-injury, sural-SNI animals display strong hypersensitivity, whereas tibial-SNI animals display 50 and 100% recovery from post-injury-induced hypersensitivity, respectively. In tibial-SNI at Day 86, but not at Day 23 the perinuclear region of the neuronal somata displayed an increase in NR2B protein. This retention of NR2B protein within the perinuclear region, which will render them non-functional, correlates with the recovery observed in tibial-SNI. In sural-SNI at Day 86, DRG displayed an increase in NR2B mRNA which correlates with the development of sustained hypersensitivity in this model. The increase in NR2B mRNA was not associated with an increase in NR2B protein within the neuronal somata. The latter may result from a decrease in kinesin Kif17, since Kif17 mediates NR2B transport to the soma's plasma membrane. In both SNIs, microglia/macrophages showed a transient increase in NR2B protein detected at Day 23 but not at Day 86, which correlates with the initial post-injury induced hypersensitivity in both SNIs. In tibial-SNI at Day 86, but not at Day 23

  15. Isolated muscle hypertrophy as a sign of radicular or peripheral nerve injury.

    PubMed Central

    Mattle, H P; Hess, C W; Ludin, H P; Mumenthaler, M

    1991-01-01

    Two patients with isolated neurogenic hypertrophy of the trapezius muscle due to accessory nerve injury and a patient with neurogenic hypertrophy of the anterior tibial muscle due to chronic radicular lesion L4 are described. Electromyography of the affected muscles showed dense continuing spontaneous discharges of complex potentials. Muscle biopsy performed in two patients showed abundant hypertrophic muscle fibres, identified in one case by ATP-ase reaction as being of predominantly type I. In the majority of previously reported patients with neurogenic muscle hypertrophy confined to the calf muscle, a passive stretch mechanism was suggested as a cause of the hypertrophy. It is assumed that the excessive spontaneous muscle activity gave rise to the hypertrophy in these patients. This may also be true in previously reported patients with neurogenic hypertrophy and similar spontaneous activity in electromyography. Images PMID:2056318

  16. Patient outcome after surgical management of the spinal accessory nerve injury: A long-term follow-up study

    PubMed Central

    Göransson, Harry; Leppänen, Olli V; Vastamäki, Martti

    2016-01-01

    Objectives: A lesion in the spinal accessory nerve is typically iatrogenic: related to lymph node biopsy or excision. This injury may cause paralysis of the trapezius muscle and thus result in a characteristic group of symptoms and signs, including depression and winging of the scapula, drooped shoulder, reduced shoulder abduction, and pain. The elements evaluated in this long-term follow-up study include range of shoulder motion, pain, patients’ satisfaction, delay of surgery, surgical procedure, occupational status, functional outcome, and other clinical findings. Methods: We reviewed the medical records of a consecutive 37 patients (11 men and 26 women) having surgery to correct spinal accessory nerve injury. Neurolysis was the procedure in 24 cases, direct nerve repair for 9 patients, and nerve grafting for 4. Time elapsed between the injury and the surgical operation ranged from 2 to 120 months. The patients were interviewed and clinically examined after an average of 10.2 years postoperatively. Results: The mean active range of movement of the shoulder improved at abduction 44° (43%) in neurolysis, 59° (71%) in direct nerve repair, and 30° (22%) in nerve-grafting patients. No or only slight atrophy of the trapezius muscle was observable in 75%, 44%, and 50%, and no or controllable pain was observable in 63%, 56%, and 50%. Restriction of shoulder abduction preceded deterioration of shoulder flexion. Patients’ overall dissatisfaction with the state of their upper extremity was associated with pain, lower strength in shoulder movements, and occupational problems. Conclusion: We recommend avoiding unnecessary delay in the exploration of the spinal accessory nerve, if a neural lesion is suspected. PMID:27152195

  17. Acute lung injury following inhalation exposure to nerve agent VX in guinea pigs.

    PubMed

    Wright, Benjamin S; Rezk, Peter E; Graham, Jacob R; Steele, Keith E; Gordon, Richard K; Sciuto, Alfred M; Nambiar, Madhusoodana P

    2006-05-01

    A microinstillation technique of inhalation exposure was utilized to assess lung injury following chemical warfare nerve agent VX [methylphosphonothioic acid S-(2-[bis(1-methylethyl)amino]ethyl) O-ethyl ester] exposure in guinea pigs. Animals were anesthetized using Telazol-meditomidine, gently intubated, and VX was aerosolized using a microcatheter placed 2 cm above the bifurcation of the trachea. Different doses (50.4 microg/m3, 70.4 micro g/m(m3), 90.4 microg/m(m3)) of VX were administered at 40 pulses/min for 5 min. Dosing of VX was calculated by the volume of aerosol produced per 200 pulses and diluting the agent accordingly. Although the survival rate of animals exposed to different doses of VX was similar to the controls, nearly a 20% weight reduction was observed in exposed animals. After 24 h of recovery, the animals were euthanized and bronchoalveolar lavage (BAL) was performed with oxygen free saline. BAL was centrifuged and separated into BAL fluid (BALF) and BAL cells (BALC) and analyzed for indication of lung injury. The edema by dry/wet weight ratio of the accessory lobe increased 11% in VX-treated animals. BAL cell number was increased in VX-treated animals compared to controls, independent of dosage. Trypan blue viability assay indicated an increase in BAL cell death in 70.4 microg/m(m3) and 90.4 microg/m(m3) VX-exposed animals. Differential cell counting of BALC indicated a decrease in macrophage/monocytes in VX-exposed animals. The total amount of BAL protein increased gradually with the exposed dose of VX and was highest in animals exposed to 90.4 microg/m(m3), indicating that this dose of VX caused lung injury that persisted at 24 h. In addition, histopathology results also suggest that inhalation exposure to VX induces acute lung injury.

  18. An in vitro model of adult mammalian nerve repair.

    PubMed

    Vyas, Alka; Li, Zhaobo; Aspalter, Manuela; Feiner, Jeffrey; Hoke, Ahmet; Zhou, Chunhua; O'Daly, Andres; Abdullah, Madeel; Rohde, Charles; Brushart, Thomas M

    2010-05-01

    The role of pathway-derived growth factors in the support of peripheral axon regeneration remains elusive. Few appropriate knock-out mice are available, and gene silencing techniques are rarely 100% effective. To overcome these difficulties, we have developed an in vitro organotypic co-culture system that accurately models peripheral nerve repair in the adult mammal. Spinal cord sections from P4 mice that express YFP in their neurons are used to innervate segments of P4 peripheral nerve. This reconstructed ventral root is then transected and joined to a nerve graft. Growth of axons across the nerve repair and into the graft can be imaged repeatedly with fluorescence microscopy to define regeneration speed, and parent neurons can be labeled in retrograde fashion to identify contributing neurons. Nerve graft harvested from adult mice remains viable in culture by both morphologic and functional criteria. Motoneurons are supported with GDNF for the first week in culture, after which they survive axotomy, and are thus functionally adult. This platform can be modified by using motoneurons from any genetically modified mouse that can be bred to express XFP, by harvesting nerve graft from any source, or by treating the culture systemically with antibodies, growth factors, or pathway inhibitors. The regeneration environment is controlled to a degree not possible in vivo, and the use of experimental animals is reduced substantially. The flexibility and control offered by this technique should thus make it a useful tool for the study of regeneration biology.

  19. The efficacy of Jing Wan Hong ointment for nerve injury diabetic foot ulcer and its mechanisms.

    PubMed

    Jin, Shumei; Zhang, Mixia; Gao, Yan; Zhang, Xuebin; Cui, Guangzhi; Zhang, Yanjun

    2014-01-01

    Jing Wan Hong ointment contains 30 kinds of Chinese herbs, with functions of activating blood circulation to disperse blood stasis, clearing heat, eliminating dampness, and reducing swelling by detoxification. Therefore, Jing Wan Hong ointment may facilitate the healing of ulcers. The aim of this study was to evaluate the efficacy and mechanisms of Jing Wan Hong ointment for healing diabetic foot ulceration in Wistar rats induced by streptozotocin and sciatic nerve damage. The results showed that Jing Wan Hong ointment had a marked effect on foot ulcers in diabetic rats induced by initial nerve injury. These effects were manifested by reducing the foot ulcer size and Wagner grade after seven days of treatment. The diabetic rats with foot ulcers were almost healed after 21 days of treatment. Moreover, the mechanisms of this effect seem to be dependent on increased expression of PDGF mRNA, but there was no influence on the expression of TGF-β, VEGF, and FLT-1 mRNA.

  20. The Efficacy of Jing Wan Hong Ointment for Nerve Injury Diabetic Foot Ulcer and Its Mechanisms

    PubMed Central

    Jin, Shumei; Zhang, Mixia; Gao, Yan; Zhang, Xuebin; Cui, Guangzhi; Zhang, Yanjun

    2014-01-01

    Jing Wan Hong ointment contains 30 kinds of Chinese herbs, with functions of activating blood circulation to disperse blood stasis, clearing heat, eliminating dampness, and reducing swelling by detoxification. Therefore, Jing Wan Hong ointment may facilitate the healing of ulcers. The aim of this study was to evaluate the efficacy and mechanisms of Jing Wan Hong ointment for healing diabetic foot ulceration in Wistar rats induced by streptozotocin and sciatic nerve damage. The results showed that Jing Wan Hong ointment had a marked effect on foot ulcers in diabetic rats induced by initial nerve injury. These effects were manifested by reducing the foot ulcer size and Wagner grade after seven days of treatment. The diabetic rats with foot ulcers were almost healed after 21 days of treatment. Moreover, the mechanisms of this effect seem to be dependent on increased expression of PDGF mRNA, but there was no influence on the expression of TGF-β, VEGF, and FLT-1 mRNA. PMID:25538944

  1. How to Avoid Ulnar Nerve Injury When Setting the 6U Wrist Arthroscopy Portal.

    PubMed

    Esplugas, Mireia; Lluch, Alex; Garcia-Elias, Marc; Llusà-Pérez, Manuel

    2014-05-01

    The dorsal sensory branch of the ulnar nerve (DSBUN) is at risk in setting the 6U wrist arthroscopy portal. Although surgeons know the risk and are careful when they set the 6U portal, DSBUN injuries still occur. The purpose of the present anatomical study was to evaluate the possibility that DSBUN undergoes dynamic anatomical variations in its location during wrist arthroscopy. The goal of the study was to clarify (1) whether the nerve-to-portal (NTP) distance changes with flexion/extension wrist and/or hand/forearm rotation, and (2) whether there is any particular combination of flexion-extension/hand-forearm rotation where the NTP distance is maximal. Six fresh cadaver arms were suspended in a traction tower with forearm rotation locked, the skin and subcutaneous tissue around the ulnar head was removed, and the NTP distance measured in three predetermined loading/positional conditions. Of all options, the one that consistently showed the longest and safest NTP distance involved wrist flexion and radiocarpal supination when forearm rotation is limited. In conclusion, when an arthroscopic traction device restricts the forearm rotation, the 6U portal should not be set under traction with the hand passively pronated. Failure to observe this precaution can result in serious neuropathic pain.

  2. Galectin-3 Inhibition Is Associated with Neuropathic Pain Attenuation after Peripheral Nerve Injury.

    PubMed

    Ma, Zhicong; Han, Qi; Wang, Xiaolei; Ai, Zisheng; Zheng, Yongjun

    2016-01-01

    Neuropathic pain remains a prevalent and persistent clinical problem because it is often poorly responsive to the currently used analgesics. It is very urgent to develop novel drugs to alleviate neuropathic pain. Galectin-3 (gal3) is a multifunctional protein belonging to the carbohydrate-ligand lectin family, which is expressed by different cells. Emerging studies showed that gal3 elicits a pro-inflammatory response by recruiting and activating lymphocytes, macrophages and microglia. In the study we investigated whether gal3 inhibition could suppress neuroinflammation and alleviate neuropathic pain following peripheral nerve injury. We found that L5 spinal nerve ligation (SNL) increases the expression of gal3 in dorsal root ganglions at the mRNA and protein level. Intrathecal administration of modified citrus pectin (MCP), a gal3 inhibitor, reduces gal3 expression in dorsal root ganglions. MCP treatment also inhibits SNL-induced gal3 expression in primary rat microglia. SNL results in an increased activation of autophagy that contributes to microglial activation and subsequent inflammatory response. Intrathecal administration of MCP significantly suppresses SNL-induced autophagy activation. MCP also inhibits lipopolysaccharide (LPS)-induced autophagy in cultured microglia in vitro. MCP further decreases LPS-induced expression of proinflammatory mediators including IL-1β, TNF-α and IL-6 by regulating autophagy. Intrathecal administration of MCP results in adecreased mechanical and cold hypersensitivity following SNL. These results demonstrated that gal3 inhibition is associated with the suppression of SNL-induced inflammatory process andneurophathic pain attenuation.

  3. Galectin-3 Inhibition Is Associated with Neuropathic Pain Attenuation after Peripheral Nerve Injury

    PubMed Central

    Ai, Zisheng; Zheng, Yongjun

    2016-01-01

    Neuropathic pain remains a prevalent and persistent clinical problem because it is often poorly responsive to the currently used analgesics. It is very urgent to develop novel drugs to alleviate neuropathic pain. Galectin-3 (gal3) is a multifunctional protein belonging to the carbohydrate-ligand lectin family, which is expressed by different cells. Emerging studies showed that gal3 elicits a pro-inflammatory response by recruiting and activating lymphocytes, macrophages and microglia. In the study we investigated whether gal3 inhibition could suppress neuroinflammation and alleviate neuropathic pain following peripheral nerve injury. We found that L5 spinal nerve ligation (SNL) increases the expression of gal3 in dorsal root ganglions at the mRNA and protein level. Intrathecal administration of modified citrus pectin (MCP), a gal3 inhibitor, reduces gal3 expression in dorsal root ganglions. MCP treatment also inhibits SNL-induced gal3 expression in primary rat microglia. SNL results in an increased activation of autophagy that contributes to microglial activation and subsequent inflammatory response. Intrathecal administration of MCP significantly suppresses SNL-induced autophagy activation. MCP also inhibits lipopolysaccharide (LPS)-induced autophagy in cultured microglia in vitro. MCP further decreases LPS-induced expression of proinflammatory mediators including IL-1β, TNF-α and IL-6 by regulating autophagy. Intrathecal administration of MCP results in adecreased mechanical and cold hypersensitivity following SNL. These results demonstrated that gal3 inhibition is associated with the suppression of SNL-induced inflammatory process andneurophathic pain attenuation. PMID:26872020

  4. Effects of Valproic Acid on Axonal Regeneration and Recovery of Motor Function after Peripheral Nerve Injury in the Rat

    PubMed Central

    Rao, Ting; Wu, Fei; Xing, Danmou; Peng, Zhengren; Ren, Dong; Feng, Wei; Chen, Yan; Zhao, Zhiming; Wang, Huan; Wang, Junweng; Kan, Wusheng; Zhang, Qingsong

    2014-01-01

    Background: Valproic acid (VPA) is used to be an effective anti-epileptic drug and mood stabilizer. It has recently been demonstrated that VPA could promote neurite outgrowth, activate the extracellular signal regulated kinase pathway, and increases bcl-2 and growth cone-associated protein 43 levels in spinal cord. In the present research we demonstrate the effect of VPA on peripheral nerve regeneration and recovery of motor function following sciatic nerve transaction in rats. Methods: The rats in VPA group and control group were administered with valproic acid (300mg/kg) and sodium chloride respectively after operation. Each animal was observed sciatic nerve index (SFI) at 2-week intervals and studied electrophysiology at 4-week intervals for 12 weeks. Histological and morphometrical analyses were performed 12 weeks after operation. Using the digital image-analysis system, thickness of the myelin sheath was measured, and total numbers of regenerated axons were counted. Results: There was a significant difference in SFI, electrophysiological index (motor-nerve conduct velocity), and morphometrical results (regenerated axon number and thickness of myelin sheath) in nerve regeneration between the VPA group and controls (P<0.05). Conclusions: The results demonstrated that VPA is able to enhance sciatic nerve regeneration in rats, suggesting the potential clinical application of VPA for the treatment of peripheral nerve injury in humans. PMID:25207308

  5. Improvement in acupoint selection for acupuncture of nerves surrounding the injury site: electro-acupuncture with Governor vessel with local meridian acupoints

    PubMed Central

    He, Guan-heng; Ruan, Jing-wen; Zeng, Yuan-shan; Zhou, Xin; Ding, Ying; Zhou, Guang-hui

    2015-01-01

    Peripheral nerve injury not only affects the site of the injury, but can also induce neuronal apoptosis at the spinal cord. However, many acupuncture clinicians still focus only on the injury site, selecting acupoints entirely along the injured nerve trunk and neglecting other regions; this may delay onset of treatment efficacy and rehabilitation. Therefore, in the present study, we compared the clinical efficacy of acupuncture at Governor vessel and local meridian acupoints combined (GV/LM group) with acupuncture at local meridian acupoints alone (LM group) in the treatment of patients with peripheral nerve injury. In the GV/LM group (n = 15), in addition to meridian acupoints at the injury site, the following acupoints on the Governor vessel were stimulated: Baihui (GV20), Fengfu (GV16), Dazhui (GV14), and Shenzhu (GV12), selected to treat nerve injury of the upper limb, and Jizhong (GV6), Mingmen (GV4), Yaoyangguan (GV3), and Yaoshu (GV2) to treat nerve injury of the lower limb. In the LM group (n = 15), only meridian acupoints along the injured nerve were selected. Both groups had electroacupuncture treatment for 30 minutes, once a day, 5 times per week, for 6 weeks. Two cases dropped out of the LM group. A good or excellent clinical response was obtained in 80% of the patients in the GV/LM group and 38.5% of the LM group. In a second study, an additional 20 patients underwent acupuncture with the same prescription as the GV/LM group. Electomyographic nerve conduction tests were performed before and after acupuncture to explore the mechanism of action of the treatment. An effective response was observed in 80.0% of the patients, with greater motor nerve conduction velocity and amplitude after treatment, indicating that electroacupuncture on specific Governor vessel acupoints promotes functional motor nerve repair after peripheral nerve injury. In addition, electromyography was performed before, during and after electroacupuncture in one patient with radial

  6. Improvement in acupoint selection for acupuncture of nerves surrounding the injury site: electro-acupuncture with Governor vessel with local meridian acupoints.

    PubMed

    He, Guan-Heng; Ruan, Jing-Wen; Zeng, Yuan-Shan; Zhou, Xin; Ding, Ying; Zhou, Guang-Hui

    2015-01-01

    Peripheral nerve injury not only affects the site of the injury, but can also induce neuronal apoptosis at the spinal cord. However, many acupuncture clinicians still focus only on the injury site, selecting acupoints entirely along the injured nerve trunk and neglecting other regions; this may delay onset of treatment efficacy and rehabilitation. Therefore, in the present study, we compared the clinical efficacy of acupuncture at Governor vessel and local meridian acupoints combined (GV/LM group) with acupuncture at local meridian acupoints alone (LM group) in the treatment of patients with peripheral nerve injury. In the GV/LM group (n = 15), in addition to meridian acupoints at the injury site, the following acupoints on the Governor vessel were stimulated: Baihui (GV20), Fengfu (GV16), Dazhui (GV14), and Shenzhu (GV12), selected to treat nerve injury of the upper limb, and Jizhong (GV6), Mingmen (GV4), Yaoyangguan (GV3), and Yaoshu (GV2) to treat nerve injury of the lower limb. In the LM group (n = 15), only meridian acupoints along the injured nerve were selected. Both groups had electroacupuncture treatment for 30 minutes, once a day, 5 times per week, for 6 weeks. Two cases dropped out of the LM group. A good or excellent clinical response was obtained in 80% of the patients in the GV/LM group and 38.5% of the LM group. In a second study, an additional 20 patients underwent acupuncture with the same prescription as the GV/LM group. Electomyographic nerve conduction tests were performed before and after acupuncture to explore the mechanism of action of the treatment. An effective response was observed in 80.0% of the patients, with greater motor nerve conduction velocity and amplitude after treatment, indicating that electroacupuncture on specific Governor vessel acupoints promotes functional motor nerve repair after peripheral nerve injury. In addition, electromyography was performed before, during and after electroacupuncture in one patient with radial

  7. Peripheral nerve injury produces a sustained shift in the balance between glutamate release and uptake in the dorsal horn of the spinal cord

    PubMed Central

    Inquimbert, Perrine; Bartels, Karsten; Babaniyi, Olusegun B.; Barrett, Lee B.; Tegeder, Irmgard; Scholz, Joachim

    2012-01-01

    Peripheral nerve injury provokes heightened excitability of primary sensory afferents including nociceptors, and elicits ectopic activity in lesioned and neighboring intact nerve fibers. The major transmitter released by sensory afferents in the superficial dorsal horn of the spinal cord is glutamate. Glutamate is critically involved in nociceptive signaling and the development of neuropathic pain. We recorded miniature excitatory postsynaptic currents (mEPSCs) from neurons in lamina II of the rat dorsal horn to assess spontaneous synaptic activity after spared nerve injury (SNI), a model of chronic neuropathic pain. Following SNI, the frequency of mEPSCs doubled, indicating heightened glutamate release from primary afferents or spinal interneurons. Consistent with this finding, glutamate concentrations in the cerebrospinal fluid were elevated at one and four weeks after SNI. Transmitter uptake was insufficient to prevent the rise in extracellular glutamate as the expression of glutamate transporters remained unchanged or decreased. 2-Methyl-6-(phenylethynyl)pyridine hydrochloride (MPEP), an antagonist of metabotropic glutamate receptor 5 (mGluR5), reduced the frequency of mEPSCs to its preinjury level, suggesting a positive feedback mechanism that involves facilitation of transmitter release by mGluR5 activation in the presence of high extracellular glutamate. Treatment with the β-lactam antibiotic ceftriaxone increased the expression of glutamate transporter 1 (Glt1) in the dorsal horn after SNI, raised transmitter uptake and lowered extracellular glutamate. Improving glutamate clearance prevented the facilitation of transmitter release by mGluR5 and attenuated neuropathic pain-like behavior. Balancing glutamate release and uptake after nerve injury should be an important target in the management of chronic neuropathic pain. PMID:23021150

  8. Depletion of Foxp3+ regulatory T cells increases severity of mechanical allodynia and significantly alters systemic cytokine levels following peripheral nerve injury.

    PubMed

    Lees, Justin G; Duffy, Samuel S; Perera, Chamini J; Moalem-Taylor, Gila

    2015-02-01

    Neuropathic pain is a debilitating condition caused by damage to the somatosensory nervous system, such as peripheral nerve injury. The immune system, and in particular the adaptive T cell response, plays a key role in mediating such pain. Regulatory T (Treg) cells are a small subpopulation of inhibitory T cells that prevent autoimmunity, limit immunopathology and maintain immune homeostasis. Here, we investigated the effects of conditional depletion of Treg cells on mechanical allodynia and serum cytokines in mice with chronic constriction injury (CCI) of the sciatic nerve, an animal model of neuropathic pain. We demonstrate that CCI induced the infiltration of small numbers of Treg cells within effected neuronal tissue. Utilising the transgenic DEREG (DEpletion of REGulatory T cells) mice, we confirmed effective depletion of Foxp3+ Treg cells by diphtheria toxin injections. Following CCI we observed a transient, though significant, increase in pain hypersensitivity for Treg-depleted DEREG mice compared to non-Treg-depleted mice. Analysis of systemic cytokine levels demonstrated significant changes in serum cytokine expression profiles. In particular, we observed significant increases in systemic concentration of RANTES, IL-2 and IL-5, and significant decreases in IL-12 and IFN-γ in nerve-injured Treg-depleted DEREG mice. Further analysis indicated a substantial increase in the serum concentration of IL-12p40 as a direct result of Treg cell depletion. These results suggest that depletion of Foxp3+ Treg cells promote nerve injury-induced pain hypersensitivity, partially by inducing altered systemic concentrations of cytokines, which may act to regulate neuropathic pain.

  9. Development of a canine model for recurrent laryngeal injury by harmonic scalpel.

    PubMed

    Lee, Kyu-Eun; Jee, Hyeon-Gun; Kim, Hoon-Yub; Park, Won-Seo; Park, Sung-Hye; Youn, Yeo-Kyu

    2012-12-01

    Various energy devices had been used in thyroid surgery. Aim of study is to develop canine model for recurrent laryngeal nerve injury by harmonic scalpel and to evaluate feasibility of using this model for evaluating the safety use of harmonic scalpel during thyroid surgery. Nine dogs were divided into 3 groups according to distance between harmonic scalpel application and recurrent laryngeal nerve; group 1 (1 mm), 2 (2 mm), and 3 (3 mm). Vocal cord function was assessed pre- and postoperatively using video laryngoscopy. Harmonic scalpel was applied adjacent to left recurrent laryngeal nerve and, two weeks later, right recurrent laryngeal nerve at assigned distances. Recurrent laryngeal nerves were evaluated for subacute and acute morphologic changes. Laryngoscopy demonstrated 3 abnormal vocal cords in group 1, 1 in group 2, and no in group 3 (P=0.020). Subacute histologic changes were observed in nerves with abnormal function. Acute histologic changes were observed 5/8 (62.5%) in group 1, 1/7 (14.3%) in group 2, and not in group 3. We developed canine model for recurrent laryngeal injury. The functional outcomes matched with the histologic changes. These warrant further study to determine the safety margin for energy device in vicinity of recurrent laryngeal nerve.

  10. Schwann cells transduced with a lentiviral vector encoding Fgf-2 promote motor neuron regeneration following sciatic nerve injury.

    PubMed

    Allodi, Ilary; Mecollari, Vasil; González-Pérez, Francisco; Eggers, Ruben; Hoyng, Stefan; Verhaagen, Joost; Navarro, Xavier; Udina, Esther

    2014-10-01

    Fibroblast growth factor 2 (FGF-2) is a trophic factor expressed by glial cells and different neuronal populations. Addition of FGF-2 to spinal cord and dorsal root ganglia (DRG) explants demonstrated that FGF-2 specifically increases motor neuron axonal growth. To further explore the potential capability of FGF-2 to promote axon regeneration, we produced a lentiviral vector (LV) to overexpress FGF-2 (LV-FGF2) in the injured rat peripheral nerve. Cultured Schwann cells transduced with FGF-2 and added to collagen matrix embedding spinal cord or DRG explants significantly increased motor but not sensory neurite outgrowth. LV-FGF2 was as effective as direct addition of the trophic factor to promote motor axon growth in vitro. Direct injection of LV-FGF2 into the rat sciatic nerve resulted in increased expression of FGF-2, which was localized in the basal lamina of Schwann cells. To investigate the in vivo effect of FGF-2 overexpression on axonal regeneration after nerve injury, Schwann cells transduced with LV-FGF2 were grafted in a silicone tube used to repair the resected rat sciatic nerve. Electrophysiological tests conducted for up to 2 months after injury revealed accelerated and more marked reinnervation of hindlimb muscles in the animals treated with LV-FGF2, with an increase in the number of motor and sensory neurons that reached the distal tibial nerve at the end of follow-up.

  11. Tactile hyperesthesia, altered epidermal innervation and plantar nerve injury in the hindfeet of rats housed on wire grates.

    PubMed

    Mizisin, A P; Kalichman, M W; Garrett, R S; Dines, K C

    1998-03-30

    The effects of wire grates on nerve injury and recovery were examined in rats housed in cages with sawdust-covered solid flooring. For the first 3 weeks of the study, 20 rats were housed on sawdust alone and 20 rats were housed in cages with wire grates placed over the sawdust. For the remaining 9 weeks, 10 animals housed on sawdust had wire grates added to their cages, while grates were removed from the cages of 10 animals. The effects of tactile stimulation on hindpaw plantar skin was measured weekly using the Von Frey filament test. Intraepidermal innervation using PGP 9.5 immunostaining and plantar nerve histology were assessed at the end of the 12-week study. After just 1 week on grates, hindpaw withdrawal thresholds were already markedly decreased and remained low until the grates were removed at 3 weeks. Thresholds returned to normal by 4 weeks after removal of the grates. Wire grates also induced increases in PGP 9.5 immunoreactive intraepidermal fine nerve endings that were normalized after grate removal. Demyelination, Wallerian degeneration and Renaut bodies were induced in the medial plantar nerve in rats housed in cages with wire-grate flooring. Nerve injury was largely resolved after 9 weeks on sawdust flooring. These data demonstrate that wire grates rapidly induce hindpaw tactile hyperesthesia and plantar neuropathy in rats and emphasize a risk of using wire-grate cage flooring in studies assessing hindlimb function and structure.

  12. Active skin perfusion and thermoregulatory response in the hand following nerve injury and repair in human upper extremities.

    PubMed

    Deng, Aidong; Liu, Dan; Gu, Chen; Gu, Xiaosong; Gu, Jianhui; Hu, Wen

    2016-01-01

    Cutaneous vasoconstriction/vasodilatation occurs in response to whole body and local cooling/heating, and the vasomotor activities play a pivotal role in thermal control of the human body. The mechanisms underlying regulation of skin blood flow involve both neurogenic and humeral/local chemical influence, contributing to the initial response to thermal stimuli and the prolonged phase of response, respectively. Previous studies have suggested the impairment of cutaneous thermal regulation after nerve injury. However, the evidence regarding how the skin perfusion and thermoregulatory response evolve after nerve injury and repair remains limited. Here we observed, by utilizing laser-Doppler perfusion imaging, baseline skin perfusion and perfusion change in response to thermal stimuli after median and ulnar nerve injury, and the results showed that baseline perfusion in autonomous skin area profoundly decreased and active rewarming after clod stress dramatically diminished before sensory recovery of the skin became detectable. In addition, baseline cutaneous perfusion was recovered as the skin regained touch sensation, and exhibited positive correlation to touch sensibility of the skin. These data indicate that both active perfusion and thermoregulatory response of the skin are markedly compromised during skin denervation and can be recovered by re-innervation. This suggests the importance of timely repair of injured nerve, especially in the practice of replantation.

  13. Resuscitation therapy for traumatic brain injury-induced coma in rats: mechanisms of median nerve electrical stimulation

    PubMed Central

    Feng, Zhen; Zhong, Ying-jun; Wang, Liang; Wei, Tian-qi

    2015-01-01

    In this study, rats were put into traumatic brain injury-induced coma and treated with median nerve electrical stimulation. We explored the wake-promoting effect, and possible mechanisms, of median nerve electrical stimulation. Electrical stimulation upregulated the expression levels of orexin-A and its receptor OX1R in the rat prefrontal cortex. Orexin-A expression gradually increased with increasing stimulation, while OX1R expression reached a peak at 12 hours and then decreased. In addition, after the OX1R antagonist, SB334867, was injected into the brain of rats after traumatic brain injury, fewer rats were restored to consciousness, and orexin-A and OXIR expression in the prefrontal cortex was downregulated. Our findings indicate that median nerve electrical stimulation induced an up-regulation of orexin-A and OX1R expression in the prefrontal cortex of traumatic brain injury-induced coma rats, which may be a potential mechanism involved in the wake-promoting effects of median nerve electrical stimulation. PMID:26170820

  14. Cholecalciferol (Vitamin D3) Improves Myelination and Recovery after Nerve Injury

    PubMed Central

    Chabas, Jean-Francois; Stephan, Delphine; Marqueste, Tanguy; Garcia, Stephane; Lavaut, Marie-Noelle; Nguyen, Catherine; Legre, Regis; Khrestchatisky, Michel

    2013-01-01

    Previously, we demonstrated i) that ergocalciferol (vitamin D2) increases axon diameter and potentiates nerve regeneration in a rat model of transected peripheral nerve and ii) that cholecalciferol (vitamin D3) improves breathing and hyper-reflexia in a rat model of paraplegia. However, before bringing this molecule to the clinic, it was of prime importance i) to assess which form – ergocalciferol versus cholecalciferol – and which dose were the most efficient and ii) to identify the molecular pathways activated by this pleiotropic molecule. The rat left peroneal nerve was cut out on a length of 10 mm and autografted in an inverted position. Animals were treated with either cholecalciferol or ergocalciferol, at the dose of 100 or 500 IU/kg/day, or excipient (Vehicle), and compared to unlesioned rats (Control). Functional recovery of hindlimb was measured weekly, during 12 weeks, using the peroneal functional index. Ventilatory, motor and sensitive responses of the regenerated axons were recorded and histological analysis was performed. In parallel, to identify the genes regulated by vitamin D in dorsal root ganglia and/or Schwann cells, we performed an in vitro transcriptome study. We observed that cholecalciferol is more efficient than ergocalciferol and, when delivered at a high dose (500 IU/kg/day), cholecalciferol induces a significant locomotor and electrophysiological recovery. We also demonstrated that cholecalciferol increases i) the number of preserved or newly formed axons in the proximal end, ii) the mean axon diameter in the distal end, and iii) neurite myelination in both distal and proximal ends. Finally, we found a modified expression of several genes involved in axogenesis and myelination, after 24 hours of vitamin supplementation. Our study is the first to demonstrate that vitamin D acts on myelination via the activation of several myelin-associated genes. It paves the way for future randomised controlled clinical trials for peripheral nerve or

  15. Comparison of trophic factors' expression between paralyzed and recovering muscles after facial nerve injury. A quantitative analysis in time course.

    PubMed

    Grosheva, Maria; Nohroudi, Klaus; Schwarz, Alisa; Rink, Svenja; Bendella, Habib; Sarikcioglu, Levent; Klimaschewski, Lars; Gordon, Tessa; Angelov, Doychin N

    2016-05-01

    After peripheral nerve injury, recovery of motor performance negatively correlates with the poly-innervation of neuromuscular junctions (NMJ) due to excessive sprouting of the terminal Schwann cells. Denervated muscles produce short-range diffusible sprouting stimuli, of which some are neurotrophic factors. Based on recent data that vibrissal whisking is restored perfectly during facial nerve regeneration in blind rats from the Sprague Dawley (SD)/RCS strain, we compared the expression of brain derived neurotrophic factor (BDNF), fibroblast growth factor-2 (FGF2), insulin growth factors 1 and 2 (IGF1, IGF2) and nerve growth factor (NGF) between SD/RCS and SD-rats with normal vision but poor recovery of whisking function after facial nerve injury. To establish which trophic factors might be responsible for proper NMJ-reinnervation, the transected facial nerve was surgically repaired (facial-facial anastomosis, FFA) for subsequent analysis of mRNA and proteins expressed in the levator labii superioris muscle. A complicated time course of expression included (1) a late rise in BDNF protein that followed earlier elevated gene expression, (2) an early increase in FGF2 and IGF2 protein after 2 days with sustained gene expression, (3) reduced IGF1 protein at 28 days coincident with decline of raised mRNA levels to baseline, and (4) reduced NGF protein between 2 and 14 days with maintained gene expression found in blind rats but not the rats with normal vision. These findings suggest that recovery of motor function after peripheral nerve injury is due, at least in part, to a complex regulation of lesion-associated neurotrophic factors and cytokines in denervated muscles. The increase of FGF-2 protein and concomittant decrease of NGF (with no significant changes in BDNF or IGF levels) during the first week following FFA in SD/RCS blind rats possibly prevents the distal branching of regenerating axons resulting in reduced poly-innervation of motor endplates.

  16. Nerve growth factor attenuates cholinergic deficits following traumatic brain injury in rats.

    PubMed

    Dixon, C E; Flinn, P; Bao, J; Venya, R; Hayes, R L

    1997-08-01

    Traumatic brain injury (TBI) results in chronic derangements in central cholinergic neurotransmission that may contribute to posttraumatic memory deficits. Intraventricular cannula (IVC) nerve growth factor (NGF) infusion can reduce axotomy-induced spatial memory deficits and morphologic changes observed in medial septal cholinergic neurons immunostained for choline acetyltransferase (ChAT). We examined the efficacy of NGF to (1) ameliorate reduced posttraumatic spatial memory performance, (2) release of hippocampal acetylcholine (ACh), and (3) ChAT immunoreactivity in the rat medial septum. Rats (n = 36) were trained prior to TBI on the functional tasks and retested on Days 1-5 (motor) and on Day 7 (memory retention). Immediately following injury, an IVC and osmotic pump were implanted, and NGF or vehicle was infused for 7 days. While there were no differences in motor performance, the NGF-treated group had significantly better spatial memory retention (P < 0.05) than the vehicle-treated group. The IVC cannula was then removed on Day 7, and a microdialysis probe was placed into the dorsal hippocampus. After a 22-h equilibration period, samples were collected prior to and after administration of scopolamine (1 mg/kg), which evoked ACh release by blocking autoreceptors. The posttraumatic reduction in scopolamine-evoked ACh release was completely reversed with NGF. Injury produced a bilateral reduction in the number and cross-sectional area of ChAT immunopositive medial septal neurons that was reversed by NGF treatment. These data suggest that cognitive but not motor deficits following TBI are, in part, mediated by chronic deficits in cholinergic systems that can be modulated by neurotrophic factors such as NGF.

  17. Inhibition of the NMDA receptor protects the rat sciatic nerve against ischemia/reperfusion injury

    PubMed Central

    KE, TIE; LI, RENBIN; CHEN, WENCHANG

    2016-01-01

    Inhibition of the N-methyl-D-aspartate (NMDA) receptor by MK-801 reduces ischemia/reperfusion (I/R) injury in the central nervous system. However, few previous studies have evaluated the neuroprotective effects of MK-801 against peripheral I/R injury. The present study aimed to investigate the protective effects of MK-801 pretreatment against I/R injury in the rat sciatic nerve (SN). Sprague-Dawley rats were subjected to a sham surgery (n=8) or to a 5-h ischemic insult by femoral artery clamping (I/R and I/R+MK-801 groups; n=48 per group). I/R+MK-801 rats were intraperitoneally injected with MK-801 (0.5 ml or 1 mg/kg) at 15 min prior to reperfusion. The rats were sacrificed at 0, 6, 12, 24, 72 h, or 7 days following reperfusion. Plasma malondialdehyde (MDA) and nitric oxide (NO) concentrations, and SN inducible NO synthase (iNOS) protein expression levels, were measured using colorimetry. In addition, the protein expression levels of tumor necrosis factor-α (TNF-α) were measured using immunohistochemistry, and histological analyses of the rat SN were conducted using light and electron microscopy. Alterations in the mRNA expression levels of TNF-α and TNF-α converting enzyme (TACE) in the rat SN were detected using reverse transcription-quantitative polymerase chain reaction. In the I/R group, plasma concentrations of NO (175.3±4.2 µmol/l) and MDA (16.2±1.9 mmol/l), and the levels of iNOS (2.5±0.3) in the SN, peaked at 24 h post-reperfusion. At 24 h, pretreatment with MK-801 significantly reduced plasma NO (107.3±3.6 µmol/l) and MDA (11.8±1.6 mmol/l), and SN iNOS (1.65±0.2) levels (all P<0.01). The mRNA expression levels of TNF-α and TACE in the SN were significantly reduced in the I/R+MK-801 group, as compared with the I/R group (P<0.05). Furthermore, MK-801 pretreatment was shown to have alleviated histological signs of I/R injury, including immune cell infiltration and axon demyelination. The results of the present study suggested that pretreatment

  18. Nerve growth factor administration attenuates cognitive but not neurobehavioral motor dysfunction or hippocampal cell loss following fluid-percussion brain injury in rats.

    PubMed

    Sinson, G; Voddi, M; McIntosh, T K

    1995-11-01

    Lateral fluid-percussion brain injury in rats results in cognitive deficits, motor dysfunction, and selective hippocampal cell loss. Neurotrophic factors have been shown to have potential therapeutic applications in neurodegenerative diseases, and nerve growth factor (NGF) has been shown to be neuroprotective in models of excitotoxicity. This study evaluated the neuroprotective efficacy of intracerebral NGF infusion after traumatic brain injury. Male Sprague-Dawley rats received lateral fluid-percussion brain injury of moderate severity (2.1-2.3 atm). A miniosmotic pump was implanted 24 h after injury to infuse NGF (n = 34) or vehicle (n = 16) directly into the region of maximal cortical injury. Infusions of NGF continued until the animal was killed at 72 h, 1 week, or 2 weeks after injury. Animals were evaluated for cognitive dysfunction (Morris Water Maze) and regional neuronal cell loss (Nissl staining) at each of the three time points. Animals surviving for 1 or 2 weeks were also evaluated for neurobehavioral motor function. Although an improvement in memory scores was not observed at 72 h after injury, animals receiving NGF infusions showed significantly improved memory scores when tested at 1 or 2 weeks after injury compared with injured animals receiving vehicle infusions (p < 0.05). Motor scores and CA3 hippocampal cell loss were not significantly different in any group of NGF-treated animals when compared with controls. These data suggest that NGF administration, in the acute, posttraumatic period following fluid-percussion brain injury, may have potential in improving post-traumatic cognitive deficits.

  19. An Argument for Salvage in Severe Lower Extremity Trauma with Posterior Tibial Nerve Injury: The Ganga Hospital Experience

    PubMed Central

    Momoh, Adeyiza O.; Kumaran, Senthil; Lyons, Daniel; Venkatramani, Hari; Ramkumar, Sanjai; Chung, Kevin C.; Sabapathy, S. Raja

    2016-01-01

    BACKGROUND Absence of plantar sensation is a critical factor considered in favor of amputation for patients with lower limb-threatening injuries. This study aims to assess outcomes of limb salvage in a group of patients with severe lower extremity injuries associated with posterior tibial nerve transection. METHODS We studied eight cases of limb salvage after traumatic injuries with documented tibial nerve laceration managed at Ganga Hospital, India. Functional and health-related quality of life outcomes were assessed. Outcomes from this case series were compared to outcomes of studies from a systematic literature review on salvage of the severely injured lower extremity. RESULTS Patients in this case series reported mild pain (median score 20 on a 100 scale visual analog scale) with some return of plantar sensation in patients with tibial nerve repairs (median score 2/5). Patients demonstrated a decrease in ankle motion (27.5 degrees plantar flexion, 10 degrees extension) and muscle strength (median heel flexor score 3/5). All patients could ambulate independently. Quality of life and function measured by validated instruments revealed minimal disability. We identified 1,767 articles on lower extremity trauma and 14 articles were systematically reviewed. Relative to the case series, published articles reported similarly diminished ankle motion and muscle strength, with reports of mild pain in select studies. Patient reported outcome instruments found variations in the degree of physical disability based on time from the injury. CONCLUSIONS Though limited in number, this case series demonstrates the value of limb salvage even for patients with posterior tibial nerve injury. PMID:26270902

  20. A Long-Gap Peripheral Nerve Injury Therapy Using Human Skeletal Muscle-Derived Stem Cells (Sk-SCs): An Achievement of Significant Morphological, Numerical and Functional Recovery

    PubMed Central

    Hirata, Maki; Nakajima, Nobuyuki; Saito, Kosuke; Hashimoto, Hiroyuki; Soeda, Shuichi; Uchiyama, Yoshiyasu; Watanabe, Masahiko

    2016-01-01

    Losses in vital functions of the somatic motor and sensory nervous system are induced by severe long-gap peripheral nerve transection injury. In such cases, autologous nerve grafts are the gold standard treatment, despite the unavoidable sacrifice of other healthy functions, whereas the prognosis is not always favorable. Here, we use human skeletal muscle-derived stem cells (Sk-SCs) to reconstitute the function after long nerve-gap injury. Muscles samples were obtained from the amputated legs from 9 patients following unforeseen accidents. The Sk-SCs were isolated using conditioned collagenase solution, and sorted as CD34+/45- (Sk-34) and CD34-/45-/29+ (Sk-DN/29+) cells. Cells were separately cultured/expanded under optimal conditions for 2 weeks, then injected into the athymic nude mice sciatic nerve long-gap model (7-mm) bridging an acellular conduit. After 8–12 weeks, active cell engraftment was observed only in the Sk-34 cell transplanted group, showing preferential differentiation into Schwann cells and perineurial/endoneurial cells, as well as formation of the myelin sheath and perineurium/endoneurium surrounding regenerated axons, resulted in 87% of numerical recovery. Differentiation into vascular cell lineage (pericyte and endothelial cells) were also observed. A significant tetanic tension recovery (over 90%) of downstream muscles following electrical stimulation of the sciatic nerve (at upper portion of the gap) was also achieved. In contrast, Sk-DN/29+ cells were completely eliminated during the first 4 weeks, but relatively higher numerical (83% vs. 41% in axon) and functional (80% vs. 60% in tetanus) recovery than control were observed. Noteworthy, significant increase in the formation of vascular networks in the conduit during the early stage (first 2 weeks) of recovery was observed in both groups with the expression of key factors (mRNA and protein levels), suggesting the paracrine effects to angiogenesis. These results suggested that the human Sk

  1. Expression of sodium channel SNS/PN3 and ankyrin(G) mRNAs in the trigeminal ganglion after inferior alveolar nerve injury in the rat.

    PubMed

    Bongenhielm, U; Nosrat, C A; Nosrat, I; Eriksson, J; Fjell, J; Fried, K

    2000-08-01

    The inferior alveolar nerve is a sensory branch of the trigeminal nerve that is frequently damaged, and such nerve injuries can give rise to persistent paraesthesia and dysaesthesia. The mechanisms behind neuropathic pain following nerve injury is poorly understood. However, remodeling of voltage-gated sodium channels in the neuronal membrane has been proposed as one possible mechanism behind injury-induced ectopic hyperexcitability. The TTX-resistant sodium channel SNS/PN3 has been implicated in the development of neuropathic pain after spinal nerve injury. We here study the effect of chronic axotomy of the inferior alveolar nerve on the expression of SNS/PN3 mRNA in trigeminal sensory neurons. The organization of sodium channels in the neuronal membrane is maintained by binding to ankyrin, which help link the sodium channel to the membrane skeleton. Ankyrin(G), which colocalizes with sodium channels in the initial segments and nodes of Ranvier, and is necessary for normal neuronal sodium channel function, could be essential in the reorganization of the axonal membrane after nerve injury. For this reason, we here study the expression of ankyrin(G) in the trigeminal ganglion and the localization of ankyrin(G) protein in the inferior alveolar nerve after injury. We show that SNS/PN3 mRNA is down-regulated in small-sized trigeminal ganglion neurons following inferior alveolar nerve injury but that, in contrast to the persistent loss of SNS/PN3 mRNA seen in dorsal root ganglion neurons following sciatic nerve injury, the levels of SNS/PN3 mRNA appear to normalize within a few weeks. We further show that the expression of ankyrin(G) mRNA also is downregulated after nerve lesion and that these changes persist for at least 13 weeks. This decrease in the ankyrin(G) mRNA expression could play a role in the reorganization of sodium channels within the damaged nerve. The changes in the levels of SNS/PN3 mRNA in the trigeminal ganglion, which follow the time course for

  2. Peripheral nerve reconstruction with epsilon-caprolactone conduits seeded with vasoactive intestinal peptide gene-transfected mesenchymal stem cells in a rat model

    NASA Astrophysics Data System (ADS)

    Hernández-Cortés, P.; Toledo-Romero, M. A.; Delgado, M.; Sánchez-González, C. E.; Martin, F.; Galindo-Moreno, P.; O'Valle, F.

    2014-08-01

    Objective. Attempts have been made to improve nerve conduits in peripheral nerve reconstruction. We investigated the potential therapeutic effect of a vasoactive intestinal peptide (VIP), a neuropeptide with neuroprotective, trophic and developmental regulatory actions, in peripheral nerve regeneration in a severe model of nerve injury that was repaired with nerve conduits. Approach. The sciatic nerve of each male Wistar rat was transected unilaterally at 10 mm and then repaired with Dl-lactic-ɛ-caprolactone conduits. The rats were treated locally with saline, with the VIP, with adipose-derived mesenchymal stem cells (ASCs) or with ASCs that were transduced with the VIP-expressing lentivirus. The rats with the transected nerve, with no repairs, were used as untreated controls. At 12 weeks post-surgery, we assessed their limb function by measuring the ankle stance angle and the percentage of their muscle mass reduction, and we evaluated the histopathology, immunohistochemistry and morphometry of the myelinated fibers. Main results. The rats that received a single injection of VIP-expressing ASCs showed a significant functional recovery in the ankle stance angle (p = 0.049) and a higher number of myelinated fibers in the middle and distal segments of the operated nerve versus the other groups (p = 0.046). Significance. These results suggest that utilization of a cellular substrate, plus a VIP source, is a promising method for enhancing nerve regeneration using Dl-lactic-ɛ-caprolactone conduits and that this method represents a potential useful clinical approach to repairing peripheral nerve damage.

  3. Effects of Distal Nerve Injuries on Dorsal-Horn Neurons and Glia: Relationships Between Lesion Size and Mechanical Hyperalgesia

    PubMed Central

    Lee, J. W.; Siegel, S. M.; Oaklander, A. L.

    2008-01-01

    Penetrating limb injuries are common and usually heal without long-lasting effects, even when nerves are cut. However, rare nerve-injury patients develop prolonged and disabling chronic pain (neuralgia). When pain severity is disproportionate to severity of the inciting injury, physicians and insurers may suspect exaggeration and limit care or benefits, although the nature of the relationship between lesion-size and the development and persistence of neuralgia remains largely unknown. We compared cellular changes in the spinal dorsal-horn (the initial CNS pain-processing area) after partial or total tibial-nerve axotomies in male Sprague–Dawley rats to determine if these changes are proportional to the numbers of peripheral axons cut. Unoperated rats provided controls. Plantar hind-paw responses to touch, pin, and cold were quantitated bilaterally to identify hyperalgesic rats. We also compared data from nerve-injured rats with or without hyperalgesic responses to mechanical hind-paw stimulation to evaluate concordance between pain behaviors and dorsal-horn cellular changes. Hyperalgesia was no less prevalent or severe after partial than after total axotomy. L5 spinal-cord sections from rats killed 7 days postoperatively were labeled for markers of primary afferents (substance P calcitonin gene-related peptide isolectin B4, gamma aminobutyric acid, and glial fibrillary acidic protein), then labeled cells were stereologically quantitated in somatotopically defined dorsal-horn regions. Total axotomy reduced markers of primary afferents more than partial axotomy. In contrast, GABA-immunoreactive profiles were similarly reduced after both lesions, and in rats with sensory loss versus hyperalgesia. Numbers of GFAP-immunoreactive astrocytes increased independently of lesion size and pain status. Small nerve injuries can thus have magnified and disproportionate effects on dorsal-horn neurons and glia, perhaps providing a biological correlate for the disproportionate

  4. Diathermy testing: a novel method with electric knife stimulation to avoid nerve injuries during lumbar pedicle screw placement. Technical note.

    PubMed

    Yamazaki, Takashi; Matsudaira, Ko

    2007-05-01

    The purpose of this retrospective study was to demonstrate the utility of diathermy in avoiding nerve injuries due to misplacement of lumbar pedicle screws (PSs). The authors used diathermy to assess whether a screw deviated from the pedicle by observing synchronous leg movements caused by intermittently touching an electric knife to the pedicular instrument. Diathermy was performed in 259 cases in which 1301 PSs had been placed. Leg movements were observed in 36 cases, and the sensitivity of diathermy was 85.7%, with a specificity of 99.5%. No neurological complications associated with the placement of PSs were observed after adding diathermy testing to conventional methods. Diathermy testing may be a way to avoid nerve injuries during lumbar PS placement.

  5. Duloxetine Inhibits Microglial P2X4 Receptor Function and Alleviates Neuropathic Pain after Peripheral Nerve Injury

    PubMed Central

    Yamashita, Tomohiro; Yamamoto, Shota; Zhang, Jiaming; Kometani, Miho; Tomiyama, Daisuke; Kohno, Keita; Tozaki-Saitoh, Hidetoshi; Inoue, Kazuhide; Tsuda, Makoto

    2016-01-01

    P2X4 receptors (P2X4R) are a family of ATP-gated non-selective cation channels. We previously demonstrated that activation of P2X4R in spinal microglia is crucial for neuropathic pain, a highly debilitating chronic pain condition, suggesting that P2X4R is a potential therapeutic target for treating neuropathic pain. Thus, the identification of a compound that has a potent inhibitory effect on P2X4R is an important clinical challenge. In the present study, we screened a chemical library of clinically approved drugs and show for the first time that duloxetine, a serotonin and noradrenaline reuptake inhibitor, has an inhibitory effect on rodent and human P2X4R. In primary cultured microglial cells, duloxetine also inhibited P2X4R-, but not P2X7R-, mediated responses. Moreover, intrathecal administration of duloxetine in a model of neuropathic pain produced a reversal of nerve injury-induced mechanical allodynia, a cardinal symptom of neuropathic pain. In rats that were pretreated with a serotonin-depleting agent and a noradrenaline neurotoxin, the antiallodynic effect of duloxetine was reduced, but still remained. Based on these results, we suggest that, in addition to duloxetine’s primary inhibitory action on serotonin and noradrenaline transporters, an inhibitory effect on P2X4R may be involved at least in part in an antiallodynic effect of intrathecal duloxetine in a model of neuropathic pain. PMID:27768754

  6. G9a inhibits CREB-triggered expression of mu opioid receptor in primary sensory neurons following peripheral nerve injury

    PubMed Central

    Liang, Lingli; Zhao, Jian-Yuan; Gu, Xiyao; Wu, Shaogen; Mo, Kai; Xiong, Ming; Marie Lutz, Brianna; Bekker, Alex

    2016-01-01

    Neuropathic pain, a distressing and debilitating disorder, is still poorly managed in clinic. Opioids, like morphine, remain the mainstay of prescribed medications in the treatment of this disorder, but their analgesic effects are highly unsatisfactory in part due to nerve injury-induced reduction of opioid receptors in the first-order sensory neurons of dorsal root ganglia. G9a is a repressor of gene expression. We found that nerve injury-induced increases in G9a and its catalyzed repressive marker H3K9m2 are responsible for epigenetic silencing of Oprm1, Oprk1, and Oprd1 genes in the injured dorsal root ganglia. Blocking these increases rescued dorsal root ganglia Oprm1, Oprk1, and Oprd1 gene expression and morphine or loperamide analgesia and prevented the development of morphine or loperamide-induced analgesic tolerance under neuropathic pain conditions. Conversely, mimicking these increases reduced the expression of three opioid receptors and promoted the mu opioid receptor-gated release of primary afferent neurotransmitters. Mechanistically, nerve injury-induced increases in the binding activity of G9a and H3K9me2 to the Oprm1 gene were associated with the reduced binding of cyclic AMP response element binding protein to the Oprm1 gene. These findings suggest that G9a participates in the nerve injury-induced reduction of the Oprm1 gene likely through G9a-triggered blockage in the access of cyclic AMP response element binding protein to this gene. PMID:27927796

  7. Use of 5% lidocaine medicated plaster to treat localized neuropathic pain secondary to traumatic injury of peripheral nerves

    PubMed Central

    Correa-Illanes, Gerardo; Roa, Ricardo; Piñeros, José Luis; Calderón, Wilfredo

    2012-01-01

    Objective The efficacy of 5% lidocaine medicated plaster (LMP) has previously been demonstrated in post-traumatic localized neuropathic pain. This study evaluated the use of LMP in localized neuropathic pain secondary to traumatic peripheral nerve injury. Patients and methods This prospective observational study enrolled patients with traumatic injuries to peripheral nerves that were accompanied by localized neuropathic pain of more than 3 months duration. Demographic variables, pain intensity (measured using the numeric rating scale; NRS), answers to the Douleur Neuropathique 4 (DN4) questionnaire, and the size of the painful area were recorded. Results Nineteen patients were included, aged (mean ± standard deviation) 41.4 ± 15.7 years. Nerve injuries affected the upper (eight patients) or lower (11 patients) limbs. The mean duration of pain before starting treatment with LMP was 22.6 ± 43.5 months (median 8 months). Mean baseline values included: NRS 6.7 ± 1.6, painful area 17.8 ± 10.4 cm2 (median 18 cm2), and DN4 score 6.7 ± 1.4. The mean duration of treatment with LMP was 19.5 ± 10.0 weeks (median 17.4 weeks). Mean values after treatment were: NRS 2.8 ± 1.5 (≥3 point reduction in 79% of patients, ≥50% reduction in 57.9% of patients) and painful area 2.1 ± 2.3 cm2 (median 1 cm2, ≥50% reduction in 94.7% of patients). Functional improvement after treatment was observed in 14/19 patients (73.7%). Conclusion LMP effectively treated traumatic injuries of peripheral nerves which presented with chronic localized neuropathic pain, reducing both pain intensity and the size of the painful area. PMID:23152700

  8. Atf3 mutant mice show reduced axon regeneration and impaired regeneration-associated gene induction after peripheral nerve injury

    PubMed Central

    Gey, Manuel; Wanner, Renate; Schilling, Corinna; Pedro, Maria T.; Sinske, Daniela

    2016-01-01

    Axon injury in the peripheral nervous system (PNS) induces a regeneration-associated gene (RAG) response. Atf3 (activating transcription factor 3) is such a RAG and ATF3's transcriptional activity might induce ‘effector’ RAGs (e.g. small proline rich protein 1a (Sprr1a), Galanin (Gal), growth-associated protein 43 (Gap43)) facilitating peripheral axon regeneration. We provide a first analysis of Atf3 mouse mutants in peripheral nerve regeneration. In Atf3 mutant mice, facial nerve regeneration and neurite outgrowth of adult ATF3-deficient primary dorsal root ganglia neurons was decreased. Using genome-wide transcriptomics, we identified a neuropeptide-encoding RAG cluster (vasoactive intestinal peptide (Vip), Ngf, Grp, Gal, Pacap) regulated by ATF3. Exogenous administration of neuropeptides enhanced neurite growth of Atf3 mutant mice suggesting that these molecules might be effector RAGs of ATF3's pro-regenerative function. In addition to the induction of growth-promoting molecules, we present data that ATF3 suppresses growth-inhibiting molecules such as chemokine (C-C motif) ligand 2. In summary, we show a pro-regenerative ATF3 function during PNS nerve regeneration involving transcriptional activation of a neuropeptide-encoding RAG cluster. ATF3 is a general injury-inducible factor, therefore ATF3-mediated mechanisms identified herein might apply to other cell and injury types. PMID:27581653

  9. The Thermal Sensitivity Test in Evaluating Outcome after Peripheral Nerve Injury

    PubMed Central

    Ceynowa, Marcin; Mazurek, Tomasz; Pankowski, Rafał; Rocławski, Marek; Treder, Mariusz

    2015-01-01

    The purpose of this study was to evaluate the ability to discriminate temperatures in patients following peripheral nerve injury. Knowing that temperature sensibility is mediated by different receptors, the scores were compared to other functional hand scores in order to determine whether the ability to discriminate temperatures is restored to a different extent compared with other commonly evaluated hand function modalities. The test was performed using the NTE-2 device (Physitemp Instruments Inc., 154 Huron Avenue, Clifton, New Jersey, USA). Out of 57 patients, 27 had normal thermal discrimination scores, and 9 could not tell the temperatures apart in the differences set on the measuring device. Overall, patients with better thermal discrimination had also better hand function as evaluated with different methods. However, some patients who did regain the ability to differentiate temperatures correctly did not have any measurable return of hand function in other tests. Thermal discrimination scores correlated similarly with different functional scores, except for vibration sensibility, which did not show any significant correlation. The development and severity of cold intolerance seem to be unrelated to temperature sense. PMID:26199942

  10. Elevated Neurosteroids in the Lateral Thalamus Relieve Neuropathic Pain in Rats with Spared Nerve Injury.

    PubMed

    Zhang, Meng; Liu, Jia; Zhou, Meng-Meng; Wu, Honghai; Hou, Yanning; Li, Yun-Feng; Yin, Yuxin; Zheng, Lemin; Liu, Feng-Yu; Yi, Ming; Wan, You

    2016-08-01

    Neurosteroids are synthesized in the nervous system from cholesterol or steroidal precursors imported from peripheral sources. These compounds are important allosteric modulators of γ-aminobutyric acid A receptors (GABAARs), which play a vital role in pain modulation in the lateral thalamus, a main gate where somatosensory information enters the cerebral cortex. Using high-performance liquid chromatography/tandem mass spectrometry, we found increased levels of neurosteroids (pregnenolone, progesterone, deoxycorticosterone, allopregnanolone, and tetrahydrodeoxycorticosterone) in the chronic stage of neuropathic pain (28 days after spared nerve injury) in rats. The expression of the translocator protein TSPO, the upstream steroidogenesis rate-limiting enzyme, increased at the same time. In vivo stereotaxic microinjection of neurosteroids or the TSPO activator AC-5216 into the lateral thalamus (AP -3.0 mm, ML ±3.0 mm, DV 6.0 mm) alleviated the mechanical allodynia in neuropathic pain, while the TSPO inhibitor PK 11195 exacerbated it. The analgesic effects of AC-5216 and neurosteroids were significantly attenuated by the GABAAR antagonist bicuculline. These results suggested that elevated neurosteroids in the lateral thalamus play a protective role in the chronic stage of neuropathic pain.

  11. Antral bony wall erosion, trigeminal nerve injury, and enophthalmos after root canal surgery

    PubMed Central

    Ferreira, Eduardo; Antunes, Luís; Dinis, Paulo Borges

    2016-01-01

    Introduction: The frequently used irrigant in dental surgery, sodium hypochlorite, is occasionally the cause of minor, usually circumscribed, adverse effects. Severe, extensive complications, with lasting sequelae, however, also can occur, as in the case we report herein. Case Report: A 55-year-old woman underwent an endodontic procedure on a maxillary molar, whose roots, unknown to the surgeon, were protruding into the maxillary sinus. After sodium hypochlorite root canal irrigation, the patient immediately developed intense facial pain, facial edema, and periorbital cellulitis. An emergency department evaluation diagnosed an intense inflammatory disease of the maxillary sinus, with significant destruction of its bony walls, accompanied by midface paraesthesia due to infraorbital nerve injury. In the following weeks, the patient slowly developed enophthalmos due to bone erosion of the orbit floor. Treatment, besides prolonged oral steroids, required the endoscopic endonasal opening of the maxillary sinus for profuse irrigation. Two years later, the patient maintained a complete loss of function of the maxillary sinus, anesthesia-paraesthesia of the midface, and inferior dystonia of the eye with an enophthalmos. Conclusion: Dentists, maxillofacial surgeons, and otorhinolaryngologists should all be aware of the whole spectrum of complications of even the simplest dental work. Sodium hypochlorite irrigations should be used cautiously in root canal surgery, with the full awareness of its potential for causing soft-tissue damage. PMID:27465790

  12. Generation of New Neurons in Dorsal Root Ganglia in Adult Rats after Peripheral Nerve Crush Injury

    PubMed Central

    2015-01-01

    The evidence of neurons generated ex novo in sensory ganglia of adult animals is still debated. In the present study, we investigated, using high resolution light microscopy and stereological analysis, the changes in the number of neurons in dorsal root ganglia after 30 days from a crush lesion of the rat brachial plexus terminal branches. Results showed, as expected, a relevant hypertrophy of dorsal root ganglion neurons. In addition, we reported, for the first time in the literature, that neuronal hypertrophy was accompanied by massive neuronal hyperplasia leading to a 42% increase of the number of primary sensory neurons. Moreover, ultrastructural analyses on sensory neurons showed that there was not a relevant neuronal loss as a consequence of the nerve injury. The evidence of BrdU-immunopositive neurons and neural progenitors labeled with Ki67, nanog, nestin, and sox-2 confirmed the stereological evidence of posttraumatic neurogenesis in dorsal root ganglia. Analysis of morphological changes following axonal damage in addition to immunofluorescence characterization of cell phenotype suggested that the neuronal precursors which give rise to the newly generated neurons could be represented by satellite glial cells that actively proliferate after the lesion and are able to differentiate toward the neuronal lineage. PMID:25722894

  13. Nerve growth factor protects against palmitic acid-induced injury in retinal ganglion cells

    PubMed Central

    Yan, Pan-shi; Tang, Shu; Zhang, Hai-feng; Guo, Yuan-yuan; Zeng, Zhi-wen; Wen, Qiang

    2016-01-01

    Accumulating evidence supports an important role for nerve growth factor (NGF) in diabetic retinopathy. We hypothesized that NGF has a protective effect on rat retinal ganglion RGC-5 cells injured by palmitic acid (PA), a metabolic factor implicated in the development of diabetes and its complications. Our results show that PA exposure caused apoptosis of RGC-5 cells, while NGF protected against PA insult in a concentration-dependent manner. Additionally, NGF significantly attenuated the levels of reactive oxygen species (ROS) and malondialdehyde (MDA) in RGC-5 cells. Pathway inhibitor tests showed that the protective effect of NGF was completely reversed by LY294002 (PI3K inhibitor), Akt VIII inhibitor, and PD98059 (ERK1/2 inhibitor). Western blot analysis revealed that NGF induced the phosphorylation of Akt/FoxO1 and ERK1/2 and reversed the PA-evoked reduction in the levels of these proteins. These results indicate that NGF protects RGC-5 cells against PA-induced injury through anti-oxidation and inhibition of apoptosis by modulation of the PI3K/Akt and ERK1/2 signaling pathways. PMID:28123432

  14. Meralgia paresthetica-like syndrome may be caused by transient lumbar nerve root injury without definite compression: a case report.

    PubMed

    Dharmasaroja, Pornpatr; Dharmasaroja, Permphan

    2010-12-01

    Meralgia paresthetica is a well-known sensory syndrome describing paresthesia and/or anesthesia in the anterolateral aspect of the thigh that is supplied by the lateral femoral cutaneous nerve. Compression of the nerve usually occurs at the point where it passes between the anterior superior iliac spine and the inguinal ligament. Proximal lesions such as lumbar radiculopathy, lumbar disc herniation, and spinal stenosis have been reported to cause meralgia paresthetica-like syndrome. These proximal lesions directly injure L2 and L3 spinal nerve roots and cause a constant compression of the nerve roots. The presented paper introduces a hypothesis that this syndrome can be caused by transient injury to the L2 and L3 nerve roots by the upper adjacent disc bulge without definite compression. This hypothesis is supported by lumbar spine magnetic resonance imaging of a patient presenting with a meralgia paresthetica-like symptom during bending forward and twisting of the body, showing no L2/L3 herniated disc but mildly posterior bulging of T12/L1 disc. This hypothesis emphasizes an importance of appropriate postures in patients with meralgia paresthetica-like symptoms in order to prevent long-term morbidity.

  15. Ameliorative potential of Vernonia cinerea on chronic constriction injury of sciatic nerve induced neuropathic pain in rats.

    PubMed

    Thiagarajan, Venkata R K; Shanmugam, Palanichamy; Krishnan, Uma M; Muthuraman, Arunachalam

    2014-09-01

    The aim of the present study is to investigate the ameliorative potential of ethanolic extract of whole plant of Vernonia cinerea in the chronic constriction injury (CCI) of sciatic nerve induced neuropathic pain in rats. Behavioral parameters such as a hot plate, acetone drop, paw pressure, Von Frey hair and tail immersion tests were performed to assess the degree of thermal, chemical and mechanical hyperalgesia and allodynia. Biochemical changes in sciatic nerve tissue were ruled out by estimating thiobarbituric acid reactive substances (TBARS), reduced glutathione (GSH) and total calcium levels. Ethanolic extract of Vernonia cinerea and pregabalin were administered for 14 consecutive days starting from the day of surgery. CCI of sciatic nerve has been shown to induce significant changes in behavioral, biochemical and histopathological assessments when compared to the sham control group. Vernonia cinerea attenuated in a dose dependent manner the above pathological changes induced by CCI of the sciatic nerve, which is similar to attenuation of the pregabalin pretreated group. The ameliorating effect of ethanolic extract of Vernonia cinerea against CCI of sciatic nerve induced neuropathic pain may be due to the presence of flavonoids and this effect is attributed to anti-oxidative, neuroprotective and calcium channel modulator actions of these compounds.

  16. Acellular allogeneic nerve grafting combined with bone marrow mesenchymal stem cell transplantation for the repair of long-segment sciatic nerve defects: biomechanics and validation of mathematical models

    PubMed Central

    Li, Ya-jun; Zhao, Bao-lin; Lv, Hao-ze; Qin, Zhi-gang; Luo, Min

    2016-01-01

    We hypothesized that a chemically extracted acellular allogeneic nerve graft used in combination with bone marrow mesenchymal stem cell transplantation would be an effective treatment for long-segment sciatic nerve defects. To test this, we established rabbit models of 30 mm sciatic nerve defects, and treated them using either an autograft or a chemically decellularized allogeneic nerve graft with or without simultaneous transplantation of bone marrow mesenchymal stem cells. We compared the tensile properties, electrophysiological function and morphology of the damaged nerve in each group. Sciatic nerves repaired by the allogeneic nerve graft combined with stem cell transplantation showed better recovery than those repaired by the acellular allogeneic nerve graft alone, and produced similar results to those observed with the autograft. These findings confirm that a chemically extracted acellular allogeneic nerve graft combined with transplantation of bone marrow mesenchymal stem cells is an effective method of repairing long-segment sciatic nerve defects. PMID:27651781

  17. Intranasal delivery of nerve growth factor attenuates aquaporins-4-induced edema following traumatic brain injury in rats.

    PubMed

    Lv, Qiushi; Fan, Xinying; Xu, Gelin; Liu, Qian; Tian, Lili; Cai, Xiaoyi; Sun, Wenshan; Wang, Xiaomeng; Cai, Qiankun; Bao, Yuanfei; Zhou, Lulu; Zhang, Yao; Ge, Liang; Guo, Ruibing; Liu, Xinfeng

    2013-02-01

    Traumatic brain injury (TBI) remains the leading cause of injury-related death and disability. Brain edema, one of the most major complications of TBI, contributes to elevated intracranial pressure, and poor prognosis following TBI. Nerve growth factor (NGF) appears to be a viable strategy to treat brain edema and TBI. Unfortunately, due to its poor blood-brain barrier (BBB) permeability, the clinical application of NGF has been greatly limited. We previously demonstrated that intranasal NGF could bypass the BBB and distribute throughout the brain. Here we further studied whether intranasal NGF could attenuate TBI-induced brain edema and its putative mechanisms. TBI was produced by a modified weight-drop model. We found that intranasal administration of NGF (5μg/d) attenuated the brain edema, as assayed by hemisphere water content, at 12h, 24h and 72h after TBI induction. This attenuation was associated with a prominent decrease of the content of aquaporin-4, which plays a pivotal role in the formation of brain edema. By the use of RT-PCR and ELISA, we showed that intranasal NGF markedly inhibited the transcription and expression of pro-inflammatory cytokines including IL-1β and TNF-α. An electrophoretic mobility shift assay (EMSA) displayed a significant activation of nuclear factor-κB following TBI, which was, however, much lowered in the NGF-treated rats. Furthermore, upon intranasal NGF supplementation, mitochondria-mediated apoptosis following TBI was minimized, as indicated by upregulation of Bcl-2 and downregulation of caspase-3. Collectively, our findings suggested that intranasal NGF may be a promising strategy to treat brain edema and TBI.

  18. Cdc42 Promotes Schwann Cell Proliferation and Migration Through Wnt/β-Catenin and p38 MAPK Signaling Pathway After Sciatic Nerve Injury.

    PubMed

    Han, Bin; Zhao, Jun-Ying; Wang, Wu-Tao; Li, Zheng-Wei; He, Ai-Ping; Song, Xiao-Yang

    2017-01-17

    Schwann cells (SCs) are unique glial cells in the peripheral nerve and may secrete multiple neurotrophic factors, adhesion molecules, extracellular matrix molecules to form the microenvironment of peripheral nerve regeneration, guiding and supporting nerve proliferation and migration. Cdc42 plays an important regulatory role in dynamic changes of the cytoskeleton. However, there is a little study referred to regulation and mechanism of Cdc42 on glial cells after peripheral nerve