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Sample records for accessory nerve injury

  1. Iatrogenic accessory nerve injury.

    PubMed Central

    London, J.; London, N. J.; Kay, S. P.

    1996-01-01

    Accessory nerve injury produces considerable disability. The nerve is most frequently damaged as a complication of radical neck dissection, cervical lymph node biopsy and other surgical procedures. The problem is frequently compounded by a failure to recognise the error immediately after surgery when surgical repair has the greatest chance of success. We present cases which outline the risk of accessory nerve injury, the spectrum of clinical presentations and the problems produced by a failure to recognise the deficit. Regional anatomy, consequences of nerve damage and management options are discussed. Diagnostic biopsy of neck nodes should not be undertaken as a primary investigation and, when indicated, surgery in this region should be performed by suitably trained staff under well-defined conditions. Awareness of iatrogenic injury and its consequences would avoid delays in diagnosis and treatment. Images Figure 2 PMID:8678450

  2. 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

  3. Role of Sonography in Surgical Decision Making for Iatrogenic Spinal Accessory Nerve Injuries: A Paradigm Shift.

    PubMed

    Cesmebasi, Alper; Smith, Jay; Spinner, Robert J

    2015-12-01

    The spinal accessory nerve (SAN) is susceptible to iatrogenic injury in the posterior cervical triangle. Early diagnosis and management of suspected SAN transection injuries are crucial in the restoration of shoulder stability and function. Although neurologic examination and electrodiagnostic testing can assess SAN function, they cannot assess nerve continuity. We report the use of sonography to prospectively evaluate the SAN in 6 patients with suspected iatrogenic SAN injury. Sonography directly visualized SAN transection in 4 cases, whereas sonographic findings were reported as "probable" transection in the fifth case and was nondiagnostic in the sixth case in the setting of extensive scarring. PMID:26543166

  4. Use of contralateral spinal accessory nerve for ipsilateral suprascapular neurotization in global brachial plexus injury: a new technique.

    PubMed

    Bhandari, Prem Singh; Deb, Prabal

    2016-01-01

    Nerve transfer between the spinal accessory nerve (SAN) and the suprascapular nerve (SSN) is a standard technique in shoulder reanimation. In cases of global brachial plexus injury, donor nerves are few and at times severely traumatized owing to extensive traction forces. This precludes the application of standard nerve transfer techniques. The authors offer the use of the contralateral SAN as an additional option in the reinnervation of an injured SSN in such circumstances. To the best of their knowledge, this is the first successful attempt of this technique to be reported in the literature.

  5. Outcome following spinal accessory to suprascapular (spinoscapular) nerve transfer in infants with brachial plexus birth injuries.

    PubMed

    Ruchelsman, David E; Ramos, Lorna E; Alfonso, Israel; Price, Andrew E; Grossman, Agatha; Grossman, John A I

    2010-06-01

    The purpose of this study is to evaluate the value of distal spinal accessory nerve (SAN) transfer to the suprascapular nerve (SSN) in children with brachial plexus birth injuries in order to better define the application and outcome of this transfer in these infants. Over a 3-year period, 34 infants with brachial plexus injuries underwent transfer of the SAN to the SSN as part of the primary surgical reconstruction. Twenty-five patients (direct repair, n = 20; interposition graft, n = 5) achieved a minimum follow-up of 24 months. Fourteen children underwent plexus reconstruction with SAN-to-SSN transfer at less than 9 months of age, and 11 underwent surgical reconstruction at the age of 9 months or older. Mean age at the time of nerve transfer was 11.6 months (range, 5-30 months). At latest follow-up, active shoulder external rotation was measured in the arm abducted position and confirmed by review of videos. The Gilbert and Miami shoulder classification scores were utilized to report shoulder-specific functional outcomes. The effects of patient age at the time of nerve transfer and the use of interpositional nerve graft were analyzed. Overall mean active external rotation measured 69.6°; mean Gilbert score was 4.1 and the mean Miami score was 7.1, corresponding to overall good shoulder functional outcomes. Similar clinical and shoulder-specific functional outcomes were obtained in patients undergoing early (<9 months of age, n = 14) and late (>9 months of age, n = 11) SAN-to-SSN transfer and primary plexus reconstruction. Nine patients (27%) were lost to follow-up and are not included in the analysis. Optimum results were achieved following direct transfer (n = 20). Results following the use of an interpositional graft (n = 5) were rated satisfactory. No patient required a secondary shoulder procedure during the study period. There were no postoperative complications. Distal SAN-to-SSN (spinoscapular) nerve transfer is a reliable

  6. Biting palsy of the accessory nerve.

    PubMed Central

    Paljärvi, L; Partanen, J

    1980-01-01

    A young man was bitten by his girl friend at the anterior border of the left trapezius muscle. Weakness of the trapezius resulted and a longstanding ache in the shoulder developed. Clinically and neurophysiologically, an axonotmesis type crush injury of the accessory nerve was verified. PMID:7431036

  7. An anatomic-based approach to the iatrogenic spinal accessory nerve injury in the posterior cervical triangle: How to avoid and treat it.

    PubMed

    Cesmebasi, Alper; Spinner, Robert J

    2015-09-01

    Iatrogenic injury of the spinal accessory nerve (SAN) is a significant reducible risk with any invasive procedure involving the posterior cervical triangle. Most commonly associated with cervical lymph node biopsy, it affects 3-6% of patients and serves as a major cause of avoidable medical malpractice litigation. Medical malpractice cases not only affect the primary surgeon but also may include the repairing surgeon through a shift of blame. For this reason, we discuss the strategies all clinicians may utilize in approaching iatrogenic SAN injuries. By taking basic precautionary measures based on simple application of anatomy in the management of these patients, clinicians may protect themselves from needless malpractice litigation. A thorough knowledge of the anatomy and application in preventative strategies may provide guidance for clinicians in reducing the incidence of iatrogenic injuries, providing effective postinjury management, and ensuring the salvaging surgeon is not at fault if litigation is pursued. PMID:26060941

  8. The clinical anatomy of accessory mental nerves and foramina.

    PubMed

    Iwanaga, Joe; Saga, Tsuyoshi; Tabira, Yoko; Nakamura, Moriyoshi; Kitashima, Sadaharu; Watanabe, Koichi; Kusukawa, Jingo; Yamaki, Koh-Ichi

    2015-10-01

    Since three-dimensional computed tomography was developed, many researchers have described accessory mental foramina. The anatomical and radiological findings have been discussed, but details of accessory mental nerves (AMNs) have only been researched in a small number of anatomical and clinical cases. For this article, we reviewed the literature relating to accessory mental foramina (AMFs) and nerves to clarify aspects important for clinical situations. The review showed that the distribution pattern of the AMN can differ according to the position of the accessory mental foramen, and the reported incidence of AMFs differs among observation methods. A review of clinical cases also revealed that injury to large AMF can result in paresthesia. This investigation did not reveal all aspects of AMNs and AMFs, but will be useful for diagnosis and treatment by many dentists and oral and maxillofacial surgeons.

  9. 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)

  10. Unusual insidious spinal accessory nerve palsy: a case report

    PubMed Central

    2010-01-01

    Introduction Isolated spinal accessory nerve dysfunction has a major detrimental impact on the functional performance of the shoulder girdle, and is a well-documented complication of surgical procedures in the posterior triangle of the neck. To the best of our knowledge, the natural course and the most effective way of handling spontaneous spinal accessory nerve palsy has been described in only a few instances in the literature. Case presentation We report the case of a 36-year-old Caucasian, Greek man with spontaneous unilateral trapezius palsy with an insidious course. To the best of our knowledge, few such cases have been documented in the literature. The unusual clinical presentation and functional performance mismatch with the imaging findings were also observed. Our patient showed a deterioration that was different from the usual course of this pathology, with an early onset of irreversible trapezius muscle dysfunction two months after the first clinical signs started to manifest. A surgical reconstruction was proposed as the most efficient treatment, but our patient declined this. Although he failed to recover fully after conservative treatment for eight months, he regained moderate function and is currently virtually pain-free. Conclusion Clinicians have to be aware that due to anatomical variation and the potential for compensation by the levator scapulae, the clinical consequences of any injury to the spinal accessory nerve may vary. PMID:20507553

  11. Morphological characteristics of the cranial root of the accessory nerve.

    PubMed

    Liu, Hong-Fu; Won, Hyung-Sun; Chung, In-Hyuk; Kim, In-Beom; Han, Seung-Ho

    2014-11-01

    There has been the controversy surrounding the cranial root (CR) of the accessory nerve. This study was performed to clarify the morphological characteristics of the CR in the cranial cavity. Fifty sides of 25 adult cadaver heads were used. The accessory nerve was easily distinguished from the vagus nerve by the dura mater in the jugular foramen in 80% of 50 specimens. The trunk of the accessory nerve from the spinal cord penetrated the dura mater at various distances before entering the jugular foramen. In 20% of the specimens there was no dural boundary. In these cases, the uppermost cranial rootlet of the accessory nerve could be identified by removing the dura mater around the jugular foramen where it joined to the trunk of the accessory nerve at the superior vagal ganglion. The cranial rootlet was formed by union of two to four short filaments emerging from the medulla oblongata (66%) and emerged single, without filament (34%), and usually joined the trunk of the accessory nerve directly before the jugular foramen. The mean number of rootlets of the CR was 4.9 (range 2-9) above the cervicomedullary junction. The CR of the accessory nerve was composed of two to nine rootlets, which were formed by the union of two to four short filaments and joined the spinal root of the accessory nerve. The CR is morphologically distinct from the vagus nerve, confirming its existence.

  12. Nerve Injuries in Athletes.

    PubMed

    Collins, K; Storey, M; Peterson, K; Nutter, P

    1988-01-01

    In brief: Nerve injuries in athletes may be serious and may delay or prevent an athlete's return to his or her sport. Over a two-year period, the authors evaluated the condition of 65 patients who had entrapments of a nerve or nerve root, documented with electromyography. They describe four case histories: Two patients had radial nerve entrapments, one caused by baseball pitching and the other by kayaking; one football player had combined suprascapular neuropathy and upper trunk brachial plexopathy; and one patient had carpal tunnel syndrome of a median nerve secondary to rowing. Sports-related peripheral nerve lesions of the lower extremity were not seen during the study period. Based on a literature review, the nerve injuries discussed represent the spectrum of nerve entrapments likely to be seen in US clinics. The authors conclude that peripheral nerve lesions should be considered in the differential diagnosis of sports injuries, particularly at the shoulder, elbow, and wrist.

  13. Accessory Upper Subscapular Nerve – The Neurotisation Tool

    PubMed Central

    Deshmukh, Vishwajit Ravindra; Mandal, Rabindra Prasad; Kusuma, Harisha

    2016-01-01

    During the routine dissection classes for undergraduate students, uncommon variation in relation to the upper subscapular nerve of posterior cord of brachial plexus was observed. Normally upper subscapular nerve takes origin from the posterior cord, but in this case report, it arises in triplet fashion, just above the circumflex scapular artery. All these accessory nerves were supplying upper part of the subscapularis muscle. As per our knowledge, this is a rare variation of brachial plexus. Many variations are encountered in the formation of brachial plexus. The normal and the abnormal origin of nerves are important considering neurotisation surgeries as well as during the infraclavicular nerve block for various axillary and upper limb surgeries. PMID:27790416

  14. Peripheral nerve response to injury.

    PubMed

    Steed, Martin B

    2011-03-01

    Oral and maxillofacial surgeons caring for patients who have sustained a nerve injury to a branch of the peripheral trigeminal nerve must possess a basic understanding of the response of the peripheral nerves to trauma. The series of events that subsequently take place are largely dependent on the injury type and severity. Regeneration of the peripheral nerve is possible in many instances and future manipulation of the regenerative microenvironment will lead to advances in the management of these difficult injuries.

  15. Compound muscle action potential cartography of an accessory peroneal nerve.

    PubMed

    Van Dijk, J G; Van der Hoeven, B J

    1998-10-01

    In daily practice, accessory peroneal nerves (APNs) are detected in less than the 18-25% of legs, as revealed by systematic searches. In one APN case, compound muscle action potential cartography showed that the APN was only apparent when the recording electrode was placed over a small lateral region of the extensor digitorum brevis muscle. Effects of recording site can explain why many APNs go unrecognized.

  16. Contralateral Spinal Accessory Nerve Transfer: A New Technique in Panavulsive Brachial Plexus Palsy.

    PubMed

    Zermeño-Rivera, Jaime; Gutiérrez-Amavizca, Bianca Ethel

    2015-06-01

    Brachial plexus avulsion results from excessive stretching and can occur secondary to motor vehicle accidents, mainly in motorcyclists. In a 28-year-old man with panavulsive brachial plexus palsy, we describe an alternative technique to repair brachial plexus avulsion and to stabilize and preserve shoulder function by transferring the contralateral spinal accessory nerve to the suprascapular nerve. We observed positive clinical and electromyographic results in sternocleidomastoid, trapezius, supraspinatus, infraspinatus, pectoralis, triceps, and biceps, with good outcome and prognosis for shoulder function at 12 months after surgery. This technique provides a unique opportunity for patients suffering from severe brachial plexus injuries and lacking enough donor nerves to obtain shoulder stability and mobility while avoiding bone fusion and preserving functionality of the contralateral shoulder with favorable postoperative outcomes.

  17. Sports and peripheral nerve injury.

    PubMed

    Hirasawa, Y; Sakakida, K

    1983-01-01

    Peripheral nerve injury is one of the serious complications of athletic injuries; however, they have rarely been reported. According to the report by Takazawa et al., there were only 28 cases of peripheral nerve injury among 9,550 cases of sports injuries which had been treated in the previous 5 years at the clinic of the Japanese Athletic Association. The authors have encountered 1,167 cases of peripheral nerve injury during the past 18 years. Sixty-six of these cases were related to sports (5.7%). The nerves most frequently involved were: brachial plexus, radial nerve, ulnar, peroneal, and axillary nerves (in their order of frequency). The most common causes of such injuries were mountain climbing, gymnastics, and baseball. More often, peripheral nerve injury seemed to be caused by continuous compression and repeated trauma to the involved nerve. Usually it appeared as an entrapment neuropathy and the symptoms could be improved by conservative treatment. Some of the cases were complicated by fractures and surgical exploration became necessary. Results of treatment produced excellent to good improvement in 87.9% of the cases. With regard to compartment syndrome, the authors stress the importance of early and precise diagnosis and a fasciotomy.

  18. Mechanisms of trigeminal nerve injuries.

    PubMed

    Ziccardi, V B; Assael, L A

    2001-09-01

    Injuries to the trigeminal nerve branches are a known and accepted risk in oral and maxillofacial surgery. It is prudent for the practitioner to explain the risks to patients as part of the informed consent process and to recognize and document the presence of nerve injury postoperatively. Patients should be referred to a surgeon experienced in microsurgical techniques in a timely fashion for evaluation and possible surgical intervention if an injury is not resolving.

  19. Management of traumatic facial nerve injuries.

    PubMed

    Greywoode, Jewel D; Ho, Hao H; Artz, Gregory J; Heffelfinger, Ryan N

    2010-12-01

    Management of facial nerve injuries requires knowledge and skills that should be in every facial plastic surgeon's armamentarium. This article will briefly review the anatomy of the facial nerve, discuss the assessment of facial nerve injury, and describe the management of facial nerve injury after soft tissue trauma. PMID:21086238

  20. 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

  1. Paediatric Extracranial Spinal Accessory Nerve Schwannoma: An Extremely Rare Case Report.

    PubMed

    Chakravarti, Arunabha; Garg, Sunil; Bhargava, Rahul

    2016-07-01

    Schwannoma in head and neck region are quiet common and generally arise from last four cranial nerves. Spinal accessory nerve involvement is very rare. We are hereby presenting an extremely rare case of paediatric XI nerve schwannoma hitherto unreported in English medical literature till date. PMID:27630872

  2. Paediatric Extracranial Spinal Accessory Nerve Schwannoma: An Extremely Rare Case Report

    PubMed Central

    Garg, Sunil; Bhargava, Rahul

    2016-01-01

    Schwannoma in head and neck region are quiet common and generally arise from last four cranial nerves. Spinal accessory nerve involvement is very rare. We are hereby presenting an extremely rare case of paediatric XI nerve schwannoma hitherto unreported in English medical literature till date. PMID:27630872

  3. High Ulnar Nerve Injuries: Nerve Transfers to Restore Function.

    PubMed

    Patterson, Jennifer Megan M

    2016-05-01

    Peripheral nerve injuries are challenging problems. Nerve transfers are one of many options available to surgeons caring for these patients, although they do not replace tendon transfers, nerve graft, or primary repair in all patients. Distal nerve transfers for the treatment of high ulnar nerve injuries allow for a shorter reinnervation period and improved ulnar intrinsic recovery, which are critical to function of the hand. PMID:27094893

  4. [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. PMID:27607069

  5. Rehabilitation of peripheral nerve injuries.

    PubMed

    Robinson, Michael D; Shannon, Steven

    2002-02-01

    Traumatic injuries to peripheral nerves pose complex challenges to both military and civilian physicians. Treatment of nerve injuries must consider all aspects of the inherent disability. Pain control is of paramount importance. Little will be accomplished until pain is brought down to tolerable levels. Rehabilitation needs to be instituted as first-line treatment. Focus must be first placed on protection of the affected area from complications stemming from disuse and immobility and then on enhancement of strength, flexibility, sensory discrimination, and dexterity. Early intervention sets the stage for optimal physiologic and functional recovery. PMID:11878078

  6. Distribution of Neuron Cell Bodies in the Intraspinal Portion of the Spinal Accessory Nerve in Humans.

    PubMed

    Boehm, Karl E; Kondrashov, Peter

    2016-01-01

    The spinal accessory nerve is often identified as a purely motor nerve innervating the trapezius and sternocleidomastoid muscles. Although it may contain proprioceptive neurons found in cervical spinal levels C2-C4, limited research has focused on the histology of the spinal accessory nerve. The objective of the present study was to examine the spinal accessory nerve to determine if there are neuronal cell bodies within the spinal accessory nerve in humans. Cervical spinal cords were dissected from eight cadavers that had previously been used for dissection in other body regions. The segmental rootlets were removed to quantify the neuron cell bodies present at each spinal level. Samples were embedded in paraffin; sectioned; stained with hematoxylin and eosin; and examined using a microscope at 4×, 10×, and 40× magnification. Digital photography was used to image the samples. Neuronal cell bodies were found in 100% of the specimens examined, with non-grossly visible ganglia found at spinal levels C1-C4. The C1 spinal level of the spinal accessory nerve had the highest number of neuron cell bodies.

  7. Transitional Nerve: A New and Original Classification of a Peripheral Nerve Supported by the Nature of the Accessory Nerve (CN XI)

    PubMed Central

    Benninger, Brion; McNeil, Jonathan

    2010-01-01

    Classically, the accessory nerve is described as having a cranial and a spinal root. Textbooks are inconsistent with regard to the modality of the spinal root of the accessory nerve. Some authors report the spinal root as general somatic efferent (GSE), while others list a special visceral efferent (SVE) modality. We investigated the comparative, anatomical, embryological, and molecular literature to determine which modality of the accessory nerve was accurate and why a discrepancy exists. We traced the origin of the incongruity to the writings of early comparative anatomists who believed the accessory nerve was either branchial or somatic depending on the origin of its target musculature. Both theories were supported entirely by empirical observations of anatomical and embryological dissections. We find ample evidence including very recent molecular experiments to show the cranial and spinal root are separate entities. Furthermore, we determined the modality of the spinal root is neither GSE or SVE, but a unique peripheral nerve with a distinct modality. We propose a new classification of the accessory nerve as a transitional nerve, which demonstrates characteristics of both spinal and cranial nerves. PMID:21318044

  8. 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.

  9. Peripheral nerve injuries in the athlete.

    PubMed

    Feinberg, J H; Nadler, S F; Krivickas, L S

    1997-12-01

    Peripheral nerves are susceptible to injury in the athlete because of the excessive physiological demands that are made on both the neurological structures and the soft tissues that protect them. The common mechanisms of injury are compression, traction, ischaemia and laceration. Seddon's original classification system for nerve injuries based on neurophysiological changes is the most widely used. Grade 1 nerve injury is a neuropraxic condition, grade 2 is axonal degeneration and grade 3 is nerve transection. Peripheral nerve injuries are more common in the upper extremities than the lower extremities, tend to be sport specific, and often have a biomechanical component. While the more acute and catastrophic neurological injuries are usually obvious, many remain subclinical and are not recognised before neurological damage is permanent. Early detection allows initiation of a proper rehabilitation programme and modification of biomechanics before the nerve injury becomes irreversible. Recognition of nerve injuries requires an understanding of peripheral neuroanatomy, knowledge of common sites of nerve injury and an awareness of the types of peripheral nerve injuries that are common and unique to each sport. The electrodiagnostic exam, usually referred to as the 'EMG', consists of nerve conduction studies and the needle electrode examination. It is used to determine the site and degree of neurological injury and to predict outcome. It should be performed by a neurologist or physiatrist (physician specialising in physical medicine and rehabilitation), trained and skilled in this procedure. Timing is essential if the study is to provide maximal information. Findings such as decreased recruitment after injury and conduction block at the site of injury may be apparent immediately after injury but other findings such as abnormal spontaneous activity may take several weeks to develop. The electrodiagnostic test assists with both diagnosis of the injury and in predicting

  10. Abnormal Origin and Course of the Accessory Phrenic Nerve: Case Report.

    PubMed

    Paraskevas, George; Koutsouflianiotis, Konstantinos; Kitsoulis, Panagiotis; Spyridakis, Ioannis

    2016-01-01

    In the current cadaveric study an unusual sizeable accessory phrenic nerve (APN) was encountered emerging from the trunk of the supraclavicular nerves and forming a triangular loop that was anastomosing with the phrenic nerve. That neural loop surrounded the superficial cervical artery which displayed a spiral course. The form of a triangular loop of APN involving the aforementioned artery and originating from the supraclavicular nerve to the best of our knowledge has not been documented previously in the literature. The variable morphological features of the APN along with its clinical applications are briefly discussed. PMID:27526310

  11. Clinico-embryological perspective of a rare accessory brachial muscle with possible musculocutaneous nerve compression.

    PubMed

    Mehta, V; Yadav, Y; Arora, Jyoti; Kumar, H; Suri, R K; Rath, G

    2009-03-01

    Both brachialis and biceps brachii are primary flexors of the arm and elbow from the biomechanical perspective. Numerous reports exist in anatomical literature regarding accessory heads of biceps brachii, although such accessory bellies in relation to brachialis muscle are less frequently elucidated. We report a unilateral case of a rare accessory muscle interposed between the biceps brachii and brachialis, having the musculocutaneous nerve (MCN) entrapped between the two. Furthermore, the muscle divided into two slips, upper slip was attached to biceps brachii and the other gained insertion to the brachial fascia. Innervation to this accessory muscle was derived from MCN. The embryological basis for such supernumerary muscle is discussed. Additionally, the case is considered under surgical and clinical perspective, highlighting the importance of familiarity with such variations. Anatomical variations of the brachial musculature may cause diagnostic perplexities while interpreting MRI or CT scans.

  12. The accessory deep peroneal nerve and anterior tarsal tunnel syndrome: case report.

    PubMed

    Sinanović, Osman; Zukić, Sanela; Šakić, Alma; Muftić, Mirsad

    2013-10-01

    The accessory deep peroneal (ADPN) nerve has been regarded as an anomalous nerve derived from the superficial peroneal nerve or its branch and supplies motor innervations for extensor digitorum brevis (EDB) and sensory innervations for the lateral part of the ankle and foot regions. The EDB is usually innervated exclusively by the deep peroneal nerve, a major branch of the the common peroneal nerve, however, in as many as 28% of patients (with same male/female frequency), one or both of the EDB muscles are (partially or exclusively) innervated by the ADPN nerve. This anomaly appears to be inherited in autosomal dominant fashion with incomplete gene penetrance. ADPN existence is of great clinical and surgical importance, and the aim of this study is to describe a very rare case of coexistence ADPN and anterior tarsal tunnel syndrome. PMID:24399869

  13. The spinal accessory nerve plexus, the trapezius muscle, and shoulder stabilization after radical neck cancer surgery.

    PubMed Central

    Brown, H; Burns, S; Kaiser, C W

    1988-01-01

    A clinical and anatomic study of the spinal accessory, the eleventh cranial nerve, and trapezius muscle function of patients who had radical neck cancer surgery was conducted. This study was done not only to document the indispensibility of the trapezius muscle to shoulder-girdle stability, but also to clarify the role of the eleventh cranial nerve in the variable motor and sensory changes occurring after the loss of this muscle. Seventeen male patients, 49-69 years of age, (average of 60 years of age) undergoing a total of 23 radical neck dissections were examined for upper extremity function, particularly in regard to the trapezius muscle, and for subjective signs of pain. The eleventh nerve, usually regarded as the sole motor innervation to the trapezius, was cut in 17 instances because of tumor involvement. Dissection of four fresh and 30 preserved adult cadavers helped to reconcile the motor and sensory differences in patients who had undergone loss of the eleventh nerve. The dissections and clinical observations corroborate that the trapezius is a key part of a "muscle continuum" that stabilizes the shoulder. Variations in origins and insertions of the trapezius may influence its function in different individuals. As regards the spinal accessory nerve, it is concluded that varying motor and sensory connections form a plexus with the eleventh nerve, accounting, in part, for the variations in motor innervation and function of the trapezius, as well as for a variable spectrum of sensory changes when the eleventh nerve is cut. For this reason, it is suggested that the term "spinal accessory nerve plexus" be used to refer to the eleventh nerve when it is considered in the context of radical neck cancer surgery. Images Fig. 4. Fig. 6. Fig. 7. Fig. 8. PMID:3056289

  14. Nerve injuries due to obstetric trauma.

    PubMed

    Bhat, V; Ravikumara; Oumachigui, A

    1995-01-01

    The incidence of nerve injuries among 32,637 deliveries over a period of ten years was 1.81/1000. Brachial plexus injury (1/1000) and facial nerve injury (0.74/1000) accounted for 98% of nerve injuries. Both the right and left side were involved equally. Bilateral nerve injury was not seen. Lack of antenatal care, macrosomia, abnormal presentations, and operative vaginal deliveries significantly increased the risk of nerve injuries. These babies had significantly higher incidence of meconium stained liquor and intrapartum asphyxia. Parity of the mother, gestational age and sex of the baby did not have significant role in the causation of nerve injuries. Injuries to brachial plexus and facial nerve were seen even in babies born by caesarean section, when it was performed for obstructed labour caused by cephalo-pelvic disproportion and abnormal presentations. Three babies with injuries expired and forty-three could be followed up for varying periods. None of the babies had residual defects. Detection of cephalopelvic disproportion and abnormal lie in the third trimester and their appropriate management would decrease the incidence of obstetric palsies to a significant extent. PMID:10829869

  15. 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

  16. Low intensity laser treatment of nerve injuries

    NASA Astrophysics Data System (ADS)

    Liu, Xiao-Guang; Liu, Timon Cheng-Yi; Luo, Qing-Ming

    2007-05-01

    The neural regeneration and functional recovery after nerve injuries has long been an important field in neuroscience. Low intensity laser (LIL) irradiation is a novel and useful tool for the treatment of many injuries and disorders. The aim of this study was to assess the role of LIL irradiation in the treatment of peripheral and central nerve injuries. Some animal experiments and clinical investigations have shown beneficial effects of LIL irradiation on neural tissues, but its therapeutic value and efficacy are controversial. Reviewing the data of experimental and clinical studies by using the biological information model of photobiomodulation, we conclude that LIL irradiation in specific parameters can promote the regeneration of injured peripheral and central nerves and LIL therapy is a safe and valuable treatment for superficial peripheral nerve injuries and spinal cord injury. The biological effects of LIL treatment depend largely on laser wavelength, power and dose per site and effective irradiation doses are location-specific.

  17. Management of Pain in Complex Nerve Injuries.

    PubMed

    Davis, Gabrielle; Curtin, Catherine M

    2016-05-01

    Traumatic nerve injuries can be devastating and life-changing events, leading to functional morbidity and psychological stress and social constraints. Even in the event of a successful surgical repair with recovered motor function, pain can result in continued disability and poor quality of life. Pain after nerve injury can also prevent recovery and return to preinjury life. It is difficult to predict which patients will develop persistent pain; once incurred, pain can be even challenging to manage. This review seeks to define the types of pain following peripheral nerve injuries, investigate the pathophysiology and causative factors, and evaluate potential treatment options. PMID:27094896

  18. Mechanisms of nerve injury in leprosy.

    PubMed

    Scollard, David M; Truman, Richard W; Ebenezer, Gigi J

    2015-01-01

    All patients with leprosy have some degree of nerve involvement. Perineural inflammation is the histopathologic hallmark of leprosy, and this localization may reflect a vascular route of entry of Mycobacterium leprae into nerves. Once inside nerves, M. leprae are ingested by Schwann cells, with a wide array of consequences. Axonal atrophy may occur early in this process; ultimately, affected nerves undergo segmental demyelination. Knowledge of the mechanisms of nerve injury in leprosy has been greatly limited by the minimal opportunities to study affected nerves in man. The nine-banded armadillo provides the only animal model of the pathogenesis of M. leprae infection. New tools available for this model enable the study and correlation of events occurring in epidermal nerve fibers, dermal nerves, and nerve trunks, including neurophysiologic parameters, bacterial load, and changes in gene transcription in both neural and inflammatory cells. The armadillo model is likely to enhance understanding of the mechanisms of nerve injury in leprosy and offers a means of testing proposed interventions. PMID:25432810

  19. Nerve injuries from mandibular third molar removal.

    PubMed

    Meyer, Roger A; Bagheri, Shahrokh C

    2011-03-01

    Injuries to peripheral branches (IAN, LN, LBN) of the trigeminal nerve during the removal of M3s are known and accepted risks in oral and maxillofacial surgery practice. These risks might be reduced by modifications of evaluation or surgical techniques, depending on the surgeon's judgment in individual patients. If a nerve injury does occur, prompt recognition, subjective and objective evaluation,and development of a treatment plan, if the sensory deficit fails to resolve in a reasonable period and is unacceptable to the patient, give the patient the best chance of achieving improvement or recovery of sensory function in the distribution of the injured nerve. Microneurosurgery may produce return of useful sensory function or complete sensory recovery, if done in a timely fashion by an experienced microsurgeon, in greater than 80% of patients who sustain nerve injuries during the removal of M3s.

  20. Tendon Transfers for Combined Peripheral Nerve Injuries.

    PubMed

    Makarewich, Christopher A; Hutchinson, Douglas T

    2016-08-01

    Combined peripheral nerve injuries present a unique set of challenges to the hand surgeon when considering tendon transfers. They are often associated with severe soft tissue trauma, including lacerations to remaining innervated muscles and tendons, significant scar formation, and substantial sensory loss. In the case of combined nerve injuries, there are typically fewer options for tendon transfers due to fewer tendons of shared function that are expendable as well as associated injuries to tendon or muscle bellies. As such, careful preoperative planning must be performed to make the most of remaining muscle tendon units. PMID:27387081

  1. 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

  2. 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.

  3. Persistent Increase in Blood Pressure After Renal Nerve Stimulation in Accessory Renal Arteries After Sympathetic Renal Denervation.

    PubMed

    de Jong, Mark R; Hoogerwaard, Annemiek F; Gal, Pim; Adiyaman, Ahmet; Smit, Jaap Jan J; Delnoy, Peter Paul H M; Ramdat Misier, Anand R; van Hasselt, Boudewijn A A M; Heeg, Jan-Evert; le Polain de Waroux, Jean-Benoit; Lau, Elizabeth O Y; Staessen, Jan A; Persu, Alexandre; Elvan, Arif

    2016-06-01

    Blood pressure response to renal denervation is highly variable, and the proportion of responders is disappointing. This may be partly because of accessory renal arteries too small for denervation, causing incomplete ablation. Renal nerve stimulation before and after renal denervation is a promising approach to assess completeness of renal denervation and may predict blood pressure response to renal denervation. The objective of the current study was to assess renal nerve stimulation-induced blood pressure increase before and after renal sympathetic denervation in main and accessory renal arteries of anaesthetized patients with drug-resistant hypertension. The study included 21 patients. Nine patients had at least 1 accessory renal artery in which renal denervation was not feasible. Renal nerve stimulation was performed in the main arteries of all patients and in accessory renal arteries of 6 of 9 patients with accessory arteries, both before and after renal sympathetic denervation. Renal nerve stimulation before renal denervation elicited a substantial increase in systolic blood pressure, both in main (25.6±2.9 mm Hg; P<0.001) and accessory (24.3±7.4 mm Hg; P=0.047) renal arteries. After renal denervation, renal nerve stimulation-induced systolic blood pressure increase was blunted in the main renal arteries (Δ systolic blood pressure, 8.6±3.7 mm Hg; P=0.020), but not in the nondenervated renal accessory renal arteries (Δ systolic blood pressure, 27.1±7.6 mm Hg; P=0.917). This residual source of renal sympathetic tone may result in persistent hypertension after ablation and partly account for the large response variability.

  4. Nerve Transfers for the Restoration of Wrist, Finger, and Thumb Extension After High Radial Nerve Injury.

    PubMed

    Pet, Mitchell A; Lipira, Angelo B; Ko, Jason H

    2016-05-01

    High radial nerve injury is a common pattern of peripheral nerve injury most often associated with orthopedic trauma. Nerve transfers to the wrist and finger extensors, often from the median nerve, offer several advantages when compared to nerve repair or grafting and tendon transfer. In this article, we discuss the forearm anatomy pertinent to performing these nerve transfers and review the literature surrounding nerve transfers for wrist, finger, and thumb extension. A suggested algorithm for management of acute traumatic high radial nerve palsy is offered, and our preferred surgical technique for treatment of high radial nerve palsy is provided. PMID:27094891

  5. Injury of the peripheral cranial nerves during carotid endarterectomy.

    PubMed

    Theodotou, B; Mahaley, M S

    1985-01-01

    The incidence of local nerve injury among 192 consecutive carotid endarterectomies in 162 patients between 1977-1983 was determined from review of the medical records. Two facial nerve, 5 hypoglossal nerve, and 2 vagus nerve injuries were discovered for a total incidence of 4.7%. Only the 2 facial nerve injuries failed to improve over 2 years. Followup ranged from 1 to 60 months in this group of patients. Careful attention to details of tissue dissection at surgery should lower the incidence of nerve injury during carotid endarterectomy. PMID:4049454

  6. Management of mandibular nerve injuries from dental implants.

    PubMed

    Bagheri, Shahrokh C; Meyer, Roger A

    2011-03-01

    Treatment of the patient who has sustained a nerve injury from dental implant procedures involves prompt recognition of this complication, evaluation of sensory dysfunction, the position of the nerve vis-à-vis the implant, and timely management of the injured nerve. In some patients, removal or repositioning of the implant and surgical exploration and repair of the injured nerve will maximize the implant patient's potential for a successful recovery from nerve injury.

  7. 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

  8. Microsurgical treatment of peripheral nerve injuries.

    PubMed

    Dolene, V

    1977-01-01

    In the period from 1972 to 1976, 536 patients with injuries of the peripheral nerves were treated at the Neurosurgical University Clinic Lyublyana. The treatment was performed according to the principles of microsurgery. Preoperative and postoperative supervision included EMG, electroneurography and nerve conduction speed. Subdivision: N. facialis 6, plexus brachialis 78, n. radialis 58, n. medianus 189, n. ulnaris 212, n. ischiadicus 17, n. femoralis 3, n. tibialis 12, n. fibularis 37. On the plexus brachialis 50 funiculolyses and 28 raphies were carried out. Immobilisation for 10 days. The length of the transplants showed no negative influence. After-observation was necessary for three and more years, especially in case of plexus injuries. Complete restoration was only found in children. Sensitivity in 80% more than Seddon III, 17% III and 3% less than III. Motor function in 60% IV, 20% III, 12% II and 8% less than II.

  9. Peripheral nerve injuries in baseball players.

    PubMed

    Cummins, Craig A; Schneider, David S

    2009-02-01

    Baseball players place significant stress across their shoulders and elbows during the throwing motion, causing unique patterns of injuries in the overhead throwing athlete. Specific nerve injuries include suprascapular neuropathy, quadrilateral space syndrome, and cubital tunnel syndrome. Nonoperative treatment includes cessation of throwing and symptom management. As symptoms improve, athletes should start rehabilitation, focusing on restoring shoulder and trunk flexibility and strength. The final rehabilitation phase involves an interval throwing program with attention directed at proper mechanics, with the goal of returning the athlete to competitive throwing. Surgery may assist in a positive outcome in particular patients who fail to improve with nonoperative treatment. Additional indications for surgery may include more profound neuropathy and nerve compression by a mass lesion.

  10. Peripheral nerve injuries in baseball players.

    PubMed

    Cummins, Craig A; Schneider, David S

    2008-02-01

    Baseball players place significant stress across their shoulders and elbows during the throwing motion, causing unique patterns of injuries in the overhead throwing athlete. Specific nerve injuries include suprascapular neuropathy, quadrilateral space syndrome, and cubital tunnel syndrome. Nonoperative treatment includes cessation of throwing and symptom management. As symptoms improve, athletes should start rehabilitation, focusing on restoring shoulder and trunk flexibility and strength. The final rehabilitation phase involves an interval throwing program with attention directed at proper mechanics, with the goal of returning the athlete to competitive throwing. Surgery may assist in a positive outcome in particular patients who fail to improve with nonoperative treatment. Additional indications for surgery may include more profound neuropathy and nerve compression by a mass lesion.

  11. Interfascicular reconstruction of the peroneal nerve after knee ligament injury.

    PubMed

    McMahon, M S; Craig, S M

    1994-06-01

    Peroneal palsy is the most common lower extremity nerve injury. Although most studies emphasize particularly poor prognosis after traction injuries to the peroneal nerve, interfascicular nerve grafting has emerged as a promising technique. We describe the case of a 20-year-old man who sustained a traction injury to the peroneal nerve (0/5 foot dorsiflexion and eversion) concomitant with tears of the anterior cruciate and lateral collateral ligaments. Interfascicular sural nerve grafting (10-14 cm in length) was performed 7 months after injury and 6 months after ligament reconstruction. The patient recovered motor strength (4+/5) in both anterior and lateral compartments by 2 years' postsurgery. The results obtained indicate that interfascicular nerve grafting is a valuable technique for reconstruction of the disrupted peroneal nerve; it provides sufficient benefit to justify the time, expense, and effort involved. An aggressive approach is thus recommended in patients with peroneal nerve disruption in the setting of multiple knee ligament injuries.

  12. Expanding what is known of the anatomy of the spinal accessory nerve.

    PubMed

    Restrepo, Carlos E; Tubbs, R Shane; Spinner, Robert J

    2015-05-01

    The spinal accessory nerve (SAN) is classically considered a motor nerve innervating the sternocleidomastoid and trapezius muscles. Its anatomical relevance derives from the high prevalence of lesions following head and neck surgeries. As expected, trapezius weakness and atrophy are the most common findings; however, it is also commonly accompanied by pain and other sensory deficits that have no clear explanation, suggesting other functions. We have recently seen two patients presenting with an unrecognized sign, that is, subclavicular/pectoral asymmetry secondary to the SAN lesion. Retrospectively, we reviewed other patients with similar findings in our case series and in the literature. We discuss the anatomical connections of the SAN with the superficial cervical plexus and propose an explanation for this finding. Of the 41 patients in our series, we identified this sign in all who had preoperative photographs. New insights on the anatomy and connections of the SAN may account for the diversity of symptoms and signs presented following an operative intervention as well as the variability of its severity. PMID:25546396

  13. Expanding what is known of the anatomy of the spinal accessory nerve.

    PubMed

    Restrepo, Carlos E; Tubbs, R Shane; Spinner, Robert J

    2015-05-01

    The spinal accessory nerve (SAN) is classically considered a motor nerve innervating the sternocleidomastoid and trapezius muscles. Its anatomical relevance derives from the high prevalence of lesions following head and neck surgeries. As expected, trapezius weakness and atrophy are the most common findings; however, it is also commonly accompanied by pain and other sensory deficits that have no clear explanation, suggesting other functions. We have recently seen two patients presenting with an unrecognized sign, that is, subclavicular/pectoral asymmetry secondary to the SAN lesion. Retrospectively, we reviewed other patients with similar findings in our case series and in the literature. We discuss the anatomical connections of the SAN with the superficial cervical plexus and propose an explanation for this finding. Of the 41 patients in our series, we identified this sign in all who had preoperative photographs. New insights on the anatomy and connections of the SAN may account for the diversity of symptoms and signs presented following an operative intervention as well as the variability of its severity.

  14. Optic nerve avulsion secondary to a basketball injury.

    PubMed

    Friedman, S M

    1999-01-01

    Optic nerve avulsion secondary to a basketball injury is a rare complication. The patient underwent a vitrectomy for a non-clearing vitreous hemorrhage. The nerve was partially avulsed with multiple choroidal ruptures in the fovea. It was concluded that optic nerve disorders rarely occur after basketball injuries. Patients with a dense vitreous hemorrhage may benefit from a vitrectomy although the vision will be limited by the optic nerve disorder.

  15. Assessment of war and accidental nerve injuries in children.

    PubMed

    Barisić, N; Perović, D; Mitrović, Z; Jurenić, D; Zagar, M

    1999-07-01

    Eleven children with war-related peripheral nerve injury and 16 children with accident-related nerve injury between the ages of 3 and 15 years were assessed clinically and electromyoneurographically for 1-15 months. Lesions of 32 peripheral nerves were registered in children with war injuries. Children with accidentally acquired injuries had lesions of 27 peripheral nerves. A complete loss of voluntary motor unit potentials and signs of total axonal damage were recorded in the upper arms of seven of 11 children with war injuries and in five of 16 children with accidental injuries. There was a diminished number of motor unit potentials and a reduction in compound muscle action potential amplitudes, indicating partial nerve lesions, in 11 of 16 children with accidental injuries (mostly after humeral fracture) and in three of 11 children with brachial plexus war injuries. Reinnervation signs first occurred after 5-9 months (mean = 6.2 months) in war-injured children receiving conservative treatment and after 2-7 months (mean = 3.4 months) in children with accidentally acquired injuries. War-related peripheral nerve injuries in children are more frequently associated with complete denervation followed by slower or delayed nerve regeneration. In children with accidentally acquired nerve injuries the course is significantly better.

  16. Electrophysiological evaluation of nerve function in inferior alveolar nerve injury: relationship between nerve action potentials and histomorphometric observations.

    PubMed

    Murayama, M; Sasaki, K; Shibahara, T

    2015-12-01

    The objective of this study was to improve the accuracy of diagnosis of inferior alveolar nerve (IAN) injury by determining degrees of nerve disturbance using the sensory nerve action potential (SNAP) and sensory nerve conduction velocity (SCV). Crush and partial and complete nerve amputation injuries were applied to the IAN of rabbits, then SNAPs and histomorphometric observations were recorded at 1, 5, and 10 weeks. For crush injury, most nerves were smaller in diameter at 5 weeks than at 1 week, however after 10 weeks, extensive nerve regeneration was observed. The SNAP showed a decrease in SCV at weeks 1 and 5, followed by an increase at week 10. For partial nerve amputation, small to medium-sized nerve fibres were observed at weeks 1 and 5, then larger nerves were seen at week 10. Minimal changes in SCV were observed at weeks 1 and 5, however SCV increased at week 10. For complete nerve amputation, nerve fibres were sparse at week 1, but gradual nerve regeneration was observed at weeks 5 and 10. SNAPs were detectable from week 10, however the SCV was extremely low. This study showed SCV to be an effective factor in the evaluation of nerve injury and regeneration. PMID:26433750

  17. A comprehensive review with potential significance during skull base and neck operations, Part II: glossopharyngeal, vagus, accessory, and hypoglossal nerves and cervical spinal nerves 1-4.

    PubMed

    Shoja, Mohammadali M; Oyesiku, Nelson M; Shokouhi, Ghaffar; Griessenauer, Christoph J; Chern, Joshua J; Rizk, Elias B; Loukas, Marios; Miller, Joseph H; Tubbs, R Shane

    2014-01-01

    Knowledge of the possible neural interconnections found between the lower cranial and upper cervical nerves may prove useful to surgeons who operate on the skull base and upper neck regions in order to avoid inadvertent traction or transection. We review the literature regarding the anatomy, function, and clinical implications of the complex neural networks formed by interconnections between the lower cranial and upper cervical nerves. A review of germane anatomic and clinical literature was performed. The review is organized into two parts. Part I discusses the anastomoses between the trigeminal, facial, and vestibulocochlear nerves or their branches and other nerve trunks or branches in the vicinity. Part II deals with the anastomoses between the glossopharyngeal, vagus, accessory and hypoglossal nerves and their branches or between these nerves and the first four cervical spinal nerves; the contribution of the autonomic nervous system to these neural plexuses is also briefly reviewed. Part II is presented in this article. Extensive and variable neural anastomoses exist between the lower cranial nerves and between the upper cervical nerves in such a way that these nerves with their extra-axial communications can be collectively considered a plexus.

  18. The longitudinal epineural incision and complete nerve transection method for modeling sciatic nerve injury

    PubMed Central

    Cheng, Xing-long; Wang, Pei; Sun, Bo; Liu, Shi-bo; Gao, Yun-feng; He, Xin-ze; Yu, Chang-yu

    2015-01-01

    Injury severity, operative technique and nerve regeneration are important factors to consider when constructing a model of peripheral nerve injury. Here, we present a novel peripheral nerve injury model and compare it with the complete sciatic nerve transection method. In the experimental group, under a microscope, a 3-mm longitudinal incision was made in the epineurium of the sciatic nerve to reveal the nerve fibers, which were then transected. The small, longitudinal incision in the epineurium was then sutured closed, requiring no stump anastomosis. In the control group, the sciatic nerve was completely transected, and the epineurium was repaired by anastomosis. At 2 and 4 weeks after surgery, Wallerian degeneration was observed in both groups. In the experimental group, at 8 and 12 weeks after surgery, distinct medullary nerve fibers and axons were observed in the injured sciatic nerve. Regular, dense myelin sheaths were visible, as well as some scarring. By 12 weeks, the myelin sheaths were normal and intact, and a tight lamellar structure was observed. Functionally, limb movement and nerve conduction recovered in the injured region between 4 and 12 weeks. The present results demonstrate that longitudinal epineural incision with nerve transection can stably replicate a model of Sunderland grade IV peripheral nerve injury. Compared with the complete sciatic nerve transection model, our method reduced the difficulties of micromanipulation and surgery time, and resulted in good stump restoration, nerve regeneration, and functional recovery. PMID:26692866

  19. Accessory mental foramina, incisive nerve plexus and lingual canals with unusual emergence paths: Report of two rare cases.

    PubMed

    Haghanifar, Sina; Poorsattar Bejeh Mir, Arash

    2015-01-01

    Being knowledgeable of neurovascularization of anterior mandible is crucial for successful local anesthesia and for safe minor and major oral surgeries of this part. The first case was 62 years old and was found to have two accessory mental foramina with buccal emergence on the left side and two accessory mental foramina with buccal and lingual emergence paths on the right side (overall five mental foramina). Incisive nerve plexus with multiple cephalic branching was obvious on both sides. The second case was 60 years of age and had two lingual foramina on the lingual side with two accessory foramina on the buccal side of the symphysis. Considering our findings, a pre-operation limited cone beam computed tomography is suggested to avoid inadvertent damage, especially when planning a surgery in the mandibular inter-mental region. PMID:25767360

  20. Behavioral and electrophysiological recovery following cryogenic nerve injury.

    PubMed

    Kalichman, M W; Myers, R R

    1987-06-01

    Postthoracotomy pain can be reduced by cryoanalgesia of intercostal nerves. The technique involves focal freezing of peripheral nerves to interrupt pain pathways, producing immediate functional changes that recover as the nerves regenerate. To assess the time-course of functional changes that follow nerve injury, unilateral freeze lesions of sciatic nerve were induced in rats with a cryosurgical unit. The contralateral nerves were used as sham-operated controls. Following nerve injury, behavioral and electrophysiologic tests were repeated to 90 days. The acute effect of nerve injury was a decrease in behavioral measures of hind limb function (P less than 0.05), an increase in electrical threshold to elicit hind limb contraction (P less than 0.005), and an absence of stimulus-evoked compound action potential (P less than 0.005). Morphologic changes included substantial endoneurial edema associated with Wallerian degeneration. Remyelination occurred subsequently during the following 35 days. Although all physiologic measures returned toward normal, nerve conduction velocities were still much slower in the experimental group. In a second study, the long-term effects of cryogenic injury were compared with neurolytic injury with 10% procaine HCl, both of which produced a conduction velocity deficit that persisted at least 90 days after the initial injury. These behavioral and electrophysiologic results complement previous reports of morphologic deficits in the nerves including incomplete recovery of nerve fiber diameter and increased thickness of the perineurial sheath. PMID:3582553

  1. Research progress of stem cells on glaucomatous optic nerve injury.

    PubMed

    Zhou, Ya-Sha; Xu, Jian; Peng, Jun; Li, Ping; Wen, Xiao-Juan; Liu, Yue; Chen, Ke-Zhu; Liu, Jia-Qi; Wang, Ying; Peng, Qing-Hua

    2016-01-01

    Glaucoma, the second leading cause of blindness, is an irreversible optic neuropathy. The mechanism of optic nerve injury caused by glaucoma is undefined at present. There is no effective treatment method for the injury. Stem cells have the capacity of self-renewal and differentiation. These two features have made them become the research focus on improving the injury at present. This paper reviews the application progress on different types of stem cells therapy for optic nerve injury caused by glaucoma. PMID:27588279

  2. Research progress of stem cells on glaucomatous optic nerve injury.

    PubMed

    Zhou, Ya-Sha; Xu, Jian; Peng, Jun; Li, Ping; Wen, Xiao-Juan; Liu, Yue; Chen, Ke-Zhu; Liu, Jia-Qi; Wang, Ying; Peng, Qing-Hua

    2016-01-01

    Glaucoma, the second leading cause of blindness, is an irreversible optic neuropathy. The mechanism of optic nerve injury caused by glaucoma is undefined at present. There is no effective treatment method for the injury. Stem cells have the capacity of self-renewal and differentiation. These two features have made them become the research focus on improving the injury at present. This paper reviews the application progress on different types of stem cells therapy for optic nerve injury caused by glaucoma.

  3. Research progress of stem cells on glaucomatous optic nerve injury

    PubMed Central

    Zhou, Ya-Sha; Xu, Jian; Peng, Jun; Li, Ping; Wen, Xiao-Juan; Liu, Yue; Chen, Ke-Zhu; Liu, Jia-Qi; Wang, Ying; Peng, Qing-Hua

    2016-01-01

    Glaucoma, the second leading cause of blindness, is an irreversible optic neuropathy. The mechanism of optic nerve injury caused by glaucoma is undefined at present. There is no effective treatment method for the injury. Stem cells have the capacity of self-renewal and differentiation. These two features have made them become the research focus on improving the injury at present. This paper reviews the application progress on different types of stem cells therapy for optic nerve injury caused by glaucoma. PMID:27588279

  4. [Surgical treatment of lower extremity peripheral nerve injuries].

    PubMed

    Kaiser, Radek

    2016-01-01

    Peripheral nerve injuries of the lower extremities are not frequent. The most common are traction injury of the peroneal nerve at the knee level or iatrogenic trauma of the pelvic nerves during abdominal surgery. Civil sharp injuries are rare.Indications for surgical revision follow the general rules of nerve surgery. Sharp injury should be treated as soon as possible, ideally within 72 hours. Closed lesions are indicated for surgery if a complete denervation remains unchanged three months after the injury. Best results can be achieved within six months from the injury. Irritations caused by bone fragments or scarring or by iatrogenic injury (clamps, cement, screws, etc.) may be revised later. However, the most important is early clinical examination in a specialized neurosurgical department. PMID:27256143

  5. 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

  6. Dynamic Regulation of Schwann Cell Enhancers after Peripheral Nerve Injury*

    PubMed Central

    Hung, Holly A.; Sun, Guannan; Keles, Sunduz; Svaren, John

    2015-01-01

    Myelination of the peripheral nervous system is required for axonal function and long term stability. After peripheral nerve injury, Schwann cells transition from axon myelination to a demyelinated state that supports neuronal survival and ultimately remyelination of axons. Reprogramming of gene expression patterns during development and injury responses is shaped by the actions of distal regulatory elements that integrate the actions of multiple transcription factors. We used ChIP-seq to measure changes in histone H3K27 acetylation, a mark of active enhancers, to identify enhancers in myelinating rat peripheral nerve and their dynamics after demyelinating nerve injury. Analysis of injury-induced enhancers identified enriched motifs for c-Jun, a transcription factor required for Schwann cells to support nerve regeneration. We identify a c-Jun-bound enhancer in the gene for Runx2, a transcription factor induced after nerve injury, and we show that Runx2 is required for activation of other induced genes. In contrast, enhancers that lose H3K27ac after nerve injury are enriched for binding sites of the Sox10 and early growth response 2 (Egr2/Krox20) transcription factors, which are critical determinants of Schwann cell differentiation. Egr2 expression is lost after nerve injury, and many Egr2-binding sites lose H3K27ac after nerve injury. However, the majority of Egr2-bound enhancers retain H3K27ac, indicating that other transcription factors maintain active enhancer status after nerve injury. The global epigenomic changes in H3K27ac deposition pinpoint dynamic changes in enhancers that mediate the effects of transcription factors that control Schwann cell myelination and peripheral nervous system responses to nerve injury. PMID:25614629

  7. Nerve injuries about the elbow in the athlete.

    PubMed

    Harris, Joshua D; Lintner, David M

    2014-09-01

    The athlete's elbow is a remarkable example of motion, strength, and durability. The stress placed on the elbow during sport, including the throwing motion, may lead to soft-tissue ligamentous and nerve injury. The thrower's elbow illustrates one example of possible nerve injury about the elbow in sport, related to chronic repetitive tensile and compressive stresses to the ulnar nerve associated with elbow flexion and valgus position. Besides the throwing athlete, nerve injury from high-energy direct-impact forces may also damage nerves around the elbow in contact sports. Detailed history and physical examination can often make the diagnosis of most upper extremity neuropathies. The clinician must be aware of the possibility of isolated or combined nerve injury as far proximal as the cervical nerve roots, through the brachial plexus, to the peripheral nerve terminal branches. Electrodiagnostic studies are occasionally beneficial for diagnosis with certain nerves. Nonoperative management is often successful in most elbow and upper extremity neuropathies. If conservative treatment fails, then surgical treatment should address all potentially offending structures. In the presence of medial laxity and concurrent ulnar neuritis, the medial ulnar collateral ligament warrants surgical treatment, in addition to transposition of the ulnar nerve. The morbidity of open surgical decompression of nerves in and around the elbow is potentially career threatening in the throwing athlete. This mandates an assessment of the adequacy of the nonsurgical treatment and a thorough preoperative discussion of the risks and benefits of surgery.

  8. Nerve injuries about the elbow in the athlete.

    PubMed

    Harris, Joshua D; Lintner, David M

    2014-09-01

    The athlete's elbow is a remarkable example of motion, strength, and durability. The stress placed on the elbow during sport, including the throwing motion, may lead to soft-tissue ligamentous and nerve injury. The thrower's elbow illustrates one example of possible nerve injury about the elbow in sport, related to chronic repetitive tensile and compressive stresses to the ulnar nerve associated with elbow flexion and valgus position. Besides the throwing athlete, nerve injury from high-energy direct-impact forces may also damage nerves around the elbow in contact sports. Detailed history and physical examination can often make the diagnosis of most upper extremity neuropathies. The clinician must be aware of the possibility of isolated or combined nerve injury as far proximal as the cervical nerve roots, through the brachial plexus, to the peripheral nerve terminal branches. Electrodiagnostic studies are occasionally beneficial for diagnosis with certain nerves. Nonoperative management is often successful in most elbow and upper extremity neuropathies. If conservative treatment fails, then surgical treatment should address all potentially offending structures. In the presence of medial laxity and concurrent ulnar neuritis, the medial ulnar collateral ligament warrants surgical treatment, in addition to transposition of the ulnar nerve. The morbidity of open surgical decompression of nerves in and around the elbow is potentially career threatening in the throwing athlete. This mandates an assessment of the adequacy of the nonsurgical treatment and a thorough preoperative discussion of the risks and benefits of surgery. PMID:25077754

  9. [Nerve injury following implant placement: prevention, diagnosis and treatment modalities].

    PubMed

    Nazarian, Y; Eliav, E; Nahlieli, O

    2003-07-01

    Nerve injury is a well-known complication following oral and maxillofacial surgery. Direct trauma, inflammation and infection are postoperative neural disturbances main causes. The most inflicted nerves associated with endosseous implant placement are those innervating the mandible: the inferior alveolar nerve, the mental nerve and the lingual nerve. Evaluation of the nerve injury characteristics and severity as early as possible has always imposed a great challenge for clinicians. We demonstrate a reliable yet simple way of dealing with this kind of problem in conjunction with comparing preoperative and postoperative sensation of the chin, the tongue and the lower lip. On the other hand, it is considerably important to take preventive measures for such injuries by using appropriate radiographic images. If a nerve damage has occurred, best prognosis is to be expected by early and appropriate treatment. It is imperative to treat such injuries in four months following the injury, otherwise a permanent nerve damage may occur. Further investigation of nerve damage risks following implant placement should be performed in order to enable patient to decide whether having implants dependent rehabilitation or choosing an alternative. PMID:14515628

  10. How to Avoid Facial Nerve Injury in Mastoidectomy?

    PubMed

    Ryu, Nam-Gyu; Kim, Jin

    2016-09-01

    Unexpected iatrogenic facial nerve paralysis not only affects facial disfiguration, but also imposes a devastating effect on the social, psychological, and economic aspects of an affected person's life at once. The aims of this study were to postulate where surgeons had mistakenly drilled or where obscured by granulations or by fibrous bands and to look for surgical approach with focused on the safety of facial nerve in mastoid surgery. We had found 14 cases of iatrogenic facial nerve injury (IFNI) during mastoid surgery for 5 years in Korea. The medical records of all the patients were obtained and analyzed injured site of facial nerve segment with surgical technique of mastoidectomy. Eleven patients underwent facial nerve exploration and three patients had conservative management. 43% (6 cases) of iatrogenic facial nerve injuries had occurred in tympanic segment, 28.5% (4 cases) of injuries in second genu combined with tympanic segment, and 28.5% (4 cases) of injuries in mastoid segment. Surgeons should try to identify the facial nerve using available landmarks and be kept in mind the anomalies of the facial nerve. With use of intraoperative facial nerve monitoring, the avoidance of in order to avoid IFNI would be possible in more cases. Many authors emphasized the importance of intraoperative facial nerve monitoring, even in primary otologic surgery. However, anatomical understanding of intratemporal landmarks with meticulous dissection could not be emphasized as possible to prevent IFNI. PMID:27626078

  11. How to Avoid Facial Nerve Injury in Mastoidectomy?

    PubMed Central

    Ryu, Nam-Gyu

    2016-01-01

    Unexpected iatrogenic facial nerve paralysis not only affects facial disfiguration, but also imposes a devastating effect on the social, psychological, and economic aspects of an affected person's life at once. The aims of this study were to postulate where surgeons had mistakenly drilled or where obscured by granulations or by fibrous bands and to look for surgical approach with focused on the safety of facial nerve in mastoid surgery. We had found 14 cases of iatrogenic facial nerve injury (IFNI) during mastoid surgery for 5 years in Korea. The medical records of all the patients were obtained and analyzed injured site of facial nerve segment with surgical technique of mastoidectomy. Eleven patients underwent facial nerve exploration and three patients had conservative management. 43% (6 cases) of iatrogenic facial nerve injuries had occurred in tympanic segment, 28.5% (4 cases) of injuries in second genu combined with tympanic segment, and 28.5% (4 cases) of injuries in mastoid segment. Surgeons should try to identify the facial nerve using available landmarks and be kept in mind the anomalies of the facial nerve. With use of intraoperative facial nerve monitoring, the avoidance of in order to avoid IFNI would be possible in more cases. Many authors emphasized the importance of intraoperative facial nerve monitoring, even in primary otologic surgery. However, anatomical understanding of intratemporal landmarks with meticulous dissection could not be emphasized as possible to prevent IFNI. PMID:27626078

  12. How to Avoid Facial Nerve Injury in Mastoidectomy?

    PubMed Central

    Ryu, Nam-Gyu

    2016-01-01

    Unexpected iatrogenic facial nerve paralysis not only affects facial disfiguration, but also imposes a devastating effect on the social, psychological, and economic aspects of an affected person's life at once. The aims of this study were to postulate where surgeons had mistakenly drilled or where obscured by granulations or by fibrous bands and to look for surgical approach with focused on the safety of facial nerve in mastoid surgery. We had found 14 cases of iatrogenic facial nerve injury (IFNI) during mastoid surgery for 5 years in Korea. The medical records of all the patients were obtained and analyzed injured site of facial nerve segment with surgical technique of mastoidectomy. Eleven patients underwent facial nerve exploration and three patients had conservative management. 43% (6 cases) of iatrogenic facial nerve injuries had occurred in tympanic segment, 28.5% (4 cases) of injuries in second genu combined with tympanic segment, and 28.5% (4 cases) of injuries in mastoid segment. Surgeons should try to identify the facial nerve using available landmarks and be kept in mind the anomalies of the facial nerve. With use of intraoperative facial nerve monitoring, the avoidance of in order to avoid IFNI would be possible in more cases. Many authors emphasized the importance of intraoperative facial nerve monitoring, even in primary otologic surgery. However, anatomical understanding of intratemporal landmarks with meticulous dissection could not be emphasized as possible to prevent IFNI.

  13. Peripheral nerve injuries attributable to sport and recreation.

    PubMed

    Toth, Cory

    2009-02-01

    Many different sports and recreational activities are associated with injuries to the peripheral nervous system (PNS). Although some of those injuries are specific to an individual sport, other peripheral nerve injuries occur ubiquitously within many sporting activities. This review of sport-specific PNS injuries should assist in the understanding of morbidity associated with particular sporting activities, professional or amateur. Proper recognition of these syndromes can prevent unnecessary diagnostic testing and delays in proper diagnosis. The sports most commonly associated with peripheral nerve injuries are likely football, hockey, and baseball, but many other sports have unique associations with peripheral nerve injury. This article should be of assistance for the neurologist, neurosurgeon, orthopedic surgeon, physiatrist, sports medicine doctor, and general physician in contact with athletes at risk for neurologic injuries.

  14. Peripheral nerve injuries attributable to sport and recreation.

    PubMed

    Toth, Cory

    2008-02-01

    Many different sports and recreational activities are associated with injuries to the peripheral nervous system (PNS). Although some of those injuries are specific to an individual sport, other peripheral nerve injuries occur ubiquitously within many sporting activities. This review of sport-specific PNS injuries should assist in the understanding of morbidity associated with particular sporting activities, professional or amateur. Proper recognition of these syndromes can prevent unnecessary diagnostic testing and delays in proper diagnosis. The sports most commonly associated with peripheral nerve injuries are likely football, hockey, and baseball, but many other sports have unique associations with peripheral nerve injury. This article should be of assistance for the neurologist, neurosurgeon, orthopedic surgeon, physiatrist, sports medicine doctor, and general physician in contact with athletes at risk for neurologic injuries.

  15. Sialolithiasis of an accessory parotid gland: an unusual case.

    PubMed

    Debnath, S C; Adhyapok, A K

    2015-09-01

    We report a rare case of sialolithiasis of an accessory parotid gland, which was located anteromedial to the masseter muscle and isolated from the main parotid gland. The calculus developed from this accessory gland, and the main gland was free of lithiasis and inflammation. To our knowledge, there is no reported case of 14 stones in an accessory parotid salivary gland. The calculus was removed through a standard incision without injury to the facial nerve or a salivary fistula. PMID:26048098

  16. 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. PMID:23060343

  17. Introduction: peripheral nerve surgery--biology, entrapment, and injuries.

    PubMed

    Friedman, Allan H; Elias, W Jeffrey; Midha, Rajiv

    2009-02-01

    Surgery aimed at repairing damaged peripheral nerves has a long history. Refuting the time-honored nihilism of Hippocrates and Galen that an injured nerve cannot regain function, a few adventurous medieval surgeons attempted to repair severed nerves. However, the ability of a peripheral nerve repair to restore function was not generally accepted until 1800. Neurosurgeons, beginning with Harvey Cushing, have had an interest in repairing damaged peripheral nerves. Significant progress in the treatment of peripheral nerve injuries resulted from experience with the numerous injuries that occurred during World Wars I and II. Surgeons steadily defined the anatomy of peripheral nerves and developed techniques for decompressing and repairing peripheral nerves. Kline and Dejonge developed an intraoperative electrophysiological technique for detecting axons regenerating across a damaged segment of nerve. In the second 2 decades of the 20th century, distal nerve transfers were rediscovered whereby the proximal end of a less essential nerve is used to reinnervate the distal end of a nerve, providing a more vital function. PMID:19435439

  18. 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.

  19. 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. PMID:26008880

  20. [Development of Researches on Acupuncture Treatment of Peripheral Nerve Injury].

    PubMed

    Tao, Xing; Ma, Tie-ming

    2016-02-01

    Peripheral nerve injury is a common clinical disease. Acupuncture therapy has been demonstrated to be effective in improving nerve injury in clinical practice, but its underlying mechanisms in prompting tissue repair basically remain unknown. In the present paper, the authors reviewed some descriptions of traditional Chinese medicine on peripheral nerve injury and treatment, and recent development of researches on acupuncture treatment of it in both clinical practice and animal studies. Clinical trials demonstrated that acupuncture treatment can relieve nerve injury induced pain, ameliorate both sensory and motor functions. Experimental studies showed that acupuncture stimulation may promote nerve repair by reducing desquamation of medullary sheath of nerve fibers, inhibiting apoptosis of nerve cells, and up-regulating expression of myelin basic protein, Slit-1 protein and gene, etc. In addition, acupuncture intervention may also improve the microenvironment of neural regeneration including increase of the proliferation and differentiation of Schwann cells and release of various types of neurotrophic factors. However, its mechanisms underlying accelerating rehabilitation of peripheral nerve injury need being researched further. PMID:27141630

  1. 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.

  2. 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

  3. Nerve transfers and neurotization in peripheral nerve injury, from surgery to rehabilitation.

    PubMed

    Korus, Lisa; Ross, Douglas C; Doherty, Christopher D; Miller, Thomas A

    2016-02-01

    Peripheral nerve injury (PNI) and recent advances in nerve reconstruction (such as neurotization with nerve transfers) have improved outcomes for patients suffering peripheral nerve trauma. The purpose of this paper is to bridge the gap between the electromyographer/clinical neurophysiologist and the peripheral nerve surgeon. Whereas the preceding literature focuses on either the basic science behind nerve injury and reconstruction, or the surgical options and algorithms, this paper demonstrates how electromyography is not just a 'decision tool' when deciding whether to operate but is also essential to all phases of PNI management including surgery and rehabilitation. The recent advances in the reconstruction and rehabilitation of PNI is demonstrated using case examples to assist the electromyographer to understand modern surgical techniques and the unique demands they ask from electrodiagnostic testing.

  4. Evulsion of the optic nerve in association with basketball injuries.

    PubMed

    Chow, A Y; Goldberg, M F; Frenkel, M

    1984-01-01

    A case of optic nerve evulsion resulted from a finger poke injury to the globe during a basketball game. Significantly, almost no external damage to the eye was evident. The damage may be caused by sudden forceful anterior-posterior displacement and rotation of the globe, inducing a tear of the optic nerve at the papilla. The seriousness and permanence of this injury stress the importance of protective eye wear in contact sports.

  5. The legal implications of lingual nerve injuries.

    PubMed

    Leggatt, David

    2002-10-01

    Hopefully this analysis is useful. In summary let us make three simple points: Be conscious of your position in the "personal injury" market, but do not be afraid to use your judgment. If you are an expert, do not set a standard of perfection when working out what is reasonable care. Your communication skills are the most important skill you have in order to avoid claims. And on a final note, a draft "consent form" that will provide complete protection is often requested. There is no such thing. The issue is communication with your patient so that they will accept what has happened to them if their lingual nerve is damaged. Ideally this involves a clear explanation, provision of a written outline and a written acknowledgement from the patient that they have received this explanation. The latter requirement is because we are all human--and humans forget things when they are in pain, or distress. The author is currently working with the Australian Dental Association Victorian Branch Inc. and other professional associations in relation to written material to be distributed to make warnings more effective. No doubt, you will receive more information about this initiative in due course.

  6. Femoral nerve regeneration and its accuracy under different injury mechanisms.

    PubMed

    Aikeremujiang Muheremu; Ao, Qiang; Wang, Yu; Cao, Peng; Peng, Jiang

    2015-10-01

    Surgical accuracy has greatly improved with the advent of microsurgical techniques. However, complete functional recovery after peripheral nerve injury has not been achieved to date. The mechanisms hindering accurate regeneration of damaged axons after peripheral nerve injury are in urgent need of exploration. The present study was designed to explore the mechanisms of peripheral nerve regeneration after different types of injury. Femoral nerves of rats were injured by crushing or freezing. At 2, 3, 6, and 12 weeks after injury, axons were retrogradely labeled using 1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine perchlorate (Dil) and True Blue, and motor and sensory axons that had regenerated at the site of injury were counted. The number and percentage of Dil-labeled neurons in the anterior horn of the spinal cord increased over time. No significant differences were found in the number of labeled neurons between the freeze and crush injury groups at any time point. Our results confirmed that the accuracy of peripheral nerve regeneration increased with time, after both crush and freeze injury, and indicated that axonal regeneration accuracy was still satisfactory after freezing, despite the prolonged damage. PMID:26692867

  7. Peripheral Nerve Injury: Principles for Repair and Regeneration

    PubMed Central

    M.F, Griffin; M, Malahias; S, Hindocha; Khan, Wasim S

    2014-01-01

    Peripheral Nerve Injuries are one of the most common causes of hand dysfunction caused by upper limb trauma but still current management has remained suboptimal. This review aims to explain the traditional view of pathophysiology of nerve repair and also describe why surgical management is still inadequate in using the new biological research that has documented the changes that occur after the nerve injury, which, could cause suboptimal clinical outcomes. Subsequently presentation and diagnosis will be described for peripheral nerve injuries. When traditional surgical repair using end-to-end anastomosis is not adequate nerve conduits are required with the gold standard being the autologous nerve. Due to associated donor site morbidity and poor functional outcome documented with autologous nerve repair several new advancements for alternatives to bridge the gap are being investigated. We will summarise the new and future advancements of non-biological and biological replacements as well as gene therapy, which are being considered as the alternatives for peripheral nerve repair. PMID:25067975

  8. Peripheral nerve injury: principles for repair and regeneration.

    PubMed

    M F, Griffin; M, Malahias; S, Hindocha; Khan, Wasim S

    2014-01-01

    Peripheral Nerve Injuries are one of the most common causes of hand dysfunction caused by upper limb trauma but still current management has remained suboptimal. This review aims to explain the traditional view of pathophysiology of nerve repair and also describe why surgical management is still inadequate in using the new biological research that has documented the changes that occur after the nerve injury, which, could cause suboptimal clinical outcomes. Subsequently presentation and diagnosis will be described for peripheral nerve injuries. When traditional surgical repair using end-to-end anastomosis is not adequate nerve conduits are required with the gold standard being the autologous nerve. Due to associated donor site morbidity and poor functional outcome documented with autologous nerve repair several new advancements for alternatives to bridge the gap are being investigated. We will summarise the new and future advancements of non-biological and biological replacements as well as gene therapy, which are being considered as the alternatives for peripheral nerve repair. PMID:25067975

  9. Nerve injury and neuropathic pain - A question of age.

    PubMed

    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.

  10. 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

  11. Iliacus haematoma causing femoral nerve palsy: an unusual trampolining injury.

    PubMed

    Chambers, Simon; Berg, Andrew James; Lupu, Andreea; Jennings, Andrew

    2015-01-01

    We report the case of a 15-year-old boy who presented to accident and emergency following a trampolining injury. Initially, the patient was discharged, diagnosed with a soft tissue injury, but he re-presented 48 h later with worsening low back pain and neurological symptoms in the left leg. Subsequent MRI revealed a left iliacus haematoma causing a femoral nerve palsy. The patient was managed conservatively and by 6 months post injury all symptoms had resolved. This is the first reported case of an iliacus haematoma causing a femoral nerve palsy, after a trampolining injury. We believe this case highlights to our fellow clinicians the importance of a detailed history when assessing patients with trampolining injuries to evaluate the true force of injury. It also acts as a reference for clinicians in managing similar cases in future. PMID:26216923

  12. [Anatomical rationale for lingual nerve injury prevention during mandibular block].

    PubMed

    Semkin, V A; Dydikin, S S; Kuzin, A V; Sogacheva, V V

    2015-01-01

    The topographic and anatomical study of lingual nerve structural features was done. It was revealed that during mandibular anesthesia possible lingual nerve injury can occur if puncture needle is lower than 1 cm. of molars occlusal surface level. The position of the lingual nerve varies withmandible movements. At the maximum open mouth lingual nerve is not mobile and is pressed against the inner surface of the mandibular ramus by the medial pterygoid muscle and the temporal muscle tendon. When closing the mouth to 1.25±0.2 cmfrom the physiological maximum, lingual nerve is displaced posteriorly from the internal oblique line of the mandible and gets mobile. On the basis of topographic and anatomic features of the lingual nervestructure the authors recommend the re-do of inferior alveolar nerve block, a semi-closed mouth position or the use the "high block techniques" (Torus anesthesia, Gow-Gates, Vazirani-Akinozi). PMID:26271698

  13. Peripheral nerve injury activates convergent nociceptive input to dorsal horn neurons from neighboring intact nerve.

    PubMed

    Terayama, Ryuji; Yamamoto, Yuya; Kishimoto, Noriko; Maruhama, Kotaro; Mizutani, Masahide; Iida, Seiji; Sugimoto, Tomosada

    2015-04-01

    Previous studies demonstrated that peripheral nerve injury induced excessive nociceptive response of spinal cord dorsal horn neurons and such change has been proposed to reflect the development of neuropathic pain state. The aim of this study was to examine the spinal dorsal horn for convergence of nociceptive input to second-order neurons deafferented by peripheral nerve injury. Double immunofluorescence labeling for c-Fos and phosphorylated extracellular signal-regulated kinase (p-ERK) was performed to detect convergent synaptic input to spinal dorsal horn neurons after the saphenous nerve injury. c-Fos expression and the phosphorylation of ERK were induced by noxious heat stimulation of the hindpaw and by electrical stimulation of the injured or uninjured saphenous nerve, respectively. Within the central terminal field of the saphenous nerve, the number of c-Fos protein-like immunoreactive (c-Fos-IR) cell profiles was significantly decreased at 3 days and returned to the control level by 14 days after the injury. p-ERK immunoreactive (p-ERK-IR) cell profiles were distributed in the central terminal field of the saphenous nerve, and the topographic distribution pattern and number of such p-ERK-IR cell profiles remained unchanged after the nerve injury. The time course of changes in the number of double-labeled cell profiles was similar to that of c-Fos-IR cell profiles after the injury. These results indicate that convergent primary nociceptive input through neighboring intact nerves contributes to increased responsiveness of spinal dorsal horn nociceptive neurons.

  14. Neuromuscular junction integrity after chronic nerve compression injury.

    PubMed

    Mozaffar, Tahseen; Strandberg, Erika; Abe, Kazuko; Hilgenberg, Lutz G; Smith, Martin A; Gupta, Ranjan

    2009-01-01

    Chronic nerve compression injuries (CNC) are progressive demyelinating disorders characterized by a gradual decline of the nerve conduction velocity (NCV) in the affected nerve region. CNC injury induces a robust Schwann cell response with axonal sprouting, but without morphologic evidence of axonal injury. We hypothesize that early CNC injury occurs without damage to neuromuscular junction of motor axons. A well-established animal model was used to assess for damage to motor axons. As sprouting is considered a hallmark of regeneration during and after axonal degeneration and sprouting was confirmed visually at 2 weeks in CNC animals, we assessed for axonal degeneration in motor nerves after CNC by evaluating the integrity of the neuromuscular junction. NCV exhibited a gradual progressive decline consistent with the human condition. Compound motor action potential amplitudes decreased slightly immediately and plateaued, indicating that there was not sustained and increasing axonal loss. Sprouting was confirmed using immunofluorescence and by an increase in number of unmyelinated axons and Remak bundles. Blind analysis of the neuromuscular junction showed no difference between control and CNC images, indicating that there was no evidence for end-unit axonal loss in the soleus muscle. Because the progressive decline in NCV was not paired with a similar progressive decline in amplitude, it is likely that axonal loss is not responsible for slowing of action potentials. Blind analysis of the neuromuscular junction provides further evidence that the axonal sprouting seen early after CNC injury is not a consequence of axonal degeneration in the motor nerves. PMID:18655131

  15. The nerves of the accessory pancreatic ducts of the common starling (Sturnus vulgaris): an ultrastructural and light microscopic study.

    PubMed Central

    McAllister, R M; Kendall, M D

    1984-01-01

    An ultrastructural and light microscopic study was undertaken to examine the nerves of the accessory pancreatic ducts of the starling (Sturnus vulgaris), previously noted (Vinnicombe, 1982) to have a particularly dense innervation. Large numbers of nerves were found in the ducts, predominantly in the lamina propria, and all contained exclusively unmyelinated axons. Probable neuron cell bodies were observed in the smooth muscle layer, but not in the lamina propria. Schwann cells invested all the axons, and these displayed terminal swellings in a 'synapse en passage' arrangement. The nerves of the lamina propria were most numerous in the region immediately beneath the epithelium and were present in the epithelial folds. One axon was observed to have penetrated the epithelial basal lamina and to lie between two epithelial cells. Examination of the terminal profiles and their contained synaptic vesicles showed the innervation to have probable pain afferent, cholinergic, adrenergic and perhaps peptidergic components. The results of this study were compared with reports on pancreatic duct innervation in other species, mostly as parts of wider studies on pancreatic innervation. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 PMID:6490527

  16. Ulnar Nerve Injury after Flexor Tendon Grafting.

    PubMed

    McCleave, Michael John

    2016-10-01

    A 43-year-old female is presented who underwent a two-stage tendon reconstruction and developed a low ulnar nerve palsy postoperatively. Exploration found that the tendon graft was passing through Guyon's canal and that the ulnar nerve was divided. This is a previously unreported complication. The reconstruction is discussed, the literature reviewed and a guide is given on how to identify the correct tissue plane when passing a tendon rod. PMID:27595967

  17. Musculocutaneous nerve injury in a high school pitcher.

    PubMed

    Stephens, Luke; Kinderknecht, James J; Wen, Dennis Y

    2014-11-01

    : Nontraumatic musculocutaneous nerve palsy is a rare injury that can occur in throwers. We present a case of musculocutaneous nerve injury in a high school pitcher, which has rarely been previously reported. The unique electromyography findings add to the overall spectrum seen with musculocutaneous nerve injuries in throwers. Sensory abnormalities may not be present at initial evaluation, but rather weakness or pain of the biceps is the most common presenting concern. Electrodiagnostic evaluation is paramount for confirmation of diagnosis, yet the timing of this study is critical for its accuracy. Rest and progressive physical therapy remain as the current treatment of choice. Resolution of symptoms, although time consuming, is complete in the majority of cases, including ours.

  18. [Advances in reconstructive options of nerve injuries in the hand].

    PubMed

    Bíró, Vilmos

    2012-11-11

    The author summarizes the most important data about the development of reconstructive techniques of nerve injuries in the hand based on literature references and the author's own experience in the past decades. A new bulk of knowledge turned into a common property related to the micro- and macroanatomic structure of peripheral nerves, the process of nerve regeneration, and the technical conditions of nerve reconstructive operations. This knowledge is a prerequisite for hand surgeons to perform their nerve reconstructive operations on a contemporary high level with an optimal result. After a critical review of literature data, the author reports his own experience and sketches the coming possible roads. A detailed list of references is also provided for those who are interested in the field.

  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. [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.

  1. [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. PMID:24071050

  2. Curcumin promotes nerve regeneration and functional recovery after sciatic nerve crush injury in diabetic rats.

    PubMed

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

    2016-01-01

    Curcumin is capable of promoting peripheral nerve regeneration in normal condition. However, it is unclear whether its beneficial effect on nerve regeneration still exists under diabetic mellitus. The present study was designed to investigate such a possibility. Diabetes in rats was developed by a single dose of streptozotocin at 50 mg/kg. Immediately after nerve crush injury, the diabetic rats were intraperitoneally administrated daily for 4 weeks with curcumin (50 mg/kg, 100 mg/kg and 300 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. Axonal regeneration and functional recovery was significantly enhanced by curcumin, which were significantly better than those in vehicle saline group. In addition, high doses of curcumin (100 mg/kg and 300 mg/kg) achieved better axonal regeneration and functional recovery than low dose (50 mg/kg). In conclusion, curcumin is capable of promoting nerve regeneration after sciatic nerve crush injury in diabetes mellitus, highlighting its therapeutic values as a neuroprotective agent for peripheral nerve injury repair in diabetes mellitus.

  3. 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

  4. (-)-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. PMID:23313191

  5. 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.

  6. 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. PMID:19903499

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

    PubMed

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

    2013-02-01

    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.

  8. Inter-hemispheric plasticity in patients with median nerve injury.

    PubMed

    Fornander, Lotta; Nyman, Torbjörn; Hansson, Thomas; Brismar, Tom; Engström, Maria

    2016-08-15

    Peripheral nerve injuries result in reorganization within the contralateral hemisphere. Furthermore, recent animal and human studies have suggested that the plastic changes in response to peripheral nerve injury also include several areas of the ipsilateral hemisphere. The objective of this study was to map the inter-hemispheric plasticity in response to median nerve injury, to investigate normal differences in contra- and ipsilateral activation, and to study the impact of event-related or blocked functional magnetic resonance imaging (fMRI) design on ipsilateral activation. Four patients with median nerve injury at the wrist (injured and epineurally sutured >2 years earlier) and ten healthy volunteers were included. 3T fMRI was used to map the hemodynamic response to brain activity during tactile stimulation of the fingers, and a laterality index (LI) was calculated. Stimulation of Digits II-III of the injured hand resulted in a reduction in contralateral activation in the somatosensory area SI. Patients had a lower LI (0.21±0.15) compared to healthy controls (0.60±0.26) indicating greater ipsilateral activation of the primary somatosensory cortex. The spatial dispersion of the coordinates for areas SI and SII was larger in the ipsilateral than in the contralateral hemisphere in the healthy controls, and was increased in the contralateral hemisphere of the patients compared to the healthy controls. There was no difference in LI between the event-related and blocked paradigms. In conclusion, patients with median nerve injury have increased ipsilateral SI area activation, and spatially more dispersed contralateral SI activation during tactile stimulation of their injured hand. In normal subjects ipsilateral activation has larger spatial distribution than the contralateral. Previous findings in patients performed with the blocked fMRI paradigm were confirmed. The increase in ipsilateral SI activation may be due to an interhemispheric disinhibition associated with

  9. 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.

  10. [Who is responsible for the postoperative nerve injury? Anesthesia? Orthopedics? Trauma?].

    PubMed

    Kelsaka, Ebru; Güldoğuş, Fuat; Erdoğan, Murat; Zengin, Eyüp Cağatay

    2014-01-01

    In the pathogenesis of peripheral nerve injury, mechanical as well as vascular pressure, and chemical reasons play a role. In the applications of peripheral nerve block, there can be mechanical injury due to the type of needle and intrafascicular injections. In humerus fractures, nerve injury can be seen due to the surgical retractions and close proximity of the nerves with the bone. In addition, trauma may be the reason for posttraumatic nerve injury. In this presentation, we discussed the causes of postoperative nerve damage, which is seen after the operation of the distal humerus fracture.

  11. 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

  12. Minimizing shoulder syndrome with intra-operative spinal accessory nerve monitoring for neck dissection.

    PubMed

    Lee, C-H; Huang, N-C; Chen, H-C; Chen, M-K

    2013-04-01

    The objective of this study was to analyze the safety and results of intra-operative SAN (spinal accessary nerve) monitoring during selective neck dissection, with emphasis on shoulder syndrome. Twenty-five consecutive patients with head and neck cancer were studied. Selective neck dissection was performed by a single clinical fellow under the supervision of the department chief using an intra-operative SAN monitor. Electrophysiological data were recorded after initial identification of the SAN and continued until just before closure. Electromyographic evaluation was carried out to assess SAN function one month postoperatively. Shoulder disability was also evaluated at this time using a questionnaire for shoulder syndrome (shrug, flexion, abduction, winging, and pain). No patients had postoperative shoulder syndrome involving shrug, flexion, abduction, or winging. Twenty-two of the 25 (88%) patients had shoulder pain, but the average pain score was low (2.3 ± 1.3). No patients had neck recurrence during at least 1 year of follow up. By using nerve monitoring during selective neck dissection, no patient developed significant "shoulder syndrome", with the exception of slight pain.

  13. Effects of external helmet accessories on biomechanical measures of head injury risk: An ATD study using the HYBRIDIII headform.

    PubMed

    Butz, Robert C; Knowles, Brooklynn M; Newman, James A; Dennison, Christopher R

    2015-11-01

    Competitive cycling is a popular activity in North America for which injuries to the head account for the majority of hospitalizations and fatalities. In cycling, use of helmet accessories (e.g. cameras) has become widespread. As a consequence, standards organizations and the popular media are discussing the role these accessories could play in altering helmet efficacy and head injury risk. We conducted impacts to a helmeted anthropomorphic headform, with and without camera accessories, at speeds of 4m/s and 6m/s, and measured head accelerations, forces on the head-form skull, and used the Simulated Injury Monitor to estimate brain tissue strain. The presence of the camera reduced peak linear head acceleration (51% - 4m/s impacts, 61% - 6m/s, p<0.05). Skull fracture risk based on kinematics was always less than 1%. For 4m/s impacts, peak angular accelerations were lower (47%, p<0.05), as were peak angular velocities (14%) with the velocity effect approaching significance (p=0.06), with the camera accessory. For 6m/s impacts, accelerations were on average higher (5%, p>0.05) as were velocities (77%, p<0.05). Skull forces were never greater than 443.2N, well below forces associated with fracture. Brain tissue strain, the cumulative strain damage measure at 25% (CSDM-25), was lower (56%, p<0.05) in 4m/s but higher (125%, p>0.05) in 6m/s impacts with the camera accessory. Based on CSDM-25 for 4m/s tests, the risk of severe concussion was reduced (p<0.05) from 25% (no camera) to 7% (camera). For 6m/s tests, risks were on average increased (p>0.05) from 18% (no camera) to 58% (camera). PMID:26477409

  14. Effects of external helmet accessories on biomechanical measures of head injury risk: An ATD study using the HYBRIDIII headform.

    PubMed

    Butz, Robert C; Knowles, Brooklynn M; Newman, James A; Dennison, Christopher R

    2015-11-01

    Competitive cycling is a popular activity in North America for which injuries to the head account for the majority of hospitalizations and fatalities. In cycling, use of helmet accessories (e.g. cameras) has become widespread. As a consequence, standards organizations and the popular media are discussing the role these accessories could play in altering helmet efficacy and head injury risk. We conducted impacts to a helmeted anthropomorphic headform, with and without camera accessories, at speeds of 4m/s and 6m/s, and measured head accelerations, forces on the head-form skull, and used the Simulated Injury Monitor to estimate brain tissue strain. The presence of the camera reduced peak linear head acceleration (51% - 4m/s impacts, 61% - 6m/s, p<0.05). Skull fracture risk based on kinematics was always less than 1%. For 4m/s impacts, peak angular accelerations were lower (47%, p<0.05), as were peak angular velocities (14%) with the velocity effect approaching significance (p=0.06), with the camera accessory. For 6m/s impacts, accelerations were on average higher (5%, p>0.05) as were velocities (77%, p<0.05). Skull forces were never greater than 443.2N, well below forces associated with fracture. Brain tissue strain, the cumulative strain damage measure at 25% (CSDM-25), was lower (56%, p<0.05) in 4m/s but higher (125%, p>0.05) in 6m/s impacts with the camera accessory. Based on CSDM-25 for 4m/s tests, the risk of severe concussion was reduced (p<0.05) from 25% (no camera) to 7% (camera). For 6m/s tests, risks were on average increased (p>0.05) from 18% (no camera) to 58% (camera).

  15. 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

  16. Spontaneous pain following spinal nerve injury in mice.

    PubMed

    Minert, Anne; Gabay, Eran; Dominguez, Cecilia; Wiesenfeld-Hallin, Zsuzsanna; Devor, Marshall

    2007-08-01

    Autotomy behavior is frequently observed in rats and mice in which the nerves of the hindlimb are severed, denervating the paw. This is the neuroma model of neuropathic pain. A large body of evidence suggests that this behavior reflects the presence of spontaneous dysesthesia and pain. In contrast, autotomy typically does not develop in partial nerve injury pain models, leading to the belief that these animals develop hypersensibility to applied stimuli (allodynia and hyperalgesia), but not spontaneous pain. We have modified the widely used Chung (spinal nerve ligation [SNL]) model of neuropathic pain in a way that retains the fundamental neural lesion, but eliminates nociceptive sensory cover of the paw. These animals performed autotomy. Moreover, the heritable across strains predisposition to spontaneous pain behavior in this new proximal denervation model (SNN) was highly correlated with pain phenotype in the neuroma model suggesting that the pain mechanism in the two models is the same. Relative reproducibility of strain predispositions across laboratories was verified. These data indicate that the neural substrate for spontaneous pain is present in the Chung-SNL model, and perhaps in the other partial nerve injury models as well, but that spontaneous pain is not expressed as autotomy in these models because there is protective nociceptive sensory cover. PMID:17585907

  17. Implant Injury Case Series and Review of the Literature Part 1: Inferior Alveolar Nerve Injury.

    PubMed

    Du Toit, Jonathan; Gluckman, Howard; Gamil, Rami; Renton, Tara

    2015-08-01

    Injury to adjacent structures is an unfortunate and avoidable outcome of oral implant placement surgery. Paramount among these is perforation into paranasal sinus; into neighboring tooth root; through cortical plate; and into vessels, canals, and, most importantly, nerves. In most cases, injudicious oral implant placement can be attributed to poor treatment planning. We present the cases of several patients referred for postsurgical radiology that illustrate injury to the inferior alveolar canal by implant impingement, penetration, and even complete obliteration of the nerve and canal in the absence of proper treatment planning and imaging modalities. The authors stress the importance of thorough implant case preparation and planning, which may include the use of cone beam computerized tomography in order to minimize nerve injury. PMID:24945089

  18. 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. PMID:26922403

  19. Risk of marginal mandibular nerve injury in neck dissection.

    PubMed

    Møller, Martin Nue; Sørensen, Christian Hjort

    2012-02-01

    The immediate and permanent frequency of injury to the marginal mandibular branch of the facial nerve (MMN) after neck dissection has only scarcely been addressed in the medical literature. We investigated the risk of injury in 159 consecutive patients after neck dissection for various reasons in level I B and level II A, respectively. In 95 patients with oral cancer 13 (14%) of the cases had malfunction of the lower lip domain 2 weeks after neck dissection in level I B indicating paresis to the MMN. Follow-up analyses 1-2 years after the operation showed permanent paralysis in 4 to 7% of the cases in whom two of them had the nerve sacrificed for oncologic reasons during the operation. In 18 patients with parotic cancer the corresponding permanent frequency of MMN paralysis was 11.1%. In 46 patients with neck dissection in level II A but not in level I B, no paresis of the MMN was registered. Recognition of the MMN during the operation, pre- or postoperative radiation therapy, re-operation for deep hemorrhage, age, gender or postoperative infection did not have any statistically significant influence on the frequency of MMN injury. In conclusion we found a moderate risk of injury to the MMN after neck dissection in level I B whereas the corresponding risk after level II A dissection was negligible. PMID:21553271

  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. Diffusion tensor magnetic resonance imaging of regeneration/degeneration after rat sciatic nerve injury

    NASA Astrophysics Data System (ADS)

    Sig Hwang, Min; Perrin, George; Muir, David; Mareci, Thomas

    2005-11-01

    Diffusion tensor imaging was performed to investigate myelination and demyelination spatiotemporally in cut or crushed excised rat sciatic nerves in a 17.6 T magnet with a solenoid RF coil. Orientation independent measures of water diffusion, fractional anisotropy (FA) and averaged diffusivity (), were examined as MR parameters for the quantification of the myelin within the major peripheral nerve. Crushed nerves initially demonstrated decreased FA, followed by increase to FA of normal nerve with time. At 14 days post injury, FA of the nerve is high, 0.85, at the site proximal to the injury then FA decreases in a proximodistal gradient because the nerve remains more demyelinated toward the distal area. Cut sciatic nerves displayed a prolonged decrease of FA with time after injury. Also FA correlates with in these nerves. Therefore FA or may be a good indicator of myelination and demyelination in rat sciatic nerves and FA appears to be a more sensitive indicator of myelin.

  2. Cranial nerve injuries with supraglottic airway devices: a systematic review of published case reports and series.

    PubMed

    Thiruvenkatarajan, V; Van Wijk, R M; Rajbhoj, A

    2015-03-01

    Cranial nerve injuries are unusual complications of supraglottic airway use. Branches of the trigeminal, glossopharyngeal, vagus and the hypoglossal nerve may all be injured. We performed a systematic review of published case reports and case series of cranial nerve injury from the use of supraglottic airway devices. Lingual nerve injury was the most commonly reported (22 patients), followed by recurrent laryngeal (17 patients), hypoglossal (11 patients), glossopharyngeal (three patients), inferior alveolar (two patients) and infra-orbital (one patient). Injury is generally thought to result from pressure neuropraxia. Contributing factors may include: an inappropriate size or misplacement of the device; patient position; overinflation of the device cuff; and poor technique. Injuries other than to the recurrent laryngeal nerve are usually mild and self-limiting. Understanding the diverse presentation of cranial nerve injuries helps to distinguish them from other complications and assists in their management. PMID:25376257

  3. 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. PMID:21133047

  4. Inferior alveolar nerve injury in implant dentistry: diagnosis, causes, prevention, and management.

    PubMed

    Alhassani, Ahmed Ali; AlGhamdi, Ali Saad Thafeed

    2010-01-01

    Inferior alveolar nerve injury is one of the most serious complications in implant dentistry. This nerve injury can occur during local anesthesia, implant osteotomy, or implant placement. Proper understanding of anatomy, surgical procedures, and implant systems and proper treatment planning is the key to reducing such an unpleasant complication. This review discusses the causes of inferior alveolar nerve injury and its diagnosis, prevention, and management. PMID:20545547

  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. 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. PMID:27212918

  7. 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.

  8. Wide resection of traction induced radial nerve injury with cable grafting leads to full recovery.

    PubMed

    Henry, Mark

    2006-12-01

    The specific clinical setting of high-energy open humerus fractures combined with radial nerve transection has typically led to poor final outcomes with respect to recovery of nerve function. Attention has focused on the issue of an expanded zone of nerve injury induced by longitudinal traction. The fundamental principle of nerve grafting is to bypass the zone of injury. If direct repair or short nerve grafts are placed within the zone of injury, limited recovery should be expected, and this is exactly what has been documented. Wide resection of the zone of traction induced injury, particularly from the distal injured nerve trunk and replacement with long cable grafts has the potential for improved outcomes. Complete nerve recovery to 5/5 manual motor power testing and bilaterally equivalent grip strength is reported in two initial cases treated according to the wide resection plan.

  9. 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. PMID:22254232

  10. Immune cell distribution and immunoglobulin levels change following sciatic nerve injury in a rat model

    PubMed Central

    Yuan, Wei; Feng, Xinhong

    2016-01-01

    Objective(s): To investigate the systemic and local immune status of two surgical rat models of sciatic nerve injury, a crushed sciatic nerve, and a sciatic nerve transection Materials and Methods: Twenty-four adult male Sprague-Dawley rats were randomly divided into three groups: sham-operation (control group), sciatic nerve crush, and sciatic nerve transaction. Sciatic nerve surgery was performed. The percentage of CD4+ cells and the CD4+/CD8+ratio were determined by flow cytometry. Serum IgM and IgG levels were analyzed by ELISA. T-cells (CD3) and macrophages (CD68) in sciatic nerve tissue sections were identified through immunohistochemistry. Results: Compared to sham-operated controls, in rats that underwent nerve injury, the percentage of CD4+ cells and the CD4+/CD8+ ratio in the peripheral blood were significantly decreased 7 days after surgery, serum IgM levels were increased 14 days after surgery, and serum IgG levels were increased 21 days after surgery. There were a large number of CD3+ cells and a small number of CD68+ cells in sciatic nerve tissue sections 21 days after surgery, indicating T-cell and macrophage activation and infiltration. Local IgG deposition was also detected at the nerve injury site 21 days after surgery. Conclusion: Rat humoral and cellular immune status changed following sciatic nerve injury, particularly with regard to the cellular immune response at the nerve injury site.

  11. Immune cell distribution and immunoglobulin levels change following sciatic nerve injury in a rat model

    PubMed Central

    Yuan, Wei; Feng, Xinhong

    2016-01-01

    Objective(s): To investigate the systemic and local immune status of two surgical rat models of sciatic nerve injury, a crushed sciatic nerve, and a sciatic nerve transection Materials and Methods: Twenty-four adult male Sprague-Dawley rats were randomly divided into three groups: sham-operation (control group), sciatic nerve crush, and sciatic nerve transaction. Sciatic nerve surgery was performed. The percentage of CD4+ cells and the CD4+/CD8+ratio were determined by flow cytometry. Serum IgM and IgG levels were analyzed by ELISA. T-cells (CD3) and macrophages (CD68) in sciatic nerve tissue sections were identified through immunohistochemistry. Results: Compared to sham-operated controls, in rats that underwent nerve injury, the percentage of CD4+ cells and the CD4+/CD8+ ratio in the peripheral blood were significantly decreased 7 days after surgery, serum IgM levels were increased 14 days after surgery, and serum IgG levels were increased 21 days after surgery. There were a large number of CD3+ cells and a small number of CD68+ cells in sciatic nerve tissue sections 21 days after surgery, indicating T-cell and macrophage activation and infiltration. Local IgG deposition was also detected at the nerve injury site 21 days after surgery. Conclusion: Rat humoral and cellular immune status changed following sciatic nerve injury, particularly with regard to the cellular immune response at the nerve injury site. PMID:27635205

  12. Clinical characteristics of trigeminal nerve injury referrals to a university centre.

    PubMed

    Tay, A B G; Zuniga, J R

    2007-10-01

    The aim of this retrospective study was to determine the aetiology and characteristics of trigeminal nerve injuries referred to a university centre with nerve injury care. Fifty-nine patients with 73 injured trigeminal nerves were referred in 10 months. The most common aetiologies were odontectomy (third molar surgery) (52.1% of nerves), local anaesthetic (LA) injections (12.3%), orthognathic surgery (12.3%) and implant surgery (11.0%). The inferior alveolar nerve (IAN) was most commonly injured nerve (64.4%), followed by the lingual nerve (LN) (28.8%). About a quarter of IAN injuries (27.3%) and half of LN injuries (57.1%) from odontectomy had severe sensory impairment. There were twice as many LN than IAN injuries from local anaesthetic injections, but all had mild or no sensory impairment. Nerve injuries from implant surgery occurred only in IAN injuries; none had severe sensory impairment. Neuropathic pain occurred in 14.9% of IAN injuries and only in those with mild or no sensory impairment. Nerve surgery was offered to 45.8% of patients; a third underwent surgery. PMID:17875382

  13. Reactive oxygen species (ROS) mediates non-freezing cold injury of rat sciatic nerve

    PubMed Central

    Geng, Zhiwei; Tong, Xiaoyan; Jia, Hongjuan

    2015-01-01

    Non-freezing cold injury is an injury characterized by neuropathy, developing when patients expose to cold environments. Reactive oxygen species (ROS) has been shown as a contributing factor for the non-freezing cold nerve injury. However, the detailed connections between non-freezing cold nerve injury and ROS have not been described. In order to investigate the relationship between non-freezing cold nerve injury and reactive oxygen species, we study the effects of two cooling methods-the continuous cooling and the intermittent cooling with warming intervals-on rat sciatic nerves. Specifically, we assess the morphological changes and ROS production of the sciatic nerves underwent different cooling treatments. Our data shows both types of cooling methods cause nerve injury and ROS production. However, despite of identical cooling degree and duration, the sciatic nerves processed by intermittent cooling with warming intervals present more ROS production, severer reperfusion injury and pathological destructions than the sciatic nerves processed by continuous cooling. This result indicates reactive oxygen species, as a product of reperfusion, facilitates non-freezing cold nerve injury. PMID:26629065

  14. Spared nerve injury model to study orofacial pain

    PubMed Central

    Pozza, Daniel Humberto; Castro-Lopes, José Manuel; Neto, Fani Lourença; Avelino, António

    2016-01-01

    Background & objectives: There are many difficulties in generating and testing orofacial pain in animal models. Thus, only a few and limited models that mimic the human condition are available. The aim of the present research was to develop a new model of trigeminal pain by using a spared nerve injury (SNI) surgical approach in the rat face (SNI-face). Methods: Under anaesthesia, a small incision was made in the infraorbital region of adult male Wistar rats. Three of the main infraorbital nerve branches were tightly ligated and a 2 mm segment distal to the ligation was resected. Control rats were sham-operated by exposing the nerves. Chemical hyperalgesia was evaluated 15 days after the surgery by analyzing the time spent in face grooming activity and the number of head withdrawals in response to the orofacial formalin test. Results: SNI-face rats presented a significant increase of the formalin-induced pain-related behaviours evaluated both in the acute and tonic phases (expected biphasic pattern), in comparison to sham controls. Interpretation & conclusions: The SNI-face model in the rat appears to be a valid approach to evaluate experimental trigeminal pain. Ongoing studies will test the usefulness of this model to evaluate therapeutic strategies for the treatment of orofacial pain. PMID:27241642

  15. Nerve growth factor enhances Clara cell proliferation after lung injury.

    PubMed

    Sonar, S S; Schwinge, D; Kilic, A; Yildirim, A O; Conrad, M L; Seidler, K; Müller, B; Renz, H; Nockher, W A

    2010-07-01

    The lung epithelia facilitate wound closure by secretion of various cytokines and growth factors. Nerve growth factor (NGF) has been well described in airway inflammation; however, its likely role in lung repair has not been examined thus far. To investigate the repair function of NGF, experiments were performed in vitro using cultured alveolar epithelial cells and in vivo using a naphthalene-induced model of Clara epithelial cell injury. Both in vitro and in vivo experiments revealed airway epithelial cell proliferation following injury to be dependent on NGF and the expression of its receptor, tropomyosin-receptor-kinase A. Additionally, NGF also augmented in vitro migration of alveolar type II cells. In vivo, transgenic mice over-expressing NGF in Clara cells (NGFtg) did not reveal any proliferation or alteration in Clara cell phenotype. However, following Clara cell specific injury, proliferation was increased in NGFtg and impaired upon inhibition of NGF. Furthermore, NGF also promoted the expression of collagen I and fibronectin in vitro and in vivo during repair, where significantly higher levels were measured in re-epithelialising NGFtg mice. Our study demonstrates that NGF promotes the proliferation of lung epithelium in vitro and the renewal of Clara cells following lung injury in vivo.

  16. Correlation between muscle electrophysiology and strength after fibular nerve injury.

    PubMed

    Won, Yu Hui; Kim, Kang-Won; Choi, Jun Tak; Ko, Myoung-Hwan; Park, Sung-Hee; Seo, Jeong-Hwan

    2016-08-01

    Muscle strength measurement is important when evaluating the degree of impairment in patients with nerve injury. However, accurate and objective evaluation may be difficult in patients with severe pain or those who intentionally try to avoid full exertion. We investigated the usefulness of the affected-to-unaffected side electrophysiological parameter ratios as a measure of objective ankle dorsiflexion (ADF) strength in patients with unilateral fibular nerve injury (FNI). ADF strength was measured in patients with FNI via handheld dynamometer and manual muscle test (MMT). Fibular nerve compound muscle action potential (CMAP) amplitude and latency and ADF strength of the affected side were presented as ratios to the corresponding measurements of the unaffected side. We analysed the correlation of the CMAP ratio with the ADF strength ratio using a dynamometer and compared the CMAP ratios according to MMT grade. Fifty-two patients with FNI were enrolled. The mean CMAP latency ratio did not differ between MMT groups (p = 0.573). The CMAP amplitude ratio proportionally increased with the quantified ADF strength ratio via dynamometer increase (ρ = 0.790; p < 0.001), but the CMAP latency ratio and the quantified ADF strength ratio did not significantly correlate (ρ = 0.052; p = 0.713). The average CMAP amplitude ratio significantly differed between MMT groups (p < 0.001), and post hoc tests showed significant differences in all paired comparisons except of Fair and Good grades (p = 0.064). Electrophysiological parameter ratio, such as the affected-to-unaffected side CMAP amplitude ratio, might be sensitive parameters for ADF power estimation after FNI. PMID:27142447

  17. Correlation between muscle electrophysiology and strength after fibular nerve injury.

    PubMed

    Won, Yu Hui; Kim, Kang-Won; Choi, Jun Tak; Ko, Myoung-Hwan; Park, Sung-Hee; Seo, Jeong-Hwan

    2016-08-01

    Muscle strength measurement is important when evaluating the degree of impairment in patients with nerve injury. However, accurate and objective evaluation may be difficult in patients with severe pain or those who intentionally try to avoid full exertion. We investigated the usefulness of the affected-to-unaffected side electrophysiological parameter ratios as a measure of objective ankle dorsiflexion (ADF) strength in patients with unilateral fibular nerve injury (FNI). ADF strength was measured in patients with FNI via handheld dynamometer and manual muscle test (MMT). Fibular nerve compound muscle action potential (CMAP) amplitude and latency and ADF strength of the affected side were presented as ratios to the corresponding measurements of the unaffected side. We analysed the correlation of the CMAP ratio with the ADF strength ratio using a dynamometer and compared the CMAP ratios according to MMT grade. Fifty-two patients with FNI were enrolled. The mean CMAP latency ratio did not differ between MMT groups (p = 0.573). The CMAP amplitude ratio proportionally increased with the quantified ADF strength ratio via dynamometer increase (ρ = 0.790; p < 0.001), but the CMAP latency ratio and the quantified ADF strength ratio did not significantly correlate (ρ = 0.052; p = 0.713). The average CMAP amplitude ratio significantly differed between MMT groups (p < 0.001), and post hoc tests showed significant differences in all paired comparisons except of Fair and Good grades (p = 0.064). Electrophysiological parameter ratio, such as the affected-to-unaffected side CMAP amplitude ratio, might be sensitive parameters for ADF power estimation after FNI.

  18. Electrodiagnostic study of peripheral nerves in high-voltage electrical injury.

    PubMed

    Kwon, Ki Han; Kim, Se Hoon; Minn, Yang Ki

    2014-01-01

    It is well known that peripheral nerves are very vulnerable to electricity. However, only a small portion of individuals who have had high-voltage electrical injury exhibit peripheral nerve damage. The aim of this study was to investigate peripheral nerve damage in high-voltage electrical injury, which often occurs in the industrial field. The authors reviewed the medical records of patients who were admitted to their hospital from January 2009 to December 2011, because of electrical injuries. The results of nerve conduction studies (NCSs) were reviewed retrospectively. NCS data of the injured site were compared with those of the opposite noninjured site and follow-up data. Thirty-seven extremities were reviewed. The authors found that 18 of 33 median nerves (48.6%) showed abnormalities in at least one parameter and 15 of 36 ulnar nerves (41.7%) exhibited abnormalities. There was no evidence of demyelination. Eight patients had undergone NCS on the opposite normal extremities. The compound muscle action potential and nerve conduction velocity were higher at the normal site. Follow-up NCS were performed in 14 patients: the compound muscle action potential and nerve conduction velocity values of all patients were improved. High-voltage electricity damaged peripheral nerves by causing axonal injury rather than demyelinating injury. Hence, even if NCSs yield normal findings, peripheral nerves may be damaged. F/U studies and opposite examinations are required for the exact evaluation of peripheral nerve damage.

  19. Electrodiagnostic study of peripheral nerves in high-voltage electrical injury.

    PubMed

    Kwon, Ki Han; Kim, Se Hoon; Minn, Yang Ki

    2014-01-01

    It is well known that peripheral nerves are very vulnerable to electricity. However, only a small portion of individuals who have had high-voltage electrical injury exhibit peripheral nerve damage. The aim of this study was to investigate peripheral nerve damage in high-voltage electrical injury, which often occurs in the industrial field. The authors reviewed the medical records of patients who were admitted to their hospital from January 2009 to December 2011, because of electrical injuries. The results of nerve conduction studies (NCSs) were reviewed retrospectively. NCS data of the injured site were compared with those of the opposite noninjured site and follow-up data. Thirty-seven extremities were reviewed. The authors found that 18 of 33 median nerves (48.6%) showed abnormalities in at least one parameter and 15 of 36 ulnar nerves (41.7%) exhibited abnormalities. There was no evidence of demyelination. Eight patients had undergone NCS on the opposite normal extremities. The compound muscle action potential and nerve conduction velocity were higher at the normal site. Follow-up NCS were performed in 14 patients: the compound muscle action potential and nerve conduction velocity values of all patients were improved. High-voltage electricity damaged peripheral nerves by causing axonal injury rather than demyelinating injury. Hence, even if NCSs yield normal findings, peripheral nerves may be damaged. F/U studies and opposite examinations are required for the exact evaluation of peripheral nerve damage. PMID:23877148

  20. 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. PMID:25119457

  1. Spinal nerve injury increases the percentage of cold-responsive DRG neurons.

    PubMed

    Djouhri, L; Wrigley, D; Thut, P D; Gold, M S

    2004-03-01

    We tested the hypothesis that cold allodynia, observed following nerve injury reflects change(s) in the cold responsiveness of sensory neurons. To test this hypothesis we assessed the impact of the spinal nerve ligation (SNL) model of nerve injury on the responses of cutaneous sensory neurons to cooling in vitro. Nerve injury induced a significant increase in the incidence of cold responsive cutaneous neurons in uninjured but not injured ganglia. Because an increase in the percentage of cold responsive neurons in uninjured ganglia should increase the total neuronal response to cooling of peripheral tissue, these findings suggest that cold allodynia reflects, at least in part, a change in sensory neurons. PMID:15094503

  2. 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.

  3. Nerve Transfers in Birth Related Brachial Plexus Injuries: Where Do We Stand?

    PubMed

    Davidge, Kristen M; Clarke, Howard M; Borschel, Gregory H

    2016-05-01

    This article reviews the assessment and management of obstetrical brachial plexus palsy. The potential role of distal nerve transfers in the treatment of infants with Erb's palsy is discussed. Current evidence for motor outcomes after traditional reconstruction via interpositional nerve grafting and extraplexal nerve transfers is reviewed and compared with the recent literature on intraplexal distal nerve transfers in obstetrical brachial plexus injury. PMID:27094890

  4. Early cyclosporin A treatment retards axonal degeneration in an experimental peripheral nerve injection injury model

    PubMed Central

    Erkutlu, Ibrahim; Alptekin, Mehmet; Geyik, Sirma; Geyik, Abidin Murat; Gezgin, Inan; Gök, Abdulvahap

    2015-01-01

    Injury to peripheral nerves during injections of therapeutic agents such as penicillin G potassium is common in developing countries. It has been shown that cyclosporin A, a powerful immunosuppressive agent, can retard Wallerian degeneration after peripheral nerve crush injury. However, few studies are reported on the effects of cyclosporin A on peripheral nerve drug injection injury. This study aimed to assess the time-dependent efficacy of cyclosporine-A as an immunosuppressant therapy in an experimental rat nerve injection injury model established by penicillin G potassium injection. The rats were randomly divided into three groups based on the length of time after nerve injury induced by cyclosporine-A administration (30 minutes, 8 or 24 hours). The compound muscle action potentials were recorded pre-injury, early post-injury (within 1 hour) and 4 weeks after injury and compared statistically. Tissue samples were taken from each animal for histological analysis. Compared to the control group, a significant improvement of the compound muscle action potential amplitude value was observed only when cyclosporine-A was administered within 30 minutes of the injection injury (P < 0.05); at 8 or 24 hours after cyclosporine-A administration, compound muscle action potential amplitude was not changed compared with the control group. Thus, early immunosuppressant drug therapy may be a good alternative neuroprotective therapy option in experimental nerve injection injury induced by penicillin G potassium injection. PMID:25883626

  5. Infraorbital nerve transpositioning into orbital floor: a modified technique to minimize nerve injury following zygomaticomaxillary complex fractures

    PubMed Central

    Kotrashetti, Sharadindu Mahadevappa; Kale, Tejraj Pundalik; Bhandage, Supriya

    2015-01-01

    Objectives Transpositioning of the inferior alveolar nerve to prevent injury in lower jaw has been advocated for orthognathic, pre-prosthetic and for implant placement procedures. However, the concept of infra-orbital nerve repositioning in cases of mid-face fractures remains unexplored. The infraorbital nerve may be involved in trauma to the zygomatic complex which often results in sensory disturbance of the area innervated by it. Ten patients with infraorbital nerve entrapment were treated in similar way at our maxillofacial surgery centre. Materials and Methods In this article we are reporting three cases of zygomatico-maxillary complex fracture in which intra-operative repositioning of infra-orbital nerve into the orbital floor was done. This was done to release the nerve from fractured segments and to reduce the postoperative neural complications, to gain better access to fracture site and ease in plate fixation. This procedure also decompresses the nerve which releases it off the soft tissue entrapment caused due to trauma and the organized clot at the fractured site. Results There was no evidence of sensory disturbance during their three month follow-up in any of the patient. Conclusion Infraorbital nerve transposition is very effective in preventing paresthesia in patients which fracture line involving the infraorbital nerve. PMID:25922818

  6. Review of Literature of Radial Nerve Injuries Associated with Humeral Fractures—An Integrated Management Strategy

    PubMed Central

    Wu, Qiang; Wu, QiuLi; Li, Yan; Feng, ShiQing

    2013-01-01

    Background Radial nerve palsy associated with fractures of the shaft of the humerus is the most common nerve lesion complicating fractures of long bones. However, the management of radial nerve injuries associated with humeral fractures is debatable. There was no consensus between observation and early exploration. Methods and Findings The PubMed, Embase, Cochrane Central Register of Controlled Trials, Google Scholar, CINAHL, International Bibliography of the Social Sciences, and Social Sciences Citation Index were searched. Two authors independently searched for relevant studies in any language from 1966 to Jan 2013. Thirty studies with 2952 humeral fractures participants were identified. Thirteen studies favored conservative strategy. No significant difference between early exploration and no exploration groups (OR, 1.03, 95% CI 0.61, 1.72; I2 = 0.0%, p = 0.918 n.s.). Three studies recommend early radial nerve exploration in patients with open fractures of humerus with radial nerve injury. Five studies proposed early exploration was performed in high-energy humeral shaft fractures with radial nerve injury. Conclusions The conservative strategy was a good choice for patients with low-energy closed fractures of humerus with radial nerve injury. We recommend early radial nerve exploration (within the first 2 weeks) in patients with open fractures or high-energy closed fractures of humerus with radial nerve injury. PMID:24250799

  7. Capsaicin avoidance as a measure of chemical hyperalgesia in orofacial nerve injury models.

    PubMed

    Boucher, Yves; Carstens, Mirela Iodi; Sawyer, Carolyn M; Zanotto, Karen L; Merrill, Austin W; Carstens, E

    2013-05-24

    Many patients suffer from trigeminal neuralgia and other types of orofacial pain that are poorly treated, necessitating preclininal animal models for development of mechanisms-based therapies. The present study assessed capsaicin avoidance and other nocifensive behavioral responses in three models of orofacial nerve injury in rats: chronic constriction injury (CCI) of the mental nerves, partial tight ligation of mental nerves, and CCI of lingual nerves. We additionally investigated if nerve injury resulted in enhanced capsaicin-evoked activation of neurons in trigeminal caudalis (Vc) or nucleus of the solitary tract (NTS) based on expression of Fos-like immunoreactivity (FLI). Mental nerve CCI resulted in an enhancement of capsaicin avoidance in a two-bottle preference paradigm, while neither mental nerve injury produced thermal hyperalgesia or mechanical allodynia. CCI of lingual nerves did not affect capsaicin avoidance. Counts of FLI in Vc were significantly higher in the lingual sham and mental nerve CCI groups compared to mental shams; FLI counts in NTS did not differ among groups. Mental nerve CCI may have induced central sensitization of chemical nociception since increased capsaicin avoidance was accompanied by greater activation of Vc neurons in response to oral capsaicin.

  8. Differential gene expression in proximal and distal nerve segments of rats with sciatic nerve injury during Wallerian degeneration

    PubMed Central

    Jiang, Nan; Li, Huaiqin; Sun, Yi; Yin, Dexin; Zhao, Qin; Cui, Shusen; Yao, Dengbing

    2014-01-01

    Wallerian degeneration is a subject of major interest in neuroscience. A large number of genes are differentially regulated during the distinct stages of Wallerian degeneration: transcription factor activation, immune response, myelin cell differentiation and dedifferentiation. Although gene expression responses in the distal segment of the sciatic nerve after peripheral nerve injury are known, differences in gene expression between the proximal and distal segments remain unclear. In the present study in rats, we used microarrays to analyze changes in gene expression, biological processes and signaling pathways in the proximal and distal segments of sciatic nerves undergoing Wallerian degeneration. More than 6,000 genes were differentially expressed and 20 types of expression tendencies were identified, mainly between proximal and distal segments at 7–14 days after injury. The differentially expressed genes were those involved in cell differentiation, cytokinesis, neuron differentiation, nerve development and axon regeneration. Furthermore, 11 biological processes were represented, related to responses to stimuli, cell apoptosis, inflammatory response, immune response, signal transduction, protein kinase activity, and cell proliferation. Using real-time quantitative PCR, western blot analysis and immunohistochemistry, microarray data were verified for four genes: aquaporin-4, interleukin 1 receptor-like 1, matrix metalloproteinase-12 and periaxin. Our study identifies differential gene expression in the proximal and distal segments of a nerve during Wallerian degeneration, analyzes dynamic biological changes of these genes, and provides a useful platform for the detailed study of nerve injury and repair during Wallerian degeneration. PMID:25206781

  9. Peripheral Nerve Reconstruction after Injury: A Review of Clinical and Experimental Therapies

    PubMed Central

    Grinsell, D.; Keating, C. P.

    2014-01-01

    Unlike other tissues in the body, peripheral nerve regeneration is slow and usually incomplete. Less than half of patients who undergo nerve repair after injury regain good to excellent motor or sensory function and current surgical techniques are similar to those described by Sunderland more than 60 years ago. Our increasing knowledge about nerve physiology and regeneration far outweighs our surgical abilities to reconstruct damaged nerves and successfully regenerate motor and sensory function. It is technically possible to reconstruct nerves at the fascicular level but not at the level of individual axons. Recent surgical options including nerve transfers demonstrate promise in improving outcomes for proximal nerve injuries and experimental molecular and bioengineering strategies are being developed to overcome biological roadblocks limiting patient recovery. PMID:25276813

  10. 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

  11. Evidence-based outcomes following inferior alveolar and lingual nerve injury and repair: a systematic review.

    PubMed

    Kushnerev, E; Yates, J M

    2015-10-01

    The inferior alveolar nerve (IAN) and lingual (LN) are susceptible to iatrogenic surgical damage. Systematically review recent clinical evidence regarding IAN/LN repair methods and to develop updated guidelines for managing injury. Recent publications on IAN/LN microsurgical repair from Medline, Embase and Cochrane Library databases were screened by title/abstract. Main texts were appraised for exclusion criteria: no treatment performed or results provided, poor/lacking procedural description, cohort <3 patients. Of 366 retrieved papers, 27 were suitable for final analysis. Treatment type for injured IANs/LNs depended on injury type, injury timing, neurosensory disturbances and intra-operative findings. Best functional nerve recovery occurred after direct apposition and suturing if nerve ending gaps were <10 mm; larger gaps required nerve grafting (sural/greater auricular nerve). Timing of microneurosurgical repair after injury remains debated. Most authors recommend surgery when neurosensory deficit shows no improvement 90 days post-diagnosis. Nerve transection diagnosed intra-operatively should be repaired in situ; minor nerve injury repair can be delayed. No consensus exists regarding optimal methods and timing for IAN/LN repair. We suggest a schematic guideline for treating IAN/LN injury, based on the most current evidence. We acknowledge that additional RCTs are required to provide definitive confirmation of optimal treatment approaches. PMID:26059454

  12. 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.

  13. 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

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

    PubMed

    Zhao, Zhan-Kui; Yu, Hong-Lian; Liu, Bo; Wang, Hui; Luo, Qiong; Ding, Xie-Gang

    2016-08-01

    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

  15. 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.

  16. Agmatine treatment and vein graft reconstruction enhance recovery after experimental facial nerve injury.

    PubMed

    Berenholz, Leonard; Segal, Shmuel; Gilad, Varda H; Klein, Collen; Yehezkeli, Eyal; Eviatar, Ephraim; Kessler, Alex; Gilad, Gad M

    2005-09-01

    The rate of nerve regeneration is a critical determinant of the degree of functional recovery after injury. Here, we sought to determine whether treatment with the neuroprotective compound, agmatine, with or without nerve reconstruction utilizing a regional autogenous vein graft would accelerate the rate of facial nerve regeneration. Experiments compared the following seven groups of adult male rats: (A) Intact untreated controls. (B) Sham operation with interruption of the nerve blood supply (controls). (C) Transection of the mandibular branch of the facial nerve (generating a gap of 3 mm) followed by saline treatment. (D) Nerve transection with unsutured autogenous vein (external jugular) graft reconstruction plus saline treatment. (E) Nerve transection with sutured vein graft approximation (coaptation of the proximal and distal nerve stumps) plus saline. (F) Nerve transection with sutured vein graft followed by agmatine treatment (four daily intraperitoneal injections of 100 mg/kg agmatine sulfate). (G) Nerve transection with unsutured vein graft followed by agmatine treatment. Functional recovery, as assessed by grading vibrissae movements and by recording nerve conduction velocity and numbers of regenerated axons, indicated that either vein reconstruction or agmatine treatment resulted in accelerated and more complete recovery as compared with controls. But best results were observed in animals that underwent combined treatment, i.e., vein reconstruction plus agmatine injection. We conclude that agmatine treatment can accelerate facial nerve regeneration and that agmatine treatment together with autogenous vein graft offers an advantageous alternative to other facial nerve reconstruction procedures.

  17. Transforming Growth Factor-β Promotes Axonal Regeneration After Chronic Nerve Injury.

    PubMed

    Sulaiman, Wale A R

    2016-04-01

    When spinal cord injury (SCI) occurs, injured cells must survive and regenerate to close gaps caused by the injury and to create functional motor units. After peripheral nerve injury, Wallerian degeneration in the distal nerve stump creates a neurotrophic and growth-supportive environment for injured neurons and axons via Schwann cells and secreted cytokines/neurotrophins. In both SCI and peripheral nerve injury, injured motor and sensory neurons must regenerate axons, eventually reaching and reinnervating target tissue (SDC Figure 1, http://links.lww.com/BRS/B116). This process is often unsuccessful after SCI, and the highly complex anatomy of branching axons and nerves in the peripheral nervous system leads to slow recovery of function, even with careful and appropriate techniques.

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

    PubMed

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

    2016-01-01

    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. PMID:27592207

  19. 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.

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

    PubMed Central

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

    2016-01-01

    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/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. PMID:27592207

  1. Sciatic nerve injury related to hip replacement surgery: imaging detection by MR neurography despite susceptibility artifacts.

    PubMed

    Wolf, Marcel; Bäumer, Philipp; Pedro, Maria; Dombert, Thomas; Staub, Frank; Heiland, Sabine; Bendszus, Martin; Pham, Mirko

    2014-01-01

    Sciatic nerve palsy related to hip replacement surgery (HRS) is among the most common causes of sciatic neuropathies. The sciatic nerve may be injured by various different periprocedural mechanisms. The precise localization and extension of the nerve lesion, the determination of nerve continuity, lesion severity, and fascicular lesion distribution are essential for assessing the potential of spontaneous recovery and thereby avoiding delayed or inappropriate therapy. Adequate therapy is in many cases limited to conservative management, but in certain cases early surgical exploration and release of the nerve is indicated. Nerve-conduction-studies and electromyography are essential in the diagnosis of nerve injuries. In postsurgical nerve injuries, additional diagnostic imaging is important as well, in particular to detect or rule out direct mechanical compromise. Especially in the presence of metallic implants, commonly applied diagnostic imaging tests generally fail to adequately visualize nervous tissue. MRI has been deemed problematic due to implant-related artifacts after HRS. In this study, we describe for the first time the spectrum of imaging findings of Magnetic Resonance neurography (MRN) employing pulse sequences relatively insensitive to susceptibility artifacts (susceptibility insensitive MRN, siMRN) in a series of 9 patients with HRS procedure related sciatic nerve palsy. We were able to determine the localization and fascicular distribution of the sciatic nerve lesion in all 9 patients, which clearly showed on imaging predominant involvement of the peroneal more than the tibial division of the sciatic nerve. In 2 patients siMRN revealed direct mechanical compromise of the nerve by surgical material, and in one of these cases indication for surgical release of the sciatic nerve was based on siMRN. Thus, in selected cases of HRS related neuropathies, especially when surgical exploration of the nerve is considered, siMRN, with its potential to largely

  2. Nerve Injury in Patients Following Hip and Knee Arthroplasties and Knee Arthroscopy

    PubMed Central

    Yacub, Jennifer N.; Rice, J. Bradford; Dillingham, Timothy R.

    2016-01-01

    Objective To examine the reporting of lower limb neuropathy within 90 days of surgery for patients undergoing hip arthroplasty, knee arthroplasty or knee arthroscopy. Design This was a retrospective study utilizing data from the 1998 MarketScan Commercial Claims and Encounter Database (The MEDSTAT Group) to identify lower limb neuropathy following these surgeries. The sample was selected within the first nine months of 1998 using ICD-9 and CPT codes for hip and knee surgical procedures. Lower limb nerve injuries as determined by ICD-9 codes within 90 days post surgery were the main outcome measures. The influence of diabetes on the rates of nerve injuries following surgery was also examined. Results 14,979 patients underwent these surgical procedures, 10 of whom were reported to have sustained a nerve injury post surgery (0.07%). A majority (53.1%) of the sample was male and the largest age groups consisted of those aged 45–54 years (27.0%) and those aged 55–64 years (27.7%). Nerve injury occurred at a rate of 0.03% after hip arthroplasty, 0.01% following knee arthroplasty and 0.02% within three months of arthroscopic knee surgery. Overall, nerve injuries were two times more prevalent in the diabetic vs. non-diabetic population (0.11% vs. 0.06%); however, this difference did not meet conventional levels of statistical significance. Specific to knee arthroplasty, there were ten-fold differences in nerve injury rates between diabetics and non-diabetics, 0.11% vs. 0.01% respectively (p ≤ 0.01) – although the overall risks were small. Conclusion Nerve injuries following hip and knee arthroplasty, and knee arthroscopy were rare in a large population of patients younger than 65 years. Although the overall rates were low, there was an increased occurrence of nerve injuries in the diabetic population. This information is useful when counseling patients and benchmarking surgical complication rates. PMID:19620828

  3. 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

    2016-01-01

    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.

  4. 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

    2016-01-01

    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. PMID:27253193

  5. 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…

  6. 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

  7. Risk of nerve injury during arthroscopy portal placement in the elbow joint: A cadaveric study

    PubMed Central

    Chaware, Prashant N; Santoshi, John A; Pakhare, Abhijit P; Rathinam, Bertha A D

    2016-01-01

    Background: Elbow arthroscopy has become a routine procedure now. However, placing portals is fraught with dangers of injuring the neurovascular structures around elbow. There are not enough data documenting the same amongst the Indians. We aimed to determine the relative distances of nerves around the elbow to the arthroscopy portals and risk of injury in different positions of the elbow. Materials and Methods: Six standard elbow arthroscopy portals were established in 12 cadaveric upper limbs after joint distension. Then using standard dissection techniques all the nerves around the elbow were exposed, and their distances from relevant portals were measured using digital vernier caliper in 90° elbow flexion and 0° extension. Descriptive statistical analysis was used for describing distance of the nerves from relevant portal. Wilcoxon-signed rank test and Friedman's test were used for comparison. Results: There was no major nerve injury at all the portals studied in both positions of the elbow. The total incidence of cutaneous nerve injury was 8.3% (12/144); medial cutaneous nerve of forearm 10/48 and posterior cutaneous nerve of forearm 2/24. No significant changes were observed in the distance of a nerve to an individual portal at 90° flexion or 0° extension position of the elbow. Conclusion: This study demonstrates the risk of injury to different nerves at the standard portals of elbow arthroscopy. In practice, the actual incidence of nerve injury may still be lower. We conclude that elbow arthroscopy is a safe procedure when all precautions as described are duly followed. PMID:26952128

  8. 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

  9. 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

  10. 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.

  11. 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

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

    PubMed

    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.

  13. Use of multimodal intra-operative monitoring in averting nerve injury during complex hip surgery.

    PubMed

    Sutter, M; Hersche, O; Leunig, M; Guggi, T; Dvorak, J; Eggspuehler, A

    2012-02-01

    Peripheral nerve injury is an uncommon but serious complication of hip surgery that can adversely affect the outcome. Several studies have described the use of electromyography and intra-operative sensory evoked potentials for early warning of nerve injury. We assessed the results of multimodal intra-operative monitoring during complex hip surgery. We retrospectively analysed data collected between 2001 and 2010 from 69 patients who underwent complex hip surgery by a single surgeon using multimodal intra-operative monitoring from a total pool of 7894 patients who underwent hip surgery during this period. In 24 (35%) procedures the surgeon was alerted to a possible lesion to the sciatic and/or femoral nerve. Alerts were observed most frequently during peri-acetabular osteotomy. The surgeon adapted his approach based on interpretation of the neurophysiological changes. From 69 monitored surgical procedures, there was only one true positive case of post-operative nerve injury. There were no false positives or false negatives, and the remaining 68 cases were all true negative. The sensitivity for predicting post-operative nerve injury was 100% and the specificity 100%. We conclude that it is possible and appropriate to use this method during complex hip surgery and it is effective for alerting the surgeon to the possibility of nerve injury.

  14. 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

  15. 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.

  16. Use of antioxidants for the prophylaxis of cold-induced peripheral nerve injury.

    PubMed

    Teixeira, Fernanda; Pollock, Martin; Karim, Alveera; Jiang, Yuying

    2002-09-01

    "Trench foot" is a particular risk for those involved in adventure tourism, for soldiers in winter mountain training exercises, and for the homeless. Nonfreezing cold nerve injury is characterized by axonal degeneration, which is attributed to free radicals released during cycles of ischemia and reperfusion. This pilot study sought to determine whether the administration of antioxidants might prevent or ameliorate the development of cold nerve injury. Twenty-six rats were divided into two groups. Group 1 animals received, by gavage, a mixture of vitamin C (150 mg/kg/d), vitamin E (100 mg/kg/d), and N-acetyl-L-cysteine (250 mg/kg/d) daily for 4 weeks. Allopurinol (20 mg/kg/d) was added in the last 4 days of treatment. Group 2 animals served as controls and did not receive any antioxidant supplements. After 1 month, two cycles of sciatic nerve cooling (0 degrees C) were induced in 10 controls and 10 experimental animals using circulating water through a nerve cuff. Six additional control animals were subjected to surgery but did not undergo nerve cooling. All animals were killed on the third postoperative day, and their nerves were processed for ultrastructural and quantitative studies. The proportion of degenerated myelinated and unmyelinated axons showed no significant difference between treated and untreated animals. We conclude that the administration of commonly used antioxidants does not prevent cold nerve injury.

  17. 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

  18. 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.

  19. 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

  20. Exogenous tissue plasminogen activator enhances peripheral nerve regeneration and functional recovery after injury in mice.

    PubMed

    Zou, Tie; Ling, Changchun; Xiao, Yao; Tao, Xianmei; Ma, Duan; Chen, Zu-Lin; Strickland, Sidney; Song, Houyan

    2006-01-01

    Tissue plasminogen activator (tPA) is an essential component of the proteolytic cascade that lyses blood clots. Various studies also suggest that tPA plays important roles in the nervous system. We show that exogenous tPA or tPA/plasminogen (plg) promotes axonal regeneration, remyelination, and functional recovery after sciatic nerve injury in the mouse. Local application of tPA or tPA/plg 7 days after sciatic nerve crush significantly increased the total number of axons and myelinated axons, which is accompanied by enhanced expression of neurofilament. Treatment with tPA or tPA/plg reduced the deposition of fibrin(ogen) after nerve injury. Moreover, tPA or tPA/plg increased the number of macrophages and induced MMP-9 expression at the injury site, coincident with reduced collagen scar formation and accelerated clearance of myelin and lipid debris after treatment. Consequently, tPA or tPA/plg treatment protected muscles from atrophy after nerve injury, indicating better functional recovery. These results suggest that administration of exogenous tPA or tPA/plg promotes axonal regeneration and remyelination through removal of fibrin deposition and activation of MMP-9-positive macrophages, which may be responsible for myelin debris clearance and preventing collagen scar formation. Therefore, tPA may be useful for treatment of peripheral nerve injury.

  1. 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

  2. Effects of acute selective pudendal nerve electrical stimulation after simulated childbirth injury

    PubMed Central

    Gill, Bradley C.; Dissaranan, Charuspong; Zutshi, Massarat; Balog, Brian M.; Lin, Danli; Damaser, Margot S.

    2013-01-01

    During childbirth, a combinatorial injury occurs and can result in stress urinary incontinence (SUI). Simulated childbirth injury, consisting of vaginal distension (VD) and pudendal nerve crush (PNC), results in slowed recovery of continence, as well as decreased expression of brain-derived neurotrophic factor (BDNF), a regenerative cytokine. Electrical stimulation has been shown to upregulate BDNF in motor neurons and facilitate axon regrowth through the increase of βII-tubulin expression after injury. In this study, female rats underwent selective pudendal nerve motor branch (PNMB) stimulation after simulated childbirth injury or sham injury to determine whether such stimulation affects bladder and anal function after injury and whether the stimulation increases BDNF expression in Onuf's nucleus after injury. Rats received 4 h of VD followed by bilateral PNC and 1 h of subthreshold electrical stimulation of the left PNMB and sham stimulation of the right PNMB. Rats underwent filling cystometry and anal pressure recording before, during, and after the stimulation. Bladder and anal contractile function were partially disrupted after injury. PNMB stimulation temporarily inhibited bladder contraction after injury. Two days and 1 wk after injury, BDNF expression in Onuf's nucleus of the stimulated side was significantly increased compared with the sham-stimulated side, whereas βII-tubulin expression in Onuf's nucleus of the stimulated side was significantly increased only 1 wk after injury. Acute electrical stimulation of the pudendal nerve proximal to the crush site upregulates BDNF and βII-tubulin in Onuf's nucleus after simulated childbirth injury, which could be a potential preventive option for SUI after childbirth injury. PMID:23152293

  3. Preoperative evaluation of peripheral nerve injuries: What is the place for ultrasound?

    PubMed

    Toia, Francesca; Gagliardo, Andrea; D'Arpa, Salvatore; Gagliardo, Cesare; Gagliardo, Giuseppe; Cordova, Adriana

    2016-09-01

    OBJECTIVE The purpose of this study was to evaluate the usefulness of ultrasound in the preoperative workup of peripheral nerve lesions and illustrate how nerve ultrasonography can be integrated in routine clinical and neurophysiological evaluation and in the management of focal peripheral nerve injuries. The diagnostic role and therapeutic implications of ultrasonography for different neuropathies are described. METHODS The authors analyzed the use of ultrasound in 119 entrapment, tumoral, posttraumatic, or postsurgical nerve injuries of limbs evaluated in 108 patients during 2013 and 2014. All patients were candidates for surgery, and in all cases the evaluation included clinical examination, electrodiagnostic studies (nerve conduction study and electromyography), and ultrasound nerve study. Ultrasound was used to explore the nerve fascicular echotexture, continuity, and surrounding tissues. The maximum cross-sectional area (CSA) and the presence of epineurial hyperechogenicity or intraneural hyper- or hypoechogenicity, of anatomical anomalies, dynamic nerve dislocations, or compressions were recorded. The concordance rate of neurophysiological and ultrasonographic data was analyzed, classifying ultrasound findings as confirming, contributive, or nonconfirming with respect to electrodiagnostic data. The correlation between maximum nerve CSA and neurophysiological severity degree in entrapment syndromes was statistically analyzed. RESULTS Ultrasonography confirmed electrodiagnostic findings in 36.1% of cases and showed a contributive role in the diagnosis and surgical planning in 53.8% of all cases; the findings were negative ("nonconfirming") in only 10.1% of the patients. In 16% of cases, ultrasound was not only contributive, but had a key diagnostic role in the presence of doubtful electrodiagnostic findings. The contributive role differed according to etiology, being higher for tumors (100%) and for posttraumatic or postsurgical neuropathies (72.2%) than for

  4. [Therapeutic failures in indirect injuries to the optic nerve].

    PubMed

    Segal, N; Spineanu, L; Drăgan, I; Coroiu, M

    1993-01-01

    Making an analysis during five years, the authors find a great number of atrophies of optic nerve after indirect trauma on the orbital area or an the head, questioning if the treatment applied had been correct. Studying the literature they find the same feeble results and controversial opinions regarding the therapy of these cases. On tried treatments with macrodoses of dexamethazone i.v., the opening of optic nerve's health or of the optic nerve's duct, the vacating of the retrobulbar haematomas, but the results remained unsatisfying. The problem is if we must console ourselves that the others have the same feeble results or we must try to add to the conservatory treatment applied till now the neurosurgical investigations of the optic duct and heaths of the optic nerve, especially when the vision is lowering progressively and especially when the other eye is also implied.

  5. 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. PMID:18390241

  6. Rac1-regulated dendritic spine remodeling contributes to neuropathic pain after peripheral nerve injury.

    PubMed

    Tan, Andrew M; Chang, Yu-Wen; Zhao, Peng; Hains, Bryan C; Waxman, Stephen G

    2011-12-01

    Although prior studies have implicated maladaptive remodeling of dendritic spines on wide-dynamic range dorsal horn neurons as a contributor to pain after spinal cord injury, there have been no studies on dendritic spines after peripheral nerve injury. To determine whether dendritic spine remodeling contributes to neuronal hyperexcitability and neuropathic pain after peripheral nerve injury, we analyzed dendritic spine morphology and functional influence in lamina IV-V dorsal horn neurons after sham, chronic constriction injury (CCI) of the sciatic nerve, and CCI treatment with NSC23766, a selective inhibitor of Rac1, which has been implicated in dendritic spine development. 10 days after CCI, spine density increased with mature, mushroom-shaped spines preferentially distributed along dendritic branch regions closer to the cell body. Because spine morphology is strongly correlated with synaptic function and transmission, we recorded the response of single units to innocuous and noxious peripheral stimuli and performed behavioral assays for tactile allodynia and thermal hyperalgesia. Wide dynamic range dorsal horn neurons of CCI animals exhibited hyperexcitable responses to a range of stimuli. They also showed reduced nociceptive thresholds in the ipsilateral hind paw. 3-day treatment with NSC23766 significantly reduced post-CCI spine dimensions and densities, and attenuated injury-induced hyperexcitability. Drug treatment reduced behavioral measures of tactile allodynia, but not for thermal hyperalgesia. Together, our results demonstrate that peripheral nerve injury induces Rac1-regulated remodeling of dendritic spines on dorsal horn neurons, and suggest that this spine remodeling contributes to neuropathic pain.

  7. [Iatrogenic injuries of the facial nerve in the mastoid region].

    PubMed

    Príhodová, J; Zelený, M; Kozák, J

    1990-09-01

    During the past ten years nine patients were referred to our hospital with lesions of the VIIth nerve. These lesions were inflicted during operation on account of chronic otitis media. One patient recovered after conservative treatment. Based on the EMG examination and clinical picture, eight patients were operated. In one who had an extensive lesion it did not prove possible to find the proximal stump and the patient improved after Normann-Dott's operation. In the remaining seven subjects also severe damage was involved: five times complete severing of the nerve occurred, twice partial severing and contusion, always in the mastoid portion of the VIIth nerve. The authors achieved as a rule a 50-75% restoration of function of the VIIth nerve Ballance-Duel's operation, using a graft of the n. suralis with microsuture of the epineurium and gluing of the nerve by plasma. Evaluation of late functional results was made 1-8 years after Ballance-Duel's operation. The authors recommend to reduce the risk of iatrogenic lesions of the VIIth nerve in beginners by assistance of experienced surgeons at several operations. PMID:2225170

  8. 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.

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

    PubMed Central

    Liu, Guangyao; Jiang, Rui; Jin, Yan

    2014-01-01

    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. PMID:25374595

  10. Signals regulating myelination in peripheral nerves and the Schwann cell response to injury

    PubMed Central

    Glenn, Thomas D.; Talbot, William S.

    2013-01-01

    In peripheral nerves, Schwann cells form myelin, which facilitates the rapid conduction of action potentials along axons in the vertebrate nervous system. Myelinating Schwann cells are derived from neural crest progenitors in a step-wise process that is regulated by extracellular signals and transcription factors. In addition to forming the myelin sheath, Schwann cells orchestrate much of the regenerative response that occurs after injury to peripheral nerves. In response to injury, myelinating Schwann cells dedifferentiate into repair cells that are essential for axonal regeneration, and then redifferentiate into myelinating Schwann cells to restore nerve function. Although this remarkable plasticity has long been recognized, many questions remain unanswered regarding the signaling pathways regulating both myelination and the Schwann cell response to injury. PMID:23896313

  11. Morphology and Nanomechanics of Sensory Neurons Growth Cones following Peripheral Nerve Injury

    PubMed Central

    Szabo, Vivien; Végh, Attila-Gergely; Lucas, Olivier; Cloitre, Thierry; Scamps, Frédérique; Gergely, Csilla

    2013-01-01

    A prior peripheral nerve injury in vivo, promotes a rapid elongated mode of sensory neurons neurite regrowth in vitro. This in vitro model of conditioned axotomy allows analysis of the cellular and molecular mechanisms leading to an improved neurite re-growth. Our differential interference contrast microscopy and immunocytochemistry results show that conditioned axotomy, induced by sciatic nerve injury, did not increase somatic size of adult lumbar sensory neurons from mice dorsal root ganglia sensory neurons but promoted the appearance of larger neurites and growth cones. Using atomic force microscopy on live neurons, we investigated whether membrane mechanical properties of growth cones of axotomized neurons were modified following sciatic nerve injury. Our data revealed that neurons having a regenerative growth were characterized by softer growth cones, compared to control neurons. The increase of the growth cone membrane elasticity suggests a modification in the ratio and the inner framework of the main structural proteins. PMID:23418549

  12. 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

  13. Blunt cavernous nerve injury: A new animal model mimicking postradical prostatectomy neurogenic impotence.

    PubMed

    Karakiewicz, P I; Bazinet, M; Zvara, P; Begin, L R; Brock, G B

    1996-01-01

    Our goal was to develop an animal model of cavernous nerve injury similar to that encountered among patients having undergone a successful nerve sparing radical prostatectomy and to compare patterns of nicotinamide adenine dinucleotide phosphate (NADPH)-diaphorase staining to quality of erections using the newly developed model. We studied 50 mature Sprague Dawley rats, which were divided into five equal groups. Animals were either observed (sham), underwent an exploratory laparotomy, underwent moderate or severe percussive injury to both cavernous nerves, or underwent ablation of both cavernous nerves. Between 28 and 30 days later, all animals underwent electrostimulation and simultaneous recording of intracavernosal pressure. After sacrifice, penes were harvested and penile tissue NADPH-diaphorase staining pattern was assessed. Severity of cavernous nerve percussive injury and NADPH-diaphorase staining patterns correlated with the quality of recorded erections. This model is a useful experimental tool for research in the field of erectile dysfunction such as is encountered following a successful nerve sparing radical prostatectomy. Penile biopsy assessing NADPH-diaphorase staining may potentially prove to be a useful minimally-invasive diagnostic modality quantifying neurogenic erectile function among patients following radical prostatectomy. PMID:21224162

  14. The effect of memantine on functional recovery of the facial nerve after crush injury.

    PubMed

    Topdag, Murat; Topdag, Deniz Ozlem; Ila, Kadri; Muezzinoglu, Bahar; Yaprak, Busra; Ozturk, Murat; Caliskan, Sebla; Iseri, Mete

    2015-02-01

    The objective of this study is to establish whether memantine is an alternative and effective treatment on facial nerve recovery after crush injury, and also to analyze the effective doses of this promising agent. This is a randomized controlled animal study. 40 rats underwent crush injury to left main trunk of the facial nerve, and divided into 4 groups; (1) control (saline treated), (2) 5-mg/kg memantine, (3) 10-mg/kg memantine, and (4) 20-mg/kg memantine group. Facial nerve functions were evaluated by eye reflex, and whisker movement compared to the unaffected side. They were scored on a 3-point scale. On day 28, the rats were sacrificed, and the facial nerves were dissected. The paraffin sections were studied with caspase-3 immunostaining. According to statistical data, the recovery in Group 4 began significantly earlier than the other groups on the basis of restoring eye blink reflexes and whisker movement. Groups 2 and 3 showed faster recovery than Group 1 on the basis of whisker movement. The caspase-3 positive staining was rarely detected in all groups. The Kruskal–Wallis test revealed that Group 4 showed fewer apoptotic cells than other groups; this was statistically significant. However, the Mann–Whitney U test with the Bonferroni correction did not reveal any significant difference between the groups. In conclusion, this study revealed that memantine acted to restore facial nerve functions, and accelerate recovery after facial nerve injury by inhibiting apoptosis.

  15. 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.

  16. Laryngeal Adductor Function in Experimental Models of Recurrent Laryngeal Nerve Injury

    PubMed Central

    Paniello, Randal C.; Rich, Jason T.; Debnath, Nick L.

    2014-01-01

    Objectives/Hypothesis Most patients with unilateral vocal fold paralysis experience some degree of spontaneous reinnervation, which depends upon the type and severity of recurrent laryngeal nerve (RLN) injury. After partial recovery, the paretic vocal fold may or may not adduct adequately to allow glottic closure, which in turn affects phonatory and swallowing outcomes. This process was studied in a series of canine laryngeal nerve injury models. Study Design Animal (canine) experiments. Methods Maximum stimulable laryngeal adductor pressure (LAP) was measured pre-treatment (baseline) and at 6 months following experimental RLN injuries (total n=59). The 9 study groups were designed to simulate a range of severities of RLN injury. Results The greatest LAP recovery, at 108% of original baseline, was seen in a 50% transection model; the least recovery was seen when the RLN underwent complete transection with repair, at 56% with precise alignment and 50% with alignment reversed. Intermediate models (partial RLN injuries) gave intermediate results. Crush models recovered 105% of LAP, while a half-transection, half-crush injury recovered 72% and cautery injuries recovered 61%. Controls (complete transection without repair) had no measurable recovery. Conclusions The injured RLN has a strong tendency to recover. Restoration of adductor strength, as determined by the LAP, was predictably related to the severity of RLN injury. The model RLN injuries studied provide a range of expected outcomes that can be used for future experiments exploring interventions that may improve post-injury adductor function. PMID:25283381

  17. Ectopic Muscle Expression of Neurotrophic Factors Improves Recovery After Nerve Injury.

    PubMed

    Glat, Micaela Johanna; Benninger, Felix; Barhum, Yael; Ben-Zur, Tali; Kogan, Elena; Steiner, Israel; Yaffe, David; Offen, Daniel

    2016-01-01

    Sciatic nerve damage is a common medical problem. The main causes include direct trauma, prolonged external nerve compression, and pressure from disk herniation. Possible complications include leg numbness and the loss of motor control. In mild cases, conservative treatment is feasible. However, following severe injury, recovery may not be possible. Neuronal regeneration, survival, and maintenance can be achieved by neurotrophic factors (NTFs). In this study, we examined the potency of combining brain-derived neurotrophic factor (BDNF), glial-derived neurotrophic factor (GDNF), vascular endothelial growth factor (VEGF), and insulin-like growth factor-1 (IGF-1) on the recovery of motor neuron function after crush injury of the sciatic nerve. We show that combined NTF application increases the survival of motor neurons exposed to a hypoxic environment. The ectopic expression of NTFs in the injured muscle improves the recovery of the sciatic nerve after crush injury. A significantly faster recovery of compound muscle action potential (CMAP) amplitude and conduction velocity is observed after muscle injections of viral vectors expressing a mixture of the four NTF genes. Our findings suggest a rationale for using genetic treatment with a combination of NTF-expressing vectors, as a potential therapeutic approach for severe peripheral nerve injury. PMID:26385386

  18. Sciatic nerve injury: a simple and subtle model for investigating many aspects of nervous system damage and recovery.

    PubMed

    Savastano, Luis E; Laurito, Sergio R; Fitt, Marcos R; Rasmussen, Jorge A; Gonzalez Polo, Virginia; Patterson, Sean I

    2014-04-30

    Sciatic nerve injury has been used for over a century to investigate the process of nerve damage, to assess the absolute and relative capacity of the central and peripheral nervous systems to recover after axotomy, and to understand the development of chronic pain in many pathologies. Here we provide a historical review of the contributions of this experimental model to our current understanding of fundamental questions in the neurosciences, and an assessment of its continuing capacity to address these and future problems. We describe the different degrees of nerve injury - neurapraxia, axonotmesis, neurotmesis - together with the consequences of selective damage to the different functional and anatomic components of this nerve. The varied techniques used to model different degrees of nerve injury and their relationship to the development of neuropathic pain states are considered. We also provide a detailed anatomical description of the sciatic nerve from the spinal cord to the peripheral branches in the leg. A standardized protocol for carrying out sciatic nerve axotomy is proposed, with guides to assist in the accurate and reliable dissection of the peripheral and central branches of the nerve. Functional, histological, and biochemical criteria for the validation of the injury are described. Thus, this paper provides a review of the principal features of sciatic nerve injury, presents detailed neuroanatomical descriptions of the rat's inferior limb and spine, compares different modes of injury, offers material for training purposes, and summarizes the immediate and longterm consequences of damage to the sciatic nerve.

  19. Sciatic nerve injury: a simple and subtle model for investigating many aspects of nervous system damage and recovery.

    PubMed

    Savastano, Luis E; Laurito, Sergio R; Fitt, Marcos R; Rasmussen, Jorge A; Gonzalez Polo, Virginia; Patterson, Sean I

    2014-04-30

    Sciatic nerve injury has been used for over a century to investigate the process of nerve damage, to assess the absolute and relative capacity of the central and peripheral nervous systems to recover after axotomy, and to understand the development of chronic pain in many pathologies. Here we provide a historical review of the contributions of this experimental model to our current understanding of fundamental questions in the neurosciences, and an assessment of its continuing capacity to address these and future problems. We describe the different degrees of nerve injury - neurapraxia, axonotmesis, neurotmesis - together with the consequences of selective damage to the different functional and anatomic components of this nerve. The varied techniques used to model different degrees of nerve injury and their relationship to the development of neuropathic pain states are considered. We also provide a detailed anatomical description of the sciatic nerve from the spinal cord to the peripheral branches in the leg. A standardized protocol for carrying out sciatic nerve axotomy is proposed, with guides to assist in the accurate and reliable dissection of the peripheral and central branches of the nerve. Functional, histological, and biochemical criteria for the validation of the injury are described. Thus, this paper provides a review of the principal features of sciatic nerve injury, presents detailed neuroanatomical descriptions of the rat's inferior limb and spine, compares different modes of injury, offers material for training purposes, and summarizes the immediate and longterm consequences of damage to the sciatic nerve. PMID:24487015

  20. 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

  1. 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.

  2. 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.

  3. Role of thermography in the assessment of infraorbital nerve injury after malar fractures.

    PubMed

    McGimpsey, J G; Vaidya, A; Biagioni, P A; Lamey, P J

    2000-12-01

    We studied 45 patients with malar fractures who had some degree of infraorbital nerve deficit. Thermographic facial images failed to show any substantial changes in the temperature profiles of the affected and the normal control sides in relation to reco very of their facial sensation. Although some patients who had thermography on the day of injury showed significant temperature differences between the affected and the normal sides, these differences were probably the result of the acute inflammatory ch anges caused by the injury. We suggest that infrared thermography has little place in the assessment of infraorbital nerve deficits. PMID:11092769

  4. Non-invasive neuromagnetic monitoring of nerve and muscle injury currents.

    PubMed

    Curio, G; Erné, S N; Burghoff, M; Wolff, K D; Pilz, A

    1993-06-01

    Structural damage inflicted on membranes of excitable cells may evoke quasi-DC injury currents driven by the transmembrane resting potential gradient. In contrast to the usually invasive electrophysiological approaches, superconducting quantum interference devices (SQUIDs) measure the concomitant weak biomagnetic fields non-invasively as is shown here for acutely excised rat nerves or muscles. Analysis of the field distributions showed slowly decaying equivalent current dipole moments in the nanoampmeter range as generated by microamp nerve injury currents extending intra-axonally over millimeter distances. The geometric and kinetic parameters of this experimental design may allow in vivo recordings in human patients.

  5. Optic Nerve Injury in a Patient with Chronic Allergic Conjunctivitis

    PubMed Central

    Hazin, Ribhi; Elia, Christopher J.; Putruss, Maria; Bazzi, Amanda

    2014-01-01

    Manipulation of the optic nerve can lead to irreversible vision changes. We present a patient with a past medical history of skin allergy and allergic conjunctivitis (AC) who presented with insidious unexplained unilateral vision loss. Physical exam revealed significant blepharospasm, mild lid edema, bulbar conjunctival hyperemia, afferent pupillary defect, and slight papillary hypertrophy. Slit lamp examination demonstrated superior and inferior conjunctival scarring as well as superior corneal scarring but no signs of external trauma or neurological damage were noted. Conjunctival cultures and cytologic evaluation demonstrated significant eosinophilic infiltration. Subsequent ophthalmoscopic examination revealed optic nerve atrophy. Upon further questioning, the patient admitted to vigorous itching of the affected eye for many months. Given the presenting symptoms, history, and negative ophthalmological workup, it was determined that the optic nerve atrophy was likely secondary to digital pressure from vigorous itching. Although AC can be a significant source of decreased vision via corneal ulceration, no reported cases have ever described AC-induced vision loss of this degree from vigorous itching and chronic pressure leading to optic nerve damage. Despite being self-limiting in nature, allergic conjunctivitis should be properly managed as extreme cases can result in mechanical compression of the optic nerve and compromise vision. PMID:25317346

  6. 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.

  7. 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

  8. Magnetometry of injury currents from human nerve and muscle specimens using superconducting quantum interferences devices.

    PubMed

    Mackert, B M; Mackert, J; Wübbeler, G; Armbrust, F; Wolff, K D; Burghoff, M; Trahms, L; Curio, G

    1999-03-12

    Acute lesions of polarized membranes lead to slowly decaying ('near-DC') injury currents driven by the transmembrane resting potential gradient. Here we report the first recordings of injury-related near-DC magnetic fields from human nerve and muscle specimens in vitro using Superconducting Quantum Interference Devices (SQUIDs) operated in a conventional magnetically shielded room in a clinical environment. The specimen position was modulated sinusoidally beneath the sensor array by a non-magnetically fabricated scissors lift to improve the signal-to-noise ratio for near-DC fields. Depending on the specimen geometry the field patterns showed dipolar or quadrupolar aspects. The slow decay of human nerve and muscle injury currents was monitored for several hours from a distance of a few centimeters. Thus DC-magnetometry provides a sensitivity which might allow the remote detection of injury currents also in vivo.

  9. Glutamate transporter dysfunction associated with nerve injury-induced pain in mice.

    PubMed

    Napier, Ian A; Mohammadi, Sarasa A; Christie, MacDonald J

    2012-01-01

    Dysfunction at glutamatergic synapses has been proposed as a mechanism in the development of neuropathic pain. Here we sought to determine whether peripheral nerve injury-induced neuropathic pain results in functional changes to primary afferent synapses. Signs of neuropathic pain as well as an induction of glial fibrillary acidic protein in immunostained spinal cord sections 4 days after partial ligation of the sciatic nerve indicated the induction of neuropathic pain. We found that following nerve injury, no discernable change to kinetics of dl-α-amino-3-hydroxy-5-methylisoxazole-propionic acid (AMPA) or N-methyl-d-aspartate receptor (NMDAR)-mediated evoked excitatory postsynaptic currents (eEPSCs) could be observed in dorsal horn (lamina I/II) neurons compared with those of naïve mice. However, we did find that nerve injury was accompanied by slowed decay of the early phase of eEPSCs in the presence of glutamate transporter inhibition by the competitive nontransportable inhibitor dl-threo-β-benzyloxyaspartic acid (TBOA). Concomitantly, expression patterns for the two major glutamate transporters in the spinal cord, excitatory amino acid transporters (EAAT) 1 and EAAT2, were found to be reduced at this time (4 days postinjury). We then sought to directly determine whether nerve injury results in glutamate spillover to NMDARs at dorsal horn synapses. By employing the use-dependent NMDAR blocker (±)MK-801 to block subsynaptic receptors, we found that although TBOA-induced spillover to extrasynaptic receptors trended to increased activation of these receptors after nerve injury, this was not significant compared with naïve mice. Together, these results suggest the development of neuropathic pain involves subtle changes to glutamate transporter expression and function that could contribute to neuropathic pain during excessive synaptic activity. PMID:22072505

  10. Bilateral common peroneal nerve injury after pediatric cardiothoracic surgery: A case report and review of the literature

    PubMed Central

    Setty, G.; Saleem, R.; Harijan, P.; Khan, A.; Hussain, N.

    2014-01-01

    Nerve injuries after thoracic and cardiovascular surgery have been reported but generally concern the brachial plexus, phrenic nerve, recurrent laryngeal, and facial nerve. Common peroneal nerve injury (CPNI) following cardiopulmonary bypass has been reported in adults (4); however bilateral injury is extremely uncommon. Age, low body weight, co-morbidities such as peripheral arteriosclerotic disease, diabetes mellitus, and arrhythmias were associated with CPNI following cardiothoracic surgery in adults. Common peroneal nerve injury (CPNI) following cardiopulmonary by-pass has been reported in adults; however, bilateral injury is extremely uncommon. The superficial course of CPN makes it vulnerable to traction or compression. We report a 5-year-old girl manifesting with bilateral CPNI following prolonged cardiopulmonary by-pass. To the best of our knowledge, she is the first pediatric patient presenting with bilateral CPNI following cardiothoracic surgery and cardiopulmonary by-pass. PMID:25624938

  11. Lingual nerve injury following use of a supraglottic airway device.

    PubMed

    Jenkinson, Andrew; Crosher, Richard; Mohammed-Ali, Ricardo; Parsons, Kirsty

    2014-03-01

    We present the case of a 64-year-old woman who lost sensation on the left side of her tongue after an orthopaedic procedure under general anaesthetic. It provides evidence that anaesthetic airway devices can injure the lingual nerve. PMID:24332877

  12. Nimodipine-mediated re-myelination after facial nerve crush injury in rats.

    PubMed

    Tang, Yin-da; Zheng, Xue-sheng; Ying, Ting-ting; Yuan, Yan; Li, Shi-ting

    2015-10-01

    This study aimed to investigate the mechanism of nimodipine-mediated neural repair after facial nerve crush injury in rats. Adult Sprague-Dawley rats were divided into three groups: healthy controls, surgery alone, and surgery plus nimodipine. A facial nerve crush injury model was constructed. Immediately after surgery, the rats in the surgery plus nimodipine group were administered nimodipine, 6 mg/kg/day, for a variable numbers of days. The animals underwent electromyography (EMG) before surgery and at 3, 10, or 20 days after surgery. After sacrifice, nerve samples were stained with hematoxylin and eosin (H&E) and luxol fast blue. The EMG at 20 days revealed an apparent recovery of eletroconductivity, with the surgery plus nimodipine group having a higher amplitude and shorter latency time than the surgery only group. H&E staining showed that at 20 days, the rats treated with nimodipine had an obvious recovery of myelination and reduction in the number of infiltrating cells, suggesting less inflammation, compared with the rats in the surgery only group. Luxol fast blue staining was relatively even in the surgery plus nimodipine group, indicating a protective effect against injury-induced demyelination. Staining for S100 calcium-binding protein B (S-100β) was not evident in the surgery alone group, but was evident in the surgery plus nimodipine group, indicating that nimodipine reversed the damage of the crush injury. After a facial nerve crush injury, treatment with nimodipine for 20 days reduced the nerve injury by mediating remyelination by Schwann cells. The protective effect of nimodipine may include a reduction of inflammation and an increase in calcium-binding S-100β protein. PMID:26169537

  13. Nimodipine-mediated re-myelination after facial nerve crush injury in rats.

    PubMed

    Tang, Yin-da; Zheng, Xue-sheng; Ying, Ting-ting; Yuan, Yan; Li, Shi-ting

    2015-10-01

    This study aimed to investigate the mechanism of nimodipine-mediated neural repair after facial nerve crush injury in rats. Adult Sprague-Dawley rats were divided into three groups: healthy controls, surgery alone, and surgery plus nimodipine. A facial nerve crush injury model was constructed. Immediately after surgery, the rats in the surgery plus nimodipine group were administered nimodipine, 6 mg/kg/day, for a variable numbers of days. The animals underwent electromyography (EMG) before surgery and at 3, 10, or 20 days after surgery. After sacrifice, nerve samples were stained with hematoxylin and eosin (H&E) and luxol fast blue. The EMG at 20 days revealed an apparent recovery of eletroconductivity, with the surgery plus nimodipine group having a higher amplitude and shorter latency time than the surgery only group. H&E staining showed that at 20 days, the rats treated with nimodipine had an obvious recovery of myelination and reduction in the number of infiltrating cells, suggesting less inflammation, compared with the rats in the surgery only group. Luxol fast blue staining was relatively even in the surgery plus nimodipine group, indicating a protective effect against injury-induced demyelination. Staining for S100 calcium-binding protein B (S-100β) was not evident in the surgery alone group, but was evident in the surgery plus nimodipine group, indicating that nimodipine reversed the damage of the crush injury. After a facial nerve crush injury, treatment with nimodipine for 20 days reduced the nerve injury by mediating remyelination by Schwann cells. The protective effect of nimodipine may include a reduction of inflammation and an increase in calcium-binding S-100β protein.

  14. Supplementary motor area deactivation impacts the recovery of hand function from severe peripheral nerve injury.

    PubMed

    Lu, Ye-Chen; Liu, Han-Qiu; Hua, Xu-Yun; Shen, Yun-Dong; Xu, Wen-Dong; Xu, Jian-Guang; Gu, Yu-Dong

    2016-04-01

    Although some patients have successful peripheral nerve regeneration, a poor recovery of hand function often occurs after peripheral nerve injury. It is believed that the capability of brain plasticity is crucial for the recovery of hand function. The supplementary motor area may play a key role in brain remodeling after peripheral nerve injury. In this study, we explored the activation mode of the supplementary motor area during a motor imagery task. We investigated the plasticity of the central nervous system after brachial plexus injury, using the motor imagery task. Results from functional magnetic resonance imaging showed that after brachial plexus injury, the motor imagery task for the affected limbs of the patients triggered no obvious activation of bilateral supplementary motor areas. This result indicates that it is difficult to excite the supplementary motor areas of brachial plexus injury patients during a motor imagery task, thereby impacting brain remodeling. Deactivation of the supplementary motor area is likely to be a serious problem for brachial plexus injury patients in terms of preparing, initiating and executing certain movements, which may be partly responsible for the unsatisfactory clinical recovery of hand function. PMID:27212933

  15. Exogenous Neuritin Promotes Nerve Regeneration After Acute Spinal Cord Injury in Rats.

    PubMed

    Gao, Rui; Li, Xingyi; Xi, Shaosong; Wang, Haiyan; Zhang, Hong; Zhu, Jingling; Shan, Liya; Song, Xiaoming; Luo, Xing; Yang, Lei; Huang, Jin

    2016-07-01

    Insufficient local levels of neurotrophic factor after spinal cord injury (SCI) are the leading cause of secondary injury and limited axonal regeneration. Neuritin belongs to a family of neurotrophic factors that promote neurite outgrowth, maintain neuronal survival, and provide a favorable microenvironment for the regeneration and repair of nerve cells after injury. However, it is not known whether the exogenously applied neuritin protein has a positive effect on nerve repair after SCI. This was investigated in the present study using purified human recombinant neuritin expressed in and purified from Pichia pastoris, which was tested in a rat SCI model. A recombinant neuritin concentration of 60 μg/ml induced the recovery of hind limb motor function and stimulated nerve regeneration in rats with SCI. Continuous administration of neuritin at this dose at an early stage after SCI inhibited poly ADP ribose polymerase (PARP) protein degradation and decreased neuronal apoptosis. In addition, during the critical postinjury period of axonal regeneration, exogenous neuritin treatment increased the expression of neurofilament 200 and growth-associated protein 43 in the damaged tissue, which was associated with the restoration of hind limb movement. These results suggest that neuritin creates an environment that promotes nerve cell survival and neurite regeneration after SCI, which contribute to nerve regeneration and the recovery of motor function. PMID:27009445

  16. Accessory parotid gland tumors

    PubMed Central

    Ramachar, Sreevathsa M.; Huliyappa, Harsha A.

    2012-01-01

    Tumors of accessory parotid gland are considered in the differential diagnosis of a mid cheek mass. Parotidectomy is the procedure of choice. All pathological types of parotid main gland tumors occur in the accessory parotid gland also. Presenting as a mid cheek or infrazygomatic mass, the tumors of this accessory parotid gland are notorious for recurrences, if adequate margins are not achieved. We describe two such cases of such a tumor. 40-year-old male with a slowly progressive mid cheek mass was operated by a mid cheek incision. Histopathology of the tumor was pleomorphic adenoma. Facial nerve paresis recovered complelety in 6 months. A 52-year-old female with progressive mid cheek mass who underwent parotidectomy and neck dissection by a modified Blair's incision was diagnosed with extranodal marginal zone lymphoma with focal transformation to a diffuse large B-cell lymphoma. Chemotherapy with CHOP regime was initiated. There was no recurrence at 6 months of follow-up. Lymphoma of accessory parotid gland is a very rare tumor. Standard parotidectomy incision is advocated to prevent damage to facial nerve branches. PMID:23483721

  17. [Progress in the effects of injury and regeneration of gustatory nerves on the taste functions in animals].

    PubMed

    Fan, Yuan-Yuan; Yu, Dong-Ming; Shi, Yu-Juan; Yan, Jian-Qun; Jiang, En-She

    2014-10-25

    The sensor of the taste is the taste bud. The signals originated from the taste buds are transmitted to the central nervous system through the gustatory taste nerves. The chorda tympani nerve (innervating the taste buds of the anterior tongue) and glossopharyngeal nerve (innervating the taste buds of the posterior tongue) are the two primary gustatory nerves. The injuries of gustatory nerves cause their innervating taste buds atrophy, degenerate and disappear. The related taste function is also impaired. The impaired taste function can be restored after the gustatory nerves regeneration. The rat model of cross-regeneration of gustatory nerves is an important platform for research in the plasticity of the central nervous system. The animal behavioral responses and the electrophysiological properties of the gustatory nerves have changed a lot after the cross-regeneration of the gustatory nerves. The effects of the injury, regeneration and cross-regeneration of the gustatory nerves on the taste function in the animals will be discussed in this review. The prospective studies on the animal model of cross-regeneration of gustatory nerves are also discussed in this review. The study on the injury, regeneration and cross-regeneration of the gustatory nerves not only benefits the understanding of mechanism for neural plasticity in gustatory nervous system, but also will provide theoretical basis and new ideas for seeking methods and techniques to cure dysgeusia.

  18. New Treatments for Spinal Nerve Root Avulsion Injury.

    PubMed

    Carlstedt, Thomas

    2016-01-01

    Further progress in the treatment of the longitudinal spinal cord injury has been made. In an inverted translational study, it has been demonstrated that return of sensory function can be achieved by bypassing the avulsed dorsal root ganglion neurons. Dendritic growth from spinal cord sensory neurons could replace dorsal root ganglion axons and re-establish a reflex arch. Another research avenue has led to the development of adjuvant therapy for regeneration following dorsal root to spinal cord implantation in root avulsion injury. A small, lipophilic molecule that can be given orally acts on the retinoic acid receptor system as an agonist. Upregulation of dorsal root ganglion regenerative ability and organization of glia reaction to injury were demonstrated in treated animals. The dual effect of this substance may open new avenues for the treatment of root avulsion and spinal cord injuries. PMID:27602018

  19. New Treatments for Spinal Nerve Root Avulsion Injury

    PubMed Central

    Carlstedt, Thomas

    2016-01-01

    Further progress in the treatment of the longitudinal spinal cord injury has been made. In an inverted translational study, it has been demonstrated that return of sensory function can be achieved by bypassing the avulsed dorsal root ganglion neurons. Dendritic growth from spinal cord sensory neurons could replace dorsal root ganglion axons and re-establish a reflex arch. Another research avenue has led to the development of adjuvant therapy for regeneration following dorsal root to spinal cord implantation in root avulsion injury. A small, lipophilic molecule that can be given orally acts on the retinoic acid receptor system as an agonist. Upregulation of dorsal root ganglion regenerative ability and organization of glia reaction to injury were demonstrated in treated animals. The dual effect of this substance may open new avenues for the treatment of root avulsion and spinal cord injuries. PMID:27602018

  20. New Treatments for Spinal Nerve Root Avulsion Injury

    PubMed Central

    Carlstedt, Thomas

    2016-01-01

    Further progress in the treatment of the longitudinal spinal cord injury has been made. In an inverted translational study, it has been demonstrated that return of sensory function can be achieved by bypassing the avulsed dorsal root ganglion neurons. Dendritic growth from spinal cord sensory neurons could replace dorsal root ganglion axons and re-establish a reflex arch. Another research avenue has led to the development of adjuvant therapy for regeneration following dorsal root to spinal cord implantation in root avulsion injury. A small, lipophilic molecule that can be given orally acts on the retinoic acid receptor system as an agonist. Upregulation of dorsal root ganglion regenerative ability and organization of glia reaction to injury were demonstrated in treated animals. The dual effect of this substance may open new avenues for the treatment of root avulsion and spinal cord injuries.

  1. The utility of ultrasound in the assessment of traumatic peripheral nerve lesions: report of 4 cases.

    PubMed

    Zeidenberg, Joshua; Burks, S Shelby; Jose, Jean; Subhawong, Ty K; Levi, Allan D

    2015-09-01

    Ultrasound technology continues to improve with better image resolution and availability. Its use in evaluating peripheral nerve lesions is increasing. The current review focuses on the utility of ultrasound in traumatic injuries. In this report, the authors present 4 illustrative cases in which high-resolution ultrasound dramatically enhanced the anatomical understanding and surgical planning of traumatic peripheral nerve lesions. Cases include a lacerating injury of the sciatic nerve at the popliteal fossa, a femoral nerve injury from a pseudoaneurysm, an ulnar nerve neuroma after attempted repair with a conduit, and, finally, a spinal accessory nerve injury after biopsy of a supraclavicular fossa lesion. Preoperative ultrasound images and intraoperative pictures are presented with a focus on how ultrasound aided with surgical decision making. These cases are set into context with a review of the literature on peripheral nerve ultrasound and a comparison between ultrasound and MRI modalities.

  2. Brachial plexus injury with emphasis on axillary nerve paralysis after thoracoscopic sympathicotomy for axillary hyperhidrosis.

    PubMed

    Chon, Soon-Ho; Suk Choi, Matthew Seung

    2006-12-01

    Thoracic sympathicotomy for the treatment of axillary hyperhidrosis with the use of 2 mm thoracoscope and instruments is a simple and safe procedure. Nerve paralysis of any type after thoracic sympathicotomy is an extremely rare event. We report a 44-year-old woman who developed brachial plexus injury of her left arm after thoracoscopic sympathicotomy for axillary hyperhidrosis. The lesion involved the whole arm. All nerves of the brachial plexus except the axillary nerve recovered quickly. An axillary nerve type lesion was observed for 7 weeks, until the patient fully recovered all functions of her arm. The mechanism is believed not to be caused by the procedure itself, but by dorsal overextension of the abducted arm during the operation. PMID:17277662

  3. 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

  4. Nerve regeneration restores supraspinal control of bladder function after complete spinal cord injury.

    PubMed

    Lee, Yu-Shang; Lin, Ching-Yi; Jiang, Hai-Hong; Depaul, Marc; Lin, Vernon W; Silver, Jerry

    2013-06-26

    A life-threatening disability after complete spinal cord injury is urinary dysfunction, which is attributable to lack of regeneration of supraspinal pathways that control the bladder. Although numerous strategies have been proposed that can promote the regrowth of severed axons in the adult CNS, at present, the approaches by which this can be accomplished after complete cord transection are quite limited. In the present study, we modified a classic peripheral nerve grafting technique with the use of chondroitinase to facilitate the regeneration of axons across and beyond an extensive thoracic spinal cord transection lesion in adult rats. The novel combination treatment allows for remarkably lengthy regeneration of certain subtypes of brainstem and propriospinal axons across the injury site and is followed by markedly improved urinary function. Our studies provide evidence that an enhanced nerve grafting strategy represents a potential regenerative treatment after severe spinal cord injury.

  5. Nerve Regeneration Restores Supraspinal Control of Bladder Function after Complete Spinal Cord Injury

    PubMed Central

    Lin, Ching-Yi; Jiang, Hai-Hong; DePaul, Marc; Lin, Vernon W.

    2013-01-01

    A life-threatening disability after complete spinal cord injury is urinary dysfunction, which is attributable to lack of regeneration of supraspinal pathways that control the bladder. Although numerous strategies have been proposed that can promote the regrowth of severed axons in the adult CNS, at present, the approaches by which this can be accomplished after complete cord transection are quite limited. In the present study, we modified a classic peripheral nerve grafting technique with the use of chondroitinase to facilitate the regeneration of axons across and beyond an extensive thoracic spinal cord transection lesion in adult rats. The novel combination treatment allows for remarkably lengthy regeneration of certain subtypes of brainstem and propriospinal axons across the injury site and is followed by markedly improved urinary function. Our studies provide evidence that an enhanced nerve grafting strategy represents a potential regenerative treatment after severe spinal cord injury. PMID:23804083

  6. Peripheral nerve injury is accompanied by chronic transcriptome-wide changes in the mouse prefrontal cortex

    PubMed Central

    2013-01-01

    Background Peripheral nerve injury can have long-term consequences including pain-related manifestations, such as hypersensitivity to cutaneous stimuli, as well as affective and cognitive disturbances, suggesting the involvement of supraspinal mechanisms. Changes in brain structure and cortical function associated with many chronic pain conditions have been reported in the prefrontal cortex (PFC). The PFC is implicated in pain-related co-morbidities such as depression, anxiety and impaired emotional decision-making ability. We recently reported that this region is subject to significant epigenetic reprogramming following peripheral nerve injury, and normalization of pain-related structural, functional and epigenetic abnormalities in the PFC are all associated with effective pain reduction. In this study, we used the Spared Nerve Injury (SNI) model of neuropathic pain to test the hypothesis that peripheral nerve injury triggers persistent long-lasting changes in gene expression in the PFC, which alter functional gene networks, thus providing a possible explanation for chronic pain associated behaviors. Results SNI or sham surgery where performed in male CD1 mice at three months of age. Six months after injury, we performed transcriptome-wide sequencing (RNAseq), which revealed 1147 differentially regulated transcripts in the PFC in nerve-injured vs. control mice. Changes in gene expression occurred across a number of functional gene clusters encoding cardinal biological processes as revealed by Ingenuity Pathway Analysis. Significantly altered biological processes included neurological disease, skeletal muscular disorders, behavior, and psychological disorders. Several of the changes detected by RNAseq were validated by RT-QPCR and included transcripts with known roles in chronic pain and/or neuronal plasticity including the NMDA receptor (glutamate receptor, ionotropic, NMDA; grin1), neurite outgrowth (roundabout 3; robo3), gliosis (glial fibrillary acidic protein

  7. 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

  8. Activation of the unfolded protein response promotes axonal regeneration after peripheral nerve injury

    PubMed Central

    Oñate, Maritza; Catenaccio, Alejandra; Martínez, Gabriela; Armentano, Donna; Parsons, Geoffrey; Kerr, Bredford; Hetz, Claudio; Court, Felipe A.

    2016-01-01

    Although protein-folding stress at the endoplasmic reticulum (ER) is emerging as a driver of neuronal dysfunction in models of spinal cord injury and neurodegeneration, the contribution of this pathway to peripheral nerve damage remains poorly explored. Here we targeted the unfolded protein response (UPR), an adaptive reaction against ER stress, in mouse models of sciatic nerve injury and found that ablation of the transcription factor XBP1, but not ATF4, significantly delay locomotor recovery. XBP1 deficiency led to decreased macrophage recruitment, a reduction in myelin removal and axonal regeneration. Conversely, overexpression of XBP1s in the nervous system in transgenic mice enhanced locomotor recovery after sciatic nerve crush, associated to an improvement in key pro-regenerative events. To assess the therapeutic potential of UPR manipulation to axonal regeneration, we locally delivered XBP1s or an shRNA targeting this transcription factor to sensory neurons of the dorsal root ganglia using a gene therapy approach and found an enhancement or reduction of axonal regeneration in vivo, respectively. Our results demonstrate a functional role of specific components of the ER proteostasis network in the cellular changes associated to regeneration and functional recovery after peripheral nerve injury. PMID:26906090

  9. Th17 Cell Response in SOD1G93A Mice following Motor Nerve Injury

    PubMed Central

    Ni, Allen; Yang, Tao; Mesnard-Hoaglin, Nichole A.; Gutierrez, Rafael; Stubbs, Evan B.; McGuire, Susan O.; Sanders, Virginia M.; Jones, Kathryn J.; Foecking, Eileen M.; Xin, Junping

    2016-01-01

    An increased risk of ALS has been reported for veterans, varsity athletes, and professional football players. The mechanism underlying the increased risk in these populations has not been identified; however, it has been proposed that motor nerve injury may trigger immune responses which, in turn, can accelerate the progression of ALS. Accumulating evidence indicates that abnormal immune reactions and inflammation are involved in the pathogenesis of ALS, but the specific immune cells involved have not been clearly defined. To understand how nerve injury and immune responses may contribute to ALS development, we investigated responses of CD4+ T cell after facial motor nerve axotomy (FNA) at a presymptomatic stage in a transgenic mouse model of ALS (B6SJL SOD1G93A). SOD1G93A mice, compared with WT mice, displayed an increase in the basal activation state of CD4+ T cells and higher frequency of Th17 cells, which were further enhanced by FNA. In conclusion, SOD1G93A mice exhibit abnormal CD4+ T cell activation with increased levels of Th17 cells prior to the onset of neurological symptoms. Motor nerve injury exacerbates Th17 cell responses and may contribute to the development of ALS, especially in those who carry genetic susceptibility to this disease. PMID:27194826

  10. Th17 Cell Response in SOD1G93A Mice following Motor Nerve Injury.

    PubMed

    Ni, Allen; Yang, Tao; Mesnard-Hoaglin, Nichole A; Gutierrez, Rafael; Stubbs, Evan B; McGuire, Susan O; Sanders, Virginia M; Jones, Kathryn J; Foecking, Eileen M; Xin, Junping

    2016-01-01

    An increased risk of ALS has been reported for veterans, varsity athletes, and professional football players. The mechanism underlying the increased risk in these populations has not been identified; however, it has been proposed that motor nerve injury may trigger immune responses which, in turn, can accelerate the progression of ALS. Accumulating evidence indicates that abnormal immune reactions and inflammation are involved in the pathogenesis of ALS, but the specific immune cells involved have not been clearly defined. To understand how nerve injury and immune responses may contribute to ALS development, we investigated responses of CD4(+) T cell after facial motor nerve axotomy (FNA) at a presymptomatic stage in a transgenic mouse model of ALS (B6SJL SOD1(G93A)). SOD1(G93A) mice, compared with WT mice, displayed an increase in the basal activation state of CD4(+) T cells and higher frequency of Th17 cells, which were further enhanced by FNA. In conclusion, SOD1(G93A) mice exhibit abnormal CD4(+) T cell activation with increased levels of Th17 cells prior to the onset of neurological symptoms. Motor nerve injury exacerbates Th17 cell responses and may contribute to the development of ALS, especially in those who carry genetic susceptibility to this disease.

  11. Pain Management for Nerve Injury following Dental Implant Surgery at Tokyo Dental College Hospital

    PubMed Central

    Fukuda, Ken-ichi; Ichinohe, Tatsuya; Kaneko, Yuzuru

    2012-01-01

    By allowing reconstruction of compromised occlusion, dental implants contribute to an improvement in quality of life (QOL) and diet. Injury to a nerve during such treatment, however, can result in a sudden decline in QOL. And once a nerve has been injured, the chances of a full recovery are slim unless the damage is only slight. If such damage causes neuropathic pain severe enough to prevent sleep, the patient's QOL will deteriorate dramatically. While damage to skin tissue or bone invariably heals over time, damage to nerves does not, indicating the need to avoid such injury while performing implant insertion, for example. This means not relying solely on X-ray images, which can be rather unclear, but also using computed tomography to allow preoperative planning and intraoperative execution to be performed as accurately as possible. Moreover, if sensory damage does occur it is essential to avoid breaking the bond of trust between dentist and patient by giving false assurances of recovery. In such cases, appropriate measures must be taken promptly. This paper describes pain management for nerve injury following dental implant surgery at the Orofacial Pain Center of Tokyo Dental College Suidoubashi Hospital. PMID:22899928

  12. Stereological and somatotopic analysis of the spinal microglial response to peripheral nerve injury

    PubMed Central

    Beggs, Simon; Salter, Michael W.

    2016-01-01

    The involvement of glia, and glia-neuronal signalling in enhancing nociceptive transmission has become an area of intense scientific interest. In particular, a role has emerged for activated microglia in the development and maintenance of neuropathic pain following peripheral nerve injury. Following activation, spinal microglia proliferate and release many substances which are capable of modulating neuronal excitability within the spinal cord. Here, we the investigated the response of spinal microglia to a unilateral spared nerve injury (SNI) in terms of the quantitative increase in cell number and the spatial distribution of the increase. Design-based stereological techniques were combined with iba-1 immunohistochemistry to estimate the total number of microglia in the spinal dorsal horn in naïve and peripheral nerve-injured adult rats. In addition, by mapping the central terminals of hindlimb nerves, the somatotopic distribution of the microglial response was mapped. Following SNI there was a marked increase in the number of spinal microglia: The total number of microglia (mean ± SD) in the dorsal horn sciatic territory of the naïve rat was estimated to be 28,591 ± 2715. Following SNI the number of microglia was 82,034 ± 8828. While the pattern of microglial activation generally followed somatotopic boundaries, with the majority of microglia within the territory occupied by peripherally axotomised primary afferents, some spread was seen into regions occupied by intact, ‘spared’ central projections of the sural nerve. This study provides a reproducible method of assaying spinal microglial dynamics following peripheral nerve injury both quantitatively and spatially. PMID:17267172

  13. 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

  14. Peripheral nerve injuries in weight training: sites, pathophysiology, diagnosis, and treatment.

    PubMed

    Lodhia, Keith R; Brahma, Barunashish; McGillicuddy, John E

    2005-07-01

    Direct trauma, compression caused by muscle hypertrophy or other soft tissue changes, or excessive stretching of a peripheral nerve in the upper extremity may lead to uncommon-but potentially serious-complications. Clinicians are seeing more of these injuries as weight training, power lifting, bodybuilding, cross-training, and general physical conditioning with weights become more popular. Symptoms of pain, weakness, paresthesia, or palsy; physical exam findings; electromyography; and nerve conduction studies are used to make the diagnosis. Most conditions respond well to conservative measures, such as rest from the offending exercise and correction of poor technique, but surgery may be required for complete clinical resolution in severe cases.

  15. Thrower's fracture of the humerus with radial nerve palsy: an unfamiliar softball injury.

    PubMed

    Curtin, P; Taylor, C; Rice, J

    2005-11-01

    A fracture of the normal humerus in a healthy young adult most commonly results from significant direct trauma. Throwing sports have become increasingly popular outside of North America and bring with them a novel injury mechanism for clinicians. A 21 year old woman sustained a "thrower's fracture" of the distal humerus and radial nerve palsy while throwing a softball. She was treated by internal fixation. Her fracture united, and radial nerve neurapraxia resolved after 8 weeks. Clinicians should be aware of this entity so that prodromal symptoms can be recognised early and thrower's fractures are not investigated unnecessarily.

  16. 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

  17. 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

  18. Reinnervation of the Tibialis Anterior Following Sciatic Nerve Crush Injury: A Confocal Microscopic Study in Transgenic Mice

    PubMed Central

    Magill, Christina K.; Tong, Alice; Kawamura, David; Hayashi, Ayato; Hunter, Daniel A.; Parsadanian, Alexander; Mackinnon, Susan E.; Myckatyn, Terence M.

    2007-01-01

    Transgenic mice whose axons and Schwann cells express fluorescent chromophores enable new imaging techniques and augment concepts in developmental neurobiology. The utility of these tools in the study of traumatic nerve injury depends on employing nerve models that are amenable to microsurgical manipulation and gauging functional recovery. Motor recovery from sciatic nerve crush injury is studied here by evaluating motor endplates of the tibialis anterior muscle, which is innervated by the deep peroneal branch of the sciatic nerve. Following sciatic nerve crush, the deep surface of the tibialis anterior muscle is examined using whole mount confocal microscopy, and reinnervation is characterized by imaging fluorescent axons or Schwann cells (SCs). One week following sciatic crush injury, 100% of motor endplates are denervated with partial reinnervation at two weeks, hyperinnervation at three and four weeks, and restoration of a 1:1 axon to motor endplate relationship six weeks after injury. Walking track analysis reveals progressive recovery of sciatic nerve function by six weeks. SCs reveal reduced S100 expression within two weeks of denervation, correlating with regression to a more immature phenotype. Reinnervation of SCs restores S100 expression and a fully differentiated phenotype. Following denervation, there is altered morphology of circumscribed terminal Schwann cells demonstrating extensive process formation between adjacent motor endplates. The thin, uniformly innervated tibialis anterior muscle is well suited for studying motor reinnervation following sciatic nerve injury. Confocal microscopy may be performed coincident with other techniques of assessing nerve regeneration and functional recovery. PMID:17628540

  19. Can "dor to dor+rec neurorrhaphy" by biodegradable chitin conduit be a new method for peripheral nerve injury?

    PubMed

    Yin, Xiao Feng; Kou, Yu Hui; Wang, Yan Hua; Zhang, Peixun; Zhang, Dian Yin; Fu, Zhong Guo; Zhang, Hong Bo; Jiang, Bao Guo

    2011-04-01

    This study aims to estimate the effects of using one donor nerve to repair the injured nerve and itself simultaneously by biodegradable chitin conduit. Proximal median nerve served as donor nerve to repair the distal median and whole ulnar nerve. Four months postoperation, the number of myelinated axons and nerve conduction velocities of the distal median and ulnar nerve were (2085 ± 215 and 24.4 ± 5.9 m/s), and (1193 ± 102 and 30.7 ± 11.2 m/s). Recovery of the tetanic muscle forces of the reinvervated muscles were also observed. It suggests that Dor to Dor+Rec neurorrhaphy is a practical method for severe peripheral nerve injury.

  20. Phrenic Nerve Transfer for Reconstruction of Elbow Extension in Severe Brachial Plexus Injuries.

    PubMed

    Flores, Leandro P; Socolovsky, Mariano

    2016-09-01

    Background Restoring elbow extension is an important objective to pursue when repairing the brachial plexus in patients with a flail arm. Based upon the good results obtained using the phrenic nerve to restore elbow flexion and shoulder stability, we hypothesized that this nerve could also be employed to reconstruct elbow extension in patients with severe brachial plexus injuries. Methods A retrospective study of 10 patients in which the phrenic nerve targeted the radial nerve (7 patients) or the branch to the long head of the triceps (3 patients) as a surgical strategy for reconstruction of the brachial plexus. Results The mean postoperative follow-up time was 34 months. At final follow-up, elbow extension graded as M4 was measured in three patients, Medical Research Council MRC M3 in five patients, and M2 in one patient, while one patient experienced no measurable recovery (M0). No patient complained or demonstrated any signs of respiratory insufficiency postoperatively. Conclusions The phrenic nerve is a reliable donor for reanimation of elbow extension in such cases, and the branch to the long head of the triceps should be considered as a better target for the nerve transfer. PMID:27144951

  1. Phrenic Nerve Transfer for Reconstruction of Elbow Extension in Severe Brachial Plexus Injuries.

    PubMed

    Flores, Leandro P; Socolovsky, Mariano

    2016-09-01

    Background Restoring elbow extension is an important objective to pursue when repairing the brachial plexus in patients with a flail arm. Based upon the good results obtained using the phrenic nerve to restore elbow flexion and shoulder stability, we hypothesized that this nerve could also be employed to reconstruct elbow extension in patients with severe brachial plexus injuries. Methods A retrospective study of 10 patients in which the phrenic nerve targeted the radial nerve (7 patients) or the branch to the long head of the triceps (3 patients) as a surgical strategy for reconstruction of the brachial plexus. Results The mean postoperative follow-up time was 34 months. At final follow-up, elbow extension graded as M4 was measured in three patients, Medical Research Council MRC M3 in five patients, and M2 in one patient, while one patient experienced no measurable recovery (M0). No patient complained or demonstrated any signs of respiratory insufficiency postoperatively. Conclusions The phrenic nerve is a reliable donor for reanimation of elbow extension in such cases, and the branch to the long head of the triceps should be considered as a better target for the nerve transfer.

  2. Functional anatomy of the mandibular nerve: consequences of nerve injury and entrapment.

    PubMed

    Piagkou, Maria; Demesticha, Theano; Skandalakis, Panayiotis; Johnson, Elizabeth O

    2011-03-01

    Various anatomic structures including bone, muscle, or fibrous bands may entrap and potentially compress branches of the mandibular nerve (MN). The infratemporal fossa is a common location for MN compression and one of the most difficult regions of the skull to access surgically. Other potential sites for entrapment of the MN and its branches include, a totally or partially ossified pterygospinous or pterygoalar ligament, a large lamina of the lateral plate of the pterygoid process, the medial fibers of the lower belly of the lateral pterygoid muscle and the inner fibers of the medial pterygoid muscle. The clinical consequences of MN entrapment are dependent upon which branches are compressed. Compression of the MN motor branches can lead to paresis or weakness in the innervated muscles, whereas compression of the sensory branches can provoke neuralgia or paresthesia. Compression of one of the major branches of the MN, the lingual nerve (LN), is associated with numbness, hypoesthesia, or even anesthesia of the tongue, loss of taste in the anterior two thirds of the tongue, anesthesia of the lingual gums, pain, and speech articulation disorders. The aim of this article is to review, the anatomy of the MN and its major branches with relation to their vulnerability to entrapment. Because the LN expresses an increased vulnerability to entrapment neuropathies as a result of its anatomical location, frequent variations, as well as from irregular osseous, fibrous, or muscular irregularities in the region of the infratemporal fossa, particular emphasis is placed on the LN.

  3. 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

  4. 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

  5. Developing Extracellular Matrix Technology to Treat Retinal or Optic Nerve Injury(1,2,3).

    PubMed

    Ren, Tanchen; van der Merwe, Yolandi; Steketee, Michael B

    2015-09-01

    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. 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

  7. Ultrasound assessment of selected peripheral nerve pathologies. Part III: Injuries and postoperative evaluation.

    PubMed

    Kowalska, Berta; Sudoł-Szopińska, Iwona

    2013-03-01

    The previous articles of the series devoted to ultrasound diagnostics of peripheral nerves concerned the most common nerve pathologies, i.e. entrapment neuropathies. The aim of the last part of the series is to present ultrasound possibilities in the postoperative control of the peripheral nerves as well as in the diagnostics of the second most common neuropathies of peripheral nerves, i.e. posttraumatic lesions. Early diagnostics of posttraumatic changes is of fundamental importance for the course of treatment and its long-term effects. It aids surgeons in making treatment decisions (whether surgical or conservative). When surgical treatment is necessary, the surgeon, based on US findings, is able to plan a given type of operative method. In certain cases, may even abandon the corrective or reconstructive surgery of the nerve trunk (when there are extensive defects of the nerve trunks) and instead, proceed with muscle transfers. Medical literature proposes a range of divisions of the kinds of peripheral nerve injuries depending on, among others, the mechanism or degree of damage. However, the most important issue in the surgeon-diagnostician communication is a detailed description of stumps of the nerve trunks, their distance and location. In the postoperative period, ultrasound is used for monitoring the operative or conservative treatment effects including the determination of the causes of a persistent or recurrent neuropathy. It facilitates decision-making concerning a repeated surgical procedure or assuming a wait-and-see attitude. It is a difficult task for a diagnostician and it requires experience, close cooperation with a clinician and knowledge concerning surgical techniques. Apart from a static assessment, a dynamic assessment of possible adhesions constitutes a crucial element of postoperative examination. This feature distinguishes ultrasound scanning from other methods used in the diagnostics of peripheral neuropathies.

  8. Hydrogen sulfide is essential for Schwann cell responses to peripheral nerve injury.

    PubMed

    Park, Byung Sun; Kim, Hyun-Wook; Rhyu, Im Joo; Park, Chan; Yeo, Seung Geun; Huh, Youngbuhm; Jeong, Na Young; Jung, Junyang

    2015-01-01

    Hydrogen sulfide (H2 S) functions as a physiological gas transmitter in both normal and pathophysiological cellular events. H2 S is produced from substances by three enzymes: cystathionine β-synthase (CBS), cystathionine γ-lyase (CSE), and 3-mercaptopyruvate sulfurtransferase (MST). In human tissues, these enzymes are involved in tissue-specific biochemical pathways for H2 S production. For example, CBS and cysteine aminotransferase/MST are present in the brain, but CSE is not. Thus, we examined the expression of H2 S production-related enzymes in peripheral nerves. Here, we found that CSE and MST/cysteine aminotransferase, but not CBS, were present in normal peripheral nerves. In addition, injured sciatic nerves in vivo up-regulated CSE in Schwann cells during Wallerian degeneration (WD); however, CSE was not up-regulated in peripheral axons. Using an ex vivo sciatic nerve explant culture, we found that the inhibition of H2 S production broadly prevented the process of nerve degeneration, including myelin fragmentation, axonal degradation, Schwann cell dedifferentiation, and Schwann cell proliferation in vitro and in vivo. Thus, these results indicate that H2 S signaling is essential for Schwann cell responses to peripheral nerve injury. Hydrogen sulfide (H2 S) functions as a physiological gas transmitter in both normal and pathophysiological cellular events. H2 S is produced from cystathionine β-synthase (CBS), cystathionine γ-lyase (CSE), and 3-mercaptopyruvate sulfur transferase (MST). Here, we found that CSE and MST/CAT were present in normal peripheral nerves. Injured static nerves in vivo up-regulated CSE in Schwann cells during Wallerian degeneration, but CSE was not up-regulated in peripheral axons.

  9. 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.

  10. The effect of mirodenafil on the penile erection and corpus cavernosum in the rat model of cavernosal nerve injury.

    PubMed

    Kim, H; Sohn, D W; Kim, S D; Hong, S-H; Suh, H J; Lee, C B; Kim, S W

    2010-01-01

    Impotence is one of the common complications after the radical prostatectomy. One of the main reasons of this complication is due to the dysfunction of the veins in corpus cavernosum. Recent studies have shown that the erectile function is improved after the long-term therapy of phosphodiesterase type 5 inhibitor among patients with post-prostatectomy erectile dysfunction. In this study, we evaluated the effects of mirodenafil on the penile erection and corpus cavernosum tissues in the rat model of cavernosal nerve injury. Rats were divided into four groups: (1) control group, (2) bilateral cavernosal nerve injury group, (3) mirodenafil 10 mg therapy group after the nerve injury and (4) mirodenafil 20 mg therapy group after the nerve injury. After we identified the nerve from the pelvic nerve complex on the lateral side of the prostate, the rats in the control group were sutured without causing any nerve injury and in other groups we damaged the nerve by compressing it with a vessel clamp. Then, 10 and 20 mg kg(-1) of mirodenafil were orally administered to two experimental groups. After 8 weeks, the intracavernosal pressure (ICP) was recorded. The immunohistochemical staining and western blot were performed, and the effect of mirodenafil on the expression of cyclic guanosine monophosphate (cGMP) was evaluated through enzyme-linked immunosorbent assay. The ICP of nerve-injured group was decreased compared with the control group; however, the ICP of the mirodenafil-administered groups was improved compared with the nerve-injured group. The Masson's trichrome staining confirmed that the smooth muscle (SM) component was increased in the mirodenafil-administered groups. The nitric oxide synthase expression and cGMP of mirodenafil-administered groups was increased compared with the nerve-injured group. Long-term therapy of mirodenafil may improve the erectile function after the radical prostatectomy by preserving the SM content and inhibiting the fibrosis of the corpus

  11. Iatrogenic injury to the inferior alveolar nerve: etiology, signs and symptoms, and observations on recovery.

    PubMed

    Hillerup, S

    2008-08-01

    The purpose of this prospective, non-randomised, descriptive study is to characterise the neurosensory deficit and associated neurogenic discomfort in 52 patients with iatrogenic injury to the inferior alveolar nerve (IAN). All patients were examined and followed up according to a protocol assessing tactile, thermal, and positional perception as well as two-point discrimination and pain. In 48 patients with IAN injuries of differing etiologies who did not undergo surgery, 32 patients with injury associated with third molar surgery exhibited significant spontaneous improvement of sensory function. Recovery improvement of sensory function was insignificant in the patients with other etiologies. In most patients the level of sensory perception was such that microsurgical repair was only occasionally indicated. Four patients had microsurgical repair; the outcome was favourable in three. IAN injuries associated with third molar surgery, other dento-alveolar surgery or implant surgery occur sufficiently often to render prevention a key issue. PMID:18501561

  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

    2012-01-01

    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. PMID:22927278

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

    PubMed

    Petrarca, Robert; Saldana, Manuel

    2012-01-01

    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.

  15. Cervical myelography of nerve root avulsion injuries using water-soluble contrast media.

    PubMed

    Cobby, M J; Leslie, I J; Watt, I

    1988-08-01

    Eight cases of cervical nerve root avulsion injury are presented which were investigated by cervical myelography using a water-soluble contrast medium. The previous literature describes the appearances of this lesion using an oil-based agent and has resulted in emphasis being placed on looking for a traumatic meningocele rather than an abnormality of the roots themselves. The excellent definition of the nerve rootlets and axillary pouch that are obtained with a water-soluble contrast medium resulted in more root lesions per patient being detected than with an oil-based medium. There was complete correlation with the surgical findings at all but one root level explored. The appearances of root avulsion injuries and the advantages of using a water-soluble contrast medium are discussed. PMID:3416107

  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. Morphology and neurophysiology of focal axonal injury experimentally induced in the guinea pig optic nerve.

    PubMed

    Tomei, G; Spagnoli, D; Ducati, A; Landi, A; Villani, R; Fumagalli, G; Sala, C; Gennarelli, T

    1990-01-01

    A new model of focal axonal injury was reproduced by rapid and controlled elongation (uniaxial stretch) of the guinea pig optic nerve. Light microscopy study of optic nerve specimens after horseradish peroxidase injection into the vitreous of the animal's eye showed that axonal lesions were identical to those seen in human and primate post-traumatic diffuse axonal injury (DAI). The lesions were characterized by the formation of terminal clubs in severed axons and focal axonal enlargements in those axons that were lesioned-in-continuity. Visual-evoked potentials upon flash stimulation were recorded before and after injury. Mean amplitude and mean latency of occipital peaks were significantly elongated in the acute post-traumatic phase. Electron microscopy examination showed that the main axonal changes observed in this model were cytoskeleton disorganization, accumulation of axoplasm membrane-bound bodies at the site of terminal balls and dilatations-in-continuity and detachment of the axolemma from the myelin sheath. Such axonal alterations were similar to those found in many other biological models of central and peripheral axonal injuries in which the lesion was produced by invasive methods. This model is unique since it reproduces the same mechanism of injury and the identical lesions that have been demonstrated in humans and primates with post-traumatic (DAI).

  18. The role of neuregulin-1 in the response to nerve injury

    PubMed Central

    Fricker, Florence R; Bennett, David LH

    2011-01-01

    Axons and Schwann cells exist in a highly interdependent relationship: damage to one cell type invariably leads to pathophysiological changes in the other. Greater understanding of communication between these cell types will not only give insight into peripheral nerve development, but also the reaction to and recovery from peripheral nerve injury. The type III isoform of neuregulin-1 (NRG1) has emerged as a key signaling factor that is expressed on axons and, through binding to erbB2/3 receptors on Schwann cells, regulates multiple phases of their development. In adulthood, NRG1 is dispensable for the maintenance of the myelin sheath; however, this factor is required for both axon regeneration and remyelination following nerve injury. The outcome of NRG1 signaling depends on interactions with other pathways within Schwann cells such as Notch, integrin and cAMP signaling. In certain circumstances, this signaling pathway may be maladaptive; for instance, direct binding of Mycobacterium leprae onto erbB2 receptors produces excessive activation and can actually promote demyelination. Attempts to modulate this pathway in order to promote nerve repair will therefore need to give consideration to the exact isoform used, as well as how it is processed and the context in which it is presented to the Schwann cell. PMID:22121335

  19. The Effect of Pulsed Radiofrequency Applied to the Peripheral Nerve in Chronic Constriction Injury Rat Model

    PubMed Central

    Lee, Jun-Beom; Byun, Jeong-Hyun; Kim, Young; Lee, Ji Shin

    2015-01-01

    Objective To investigate the effect of pulsed radiofrequency (PRF) applied proximal to the injured peripheral nerve on the expression of tumor necrosis factor-α (TNF-α) in a neuropathic pain rat model. Methods Nineteen male Sprague-Dawley rats were used in the study. All rats underwent chronic constriction injury (CCI) procedure. After 7 days of CCI, withdrawal frequency of affected hind paw to mechanical stimuli and withdrawal latency of affected hind paw to heat stimulus were measured. They were randomly divided into two groups: group A, CCI group (n=9) and group B, CCI treated with PRF group (n=10). Rats of group B underwent PRF procedure on the sciatic nerve. Withdrawal frequency and withdrawal latency were measured at 12 hours, and 7 days after PRF. Immunohistochemistry and Western blot analysis were performed using a TNF-α antibody. Results Before PRF, withdrawal frequency and withdrawal latency were not different in both groups. After PRF, withdrawal frequency decreased and withdrawal latency prolonged over time in group B. There was significant interaction between time and group for each withdrawal frequency and withdrawal latency. Group B showed decreased TNF-α immunoreactivity of the spinal cord and sciatic nerve at 7 days. Conclusion PRF applied proximal to the peripheral nerve injury is potentially helpful for the reduction of neuropathic pain by neuromodulation of inflammatory markers. PMID:26605164

  20. 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

  1. Median Nerve Injury Due to High-Pressure Water Jet Injection: A Case Report and Review of Literature.

    PubMed

    Emre, Ufuk; Unal, Aysun

    2009-08-01

    High-pressure injuries that occur accidentally are potentially destructive injuries that often affect the nondominant hands of young men. A variety of products such as paint, gasoline, grease, fuel oil, cement, thinner and solvents have been reported as destructive agents. High-pressure water jet injection injuries to soft tissues have rarely been reported. In this study, we present the first case of median nerve injury due to high-pressure water jet injection by a water spray gun. PMID:26815059

  2. Wallerian degeneration: gaining perspective on inflammatory events after peripheral nerve injury

    PubMed Central

    2011-01-01

    In this review, we first provide a brief historical perspective, discussing how peripheral nerve injury (PNI) may have caused World War I. We then consider the initiation, progression, and resolution of the cellular inflammatory response after PNI, before comparing the PNI inflammatory response with that induced by spinal cord injury (SCI). In contrast with central nervous system (CNS) axons, those in the periphery have the remarkable ability to regenerate after injury. Nevertheless, peripheral nervous system (PNS) axon regrowth is hampered by nerve gaps created by injury. In addition, the growth-supportive milieu of PNS axons is not sustained over time, precluding long-distance regeneration. Therefore, studying PNI could be instructive for both improving PNS regeneration and recovery after CNS injury. In addition to requiring a robust regenerative response from the injured neuron itself, successful axon regeneration is dependent on the coordinated efforts of non-neuronal cells which release extracellular matrix molecules, cytokines, and growth factors that support axon regrowth. The inflammatory response is initiated by axonal disintegration in the distal nerve stump: this causes blood-nerve barrier permeabilization and activates nearby Schwann cells and resident macrophages via receptors sensitive to tissue damage. Denervated Schwann cells respond to injury by shedding myelin, proliferating, phagocytosing debris, and releasing cytokines that recruit blood-borne monocytes/macrophages. Macrophages take over the bulk of phagocytosis within days of PNI, before exiting the nerve by the circulation once remyelination has occurred. The efficacy of the PNS inflammatory response (although transient) stands in stark contrast with that of the CNS, where the response of nearby cells is associated with inhibitory scar formation, quiescence, and degeneration/apoptosis. Rather than efficiently removing debris before resolving the inflammatory response as in other tissues

  3. 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.

  4. Managing iatrogenic trigeminal nerve injury: a case series and review of the literature.

    PubMed

    Renton, T; Yilmaz, Z

    2012-05-01

    This study describes the management of 216 patients with post-traumatic iatrogenic lingual nerve injuries (LNIs; n=93) and inferior alveolar nerve injuries (IANI; n=123). At initial consultation, 6% IANI and 2% LNI patients had undergone significant resolution requiring no further reviews. Reassurance and counselling was adequate management for 51% IANI and 55% LNI patients. Systemic or topical medication was offered as pain relief to 5% of patients. Additional cognitive behaviour therapy (CBT) was offered to 8% of patients. Topical 5% lidocaine patches reduced pain and allodynia in 7% of IANI patients, most often used without any other form of management. A small percentage of IANI patients (4%) received a combination of therapies involving CBT, surgery, medication and 5% lidocaine patches. Exploratory surgery improved symptoms and reduced neuropathic area in 18 LNI and 15 IANI patients resulting in improved quality of life. In conclusion, the authors suggest a more diverse and perhaps holistic strategy for management of patients with iatrogenic trigeminal nerve injuries and recommend pragmatic assessment criteria for measurement of treatment success in these patients.

  5. The VGF-derived peptide TLQP-21 contributes to inflammatory and nerve injury-induced hypersensitivity

    PubMed Central

    Fairbanks, Carolyn A.; Peterson, Cristina D.; Speltz, Rebecca H.; Riedl, Maureen S.; Kitto, Kelley F.; Dykstra, Jaclyn A.; Braun, Patrick D.; Sadahiro, Masato; Salton, Stephen R.; Vulchanova, Lucy

    2014-01-01

    VGF (non-acronymic) is a granin-like protein that is packaged and proteolytically processed within the regulated secretory pathway. VGF and peptides derived from its processing have been implicated in neuroplasticity associated with learning, memory, depression, and chronic pain. In sensory neurons, VGF is rapidly increased following peripheral nerve injury and inflammation. Several bioactive peptides generated from the C-terminus of VGF have pro-nociceptive spinal effects. The goal of the present study was to examine the spinal effects of the peptide TLQP-21 and determine whether it participates in spinal mechanisms of persistent pain. Application of exogenous TLQP-21 induced dose-dependent thermal hyperalgesia in the warm water immersion tail withdrawal test. This hyperalgesia was inhibited by a p38 MAPK inhibitor as well as inhibitors of cyclooxygenase and lipoxygenase. We used immunoneutralization of TLQP-21 to determine the function of the endogenous peptide in mechanisms underlying persistent pain. In mice injected intradermally with complete Freund’s adjuvant, intrathecal treatment with anti-TLQP21 IgG immediately prior to or 5 h after induction of inflammation dose-dependently inhibited tactile hypersensitivity and thermal hyperalgesia. Intrathecal anti-TL21 administration also attenuated the development and maintenance of tactile hypersensitivity in the spared nerve injury model of neuropathic pain. These results provide evidence that endogenous TLQP-21 peptide contributes to the mechanisms of spinal neuroplasticity after inflammation and nerve injury. PMID:24657450

  6. Transforming growth factor-β3 promotes facial nerve injury repair in rabbits

    PubMed Central

    WANG, YANMEI; ZHAO, XINXIANG; HUOJIA, MUHTER; XU, HUI; ZHUANG, YOUMEI

    2016-01-01

    The present study investigated the effects of transforming growth factor (TGF)-β3 on the regeneration of facial nerves in rabbits. A total of 20 adult rabbits were randomly divided into three equal groups: Normal control (n=10), surgical control (n=10) and TGF-β3 treatment (n=10). The total number and diameter of the regenerated nerve fibers was significantly increased in the TGF-β3 treatment group, as compared with in the surgical control group (P<0.01). Furthermore, in the TGF-β3 treatment group, the epineurial repair of the facial nerves was intact and the nerve fibers, which were arranged in neat rows, were morphologically intact with visible myelin swelling. However, in the surgical control group, the epineurial repair was incomplete, as demonstrated by: Atrophic nerve fibers, partially disappeared axons and myelin of uneven thickness with fuzzy borders. Electron microscopy demonstrated that the regenerated fibers in the TGF-β3 treatment group were predominantly myelinated, with clear-layered myelin sheath structures and axoplasms rich in organelles. Although typical layered myelin sheath structures were observed in the surgical control group, the myelin sheaths of the myelinated nerve fibers were poorly developed and few organelles were detected in the axoplasms. Neuro-electrophysiological examination demonstrated that, as compared with the surgical control group, the latency period of the action potentials in the TGF-β3 treatment group were shorter, whereas the stimulus amplitudes of the action potentials were significantly increased (P<0.01). The results of the present study suggest that TGF-β3 may improve the regeneration of facial nerves following trauma or injury. PMID:26997982

  7. Peripheral nerve injury sensitizes neonatal dorsal horn neurons to tumor necrosis factor-α

    PubMed Central

    Li, Jie; Xie, Wenrui; Zhang, Jun-Ming; Baccei, Mark L

    2009-01-01

    Background Little is known about whether peripheral nerve injury during the early postnatal period modulates synaptic efficacy in the immature superficial dorsal horn (SDH) of the spinal cord, or whether the neonatal SDH network is sensitive to the proinflammatory cytokine TNFα under neuropathic conditions. Thus we examined the effects of TNFα on synaptic transmission and intrinsic membrane excitability in developing rat SDH neurons in the absence or presence of sciatic nerve damage. Results The spared nerve injury (SNI) model of peripheral neuropathy at postnatal day (P)6 failed to significantly alter miniature excitatory (mEPSCs) or inhibitory (mIPSCs) postsynaptic currents in SDH neurons at P9-11. However, SNI did alter the sensitivity of excitatory synapses in the immature SDH to TNFα. While TNFα failed to influence mEPSCs or mIPSCs in slices from sham-operated controls, it significantly increased mEPSC frequency and amplitude following SNI without modulating synaptic inhibition onto the same neurons. This was accompanied by a significant decrease in the paired-pulse ratio of evoked EPSCs, suggesting TNFα increases the probability of glutamate release in the SDH under neuropathic conditions. Similarly, while SNI alone did not alter action potential (AP) threshold or rheobase in SDH neurons at this age, TNFα significantly decreased AP threshold and rheobase in the SNI group but not in sham-operated littermates. However, unlike the adult, the expression of TNFα in the immature dorsal horn was not significantly elevated during the first week following the SNI. Conclusion Developing SDH neurons become susceptible to regulation by TNFα following peripheral nerve injury in the neonate. This may include both a greater efficacy of glutamatergic synapses as well as an increase in the intrinsic excitability of immature dorsal horn neurons. However, neonatal sciatic nerve damage alone did not significantly modulate synaptic transmission or neuronal excitability in

  8. Localized regulation of axonal RanGTPase controls retrograde injury signaling in peripheral nerve

    PubMed Central

    Yudin, Dmitry; Hanz, Shlomit; Yoo, Soonmoon; Iavnilovitch, Elena; Willis, Dianna; Gradus, Tal; Vuppalanchi, Deepika; Segal-Ruder, Yael; Ben-Yaakov, Keren; Hieda, Miki; Yoneda, Yoshihiro; Twiss, Jeffery L.; Fainzilber, Mike

    2008-01-01

    Summary Peripheral sensory neurons respond to axon injury by activating an importin-dependent retrograde signaling mechanism. How is this mechanism regulated? Here we show that Ran GTPase and its associated effectors RanBP1 and RanGAP regulate the formation of importin signaling complexes in injured axons. A gradient of nuclear RanGTP versus cytoplasmic RanGDP is thought to be fundamental for the organization of eukaryotic cells. Surprisingly, we find RanGTP in sciatic nerve axoplasm, distant from neuronal cell bodies and nuclei, and in association with dynein and importin α. Following injury, localized translation of RanBP1 stimulates RanGTP dissociation from importins and subsequent hydrolysis, thereby allowing binding of newly synthesized importin β to importin α and dynein. Perturbation of RanGTP hydrolysis or RanBP1 blockade at axonal injury sites reduces the neuronal conditioning lesion response. Thus, neurons employ localized mechanisms of Ran regulation to control retrograde injury signaling in peripheral nerve. PMID:18667152

  9. Axon regeneration across the site of injury in the optic nerve of the newt Triturus pyrrhogaster.

    PubMed

    Stensaas, L J; Feringa, E R

    1977-04-29

    The process by which axons regenerate following a freeze injury to the optic nerve of the newt was analyzed by light and electron microscopy. Freezing destroys cellular constituents in a one millimeter segment of the nerve, leaving intact the basal lamina and the blood supply to the eye. No axons are seen at the site of injury one to seven days post lesion. This contrasts with the persistence of normal-appearing but severed unmyelinated axons within the cranial stump which thus give a false appearance of early regeneration. The first axon sprouts traverse the lesion and enter the cranial strump by ten days. The number of regenerating axons increases rapidly thereafter with no signs of random growth at the site of injury. These axon sprouts tend to be somewhat larger than normal unmyelinated axons and contain dense core vesicles and abnormal organelles similar to those in growing axons in tissue culture. The persisting basal lamina inside the optic sheath appears to provide continuity across the site of injury, to orient axon sprouts, and to favor an orderly process of axon regeneration without neuroma formation.

  10. Spinal expression of Hippo signaling components YAP and TAZ following peripheral nerve injury in rats.

    PubMed

    Li, Na; Lim, Grewo; Chen, Lucy; McCabe, Michael F; Kim, Hyangin; Zhang, Shuzhuo; Mao, Jianren

    2013-10-16

    Previous studies have shown that the morphology and number of cells in the spinal cord dorsal horn could change following peripheral nerve injury and that the Hippo signaling pathway plays an important role in cell growth, proliferation, apoptosis, and dendritic remolding. In the present study, we examined whether the expression of YAP and TAZ, two critical components regulated by Hippo signaling, in the spinal cord dorsal horn would be altered by chronic constriction sciatic nerve injury (CCI). We found that (1) YAP was mainly expressed on CGRP- and IB4-immunoreactive primary afferent nerve terminals without noticeable expression on glial cells, whereas TAZ was mainly expressed on spinal cord second order neurons as well as microglia; (2) upregulation of YAP and TAZ expression followed two distinct temporal patterns after CCI, such that the highest expression of YAP and TAZ was on day 14 and day 1 after CCI, respectively; (3) there were also unique topographic patterns of YAP and TAZ distribution in the spinal cord dorsal horn consistent with their distinctive association with primary afferents and second order neurons; (4) changes in the YAP expression were selectively induced by CCI but not CFA-induced hindpaw inflammation; and (5) the number of nuclear profiles of TAZ expression was significantly increased after CCI, indicating translocation of TAZ from the cytoplasma to nucleus. These findings indicate that peripheral nerve injury induced time-dependent and region-specific changes in the spinal YAP and TAZ expression. A role for Hippo signaling in synaptic and structural plasticity is discussed in relation to the cellular mechanism of neuropathic pain.

  11. Possible involvement of convergent nociceptive input to medullary dorsal horn neurons in intraoral hyperalgesia following peripheral nerve injury.

    PubMed

    Terayama, Ryuji; Tsuchiya, Hiroki; Omura, Shinji; Maruhama, Kotaro; Mizutani, Masahide; Iida, Seiji; Sugimoto, Tomosada

    2015-04-01

    Previous studies demonstrated that the number of c-Fos protein-like immunoreactive (c-Fos-IR) neurons in the medullary dorsal horn (MDH) evoked by noxious stimulation was increased after peripheral nerve injury, and such increase has been proposed to reflect the development of neuropathic pain state. The aim of this study was to examine the MDH for convergent collateral primary afferent input to second order neurons deafferented by peripheral nerve injury, and to explore a possibility of its contribution to the c-Fos hyperinducibility. Double immunofluorescence labeling for c-Fos and phosphorylated extracellular signal-regulated kinase (p-ERK) was performed to detect convergent synaptic input. c-Fos expression and the phosphorylation of ERK were induced by the intraoral application of capsaicin and by electrical stimulation of the inferior alveolar nerve (IAN), respectively. The number of c-Fos-IR neurons in the MDH induced by the intraoral application of capsaicin was increased after IAN injury, whereas the number of p-ERK immunoreactive neurons remained unchanged. The number of double-labeled neurons, that presumably received convergent primary afferent input from the lingual nerve and the IAN, was significantly increased after IAN injury. These results indicated that convergent primary nociceptive input through neighboring intact nerves may contribute to the c-Fos hyperinducibility in the MDH and the pathogenesis of neuropathic pain following trigeminal nerve injury. PMID:25407627

  12. 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

  13. Short-term peripheral nerve stimulation ameliorates axonal dysfunction after spinal cord injury.

    PubMed

    Lee, Michael; Kiernan, Matthew C; Macefield, Vaughan G; Lee, Bonne B; Lin, Cindy S-Y

    2015-05-01

    There is accumulating evidence that peripheral motor axons deteriorate following spinal cord injury (SCI). Secondary axonal dysfunction can exacerbate muscle atrophy, contribute to peripheral neuropathies and neuropathic pain, and lead to further functional impairment. In an attempt to ameliorate the adverse downstream effects that developed following SCI, we investigated the effects of a short-term peripheral nerve stimulation (PNS) program on motor axonal excitability in 22 SCI patients. Axonal excitability studies were undertaken in the median and common peroneal nerves (CPN) bilaterally before and after a 6-wk unilateral PNS program. PNS was delivered percutaneously over the median nerve at the wrist and CPN around the fibular head, and the compound muscle action potential (CMAP) from the abductor pollicis brevis and tibialis anterior was recorded. Stimulus intensity was above motor threshold, and pulses (450 μs) were delivered at 100 Hz with a 2-s on/off cycle for 30 min 5 days/wk. SCI patients had consistently high thresholds with a reduced CMAP consistent with axonal loss; in some patients the peripheral nerves were completely inexcitable. Nerve excitability studies revealed profound changes in membrane potential, with a "fanned-in" appearance in threshold electrotonus, consistent with membrane depolarization, and significantly reduced superexcitability during the recovery cycle. These membrane dysfunctions were ameliorated after 6 wk of PNS, which produced a significant hyperpolarizing effect. The contralateral, nonstimulated nerves remained depolarized. Short-term PNS reversed axonal dysfunction following SCI, may provide an opportunity to prevent chronic changes in axonal and muscular function, and may improve rehabilitation outcomes. PMID:25787956

  14. Bilateral accessory thoracodorsal artery.

    PubMed

    Natsis, Konstantinos; Totlis, Trifon; Tsikaras, Prokopios; Skandalakis, Panagiotis

    2006-09-01

    The subscapular artery arises from the third part of the axillary artery and gives off the circumflex scapular and the thoracodorsal arteries. Although anatomical variations of the axillary artery are very common, the existence of a unilateral accessory thoracodorsal artery has been described in the literature only once. There are no reports of bilateral accessory thoracodorsal artery, in the literature. In the present study, a bilateral accessory thoracodorsal artery, originating on either side of the third part of the axillary artery, is described in a 68-year-old female cadaver. All the other branches of the axillary artery had a typical origin, course, distribution and termination. This extremely rare anatomical variation apart from the anatomical importance also has clinical significance for surgeons in this area. Especially, during the dissection or mobilization of the latissimus dorsi that is partly used for coverage problems in many regions of the body and also in dynamic cardiomyoplasty, any iatrogenic injury of this accessory artery may result in ischemia and functional loss of the graft.

  15. Upslope treadmill exercise enhances motor axon regeneration but not functional recovery following peripheral nerve injury.

    PubMed

    Cannoy, Jill; Crowley, Sam; Jarratt, Allen; Werts, Kelly LeFevere; Osborne, Krista; Park, Sohee; English, Arthur W

    2016-09-01

    Following peripheral nerve injury, moderate daily exercise conducted on a level treadmill results in enhanced axon regeneration and modest improvements in functional recovery. If the exercise is conducted on an upwardly inclined treadmill, even more motor axons regenerate successfully and reinnervate muscle targets. Whether this increased motor axon regeneration also results in greater improvement in functional recovery from sciatic nerve injury was studied. Axon regeneration and muscle reinnervation were studied in Lewis rats over an 11 wk postinjury period using stimulus evoked electromyographic (EMG) responses in the soleus muscle of awake animals. Motor axon regeneration and muscle reinnervation were enhanced in slope-trained rats. Direct muscle (M) responses reappeared faster in slope-trained animals than in other groups and ultimately were larger than untreated animals. The amplitude of monosynaptic H reflexes recorded from slope-trained rats remained significantly smaller than all other groups of animals for the duration of the study. The restoration of the amplitude and pattern of locomotor EMG activity in soleus and tibialis anterior and of hindblimb kinematics was studied during treadmill walking on different slopes. Slope-trained rats did not recover the ability to modulate the intensity of locomotor EMG activity with slope. Patterned EMG activity in flexor and extensor muscles was not noted in slope-trained rats. Neither hindblimb length nor limb orientation during level, upslope, or downslope walking was restored in slope-trained rats. Slope training enhanced motor axon regeneration but did not improve functional recovery following sciatic nerve transection and repair. PMID:27466130

  16. Differential proteomics reveals multiple components in retrogradely transported axoplasm after nerve injury.

    PubMed

    Perlson, Eran; Medzihradszky, Katalin F; Darula, Zsuzsanna; Munno, David W; Syed, Naweed I; Burlingame, Alma L; Fainzilber, Mike

    2004-05-01

    Information on axonal damage is conveyed to neuronal cell bodies by a number of signaling modalities, including the post-translational modification of axoplasmic proteins. Retrograde transport of a subset of such proteins is thought to induce or enhance a regenerative response in the cell body. Here we report the use of a differential 2D-PAGE approach to identify injury-correlated retrogradely transported proteins in nerves of the mollusk Lymnaea. A comprehensive series of gels at different pI ranges allowed resolution of approximately 4000 spots by silver staining, and 172 of these were found to differ between lesioned versus control nerves. Mass spectrometric sequencing of 134 differential spots allowed their assignment to over 40 different proteins, some belonging to a vesicular ensemble blocked by the lesion and others comprising an up-regulated ensemble highly enriched in calpain cleavage products of an intermediate filament termed RGP51 (retrograde protein of 51 kDa). Inhibition of RGP51 expression by RNA interference inhibits regenerative outgrowth of adult Lymnaea neurons in culture. These results implicate regulated proteolysis in the formation of retrograde injury signaling complexes after nerve lesion and suggest that this signaling modality utilizes a wide range of protein components.

  17. 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

  18. Cellular reactions of the choroid plexus induced by peripheral nerve injury.

    PubMed

    Joukal, Marek; Klusáková, Ilona; Solár, Peter; Kuklová, Adéla; Dubový, Petr

    2016-08-15

    The choroid plexus (CP) of brain ventricles forms the blood-cerebrospinal fluid (blood-CSF) barrier that is involved in many diseases affecting the central nervous system (CNS). We used ED1 and ED2 immunostaining to investigate epiplexus cell changes in rat CP after chronic constriction injury (CCI). In contrast to naïve CP, the CP of sham-operated rats showed an increase in the number of ED1+ cells of a similar magnitude during all periods of survival up to 3 weeks, while the number of ED2+ increased only at 3 days from operation. In comparison to naïve and sham-operated animals, the number of ED1+ and ED2+ cells in the epiplexus position increased with the duration of nerve compression. We detected no or negligible cell proliferation in the CP after sham- or CCI-operation. This suggests that increased number of ED1+ and ED2+ cells in the epiplexus position of the CP is derived from peripheral monocytes passing through altered blood-CSF barrier. The changes in epiplexus cells indicate that the CP reacts to tissue injury after the surgical approach itself and that the response to peripheral nerve lesion is greater. This suggests a role for an altered blood-CSF barrier allowing for propagation of signal molecules from damaged tissue and nerve to the CNS. PMID:27291457

  19. 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

  20. 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. PMID:24472724

  1. Sympathetic sprouting near sensory neurons after nerve injury occurs preferentially on spontaneously active cells and is reduced by early nerve block

    PubMed Central

    Xie, Wenrui; Strong, Judith Ann; Li, Huiqing; Zhang, Jun-Ming

    2006-01-01

    Some chronic pain conditions are maintained or enhanced by sympathetic activity. In animal models of pathological pain, abnormal sprouting of sympathetic fibers around large- and medium-size sensory neurons is observed in dorsal root ganglia (DRG). Large and medium size cells are also more likely to be spontaneously active, suggesting that sprouting may be related to neuron activity. We previously showed that sprouting could be reduced by systemic or locally applied lidocaine. In the complete sciatic nerve transection model in rats, spontaneous activity initially originates in the injury site; later, the DRG become the major source of spontaneous activity. In this study, spontaneous activity reaching the DRG soma was reduced by early nerve blockade (local perfusion of the transected nerve with TTX for the first 7 days after injury). This significantly reduced sympathetic sprouting. Conversely, increasing spontaneous activity by local nerve perfusion with K+ channel blockers increased sprouting. The hyperexcitability and spontaneous activity of DRG neurons observed in this model were also significantly reduced by early nerve blockade. These effects of early nerve blockade on sprouting, excitability, and spontaneous activity were all observed 4 to 5 weeks after the end of early nerve blockade, indicating that the early period of spontaneous activity in the injured nerve is critical for establishing the more long-lasting pathologies observed in the DRG. Individual spontaneously active neurons, labeled with fluorescent dye, were 5–6 times more likely than quiescent cells to be co-localized with sympathetic fibers, suggesting a highly localized correlation of activity and sprouting. PMID:17065247

  2. Microglia and monocytes synergistically promote the transition from acute to chronic pain after nerve injury

    PubMed Central

    Peng, Jiyun; Gu, Nan; Zhou, Lijun; B Eyo, Ukpong; Murugan, Madhuvika; Gan, Wen-Biao; Wu, Long-Jun

    2016-01-01

    Microglia and peripheral monocytes contribute to hypersensitivity in rodent models of neuropathic pain. However, the precise respective function of microglia and peripheral monocytes has not been investigated in these models. To address this question, here we combined transgenic mice and pharmacological tools to specifically and temporally control the depletion of microglia and monocytes in a mouse model of spinal nerve transection (SNT). We found that although microglia and monocytes are required during the initiation of mechanical allodynia or thermal hyperalgesia, these cells may not be as important for the maintenance of hypersensitivity. Moreover, we demonstrated that either resident microglia or peripheral monocytes are sufficient in gating neuropathic pain after SNT. We propose that resident microglia and peripheral monocytes act synergistically to initiate hypersensitivity and promote the transition from acute to chronic pain after peripheral nerve injury. PMID:27349690

  3. 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.

  4. 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. PMID:25674823

  5. 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.

  6. Permanent implantation of peripheral nerve stimulator for combat injury-related ilioinguinal neuralgia.

    PubMed

    Banh, Diem Phuc T; Moujan, Pablo M; Haque, Quazi; Han, Tae-Hyung

    2013-01-01

    A peripheral nerve stimulator (PNS) can be an alternative for long-term pain relief refractory to conventional therapeutic modalities. We present a case of chronic incapacitating ilioinguinal neuralgia, which was successfully managed with permanent implantation of a peripheral nerve stimulator. A 26-year-old active duty African American man was referred to the University Pain Clinic with left ilioinguinal neuralgia due to shrapnel injury during his military service 6 years prior to his visit. Most of the shrapnel were surgically removed, but the patient subsequently developed left lower abdominal pain. Multiple surgeries, including inguinal herniorrhaphy, varicocelectomy, and orchiectomy, failed to provide satisfactory relief of his neuralgia. Other therapies tried resulting in limited outcomes were multiple ilioinguinal nerve blocks and cryoanalgesia. A trial of PNS was successful and the implantation of permanent leads was carried out. At his 3-month visit, the patient reported to have minimal pain, was tapered off oral analgesics, was able to return to work, and had resumed his normal daily activities. Recent technological advances in programming software and surgical techniques have led to renewed interest in PNS for the treatment of chronic refractory peripheral nerve injury. Despite our limited understanding of its exact mechanism of action, it can be considered as a therapeutic potential for a few carefully selected, intractable cases. Its minimally invasive and reversible features make PNS a favorable option for these patients. The stringent and rigorous screening procedures for suitable candidacy, documentation of previously failed treatments, psychiatric evaluation, and 3-5 days of preplacement trial, improve the success rate. PMID:24284860

  7. Netrin-1 overexpression in bone marrow mesenchymal stem cells promotes functional recovery in a rat model of peripheral nerve injury

    PubMed Central

    Ke, Xianjin; Li, Qian; Xu, Li; Zhang, Ying; Li, Dongmei; Ma, Jianhua; Mao, Xiaoming

    2015-01-01

    Abstract Transplantation of bone marrow mesenchymal stem cells (BMSCs) has been developed as a new method of treating diseases of the peripheral nervous system. While netrin-1 is a critical molecule for axonal path finding and nerve growth, it may also affect vascular network formation. Here, we investigated the effect of transplanting BMSCs that produce netrin-1 in a rat model of sciatic nerve crush injury. We introduced a sciatic nerve crush injury, and then injected 1×106 BMSCs infected by a recombinant adenovirus expressing netrin-1 Ad5-Netrin-1-EGFP or culture medium into the injured part in the next day. At day 7, 14 and 28 after injection, we measured motor nerve conduction and detected mRNA expressions of netrin-1 receptors UNC5B and Deleted in Colorectal Cancer (DCC), and neurotrophic factors brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) by real-time PCR. We also detected protein expressions of BDNF and NGF by Western blotting assays and examined BMSCs that incorporated into myelin and vascellum. The results showed that BMSCs infected by Ad5-Netrin-1-EGFP significantly improved the function of the sciatic nerve, and led to increased expression of BDNF and NGF (P<0.05). Moreover, 28 days after injury, more Schwann cells were found in BMSCs infected by Ad5-Netrin-1-EGFP compared to control BMSCs. In conclusion, transplantation of BMSCs that produce netrin-1 improved the function of the sciatic nerve after injury. This method may be a new treatment of nerve injury. PMID:26445571

  8. Contribution of afferent pathways to nerve injury-induced spontaneous pain and evoked hypersensitivity.

    PubMed

    King, Tamara; Qu, Chaoling; Okun, Alec; Mercado, Ramon; Ren, Jiyang; Brion, Triza; Lai, Josephine; Porreca, Frank

    2011-09-01

    A predominant complaint in patients with neuropathic pain is spontaneous pain, often described as burning. Recent studies have demonstrated that negative reinforcement can be used to unmask spontaneous neuropathic pain, allowing for mechanistic investigations. Here, ascending pathways that might contribute to evoked and spontaneous components of an experimental neuropathic pain model were explored. Desensitization of TRPV1-positive fibers with systemic resiniferatoxin (RTX) abolished spinal nerve ligation (SNL) injury-induced thermal hypersensitivity and spontaneous pain, but had no effect on tactile hypersensitivity. Ablation of spinal NK-1 receptor-expressing neurons blocked SNL-induced thermal and tactile hypersensitivity as well as spontaneous pain. After nerve injury, upregulation of neuropeptide Y (NPY) is observed almost exclusively in large-diameter fibers, and inactivation of the brainstem target of these fibers in the nucleus gracilis prevents tactile but not thermal hypersensitivity. Blockade of NPY signaling within the nucleus gracilis failed to block SNL-induced spontaneous pain or thermal hyperalgesia while fully reversing tactile hypersensitivity. Moreover, microinjection of NPY into nucleus gracilis produced robust tactile hypersensitivity, but failed to induce conditioned place aversion. These data suggest that spontaneous neuropathic pain and thermal hyperalgesia are mediated by TRPV1-positive fibers and spinal NK-1-positive ascending projections. In contrast, the large-diameter dorsal column projection can mediate nerve injury-induced tactile hypersensitivity, but does not contribute to spontaneous pain. Because inhibition of tactile hypersensitivity can be achieved either by spinal manipulations or by inactivation of signaling within the nucleus gracilis, the enhanced paw withdrawal response evoked by tactile stimulation does not necessarily reflect allodynia.

  9. Peripheral nerve injury induces aquaporin-4 expression and astrocytic enlargement in spinal cord.

    PubMed

    Oklinski, M K; Choi, H-J; Kwon, T-H

    2015-12-17

    Aquaporin-4 (AQP4), a water channel protein, is expressed mainly in the perivascular end-feet of astrocytes in the brain and spinal cord. Dysregulation of AQP4 is critically associated with abnormal water transport in the astrocytes. We aimed to examine whether peripheral nerve injury (PNI) could induce the changes of AQP4 expression and astrocytic morphology in the spinal cord. Two different PNI models [partial sciatic nerve transection (PST) and chronic constriction injury (CCI)] were established on the left sciatic nerve in Sprague-Dawley rats, which decreased the pain withdrawal threshold in the ipsilateral hind paws. Both PNI models were associated with a persistent up-regulation of AQP4 in the ipsilateral dorsal horn at the lower lumbar region over 3 weeks, despite an absence of direct injury to the spinal cord. Three-dimensional reconstruction of astrocytes was made and morphometric analysis was done. Up-regulation of AQP4 was accompanied by a significant increase in the length and volume of astrocytic processes and the number of branch points. The most prominent changes were present in the distal processes of the astrocytes and the changes were maintained throughout the whole experimental period. Extravasation of systemically administered tracers Evans Blue and sodium fluorescein was not seen in both models. Taken together, PNI was associated with a long-lasting AQP4 up-regulation and enlargement of astrocytic processes in the spinal cord in rats, both of which were not related to the disruption of blood-spinal cord barrier. The findings could provide novel insights on the understanding of pathophysiology of spinal cords after PNI.

  10. 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.

  11. Nociceptive and Neuronal Evaluation of the Sciatic Nerve of Wistar Rats Subjected to Compression Injury and Treated with Resistive Exercise.

    PubMed

    Antunes, Juliana Sobral; Lovison, Keli; Karvat, Jhenifer; Peretti, Ana Luiza; Vieira, Lizyana; Higuchi, Guilherme Hideaki; Brancalhão, Rose Meire Costa; Ribeiro, Lucinéia de Fátima Chasko; Bertolini, Gladson Ricardo Flor

    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

  12. 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

  13. 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

  14. 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.

  15. Peripheral Nerve Regeneration Following Crush Injury to Rat Peroneal Nerve by Aqueous Extract of Medicinal Mushroom Hericium erinaceus (Bull.: Fr) Pers. (Aphyllophoromycetideae)

    PubMed Central

    Wong, Kah-Hui; Naidu, Murali; David, Pamela; Abdulla, Mahmood Ameen; Abdullah, Noorlidah; Kuppusamy, Umah Rani; Sabaratnam, Vikineswary

    2011-01-01

    Nerve crush injury is a well-established axonotmetic model in experimental regeneration studies to investigate the impact of various pharmacological treatments. Hericium erinaceus is a temperate mushroom but is now being cultivated in tropical Malaysia. In this study, we investigated the activity of aqueous extract of H. erinaceus fresh fruiting bodies in promoting functional recovery following an axonotmetic peroneal nerve injury in adult female Sprague-Dawley rats by daily oral administration. The aim was to investigate the possible use of this mushroom in the treatment of injured nerve. Functional recovery was assessed in behavioral experiment by walking track analysis. Peroneal functional index (PFI) was determined before surgery and after surgery as rats showed signs of recovery. Histological examinations were performed on peroneal nerve by immunofluorescence staining and neuromuscular junction by combined silver-cholinesterase stain. Analysis of PFI indicated that return of hind limb function occurred earlier in rats of aqueous extract or mecobalamin (positive control) group compared to negative control group. Regeneration of axons and reinnervation of motor endplates in extensor digitorum longus muscle in rats of aqueous extract or mecobalamin group developed better than in negative control group. These data suggest that daily oral administration of aqueous extract of H. erinaceus fresh fruiting bodies could promote the regeneration of injured rat peroneal nerve in the early stage of recovery. PMID:21941586

  16. Injury-Dependent and Disability-Specific Lumbar Spinal Gene Regulation following Sciatic Nerve Injury in the Rat.

    PubMed

    Austin, Paul J; Bembrick, Alison L; 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

  17. 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

  18. Neuroimmunophilin Ligands Protect Cavernous Nerves after Crush Injury in the Rat: New Experimental Paradigms

    PubMed Central

    Valentine, Heather; Chen, Yi; Guo, Hongzhi; McCormick, Jocelyn; Wu, Yong; Sezen, Sena F.; Hoke, Ahmet; Burnett, Arthur L.; Steiner, Joseph P.

    2009-01-01

    Objectives We investigated the effects of the orally bioavailable non-immunosuppressive immunophilin ligand GPI 1046 (GPI) on erectile function and cavernous nerve (CN) histology following unilateral or bilateral crush injury (UCI, BCI, respectively) of the CNs. Methods Adult male Sprague-Dawley rats were administered GPI 15 mg/kg intraperitoneally (ip) or 30 mg/kg orally (po), FK506 1 mg/kg, ip, or vehicle controls for each route of administration just prior to UCI or BCI and daily up to 7 d following injury. At day 1 or 7 of treatment, erectile function induced by CN electrical stimulation was measured, and electron microscopic analysis of the injured CN was performed. Results Intraperitoneal administration of GPI to rats with injured CN protected erectile function, in a fashion similar to the prototypic immunophilin ligand FK506, compared with vehicle-treated animals (93% ± 9% vs. 70% ± 5% vs. 45% ± 1%, p < 0.01, respectively). Oral administration of GPI elicited the same level of significant protection from CN injury. GPI administered PO at 30 mg/kg/d, dosing either once daily or four times daily with 7.5 mg/kg, provided nearly complete protection of erectile function. In a more severe BCI model, PO administration of GPI maintained erectile function at 24 h after CN injury. Ultrastructural analysis of injured CNs indicated that GPI administered at the time of CN injury prevents degeneration of about 83% of the unmyelinated axons at 7 d after CN injury. Conclusions The orally administered immunophilin ligand GPI neuroprotects CNs and maintains erectile function in rats under various conditions of CN crush injury. PMID:17145129

  19. Publications on Peripheral Nerve Injuries during World War I: A Dramatic Increase in Knowledge.

    PubMed

    Koehler, Peter J

    2016-01-01

    Publications from French (Jules Tinel and Chiriachitza Athanassio-Bénisty), English (James Purves-Stewart, Arthur Henry Evans and Hartley Sidney Carter), German (Otfrid Foerster and Hermann Oppenheim) and American (Charles Harrison Frazier and Byron Stookey) physicians from both sides of the front during World War I (WWI) contributed to a dramatic increase in knowledge about peripheral nerve injuries. Silas Weir Mitchell's original experience with respect to these injuries, and particularly causalgia, during the American Civil War was further expanded in Europe during WWI. Following the translation of one of his books, he was referred to mainly by French physicians. During WWI, several French books were in turn translated into English, which influenced American physicians, as was observed in the case of Byron Stookey. The establishment of neurological centres played an important role in the concentration of experience and knowledge. Several eponyms originated during this period (including the Hoffmann-Tinel sign and the Froment sign). Electrodiagnostic tools were increasingly used.

  20. Outcomes of recurrent laryngeal nerve injury following congenital heart surgery: A contemporary experience

    PubMed Central

    Alfares, Fahad A.; Hynes, Conor F.; Ansari, Ghedak; Chounoune, Reginald; Ramadan, Manelle; Shaughnessy, Conner; Reilly, Brian K.; Zurakowski, David; Jonas, Richard A.; Nath, Dilip S.

    2015-01-01

    Objective Injury to the recurrent laryngeal nerve can lead to significant morbidity during congenital cardiac surgery. The objective is to expand on the limited understanding of the severity and recovery of this iatrogenic condition. Design A six-year retrospective review of all congenital heart operations at a single institution from January 1, 2008 to December 31, 2013 was performed. All patients with documented vocal cord paralysis on laryngoscopic examination comprised the study cohort. Evaluation of time to vocal cord recovery and need for further surgical intervention was the primary focus. Results The incidence of post-operative vocal cord paralysis was 1.1% (32 out of 3036 patients; 95% confidence interval: 0.7–1.5%). The majority were left-sided injuries (71%). Overall rate of recovery was 61% with a median time of 10 months in those who recovered, and a total follow up of 46 months. Due to feeding complications, 45% of patients required gastrostomy tube after the injury, and these patients were found to have longer duration of post-operative days of intubation (median 10 vs. 5 days, p = 0.03), ICU length of stay (50 vs. 8 days, p = 0.002), and hospital length of stay (92 vs. 41 days, p = 0.01). No pre-operative variables were identified as predictive of recovery or need for gastrostomy placement. Conclusion Recurrent laryngeal nerve injury is a serious complication of congenital heart surgery that impacts post-operative morbidity, in some cases leading to a need for further intervention, in particular, gastrostomy tube placement. A prospective, multi-center study is needed to fully evaluate factors that influence severity and time to recovery. PMID:26778899

  1. 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

  2. Inferior alveolar nerve injuries associated with mandibular fractures at risk: a two-center retrospective study.

    PubMed

    Boffano, Paolo; Roccia, Fabio; Gallesio, Cesare; Karagozoglu, K; Forouzanfar, Tymour

    2014-12-01

    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. Laser-induced retinal nerve fiber layer injury in the nonhuman primate

    NASA Astrophysics Data System (ADS)

    Zwick, Harry; Belkin, Michael; Zuclich, Joseph A.; Lund, David J.; Schuschereba, Steven T.; Scales, David K.

    1996-04-01

    We have evaluated the acute effects of Argon laser injury to the retinal nerve fiber layer (NFL) in the non-human primate. Single Argon laser exposures of 150 millijoules were employed to induce retinal NFL injury. Retinal NFL injury is not acute; unlike its parallel in retinal disease it has two components that emanate from the acute retinal injury site. The ascending component is more visible, primarily because it is ascending toward the disk, representing ganglion cell axons cut off from their nutrient base, the ganglion cell body; the descending component may require up to 3 weeks to develop. Its characterization depends on the distribution of retinal NFL and the slower degeneration of the ganglion cell bodies. Fluorescein angiography suggest a retinal capillary loss that occurs in the capillary bed of the retinal NFL defect. It may reflect a reduced capillary vascular requirement of the NFL as well as a possible reduction of activity in the axonal transport mechanisms in the ascending NFL defect.

  4. 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.

  5. Effects of nerve injury and segmental regeneration on the cellular correlates of neural morphallaxis.

    PubMed

    Martinez, Veronica G; Manson, Josiah M B; Zoran, Mark J

    2008-09-15

    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

  6. 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

  7. 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.

  8. Cortical edema in moderate fluid percussion brain injury is attenuated by vagus nerve stimulation.

    PubMed

    Clough, R W; Neese, S L; Sherill, L K; Tan, A A; Duke, A; Roosevelt, R W; Browning, R A; Smith, D C

    2007-06-29

    Development of cerebral edema (intracellular and/or extracellular water accumulation) following traumatic brain injury contributes to mortality and morbidity that accompanies brain injury. Chronic intermittent vagus nerve stimulation (VNS) initiated at either 2 h or 24 h (VNS: 30 s train of 0.5 mA, 20 Hz, biphasic pulses every 30 min) following traumatic brain injury enhances recovery of motor and cognitive function in rats in the weeks following brain injury; however, the mechanisms of facilitated recovery are unknown. The present study examines the effects of VNS on development of acute cerebral edema following unilateral fluid percussion brain injury (FPI) in rats, concomitant with assessment of their behavioral recovery. Two hours following FPI, VNS was initiated. Behavioral testing, using both beam walk and locomotor placing tasks, was conducted at 1 and 2 days following FPI. Edema was measured 48 h post-FPI by the customary method of region-specific brain weights before and after complete dehydration. Results of this study replicated that VNS initiated at 2 h after FPI: 1) effectively facilitated the recovery of vestibulomotor function at 2 days after FPI assessed by beam walk performance (P<0.01); and 2) tended to improve locomotor placing performance at the same time point (P=0.18). Most interestingly, results of this study showed that development of edema within the cerebral cortex ipsilateral to FPI was significantly attenuated at 48 h in FPI rats receiving VNS compared with non-VNS FPI rats (P<0.04). Finally, a correlation analysis between beam walk performance and cerebral edema following FPI revealed a significant inverse correlation between behavior performance and cerebral edema. Together, these results suggest that VNS facilitation of motor recovery following experimental brain injury in rats is associated with VNS-mediated attenuation of cerebral edema. PMID:17543463

  9. Activation of the galanin receptor 2 in the periphery reverses nerve injury-induced allodynia

    PubMed Central

    2011-01-01

    Background Galanin is expressed at low levels in the intact sensory neurons of the dorsal root ganglia with a dramatic increase after peripheral nerve injury. The neuropeptide is also expressed in primary afferent terminals in the dorsal horn, spinal inter-neurons and in a number of brain regions known to modulate nociception. Intrathecal administration of galanin modulates sensory responses in a dose-dependent manner with inhibition at high doses. To date it is unclear which of the galanin receptors mediates the anti-nociceptive effects of the neuropeptide and whether their actions are peripherally and/or centrally mediated. In the present study we investigated the effects of direct administration into the receptive field of galanin and the galanin receptor-2/3-agonist Gal2-11 on nociceptive primary afferent mechanical responses in intact rats and mice and in the partial saphenous nerve injury (PSNI) model of neuropathic pain. Results Exogenous galanin altered the responses of mechano-nociceptive C-fibre afferents in a dose-dependent manner in both naive and nerve injured animals, with low concentrations facilitating and high concentrations markedly inhibiting mechano-nociceptor activity. Further, use of the galanin fragment Gal2-11 confirmed that the effects of galanin were mediated by activation of galanin receptor-2 (GalR2). The inhibitory effects of peripheral GalR2 activation were further supported by our demonstration that after PSNI, mechano-sensitive nociceptors in galanin over-expressing transgenic mice had significantly higher thresholds than in wild type animals, associated with a marked reduction in spontaneous neuronal firing and C-fibre barrage into the spinal cord. Conclusions These findings are consistent with the hypothesis that the high level of endogenous galanin in injured primary afferents activates peripheral GalR2, which leads to an increase in C-fibre mechanical activation thresholds and a marked reduction in evoked and ongoing nociceptive

  10. 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

  11. Recovery of function after vagus nerve stimulation initiated 24 hours after fluid percussion brain injury.

    PubMed

    Smith, Douglas C; Tan, Arlene A; Duke, Andrea; Neese, Steven L; Clough, Richard W; Browning, Ronald A; Jensen, Robert A

    2006-10-01

    Recent evidence from our laboratory demonstrated in laboratory rats that stimulation of the vagus nerve (VNS) initiated 2 h after lateral fluid percussion brain injury (FPI) accelerates the rate of recovery on a variety of behavioral and cognitive tests. VNS animals exhibited a level of performance comparable to that of sham-operated uninjured animals by the end of a 2-week testing period. The effectiveness of VNS was further evaluated in the present study in which initiation of stimulation was delayed until 24 h post-injury. Rats were subjected to a moderate FPI and tested on the beam walk, skilled forelimb reaching, locomotor placing, forelimb flexion and Morris water maze tasks for 2 weeks following injury. VNS (30 sec trains of 0.5 mA, 20.0-Hz biphasic pulses) was initiated 24 h post-injury and continued at 30-min intervals for the duration of the study, except for brief periods when the animals were detached for behavioral assessments. Consistent with our previous findings when stimulation was initiated 2 h post-injury, VNS animals showed significantly faster rates of recovery compared to controls. By the last day of testing (day 14 post-injury), the FPI-VNS animals were performing significantly better than the FPI-no-VNS animals and were not significantly different from shams in all motor and sensorimotor tasks. Performance in the Morris water maze indicated that the VNS animals acquired the task more rapidly on days 11-13 post-injury. On day 14, the FPI-VNS animals did not differ in the latency to find the platform from sham controls, whereas the injured controls did; however, the FPI-VNS animals and injured controls were not significantly different. Despite the lack of significant histological differences between the FPI groups, VNS, when initiated 24 h following injury, clearly attenuated the ensuing behavioral deficits and enhanced acquisition of the cognitive task. The results are discussed with respect to the norepinephrine hypothesis. PMID:17020489

  12. 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

  13. 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

  14. Redistribution of voltage-gated sodium channels after nerve decompression contributes to relieve neuropathic pain in chronic constriction injury.

    PubMed

    Tseng, To-Jung; Hsieh, Yu-Lin; Ko, Miau-Hwa; Hsieh, Sung-Tsang

    2014-11-17

    Nerve decompression is an important therapeutic strategy to relieve neuropathic pain and promote the peripheral nerve regeneration. To address these issues, we investigated the effects of nerve decompression on relief of neuropathic pain behaviors, redistribution of voltage-gated sodium channels (VGSCs), and skin reinnervation with chronic constriction injury (CCI). At post-operative week (POW) 4, animals were divided into a decompression group, in which the ligatures were removed, and a CCI group, in which the ligatures remained. Thermal hyperalgesia and mechanical allodynia at POW 8 had distinct reductions in decompression group compared to CCI group. At that time in CCI group, morphological evidence of pan VGSCs (Pan Nav) and isoforms of VGSCs (Nav1.6, Nav1.9, except for Nav1.8) were shown the widely distribution along the injured sciatic nerve. All of the VGSCs in decompression group became clustering around the node of Ranvier, similar to the pattern of control sciatic nerve at POW 8. Skin reinnervation was demonstrated by epidermal nerve density (END) for protein gene product 9.5 (PGP 9.5)-immunoreactive (IR) nerve fibers and a significant difference between groups only at POW 24 (p=0.01). Growth-associated protein 43 (GAP-43) is participated in the nerve fiber growth and sprouting, a difference in END for GAP-43-IR nerve fibers at POW 24 between groups were also significant (p=0.02). These observations demonstrated that nerve decompression was accompanied with the disappearance of neuropathic pain behaviors after CCI. Morphological studies provided the evidence that redistribution of VGSCs along the injured sciatic nerve but still with an incomplete skin reinnervation. These significant findings demonstrated a role of VGSCs in the pathogenesis of neuropathic pain, and gave an approaching in pharmacological basis of therapeutics. PMID:25038561

  15. Pre-emptive morphine treatment abolishes nerve injury-induced lysophospholipid synthesis in mass spectrometrical analysis.

    PubMed

    Nagai, Jun; Ueda, Hiroshi

    2011-07-01

    We have previously demonstrated that lysophosphatidic acid (LPA) production in the spinal cord following partial sciatic nerve injury (SCNI) and its signaling initiate neuropathic pain. In order to examine whether LPA production depends on the intense nociceptive signal, we have attempted to see suppression by pre-emptive treatment with centrally administered morphine, which mainly inhibits nociceptive signal at the level of spinal cord. In the present study, we developed a quantitative mass spectrometry assay to simultaneously analyze several species of lysophosphatidyl choline (LPC). The levels of 16:0-, 18:0- and 18:1-LPC in the spinal cord and dorsal root were maximally increased at 75 min after SCNI and then declined, as LPC is converted to LPA by autotaxin (ATX). In atx(+/-)-mice, on the other hand, these levels were similar to wild-type mice at 75 min, but maximal at 120 min, suggesting that this difference is partly due to the low conversion of LPC to LPA in atx(+/-)-mice. When morphine was centrally administered before SCNI, the injury-induced increase of LPC was completely abolished. These results suggest that LPC (or LPA) is produced by injury-induced nociceptive signal, which is effectively and pre-emptively suppressed by central morphine, possibly through known descending anti-nociceptive pathways. PMID:21542849

  16. Diffuse Traumatic Axonal Injury in the Optic Nerve Does Not Elicit Retinal Ganglion Cell Loss

    PubMed Central

    Wang, Jiaqiong; Fox, Michael A.; Povlishock, John T.

    2013-01-01

    Much of the morbidity following traumatic brain injury (TBI) is associated with traumatic axonal injury (TAI). Although most TAI studies focus on corpus callosum white matter, the visual system has received increased interest. To assess visual system TAI, we developed a mouse model of optic nerve TAI. It is unknown, however, whether this TAI causes retinal ganglion cell (RGC) death. To address this issue, YFP-16 transgenic mice were subjected to mild TBI and followed from 2 to 28 days. Neither TUNEL-positive or cleaved caspase-3 immunoreactive RGCs were observed from 2 to 28 days post-TBI. Quantification of immunoreactivity of Brn3a, an RGC marker, demonstrated no RGC loss; parallel electron microscopic analysis confirmed RGC viability. Persistent RGC survival was also consistent with the finding of reorganization in the proximal axonal segments following TAI wherein microglia/macrophages remained inactive. In contrast, activated microglia/macrophages closely enveloped the distal disconnected, degenerating axonal segments at 7 to 28 days post-injury, thereby confirming that this model consistently evoked TAI followed by disconnection. Collectively, these data provide novel insight into the evolving pathobiology associated with TAI that will form a foundation for future studies exploring TAI therapy and its downstream consequences. PMID:23860030

  17. Phrenic nerve conduction studies in spinal cord injury: applications for diaphragmatic pacing.

    PubMed

    Alshekhlee, Amer; Onders, Raymond P; Syed, Tanvir U; Elmo, Maryjo; Katirji, Bashar

    2008-12-01

    The diaphragm pacing system (DPS) is a minimally invasive alternative to mechanical ventilation in patients with quadriplegia due to cervical myelopathy primarily caused by high cervical spinal cord injury. We evaluated 36 patients, 29 of whom had traumatic spinal cord injury, two who had a history of remote meningitis and demyelinating disease, and five who had cervical myelopathies of unknown etiology. Phrenic nerve conduction studies were performed with simultaneous fluoroscopic observation of diaphragm excursion to assess diaphragm viability. In the preoperative evaluation, diaphragm compound muscle action potentials (CMAPs) were recorded only when the diaphragm moved on fluoroscopy with ipsilateral stimulation. Twenty-six patients who were determined to have a viable diaphragm underwent DPS. Following DPS the primary outcome was the time (hours per day) that patients were able to pace and stay off the ventilator. Of 26 implanted patients, 96% (25 patients) were able to pace and tolerate being off the ventilator for more than 4 h per day. This study demonstrates that the presence of a diaphragm CMAP is associated with diaphragm movement observed by fluoroscopy in cervical myelopathy. In addition, DPS can help patients with cervical spinal cord injury to breathe unassisted by a ventilator.

  18. Up-regulated uridine kinase gene identified by RLCS in the ventral horn after crush injury to rat sciatic nerves.

    PubMed

    Yuh, I; Yaoi, T; Watanabe, S; Okajima, S; Hirasawa, Y; Fushiki, S

    1999-12-01

    Rat sciatic nerve crush injury is one of the models commonly employed for studying the mechanisms of nerve regeneration. In this study, we analyzed the temporal change of gene expression after injury in this model, to elucidate the molecular mechanisms involved in nerve regeneration. First, a cDNA analysis method, Restriction Landmark cDNA Scanning (RLCS), was applied to cells in the ventral horn of the spinal cord during a 7-day period after the crush injury. A total of 1991 cDNA species were detected as spots on gels, and 37 of these were shown to change after the injury. Temporally changed patterns were classified into three categories: the continuously up-regulated type (10 species), the transiently up-regulated type (22 species), and the down-regulated type (5 species). These complex patterns of gene expression demonstrated after the injury suggest that precise regulation in molecular pathways is required for accomplishing nerve regeneration. Secondly, the rat homologue of uridine kinase gene was identified as one of the up-regulated genes. Northern blot analysis on rat ventral horn tissue and brain revealed that the UK gene had three transcripts with different sizes (4.3, 1. 4, and 1.35 kb, respectively). All of the transcripts, especially the 4.3 kb one, were up-regulated mainly in a bimodal fashion during the 28-day period after the injury. The RLCS method that we employed in the present study shows promise as a means to fully analyze molecular changes in nerve regeneration in detail. PMID:10581173

  19. 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

  20. Plasticity-Related PKMζ Signaling in the Insular Cortex Is Involved in the Modulation of Neuropathic Pain after Nerve Injury

    PubMed Central

    Han, Jeongsoo; Kwon, Minjee; Cha, Myeounghoon; Tanioka, Motomasa; Hong, Seong-Karp; Bai, Sun Joon; Lee, Bae Hwan

    2015-01-01

    The insular cortex (IC) is associated with important functions linked with pain and emotions. According to recent reports, neural plasticity in the brain including the IC can be induced by nerve injury and may contribute to chronic pain. Continuous active kinase, protein kinase Mζ (PKMζ), has been known to maintain the long-term potentiation. This study was conducted to determine the role of PKMζ in the IC, which may be involved in the modulation of neuropathic pain. Mechanical allodynia test and immunohistochemistry (IHC) of zif268, an activity-dependent transcription factor required for neuronal plasticity, were performed after nerve injury. After ζ-pseudosubstrate inhibitory peptide (ZIP, a selective inhibitor of PKMζ) injection, mechanical allodynia test and immunoblotting of PKMζ, phospho-PKMζ (p-PKMζ), and GluR1 and GluR2 were observed. IHC demonstrated that zif268 expression significantly increased in the IC after nerve injury. Mechanical allodynia was significantly decreased by ZIP microinjection into the IC. The analgesic effect lasted for 12 hours. Moreover, the levels of GluR1, GluR2, and p-PKMζ were decreased after ZIP microinjection. These results suggest that peripheral nerve injury induces neural plasticity related to PKMζ and that ZIP has potential applications for relieving chronic pain. PMID:26457205

  1. Comparison of cutaneous nerve injury and vessel disruption complications following saphenous vein stripping using big or small olive heads

    PubMed Central

    Cicek, Mustafa Cuneyt; Cicek, Omer Faruk; Lafci, Gokhan; Uzun, Alper

    2016-01-01

    Objective: To compare the nerve injury and vessel disruption complicaitons in patients undergoing saphenous vein stripping using olive heads of different sizes. Methods: Big olive heads were used in group A (n=50) and small olive heads were used in group B (n=50) from the ankle to the groin; in group C (n=50), the vein was stripped in two sections; in an upward fashion by stripping the distal portion from the ankle to the level of the knee using small olive heads and by stripping the proximal portion from the knee to the level of the groin using big olive heads. Results: Six months after the operation, nerve injury symptoms were identified in 26%, 4%, 6% of patients in groups A, B, and C respectively. Vessel disruption occurred 2% in group A, 32% in group B, and 4% in group C. Both vessel disruption and nerve injury complications of group C were significantly lower than group A and B (p<0.001). Conclusion: Saphenous stripping using big olive heads for the proximal portion from the groin down to the level of the knee and using small olive heads for the distal portion from the knee to the level of the ankle is the alternative method which results in minimal nerve injury and vessel disruption. PMID:27375703

  2. 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. PMID:27424529

  3. 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

  4. 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

  5. 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

  6. Stem cell therapy for central nerve system injuries: glial cells hold the key

    PubMed Central

    Xiao, Li; Saiki, Chikako; Ide, Ryoji

    2014-01-01

    Mammalian adult central nerve system (CNS) injuries are devastating because of the intrinsic difficulties for effective neuronal regeneration. The greatest problem to be overcome for CNS recovery is the poor regeneration of neurons and myelin-forming cells, oligodendrocytes. Endogenous neural progenitors and transplanted exogenous neuronal stem cells can be the source for neuronal regeneration. However, because of the harsh local microenvironment, they usually have very low efficacy for functional neural regeneration which cannot compensate for the loss of neurons and oligodendrocytes. Glial cells (including astrocytes, microglia, oligodendrocytes and NG2 glia) are the majority of cells in CNS that provide support and protection for neurons. Inside the local microenvironment, glial cells largely influence local and transplanted neural stem cells survival and fates. This review critically analyzes current finding of the roles of glial cells in CNS regeneration, and highlights strategies for regulating glial cells’ behavior to create a permissive microenvironment for neuronal stem cells. PMID:25221575

  7. Effect of Pulsed Radiofrequency on Rat Sciatic Nerve Chronic Constriction Injury: A Preliminary Study

    PubMed Central

    Li, Duo-Yi; Meng, Lan; Ji, Nan; Luo, Fang

    2015-01-01

    Background: Pulsed radiofrequency (PRF) application to the dorsal root ganglia can reduce neuropathic pain (NP) in animal models, but the effect of PRF on damaged peripheral nerves has not been examined. We investigated the effect of PRF to the rat sciatic nerve (SN) on pain-related behavior and SN ultrastructure following chronic constriction injury (CCI). Methods: The analgesic effect was measured by hindpaw mechanical withdrawal threshold (MWT) and thermal withdrawal latency (TWL). Twenty rats with NP induced by ligating the common SN were then randomly divided into a PRF treatment group and a sham group. The contralateral SN served as a control. The MWT and TWL were determined again 2, 4, 6, 8, 10, 12, and 14 days after the PRF or sham treatment. On day 14, ipsilateral and contralateral common SNs were excised and examined by electron microscopy. Results: Ipsilateral MWT was significantly reduced and TWL significantly shorter compared to the contralateral side 14 days after CCI (both P = 0.000). In the PRF group, MWT was significantly higher and TWL significantly longer 14 days after the PRF treatment compared to before PRF treatment (both P = 0.000), while no such difference was observed in the sham group (P > 0.05). Electron microscopy revealed extensive demyelination and collagen fiber formation in the ipsilateral SN of sham-treated rats but sparse demyelination and some nerve fiber regrowth in the PRF treatment group. Conclusions: Hyperalgesia is relieved, and ultrastructural damage ameliorated after direct PRF treatment to the SN in the CCI rat model of NP. PMID:25673460

  8. 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

  9. 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

  10. Sensory signs in complex regional pain syndrome and peripheral nerve injury.

    PubMed

    Gierthmühlen, Janne; Maier, Christoph; Baron, Ralf; Tölle, Thomas; Treede, Rolf-Detlef; Birbaumer, Niels; Huge, Volker; Koroschetz, Jana; Krumova, Elena K; Lauchart, Meike; Maihöfner, Christian; Richter, Helmut; Westermann, Andrea

    2012-04-01

    This study determined patterns of sensory signs in complex regional pain syndrome (CRPS) type I and II and peripheral nerve injury (PNI). Patients with upper-limb CRPS-I (n=298), CRPS-II (n=46), and PNI (n=72) were examined with quantitative sensory testing according to the protocol of the German Research Network on Neuropathic Pain. The majority of patients (66%-69%) exhibited a combination of sensory loss and gain. Patients with CRPS-I had more sensory gain (heat and pressure pain) and less sensory loss than patients with PNI (thermal and mechanical detection, hypoalgesia to heat or pinprick). CRPS-II patients shared features of CRPS-I and PNI. CRPS-I and CRPS-II had almost identical somatosensory profiles, with the exception of a stronger loss of mechanical detection in CRPS-II. In CRPS-I and -II, cold hyperalgesia/allodynia (28%-31%) and dynamic mechanical allodynia (24%-28%) were less frequent than heat or pressure hyperalgesia (36%-44%, 67%-73%), and mechanical hypoesthesia (31%-55%) was more frequent than thermal hypoesthesia (30%-44%). About 82% of PNI patients had at least one type of sensory gain. QST demonstrates more sensory loss in CRPS-I than hitherto considered, suggesting either minimal nerve injury or central inhibition. Sensory profiles suggest that CRPS-I and CRPS-II may represent one disease continuum. However, in contrast to recent suggestions, small fiber deficits were less frequent than large fiber deficits. Sensory gain is highly prevalent in PNI, indicating a better similarity of animal models to human patients than previously thought. These sensory profiles should help prioritize approaches for translation between animal and human research.

  11. 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

  12. Ultrasound-Guided Forearm Nerve Blocks: A Novel Application for Pain Control in Adult Patients with Digit Injuries

    PubMed Central

    Patricia Javedani, Parisa; Amini, Albert

    2016-01-01

    Phalanx fractures and interphalangeal joint dislocations commonly present to the emergency department. Although these orthopedic injuries are not complex, the four-point digital block used for anesthesia during the reduction can be painful. Additionally, cases requiring prolonged manipulation or consultation for adequate reduction may require repeat blockade. This case series reports four patients presenting after mechanical injuries resulting in phalanx fracture or interphalangeal joint dislocations. These patients received an ultrasound-guided peripheral nerve block of the forearm with successful subsequent reduction. To our knowledge, use of ultrasound-guided peripheral nerve blocks of the forearm for anesthesia in reduction of upper extremity digit injuries in adult patients in the emergency department setting has not been described before. PMID:27555971

  13. Inside-out autologous vein grafts fail to restore erectile function in a rat model of cavernous nerve crush injury after nerve-sparing prostatectomy.

    PubMed

    Bessede, T; Moszkowicz, D; Alsaid, B; Zaitouna, M; Diallo, D; Peschaud, F; Benoit, G; Droupy, S

    2015-01-01

    Some autologous tissues can restore erectile function (EF) in rats after a resection of the cavernous nerve (CN). However, a cavernous nerve crush injury (CNCI) better reproduces ED occurring after a nerve-sparing radical prostatectomy (RP). The aim was to evaluate the effect on EF of an autologous vein graft after CNCI, compared with an artificial conduit. Five groups of rats were studied: those with CN exposure, exposure+vein, crush, crush+guide and crush+vein. Four weeks after surgery, the EF of rats was assessed by electrical stimulation of the CNs. The intracavernous pressure (ICP) and mean arterial pressure (MAP) were monitored during stimulations at various frequencies. The main outcome, that is, the rigidity of the erections, was defined as the ICP/MAP ratio. At 10 Hz, the ICP/MAP ratios were 41.8%, 34.7%, 20.9%, 33.9% and 20.5%, respectively. The EF was significantly lower in rats if the CNCI was treated with a vein graft instead of an artificial guide. Contrary to cases of CN resection, autologous vein grafts did not improve EF after CNCI. In terms of clinical use, the study suggests to limit an eventual use of autologous vein grafts to non-nerve-sparing RPs.

  14. Publications on Peripheral Nerve Injuries during World War I: A Dramatic Increase in Knowledge.

    PubMed

    Koehler, Peter J

    2016-01-01

    Publications from French (Jules Tinel and Chiriachitza Athanassio-Bénisty), English (James Purves-Stewart, Arthur Henry Evans and Hartley Sidney Carter), German (Otfrid Foerster and Hermann Oppenheim) and American (Charles Harrison Frazier and Byron Stookey) physicians from both sides of the front during World War I (WWI) contributed to a dramatic increase in knowledge about peripheral nerve injuries. Silas Weir Mitchell's original experience with respect to these injuries, and particularly causalgia, during the American Civil War was further expanded in Europe during WWI. Following the translation of one of his books, he was referred to mainly by French physicians. During WWI, several French books were in turn translated into English, which influenced American physicians, as was observed in the case of Byron Stookey. The establishment of neurological centres played an important role in the concentration of experience and knowledge. Several eponyms originated during this period (including the Hoffmann-Tinel sign and the Froment sign). Electrodiagnostic tools were increasingly used. PMID:27035152

  15. Astragalus extract alleviates nerve injury after cerebral ischemia by improving energy metabolism and inhibiting apoptosis.

    PubMed

    Huang, Xiao-Ping; Tan, Hua; Chen, Bei-Yang; Deng, Chang-Qing

    2012-01-01

    This aim of this study was to explore the effects and molecular mechanisms of Astragalus extract against cerebral ischemia injury through the energy metabolism and apoptosis pathways of c‑Jun N-terminal kinase (JNK) signal transduction. After the bilateral common carotid artery of C57BL/6 mice was occluded for 20 min followed by 1-h reperfusion, the ATP content, total adenine nucleotides (TAN), energy charge (EC), and sodium potassium ATPase (Na(+)-K(+)‑ATPase) activity were decreased markedly in brain tissues. Astragalus extract markedly increased the ATP and ADP levels, EC value, and Na(+)-K(+)-ATPase activity. Twenty-four and 48 h after reperfusion, the neurocyte survival rate decreased and apoptosis rate increased, while the expression of phosphorylated JNK1/2, cytochrome c (Cyt C), and cysteine aspartic acid-specific protease (caspase)-9 and -3 were significantly enhanced in brain tissues. Astragalus extract significantly increased neurocyte survival and decreased the apoptosis rate as well as down-regulated the expression of p-JNK1/2, Cyt C, caspase-9, and caspase-3. These results suggest that Astragalus extract has neuroprotective effects against nerve injury after cerebral ischemia-reperfusion, and the underlying mechanism may be associated with improved cellular energy metabolism, inhibition of JNK signal transduction pathway activation, and then suppression of the mitochondrial apoptosis pathway.

  16. Injury-induced activation of ERK 1/2 in the sciatic nerve of healthy and diabetic rats.

    PubMed

    Stenberg, Lena; Kanje, Martin; Mårtensson, Lisa; Dahlin, Lars B

    2011-01-26

    Phosphorylation of extracellular-signal-regulated kinase 1/2 (p-ERK 1/2) was investigated by immunohistochemistry at 30 min, 1 h, and 48 h after nerve transection in the sciatic nerve of healthy and diabetic [streptozotocin (STZ)-induced diabetes mellitus and BioBreeding (BB; i.e. DR.lyp/lyp or BBDP)] rats. Transection injury increased the intensity of p-ERK 1/2 in nerve stumps at all time points. Staining was confined to Schwann cells with occasional faint staining in single axons. In diabetic rats, a lower intensity of p-ERK 1/2 was found at 1 and 48 h in the distal and proximal nerve stumps compared with healthy rats. STZ-induced diabetic rats were not different from BB rats. p-ERK 1/2 is activated differentially in Schwann cells after nerve injury in diabetic rats, whereas activation in STZ-induced diabetic rats did not differ from BB rats.

  17. 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. PMID:26529641

  18. Effects of exogenous neurotrophin-3 on myocyte apoptosis and Ca2+-ATP enzyme levels following nerve injury in rats

    PubMed Central

    Dong, Yu-Zhen; Yang, Lin; Lu, Tan; Zhao, Hong-Xing; Ma, Chao; Zhao, Yi-Lei

    2015-01-01

    This study aims to determine the influence of neurotrophin-3 (NT-3) plasmids on neuronal apoptosis and Ca2+-ATP enzyme levels in injured muscles. We also investigated the mechanism underlying the role of NT-3 in delaying muscle atrophy following a peripheral nerve injury. Sixty adult Wistar rats were used to generate the peripheral nerve injury models. The rats were randomly assigned to the saline and NT-3 groups. Related indicators, such as caspase-3 protein expression, skeletal muscle cell apoptosis, and Ca2+-ATP enzyme expression were quantified. The expression levels of caspase-3 and the histone-muscle cell apoptosis rate in the NT-3 group decreased at different post-operative times following peripheral nerve injury, whereas NT-3 expression and the sarcoplasmic reticulum Ca2+-ATP enzyme levels increased. Statistically significant differences were observed in the NT-3 group as compared to the saline group (P < 0.05). NT-3 mitigated muscle atrophy following peripheral nerve damage by inhibiting caspase-3 gene expression and increasing Ca2+-ATP enzymatic activity, ultimately reducing muscle apoptosis. PMID:26770627

  19. 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.

  20. 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.

  1. Transcriptional repression of the M channel subunit Kv7.2 in chronic nerve injury

    PubMed Central

    Rose, Kirstin; Ooi, Lezanne; Dalle, Carine; Robertson, Brian; Wood, Ian C.; Gamper, Nikita

    2011-01-01

    Neuropathic pain is a severe health problem for which there is a lack of effective therapy. A frequent underlying condition of neuropathic pain is a sustained overexcitability of pain-sensing (nociceptive) sensory fibres. Therefore, the identification of mechanisms for such abnormal neuronal excitability is of utmost importance for understanding neuropathic pain. Despite much effort, an inclusive model explaining peripheral overexcitability is missing. We investigated transcriptional regulation of the Kcnq2 gene, which encodes the Kv7.2 subunit of membrane potential-stabilizing M channel, in peripheral sensory neurons in a model of neuropathic pain—partial sciatic nerve ligation (PSNL). We show that Kcnq2 is the major Kcnq gene transcript in dorsal root ganglion (DRG); immunostaining and patch-clamp recordings from acute ganglionic slices verified functional expression of Kv7.2 in small-diameter nociceptive DRG neurons. Neuropathic injury induced substantial downregulation of Kv7.2 expression. Levels of repressor element 1–silencing transcription factor (REST), which is known to suppress Kcnq2 expression, were upregulated in response to neuropathic injury identifying the likely mechanism of Kcnq2 regulation. Behavioural experiments demonstrated that neuropathic hyperalgesia following PSNL developed faster than the downregulation of Kcnq2 expression could be detected, suggesting that this transcriptional mechanism may contribute to the maintenance rather than the initiation of neuropathic pain. Importantly, the decrease in the peripheral M channel abundance could be functionally compensated by peripherally applied M channel opener flupirtine, which alleviated neuropathic hyperalgesia. Our work suggests a novel mechanism for neuropathic overexcitability and brings focus on M channels and REST as peripheral targets for the treatment of neuropathic pain. Neuropathic injury induces transcriptional downregulation of the Kcnq2 potassium channel gene by the

  2. 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

  3. Nerve injury reduces responses of hypoglossal motoneurones to baseline and chemoreceptor-modulated inspiratory drive in the adult rat

    PubMed Central

    González-Forero, David; Portillo, Federico; Sunico, Carmen R; Moreno-López, Bernardo

    2004-01-01

    The effects of peripheral nerve lesions on the membrane and synaptic properties of motoneurones have been extensively studied. However, minimal information exists about how these alterations finally influence discharge activity and motor output under physiological afferent drive. The aim of this work was to evaluate the effect of hypoglossal (XIIth) nerve crushing on hypoglossal motoneurone (HMN) discharge in response to the basal inspiratory afferent drive and its chemosensory modulation by CO2. The evolution of the lesion was assessed by recording the compound muscle action potential evoked by XIIth nerve stimulation, which was lost on crushing and then recovered gradually to control values from the second to fourth weeks post-lesion. Basal inspiratory activities recorded 7 days post-injury in the nerve proximal to the lesion site, and in the nucleus, were reduced by 51.6% and 35.8%, respectively. Single unit antidromic latencies were lengthened by lesion, and unusually high stimulation intensities were frequently required to elicit antidromic spikes. Likewise, inspiratory modulation of unitary discharge under conditions in which chemoreceptor drive was varied by altering end-tidal CO2 was reduced by more than 60%. Although the general recruitment scheme was preserved after XIIth nerve lesion, we noticed an increased proportion of low-threshold units and a reduced recruitment gain across the physiological range. Immunohistochemical staining of synaptophysin in the hypoglossal nuclei revealed significant reductions of this synaptic marker after nerve injury. Morphological and functional alterations recovered with muscle re-innervation. Thus, we report here that nerve lesion induced changes in the basal activity and discharge modulation of HMNs, concurrent with the loss of afferent inputs. Nevertheless, we suggest that an increase in membrane excitability, reported by others, and in the proportion of low-threshold units, could serve to preserve minimal electrical

  4. Preliminary Investigation on Use of High-Resolution Optical Coherence Tomography to Monitor Injury and Repair in the Rat Sciatic Nerve

    PubMed Central

    Chlebicki, Cara A.; Lee, Alice D.; Jung, Woonggyu; Li, Hongrui; Liaw, Lih-Huei; Chen, Zhongping; Wong, Brian J.

    2010-01-01

    Background and Objective Optical coherence tomography (OCT) has been used in limited settings to study peripheral nerve injury. The purpose of the study is to determine whether high-resolution OCT can be used to monitor nerve injury and regeneration in the rat sciatic nerve following crush injury, ligation, and transection with microsurgical repair. Study Design/Materials and Methods Forty-five rats were segregated into three groups. The right sciatic nerve was suture ligated (n = 15), cut then microsurgically repaired (n = 15), or crushed (n = 15). The left sciatic nerve served as the control; only surgical exposure and skin closure were performed. Each group was further divided into three subgroups where they were assigned survival durations of 4, 15, or 24 weeks. Following euthanasia, nerves were harvested, fixed in formalin, and imaged at the injury site, as well as proximal and distal ends. The OCT system resolution was approximately 7 μm in tissue with a 1,060 nm central wavelength. Results Control (uninjured) nerve tissue showed homogenous signal distribution to a relatively uniform depth; in contrast, damaged nerves showed irregular signal distribution and intensity. Changes in signal distribution were most significant at the injury site and distal regions. Increases in signal irregularity were evident during longer recovery times. Histological analysis determined that OCT imaging was limited to the surrounding perineurium and scar tissue. Conclusion OCT has the potential to be a valuable tool for monitoring nerve injury and repair, and the changes that accompany wound healing, providing clinicians with a non-invasive tool to treat nerve injuries. PMID:20432279

  5. 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

  6. Periprostatic implantation of neural differentiated mesenchymal stem cells restores cavernous nerve injury-mediated erectile dysfunction

    PubMed Central

    Fang, Jia-Feng; Jia, Chang-Chang; Zheng, Zong-Heng; Ye, Xiao-Long; Wei, Bo; Huang, Li-Jun; Wei, Hong-Bo

    2016-01-01

    Mesenchymal stem cells (MSCs) have been utilized to restore erectile function in animal models of cavernous nerve injury (CNI). However, transplantation of primary MSCs may lead to unpredictable therapeutic outcomes. In this study, we investigated the efficiency of neural differentiated MSCs (d-MSCs) on the restoration of erectile function in CNI rats. Rat bone marrow MSCs (r-BM-MSCs) were treated with all-trans retinoic acid to induce neural differentiation. Rats were divided into five groups: a sham operation group; a bilateral CNI group that received an intracavernous injection of r-BM-MSCs (IC group); and three groups that received periprostatic implantation of either r-BM-MSCs (IP group), d-MSCs (IP-d group), or PBS (PBS group). The data revealed that IP injection of d-MSCs ameliorated erectile function in a similar manner to an IC injection of MSCs and enhanced erectile function compared to an IP injection of MSCs. An in vivo time course of d-MSCs survival revealed that PKH26-labled d-MSCs were detectable either within or surrounding the cavernous nerve tissue. In addition, the expression of caspase-3 significantly increased in the PBS group and decreased after treatment with MSCs, especially in the IC and IP-d groups. Furthermore, the expression levels of neurotrophic factors increased significantly in d-MSCs. This study demonstrated that periprostatic implantation of d-MSCs effectively restored erectile function in CNI rats. The mechanism might be ascribed to decreases in the frequency of apoptotic cells, as well as paracrine signaling by factors derived from d-MSCs. PMID:27398139

  7. FK506 Neuroprotection after Cavernous Nerve Injury is Mediated by Thioredoxin and Glutathione Redox Systems

    PubMed Central

    Lagoda, Gwen; Xie, Yi; Sezen, Sena F.; Hurt, K. Joseph; Liu, Limin; Musicki, Biljana; Burnett, Arthur L.

    2015-01-01

    Introduction Immunophilin ligands such as FK506 (FK) preserve erectile function (EF) following cavernous nerve injury (CNI), although the precise mechanisms are unclear. We examined whether the thioredoxin (Trx) and glutathione (GSH) redox systems mediate this effect after CNI. Aim Investigate the roles of Trx reductase 2 (TrxR2) and S-Nitrosoglutathione reductase (GSNOR) as antioxidative/nitrosative and antiapoptotic mediators of the neuroprotective effect of FK in the penis after CNI. Methods Adult male rats, wild-type (WT) mice, and GSNOR deficient (GSNOR −/−) mice were divided into four groups: sham surgery (CN exposure only) + vehicle; sham surgery + FK (5mg/kg/day/rat or 2mg/kg/day/mouse, for 2 days, subcutaneous); CNI + vehicle; and CNI + FK. At day 4 after injury, electrically stimulated changes in intracavernosal pressure (ICP) were measured. Penes were collected for Western blot analysis of TrxR2, GSNOR and Bcl-2 and for immunolocalization of TrxR2 and GSNOR. Main Outcome Measures EF assessment represented by maximal ICP and total ICP in response to electrical stimulation. Evaluation of protein expression levels and distribution patterns of antioxidative/nitrosative and antiapoptotic factors in penile tissue. Results EF decreased after CNI compared with sham surgery values in both rats (p<0.01) and WT and GSNOR −/− mice (p<0.05). FK treatment preserved EF after CNI compared with vehicle treatment in rats (p<0.01) and WT mice (p<0.05) but not in GSNOR −/− mice. In rats, GSNOR (p<0.01) and Bcl-2 (p<0.05) expressions were significantly decreased after CNI. FK treatment in CN-injured rats restored expression of GSNOR and upregulated TrxR2 (p<0.001) and Bcl-2 (p<0.001) expressions compared with vehicle treatment. Localizations of proteins in the penis were observed for: TrxR2 (endothelium, smooth muscle) and for GSNOR (nerves, endothelium, smooth muscle). Conclusions The neuroprotective effect of FK in preserving EF after CNI involves antioxidative

  8. Lingual nerve injury subsequent to wisdom teeth removal--a 5-year retrospective audit from a high street dental practice.

    PubMed

    Malden, N J; Maidment, Y G

    2002-08-24

    Lingual nerve damage subsequent to lower wisdom tooth removal affects a small number of patients, sometimes producing permanent sensory loss or impairment. A number of surgical techniques have been described which are associated with low incidences of this distressing post-operative complication. When a technique is adopted by an individual clinician then a personal audit may be prudent to establish how effective it is in relation to established nerve injury rates. This audit looks at a technique involving the minimal interference of lingual soft tissues during lower wisdom tooth removal in a high street practice situation for patients having mild to moderate impacted wisdom teeth removed under local anaesthetic. It was concluded that the technique employed was associated with a low incidence of lingual nerve trauma, comparable with that reported elsewhere. PMID:12222906

  9. 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

  10. 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.

  11. A comparison between complete immobilisation and protected active mobilisation in sensory nerve recovery following isolated digital nerve injury.

    PubMed

    Henry, F P; Farkhad, R I; Butt, F S; O'Shaughnessy, M; O'Sullivan, S T

    2012-06-01

    Post-operative immobilisation following isolated digital nerve repair remains a controversial issue amongst the microsurgical community. Protocols differ from unit to unit and even, as evidenced in our unit, may differ from consultant to consultant. We undertook a retrospective review of 46 patients who underwent isolated digital nerve repair over a 6-month period. Follow-up ranged from 6 to 18 months. Twenty-four were managed with protected active mobilisation over a 4-week period while 22 were immobilised over the same period. Outcomes such as return to work, cold intolerance, two-point discrimination and temperature differentiation were used as indicators of clinical recovery. Our results showed that there was no significant difference noted in either clinical assessment of recovery or return to work following either post-operative protocol, suggesting that either regime may be adopted, tailored to the patient's needs and resources of the unit.

  12. Effect of an Adipose-Derived Stem Cell and Nerve Growth Factor-Incorporated Hydrogel on Recovery of Erectile Function in a Rat Model of Cavernous Nerve Injury

    PubMed Central

    Kim, In Gul; Piao, Shuyu; Lee, Ji Young; Hong, Sung Hoo; Hwang, Tae-Kon; Kim, Sae Woong; Kim, Choung Soo; Ra, Jeong Chan; Noh, Insup

    2013-01-01

    Postprostatectomy erectile dysfunction (ED) is the major problem for patients with clinically localized prostate cancer. Recently, gene and stem cell-based therapy of the corpus cavernosum has been attempted for postprostatectomy ED, but those therapies are limited by rapid blood flow and disruption of the normal architecture of the corpus cavernosum. In this study, we attempted to regenerate the damaged cavernous nerve (CN), which is the main cause of ED. We investigated the effectiveness of human adipose-derived stem cell (hADSC) and nerve growth factor-incorporated hyaluronic acid-based hydrogel (NGF-hydrogel) application on the CN in a rat model of bilateral cavernous nerve crush injury. Four weeks after the operation, erectile function was assessed by detecting the intracavernous pressure (ICP)/arterial pressure level by CN electrostimulation. The ICP was significantly increased by application of hADSC with NGF-hydrogel compared to the other experimental groups. CN and penile tissue were collected for histological examination. PKH-26 labeled hADSC colocalized with beta III tubulin were shown in CN tissue sections. hADSC/NGF-hydrogel treatment prevented smooth muscle atrophy in the corpus cavernosum. In addition, the hADSC/NGF-hydrogel group showed increased endothelial nitric oxide synthase protein expression. This study suggests that application of hADSCs with NGF-hydrogel on the CN might be a promising treatment for postprostatectomy ED. PMID:22834730

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

    PubMed

    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

  14. 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

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

    PubMed

    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.

  16. Combinatorial therapy stimulates long-distance regeneration, target reinnervation, and partial recovery of vision after optic nerve injury in mice.

    PubMed

    de Lima, Silmara; Habboub, Ghaith; Benowitz, Larry I

    2012-01-01

    The optic nerve has been widely studied for insights into mechanisms that suppress or promote axon regeneration after central nervous system injury. Following optic nerve damage in adult mammals, retinal ganglion cells (RGCs) normally fail to regenerate their axons, resulting in blindness in patients who suffer from neurodegenerative diseases such as glaucoma or who have sustained traumatic injury to the optic nerve. Over the past several decades, many groups have investigated the basis of regenerative failure in the hope of developing strategies to stimulate the regrowth of axons and restore visual function. New findings show that a combination of therapies that act synergistically to activate RGCs' intrinsic growth state enables these cells to regenerate their axons the full length of the optic nerve, across the optic chiasm, and into the brain, where they establish synapses in appropriate target zones and restore limited visual responses. These treatments involve the induction of a limited inflammatory response in the eye to increase levels of oncomodulin and other growth factors; elevation of intracellular cAMP; and deletion of the pten gene in RGCs. Although these methods cannot be applied in the clinic, they point to strategies that might be.

  17. 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

  18. Sleep Deprivation Aggravates Median Nerve Injury-Induced Neuropathic Pain and Enhances Microglial Activation by Suppressing Melatonin Secretion

    PubMed Central

    Huang, Chun-Ta; Chiang, Rayleigh Ping-Ying; Chen, Chih-Li; Tsai, Yi-Ju

    2014-01-01

    Study Objectives: Sleep deprivation is common in patients with neuropathic pain, but the effect of sleep deprivation on pathological pain remains uncertain. This study investigated whether sleep deprivation aggravates neuropathic symptoms and enhances microglial activation in the cuneate nucleus (CN) in a median nerve chronic constriction injury (CCI) model. Also, we assessed if melatonin supplements during the sleep deprived period attenuates these effects. Design: Rats were subjected to sleep deprivation for 3 days by the disc-on-water method either before or after CCI. In the melatonin treatment group, CCI rats received melatonin supplements at doses of 37.5, 75, 150, or 300 mg/kg during sleep deprivation. Melatonin was administered at 23:00 once a day. Participants: Male Sprague-Dawley rats, weighing 180-250 g (n = 190), were used. Measurements: Seven days after CCI, behavioral testing was conducted, and immunohistochemistry, immunoblotting, and enzyme-linked immunosorbent assay were used for qualitative and quantitative analyses of microglial activation and measurements of proinflammatory cytokines. Results: In rats who underwent post-CCI sleep deprivation, microglia were more profoundly activated and neuropathic pain was worse than those receiving pre-CCI sleep deprivation. During the sleep deprived period, serum melatonin levels were low over the 24-h period. Administration of melatonin to CCI rats with sleep deprivation significantly attenuated activation of microglia and development of neuropathic pain, and markedly decreased concentrations of proinflammatory cytokines. Conclusions: Sleep deprivation makes rats more vulnerable to nerve injury-induced neuropathic pain, probably because of associated lower melatonin levels. Melatonin supplements to restore a circadian variation in melatonin concentrations during the sleep deprived period could alleviate nerve injury-induced behavioral hypersensitivity. Citation: Huang CT, Chiang RP, Chen CL, Tsai YJ. Sleep

  19. Vagus Nerve Stimulation and Other Neuromodulation Methods for Treatment of Traumatic Brain Injury.

    PubMed

    Neren, Daniel; Johnson, Matthew D; Legon, Wynn; Bachour, Salam P; Ling, Geoffrey; Divani, Afshin A

    2016-04-01

    The objective of this paper is to review the current literature regarding the use of vagus nerve stimulation (VNS) in preclinical models of traumatic brain injury (TBI) as well as discuss the potential role of VNS along with alternative neuromodulation approaches in the treatment of human TBI. Data from previous studies have demonstrated VNS-mediated improvement following TBI in animal models. In these cases, VNS was observed to enhance motor and cognitive recovery, attenuate cerebral edema and inflammation, reduce blood brain barrier breakdown, and confer neuroprotective effects. Yet, the underlying mechanisms by which VNS enhances recovery following TBI remain to be fully elucidated. Several hypotheses have been offered including: a noradrenergic mechanism, reduction in post-TBI seizures and hyper-excitability, anti-inflammatory effects, attenuation of blood-brain barrier breakdown, and cerebral edema. We present other potential mechanisms by which VNS acts including enhancement of synaptic plasticity and recruitment of endogenous neural stem cells, stabilization of intracranial pressure, and interaction with the ghrelin system. In addition, alternative methods for the treatment of TBI including deep brain stimulation, transcranial magnetic stimulation, transcranial direct current stimulation, and focused ultrasound stimulation are discussed. Although the primary source data show that VNS improves TBI outcomes, it remains to be determined if these findings can be translated to clinical settings. PMID:26399249

  20. 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

  1. 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

  2. Patterns of Phrenic Nerve Discharge after Complete High Cervical Spinal Cord Injury in the Decerebrate Rat.

    PubMed

    Ghali, Michael George Zaki; Marchenko, Vitaliy

    2016-06-15

    Studies conducted since the second half of the 19th century have revealed spontaneous as well as pharmacologically induced phasic/rhythmic discharge in spinal respiratory motor outputs of cats, dogs, rabbits, and neonatal rats following high cervical transection (Tx). The extent to which these various studies validate the existence of a true spinal respiratory rhythm generator remains debated. In this set of studies, we seek to characterize patterns of spontaneous phasic/rhythmic, asphyxia-induced, and pharmacologically induced activity occurring in phrenic nerve (PhN) discharge after complete high cervical (C1-C2) spinal cord transection. Experiments were performed on 20 unanesthetized decerebrate Sprague-Dawley adult male rats. Patterns of spontaneous activity after spinalization included tonic, phasic, slow oscillatory, and long-lasting tonic discharges. Topical application of antagonists of GABAA and glycine receptors to C1- and C2- spinal segments induced left-right synchronized phasic decrementing activity in PhN discharge that was abolished by an additional C2Tx. Asphyxia elicited increases in tonic activity and left-right synchronized gasp-like bursts in PhN discharge, demonstrating the presence of spinal circuits that may underlie a spinal gasping-like mechanism. We conclude that intrinsic slow oscillators and a phasic burst/rhythm generator exist in the spinal cord of the adult rat. If present in humans, this mechanism may be exploited to recover respiratory function in patients sustaining severe spinal cord injury. PMID:26239508

  3. 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

  4. 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

  5. Susceptibility to chronic pain following nerve injury is genetically affected by CACNG2.

    PubMed

    Nissenbaum, Jonathan; Devor, Marshall; Seltzer, Ze'ev; Gebauer, Mathias; Michaelis, Martin; Tal, Michael; Dorfman, Ruslan; Abitbul-Yarkoni, Merav; Lu, Yan; Elahipanah, Tina; delCanho, Sonia; Minert, Anne; Fried, Kaj; Persson, Anna-Karin; Shpigler, Hagai; Shabo, Erez; Yakir, Benjamin; Pisanté, Anne; Darvasi, Ariel

    2010-09-01

    Chronic neuropathic pain is affected by specifics of the precipitating neural pathology, psychosocial factors, and by genetic predisposition. Little is known about the identity of predisposing genes. Using an integrative approach, we discovered that CACNG2 significantly affects susceptibility to chronic pain following nerve injury. CACNG2 encodes for stargazin, a protein intimately involved in the trafficking of glutamatergic AMPA receptors. The protein might also be a Ca(2+) channel subunit. CACNG2 has previously been implicated in epilepsy. Initially, using two fine-mapping strategies in a mouse model (recombinant progeny testing [RPT] and recombinant inbred segregation test [RIST]), we mapped a pain-related quantitative trait locus (QTL) (Pain1) into a 4.2-Mb interval on chromosome 15. This interval includes 155 genes. Subsequently, bioinformatics and whole-genome microarray expression analysis were used to narrow the list of candidates and ultimately to pinpoint Cacng2 as a likely candidate. Analysis of stargazer mice, a Cacng2 hypomorphic mutant, provided electrophysiological and behavioral evidence for the gene's functional role in pain processing. Finally, we showed that human CACNG2 polymorphisms are associated with chronic pain in a cohort of cancer patients who underwent breast surgery. Our findings provide novel information on the genetic basis of neuropathic pain and new insights into pain physiology that may ultimately enable better treatments.

  6. Susceptibility to chronic pain following nerve injury is genetically affected by CACNG2

    PubMed Central

    Nissenbaum, Jonathan; Devor, Marshall; Seltzer, Ze'ev; Gebauer, Mathias; Michaelis, Martin; Tal, Michael; Dorfman, Ruslan; Abitbul-Yarkoni, Merav; Lu, Yan; Elahipanah, Tina; delCanho, Sonia; Minert, Anne; Fried, Kaj; Persson, Anna-Karin; Shpigler, Hagai; Shabo, Erez; Yakir, Benjamin; Pisanté, Anne; Darvasi, Ariel

    2010-01-01

    Chronic neuropathic pain is affected by specifics of the precipitating neural pathology, psychosocial factors, and by genetic predisposition. Little is known about the identity of predisposing genes. Using an integrative approach, we discovered that CACNG2 significantly affects susceptibility to chronic pain following nerve injury. CACNG2 encodes for stargazin, a protein intimately involved in the trafficking of glutamatergic AMPA receptors. The protein might also be a Ca2+ channel subunit. CACNG2 has previously been implicated in epilepsy. Initially, using two fine-mapping strategies in a mouse model (recombinant progeny testing [RPT] and recombinant inbred segregation test [RIST]), we mapped a pain-related quantitative trait locus (QTL) (Pain1) into a 4.2-Mb interval on chromosome 15. This interval includes 155 genes. Subsequently, bioinformatics and whole-genome microarray expression analysis were used to narrow the list of candidates and ultimately to pinpoint Cacng2 as a likely candidate. Analysis of stargazer mice, a Cacng2 hypomorphic mutant, provided electrophysiological and behavioral evidence for the gene's functional role in pain processing. Finally, we showed that human CACNG2 polymorphisms are associated with chronic pain in a cohort of cancer patients who underwent breast surgery. Our findings provide novel information on the genetic basis of neuropathic pain and new insights into pain physiology that may ultimately enable better treatments. PMID:20688780

  7. Vagus Nerve Stimulation and Other Neuromodulation Methods for Treatment of Traumatic Brain Injury.

    PubMed

    Neren, Daniel; Johnson, Matthew D; Legon, Wynn; Bachour, Salam P; Ling, Geoffrey; Divani, Afshin A

    2016-04-01

    The objective of this paper is to review the current literature regarding the use of vagus nerve stimulation (VNS) in preclinical models of traumatic brain injury (TBI) as well as discuss the potential role of VNS along with alternative neuromodulation approaches in the treatment of human TBI. Data from previous studies have demonstrated VNS-mediated improvement following TBI in animal models. In these cases, VNS was observed to enhance motor and cognitive recovery, attenuate cerebral edema and inflammation, reduce blood brain barrier breakdown, and confer neuroprotective effects. Yet, the underlying mechanisms by which VNS enhances recovery following TBI remain to be fully elucidated. Several hypotheses have been offered including: a noradrenergic mechanism, reduction in post-TBI seizures and hyper-excitability, anti-inflammatory effects, attenuation of blood-brain barrier breakdown, and cerebral edema. We present other potential mechanisms by which VNS acts including enhancement of synaptic plasticity and recruitment of endogenous neural stem cells, stabilization of intracranial pressure, and interaction with the ghrelin system. In addition, alternative methods for the treatment of TBI including deep brain stimulation, transcranial magnetic stimulation, transcranial direct current stimulation, and focused ultrasound stimulation are discussed. Although the primary source data show that VNS improves TBI outcomes, it remains to be determined if these findings can be translated to clinical settings.

  8. Atf3 mutant mice show reduced axon regeneration and impaired regeneration-associated gene induction after peripheral nerve injury.

    PubMed

    Gey, Manuel; Wanner, Renate; Schilling, Corinna; Pedro, Maria T; Sinske, Daniela; Knöll, Bernd

    2016-08-01

    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. Epigenetic modification of DRG neuronal gene expression subsequent to nerve injury: Etiological contribution to complex regional pain syndromes (Part I)

    PubMed Central

    Wang, Fuzhou; Stefano, George B.; Kream, Richard M.

    2014-01-01

    DRG is of importance in relaying painful stimulation to the higher pain centers and therefore could be a crucial target for early intervention aimed at suppressing primary afferent stimulation. Complex regional pain syndrome (CRPS) is a common pain condition with an unknown etiology. Recently added new information enriches our understanding of CRPS pathophysiology. Researches on genetics, biogenic amines, neurotransmitters, and mechanisms of pain modulation, central sensitization, and autonomic functions in CRPS revealed various abnormalities indicating that multiple factors and mechanisms are involved in the pathogenesis of CRPS. Epigenetics refers to mitotically and meiotically heritable changes in gene expression that do not affect the DNA sequence. As epigenetic modifications potentially play an important role in inflammatory cytokine metabolism, neurotransmitter responsiveness, and analgesic sensitivity, they are likely key factors in the development of chronic pain. In this dyad review series, we systematically examine the nerve injury-related changes in the neurological system and their contribution to CRPS. In this part, we first reviewed and summarized the role of neural sensitization in DRG neurons in performing function in the context of pain processing. Particular emphasis is placed on the cellular and molecular changes after nerve injury as well as different models of inflammatory and neuropathic pain. These were considered as the potential molecular bases that underlie nerve injury-associated pathogenesis of CRPS. PMID:24961509

  10. 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. PMID:27460962

  11. 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.

  12. 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

  13. 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

  14. Inhibition of Rho-Kinase Improves Erectile Function, Increases Nitric Oxide Signaling and Decreases Penile Apoptosis in a Rat Model of Cavernous Nerve Injury

    PubMed Central

    Hannan, Johanna L.; Albersen, Maarten; Kutlu, Omer; Gratzke, Christian; Stief, Christian G.; Burnett, Arthur L.; Lysiak, Jeffrey J.; Hedlund, Petter; Bivalacqua, Trinity J.

    2014-01-01

    Purpose Bilateral cavernous nerve injury results in up-regulation of ROCK signaling in the penis. This is linked to erectile dysfunction in an animal model of post-prostatectomy erectile dysfunction. We evaluated whether daily treatment with the ROCK inhibitor Y-27632 (Tocris Bioscience, Ellisville, Missouri) would prevent erectile dysfunction in a rat model of bilateral cavernous nerve injury. Materials and Methods Sprague-Dawley® rats underwent surgery to create sham (14) or bilateral (27) cavernous nerve injury. In the injury group 13 rats received treatment with Y-27632 (5 mg/kg twice daily) and 14 received vehicle. At 14 days after injury, rats underwent cavernous nerve stimulation to determine erectile function. Penes were assessed for neuronal and nitric oxide synthase membrane-endothelial nitric oxide synthase. ROCK2 was assessed by Western blot. Cyclic guanosine monophosphate was determined by enzyme-linked immunosorbent assay. Cavernous homogenates were tested for ROCK and protein kinase G enzymatic activity. Penile apoptosis was evaluated using the Apostain technique (Alexis, San Diego, California). Data were analyzed on ROCK using ANOVA and the t test. Results While erectile function was decreased in rats with bilateral cavernous nerve injury, daily administration of Y-27632 improved erectile responses. Injury decreased neuronal and nitric oxide synthase membrane-endothelial nitric oxide synthase but ROCK2 was significantly increased. Y-27632 treatment restored neuronal nitric oxide synthase, nitric oxide synthase membrane-endothelial nitric oxide synthase and cyclic guanosine monophosphate levels, and protein kinase G activity. Treatment significantly decreased ROCK2 protein and ROCK activity. There were significantly fewer apoptotic cells after treatment than in injured controls. Conclusions These results provide evidence for up-regulation of the RhoA/ROCK signaling pathway with detrimental effects on erectile function after bilateral cavernous nerve

  15. Dopaminergic inhibition by G9a/Glp complex on tyrosine hydroxylase in nerve injury-induced hypersensitivity

    PubMed Central

    Wang, Nan; Shen, Xiaofeng; Bao, Senzhu; Feng, Shan-Wu; Wang, Wei; Liu, Yusheng; Wang, Yiquan; Wang, Xian; Guo, Xirong; Shen, Rong; Wu, Haibo; Lei, Liming; Wang, Fuzhou

    2016-01-01

    The neural balance between facilitation and inhibition determines the final tendency of central sensitization. Nerve injury-induced hypersensitivity was considered as the results from the enhanced ascending facilitation and the diminished descending inhibition. The role of dopaminergic transmission in the descending inhibition has been well documented, but its underlying molecular mechanisms are unclear. Previous studies demonstrated that the lysine dimethyltransferase G9a/G9a-like protein (Glp) complex plays a critical role in cocaine-induced central plasticity, and given cocaine’s role in the nerve system is relied on its function on dopamine system, we herein proposed that the reduced inhibition of dopaminergic transmission was from the downregulation of tyrosine hydroxylase expression by G9a/Glp complex through methylating its gene Th. After approval by the Animal Care and Use Committee, C57BL/6 mice were used for pain behavior using von Frey after spared nerve injury, and Th CpG islands methylation was measured using bisulfite sequencing at different nerve areas. The inhibitor of G9a/Glp, BIX 01294, was administered intraventricularly daily with bolus injection. The protein levels of G9a, Glp, and tyrosine hydroxylase were measured with immunoblotting. Dopamine levels were detected using high-performance liquid chromatography. The expression of G9a but not Glp was upregulated in ventral tegmental area at post-injury day 4 till day 49 (the last day of the behavioral test). Correspondingly, the Th CpG methylation is increased, but the tyrosine hydroxylase expression was downregulated and the dopamine level was decreased. After the intracerebroventriclar injection of BIX 01294 since the post-injury days 7 and 14 for consecutive three days, three weeks, and six weeks, the expression of tyrosine hydroxylase was upregulated with a significant decrease in Th methylation and increase in dopamine level. Moreover, the pain after G9a/Glp inhibitor was attenuated

  16. Dopaminergic inhibition by G9a/Glp complex on tyrosine hydroxylase in nerve injury-induced hypersensitivity.

    PubMed

    Wang, Nan; Shen, Xiaofeng; Bao, Senzhu; Feng, Shan-Wu; Wang, Wei; Liu, Yusheng; Wang, Yiquan; Wang, Xian; Guo, Xirong; Shen, Rong; Wu, Haibo; Lei, Liming; Xu, Shiqin; Wang, Fuzhou

    2016-01-01

    The neural balance between facilitation and inhibition determines the final tendency of central sensitization. Nerve injury-induced hypersensitivity was considered as the results from the enhanced ascending facilitation and the diminished descending inhibition. The role of dopaminergic transmission in the descending inhibition has been well documented, but its underlying molecular mechanisms are unclear. Previous studies demonstrated that the lysine dimethyltransferase G9a/G9a-like protein (Glp) complex plays a critical role in cocaine-induced central plasticity, and given cocaine's role in the nerve system is relied on its function on dopamine system, we herein proposed that the reduced inhibition of dopaminergic transmission was from the downregulation of tyrosine hydroxylase expression by G9a/Glp complex through methylating its gene Th After approval by the Animal Care and Use Committee, C57BL/6 mice were used for pain behavior using von Frey after spared nerve injury, and Th CpG islands methylation was measured using bisulfite sequencing at different nerve areas. The inhibitor of G9a/Glp, BIX 01294, was administered intraventricularly daily with bolus injection. The protein levels of G9a, Glp, and tyrosine hydroxylase were measured with immunoblotting. Dopamine levels were detected using high-performance liquid chromatography. The expression of G9a but not Glp was upregulated in ventral tegmental area at post-injury day 4 till day 49 (the last day of the behavioral test). Correspondingly, the Th CpG methylation is increased, but the tyrosine hydroxylase expression was downregulated and the dopamine level was decreased. After the intracerebroventriclar injection of BIX 01294 since the post-injury days 7 and 14 for consecutive three days, three weeks, and six weeks, the expression of tyrosine hydroxylase was upregulated with a significant decrease in Th methylation and increase in dopamine level. Moreover, the pain after G9a/Glp inhibitor was attenuated

  17. Electrospun and woven silk fibroin/poly(lactic-co-glycolic acid) nerve guidance conduits for repairing peripheral nerve injury

    PubMed Central

    Wang, Ya-ling; Gu, Xiao-mei; Kong, Yan; Feng, Qi-lin; Yang, Yu-min

    2015-01-01

    We have designed a novel nerve guidance conduit (NGC) made from silk fibroin and poly(lactic-co-glycolic acid) through electrospinning and weaving (ESP-NGCs). Several physical and biological properties of the ESP-NGCs were assessed in order to evaluate their biocompatibility. The physical properties, including thickness, tensile stiffness, infrared spectroscopy, porosity, and water absorption were determined in vitro. To assess the biological properties, Schwann cells were cultured in ESP-NGC extracts and were assessed by morphological observation, the MTT assay, and immunohistochemistry. In addition, ESP-NGCs were subcutaneously implanted in the backs of rabbits to evaluate their biocompatibility in vivo. The results showed that ESP-NGCs have high porosity, strong hydrophilicity, and strong tensile stiffness. Schwann cells cultured in the ESP-NGC extract fluids showed no significant differences compared to control cells in their morphology or viability. Histological evaluation of the ESP-NGCs implanted in vivo indicated a mild inflammatory reaction and high biocompatibility. Together, these data suggest that these novel ESP-NGCs are biocompatible, and may thus provide a reliable scaffold for peripheral nerve repair in clinical application. PMID:26692862

  18. Electrospun and woven silk fibroin/poly(lactic-co-glycolic acid) nerve guidance conduits for repairing peripheral nerve injury.

    PubMed

    Wang, Ya-Ling; Gu, Xiao-Mei; Kong, Yan; Feng, Qi-Lin; Yang, Yu-Min

    2015-10-01

    We have designed a novel nerve guidance conduit (NGC) made from silk fibroin and poly(lactic-co-glycolic acid) through electrospinning and weaving (ESP-NGCs). Several physical and biological properties of the ESP-NGCs were assessed in order to evaluate their biocompatibility. The physical properties, including thickness, tensile stiffness, infrared spectroscopy, porosity, and water absorption were determined in vitro. To assess the biological properties, Schwann cells were cultured in ESP-NGC extracts and were assessed by morphological observation, the MTT assay, and immunohistochemistry. In addition, ESP-NGCs were subcutaneously implanted in the backs of rabbits to evaluate their biocompatibility in vivo. The results showed that ESP-NGCs have high porosity, strong hydrophilicity, and strong tensile stiffness. Schwann cells cultured in the ESP-NGC extract fluids showed no significant differences compared to control cells in their morphology or viability. Histological evaluation of the ESP-NGCs implanted in vivo indicated a mild inflammatory reaction and high biocompatibility. Together, these data suggest that these novel ESP-NGCs are biocompatible, and may thus provide a reliable scaffold for peripheral nerve repair in clinical application. PMID:26692862

  19. Delaying the onset of treadmill exercise following peripheral nerve injury has different effects on axon regeneration and motoneuron synaptic plasticity.

    PubMed

    Brandt, Jaclyn; Evans, Jonathan T; Mildenhall, Taylor; Mulligan, Amanda; Konieczny, Aimee; Rose, Samuel J; English, Arthur W

    2015-04-01

    Transection of a peripheral nerve results in withdrawal of synapses from motoneurons. Some of the withdrawn synapses are restored spontaneously, but those containing the vesicular glutamate transporter 1 (VGLUT1), and arising mainly from primary afferent neurons, are withdrawn permanently. If animals are exercised immediately after nerve injury, regeneration of the damaged axons is enhanced and no withdrawal of synapses from injured motoneurons can be detected. We investigated whether delaying the onset of exercise until after synapse withdrawal had occurred would yield similar results. In Lewis rats, the right sciatic nerve was cut and repaired. Reinnervation of the soleus muscle was monitored until a direct muscle (M) response was observed to stimulation of the tibial nerve. At that time, rats began 2 wk of daily treadmill exercise using an interval training protocol. Both M responses and electrically-evoked H reflexes were monitored weekly for an additional seven wk. Contacts made by structures containing VGLUT1 or glutamic acid decarboxylase (GAD67) with motoneurons were studied from confocal images of retrogradely labeled cells. Timing of full muscle reinnervation was similar in both delayed and immediately exercised rats. H reflex amplitude in delayed exercised rats was only half that found in immediately exercised animals. Unlike immediately exercised animals, motoneuron contacts containing VGLUT1 in delayed exercised rats were reduced significantly, relative to intact rats. The therapeutic window for application of exercise as a treatment to promote restoration of synaptic inputs onto motoneurons following peripheral nerve injury is different from that for promoting axon regeneration in the periphery. PMID:25632080

  20. Function-triggering antibodies to the adhesion molecule L1 enhance recovery after injury of the adult mouse femoral nerve.

    PubMed

    Guseva, Daria; Loers, Gabriele; Schachner, Melitta

    2014-01-01

    L1 is among the few adhesion molecules that favors repair after trauma in the adult central nervous system of vertebrates by promoting neuritogenesis and neuronal survival, among other beneficial features. In the peripheral nervous system, L1 is up-regulated in Schwann cells and regrowing axons after nerve damage, but the functional consequences of this expression remain unclear. Our previous study of L1-deficient mice in a femoral nerve injury model showed an unexpected improved functional recovery, attenuated motoneuronal cell death, and enhanced Schwann cell proliferation, being attributed to the persistent synthesis of neurotrophic factors. On the other hand, transgenic mice over-expressing L1 in neurons led to improved remyelination, but not improved functional recovery. The present study was undertaken to investigate whether the monoclonal L1 antibody 557 that triggers beneficial L1 functions in vitro would trigger these also in femoral nerve repair. We analyzed femoral nerve regeneration in C57BL/6J mice that received this antibody in a hydrogel filled conduit connecting the cut and sutured nerve before its bifurcation, leading to short-term release of antibody by diffusion. Video-based quantitative analysis of motor functions showed improved recovery when compared to mice treated with conduits containing PBS in the hydrogel scaffold, as a vehicle control. This improved recovery was associated with attenuated motoneuron loss, remyelination and improved precision of preferential motor reinnervation. We suggest that function-triggering L1 antibodies applied to the lesion site at the time of injury over a limited time period will not only be beneficial in peripheral, but also central nervous system regeneration. PMID:25393007

  1. Morphogenesis and morphology of the brain stem nuclei of Cetacea. II. The nuclei of the accessory, vagal and glossopharyngeal nerves in baleen whales.

    PubMed

    Jansen, J; Osen, K K

    1984-01-01

    The development and final structure of the IXth, Xth and XIth cranial nerve nuclei are studied in ironhematoxylin -, thionin - and protargol -stained serial sections of about 50 baleen whale fetuses (blue whale, Balaenoptera musculus, and fin whale, Balaenoptera physalus ) and one adult fin whale. The nucleus ambiguus is composed of three subdivisions, oral, intermediate and caudal, the last mentioned being contiguous caudally with the dorsal motor Xth nucleus. The oral division develops as three parallel cell columns which merge into a well circumscribed solitary structure with a rostrally expanded "head". It is composed of medium-sized multipolar neurons in a myelin-poor neuropil. In the fin whale a minor group of larger cells is found medial to the "head". In both species a peculiar small-celled nucleus rich in capillaries is found ventral to the "head". The intermediate division initially contains a lateral cell column and a medial region of scattered cells. The lateral column persists throughout life, while the medial field develops into three columns only one of which remains distinct in mature individuals. The cells are larger than in the oral division with the largest cells in the medial column. The two columns are surrounded by a field of scattered neurons which continues without a sharp border into the caudal division which is composed of scattered cells throughout. In its rostral half the cells are of the same multipolar type as in the intermediate division while caudally they appear flattened in the horizontal plane. The dorsal motor Xth nucleus develops as three longitudinal columns. In the fetal brain these are cytologically distinct due to different proportions of small, medium-sized and larger multipolar neurons. The spindle-shaped ventromedial column extends the entire length of the nucleus. It is composed mostly of small to medium-sized cells which caudal to the obex are elongated parallel with the neuroaxis . The dorsolateral and ventrolateral

  2. Enduring attentional deficits in rats treated with a peripheral nerve injury.

    PubMed

    Higgins, Guy A; Silenieks, Leo B; Van Niekerk, Annalise; Desnoyer, Jill; Patrick, Amy; Lau, Winnie; Thevarkunnel, Sandy

    2015-06-01

    The present study investigated the impact of a spared nerve injury (SNI) on the daily performance of rats tested in two instrumental conditioning procedures: the progressive ratio (PR) schedule of food reinforcement to study motivation for an appetitive stimulus, and the 5-choice serial reaction time task (5-CSRTT), a test of attention and reaction time. Separate groups of male, Sprague-Dawley rats of age 8-10 months were trained to asymptotic performance in either task, before undergoing either SNI or sham surgery. After a recovery period of 3-4 days the animals were run 5 days/week for 3 months in either task. Tests of responsivity to evoked tactile (Von Frey) and thermal (acetone) stimuli were also conducted over this period to check integrity of the model. Post SNI surgery, rats showed equivalent responding to sham controls for food available under a PR schedule throughout the test period, implying a similar level of motivation for a food reward. In contrast, a performance deficit emerged in SNI treated rats run in the 5-CSRTT, consistent with an attentional deficit. This deficit emerged during the second month post-surgery and was characterized by slower response speed, reduced accuracy and increased trial omissions. Both SNI groups showed equivalent hypersensitivity to evoked sensory stimuli compared to controls. Since attention based deficits have been reported in individuals with clinical forms of neuropathic pain, the present studies suggest a novel approach to study this phenomena and a means to study the effect of treatments against this cognitive endpoint. PMID:25746510

  3. Sialylated intravenous immunoglobulin suppress anti-ganglioside antibody mediated nerve injury.

    PubMed

    Zhang, Gang; Massaad, Cynthia A; Gao, Tong; Pillai, Laila; Bogdanova, Nataliia; Ghauri, Sameera; Sheikh, Kazim A

    2016-08-01

    The precise mechanisms underlying the efficacy of intravenous immunoglobulin (IVIg) in autoimmune neurological disorders including Guillain-Barré syndrome (GBS) are not known. Anti-ganglioside antibodies have been reported to be pathogenic in some variants of GBS, and we have developed passive transfer animal models to study anti-ganglioside antibody mediated-endoneurial inflammation and associated neuropathological effects and to evaluate the efficacy of new therapeutic approaches. Some studies indicate that IVIg's anti-inflammatory activity resides in a minor sialylated IVIg (sIVIg) fractions and is dependent on an innate Th2 response via binding to a specific ICAM3-grabbing nonintegrin related 1 receptor (SIGN-R1). Therefore the efficacy of IVIg, IVIg fractions with various IgG Fc sialylation status, and the involvement of Th2 pathway were examined in one of our animal model of antibody-mediated inhibition of axonal regeneration. We demonstrate that both IVIg and sIVIg ameliorated anti-glycan antibody mediated-pathological effect, whereas, the unsialylated fractions of IVIg were not beneficial in our model. Tenfold lower doses of sIVIg compared to whole IVIg provided equivalent efficacy in our studies. Moreover, we found that whole IVIg and sIVIg significantly upregulates the gene expression of IL-33, which itself can provide protection from antibody-mediated nerve injury in our model. Our results support that the SIGN-R1-Th2 pathway is involved in the anti-inflammatory effects of IVIg on endoneurium in our model and elements of this pathway including IL-33 can provide novel therapeutics in inflammatory neuropathies. PMID:27208700

  4. Increased production of omega-3 fatty acids protects retinal ganglion cells after optic nerve injury in mice.

    PubMed

    Peng, Shanshan; Shi, Zhe; Su, Huanxing; So, Kwok-Fai; Cui, Qi

    2016-07-01

    Injury to the central nervous system causes progressive degeneration of injured axons, leading to loss of the neuronal bodies. Neuronal survival after injury is a prerequisite for successful regeneration of injured axons. In this study, we investigated the effects of increased production of omega-3 fatty acids and elevation of cAMP on retinal ganglion cell (RGC) survival and axonal regeneration after optic nerve (ON) crush injury in adult mice. We found that increased production of omega-3 fatty acids in mice enhanced RGC survival, but not axonal regeneration, over a period of 3 weeks after ON injury. cAMP elevation promoted RGC survival in wild type mice, but no significant difference in cell survival was seen in mice over-producing omega-3 fatty acids and receiving intravitreal injections of CPT-cAMP, suggesting that cAMP elevation protects RGCs after injury but does not potentiate the actions of the omega-3 fatty acids. The observed omega-3 fatty acid-mediated neuroprotection is likely achieved partially through ERK1/2 signaling as inhibition of this pathway by PD98059 hindered, but did not completely block, RGC protection. Our study thus enhances our current understanding of neural repair after CNS injury, including the visual system.

  5. Accidental injury of the inferior alveolar nerve due to the extrusion of calcium hydroxide in endodontic treatment: a case report.

    PubMed

    Shin, Yooseok; Roh, Byoung-Duck; Kim, Yemi; Kim, Taehyeon; Kim, Hyungjun

    2016-02-01

    During clinical endodontic treatment, we often find radiopaque filling material beyond the root apex. Accidental extrusion of calcium hydroxide could cause the injury of inferior alveolar nerve, such as paresthesia or continuous inflammatory response. This case report presents the extrusion of calcium hydroxide and treatment procedures including surgical intervention. A 48 yr old female patient experienced Calcipex II extrusion in to the inferior alveolar canal on left mandibular area during endodontic treatment. After completion of endodontic treatment on left mandibular first molar, surgical intervention was planned under general anesthesia. After cortical bone osteotomy and debridement, neuroma resection and neurorrhaphy was performed, and prognosis was observed. But no improvement in sensory nerve was seen following surgical intervention after 20 mon. A clinician should be aware of extrusion of intracanal medicaments and the possibility of damage on inferior alveolar canal. Injectable type of calcium hydroxide should be applied with care for preventing nerve injury. The alternative delivery method such as lentulo spiral was suggested on the posterior mandibular molar. PMID:26877992

  6. Accidental injury of the inferior alveolar nerve due to the extrusion of calcium hydroxide in endodontic treatment: a case report

    PubMed Central

    2016-01-01

    During clinical endodontic treatment, we often find radiopaque filling material beyond the root apex. Accidental extrusion of calcium hydroxide could cause the injury of inferior alveolar nerve, such as paresthesia or continuous inflammatory response. This case report presents the extrusion of calcium hydroxide and treatment procedures including surgical intervention. A 48 yr old female patient experienced Calcipex II extrusion in to the inferior alveolar canal on left mandibular area during endodontic treatment. After completion of endodontic treatment on left mandibular first molar, surgical intervention was planned under general anesthesia. After cortical bone osteotomy and debridement, neuroma resection and neurorrhaphy was performed, and prognosis was observed. But no improvement in sensory nerve was seen following surgical intervention after 20 mon. A clinician should be aware of extrusion of intracanal medicaments and the possibility of damage on inferior alveolar canal. Injectable type of calcium hydroxide should be applied with care for preventing nerve injury. The alternative delivery method such as lentulo spiral was suggested on the posterior mandibular molar. PMID:26877992

  7. 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

  8. Oxidative injury to blood vessels and glia of the pre-laminar optic nerve head in human glaucoma.

    PubMed

    Feilchenfeld, Zac; Yücel, Yeni H; Gupta, Neeru

    2008-11-01

    Glaucoma is a leading cause of irreversible world blindness. Oxidative damage and vascular injury have been implicated in the pathogenesis of this disease. The purpose of this study was to determine in human primary open angle glaucoma whether oxidative injury occurs in pre-laminar optic nerve blood vessels and glial cells. Following IRB approval, sections from post-mortem primary open angle glaucoma eyes (n=5) with mean age of 77 +/- 9 yrs (+/-SD) were compared to normal control eyes (n=4) with mean age 70 +/- 9 yrs (Eye Bank of Canada). Immunostaining with nitrotyrosine, a footprint for peroxynitrite-mediated injury, was performed and sections were double-labeled with markers for vascular endothelial cells, perivascular smooth muscle cells, and astrocytes with CD34, smooth muscle actin (SMA), and glial fibrillary acidic protein (GFAP), respectively. Immunostaining was captured in a masked fashion using confocal microscopy, and defined regions of interest for blood vessels and glial tissue. Intensity measurements of supra-threshold area in pixels as percent of the total number of pixels were calculated using ImageJ (NIH) and compared using two-tailed Mann-Whitney nonparametric tests between glaucoma and control groups. Colocalization coefficients with cell-specific markers were determined and compared with random coefficients of correlation. Increased nitrotyrosine immunoreactivity was observed in pre-laminar optic nerve head blood vessels of primary open angle glaucoma eyes compared to controls and this difference was statistically significant (1.35 +/- 1.11% [+/-SD] vs. 0.01 +/- 0.01%, P=0.016). NT-immunoreactivity was also increased in the glial tissue surrounding the pre-laminar optic nerve head in the glaucoma group and compared to controls, and this difference was statistically significant (18.37 +/-12.80% vs. 0.08 +/- 0.04%, P=0.016). Colocalization studies demonstrated nitrotyrosine staining in vascular endothelial and smooth muscle cells, in addition to

  9. Electrical stimulation of the vagus nerve enhances cognitive and motor recovery following moderate fluid percussion injury in the rat.

    PubMed

    Smith, Douglas C; Modglin, Arlene A; Roosevelt, Rodney W; Neese, Steven L; Jensen, Robert A; Browning, Ronald A; Clough, Richard W

    2005-12-01

    Intermittent, chronically delivered electrical stimulation of the vagus nerve (VNS) is an FDA-approved procedure for the treatment of refractory complex/partial epilepsy in humans. Stimulation of the vagus has also been shown to enhance memory storage processes in laboratory rats and human subjects. Recent evidence suggests that some of these effects of VNS may be due to the activation of neurons in the nucleus locus coeruleus resulting in the release of norepinephrine (NE) throughout the neuraxis. Because antagonism of NE systems has been shown to delay recovery of function following brain damage, it is possible that enhanced release of NE in the CNS may facilitate recovery of function. To evaluate this hypothesis the lateral fluid percussion injury (LFP) model of traumatic brain injury was used and a variety of motor and cognitive behavioral tests were employed to assess recovery in pre-trained stimulated, control, and sham-injured laboratory rats. Two hours following moderate LFP, vagus nerve stimulation (30.0-sec trains of 0.5 mA, 20.0 Hz, biphasic pulses) was initiated. Stimulation continued in each animal's home cage at 30-min intervals for a period of 14 days, with the exception of brief periods when the animals were disconnected for behavioral assessments. Motor behaviors were evaluated every other day following LFP and tests included beam walk, locomotor placing, and skilled forelimb reaching. In each measure an enhanced rate of recovery and /or level of final performance was observed in the VNS-LFP animals compared to nonstimulated LFP controls. Behavior in the Morris water maze was assessed on days 11-14 following injury. Stimulated LFP animals showed significantly shorter latencies to find the hidden platform than did controls. Despite these behavioral effects, neurohistological examination did not reveal significant differences in lesion extent, density of fluorojade positive neurons, reactive astrocytes or numbers of spared neurons in the CA3 subarea

  10. Profiling of dynamically changed gene expression in dorsal root ganglia post peripheral nerve injury and a critical role of injury-induced glial fibrillary acidic protein in maintenance of pain behaviors [corrected].

    PubMed

    Kim, Doo-Sik; Figueroa, Katherine W; Li, Kang-Wu; Boroujerdi, Amin; Yolo, Tim; Luo, Z David

    2009-05-01

    To explore cellular changes in sensory neurons after nerve injury and to identify potential target genes contributing to different stages of neuropathic pain development, we used Affymetrix oligo arrays to profile gene expression patterns in L5/6 dorsal root ganglia (DRG) from the neuropathic pain model of left L5/6 spinal nerve ligation at different stages of neuropathic pain development. Our data indicated that nerve injury induced changes in expression of genes with similar biological functions in a temporal specific manner that correlates with particular stages of neuropathic pain development, indicating dynamic neuroplasticity in the DRG in response to peripheral nerve injury and during neuropathic pain development. Data from post-array validation indicated that there was a temporal correlation between injury-induced expression of the glial fibrillary acidic protein (GFAP), a marker for activated astrocytes, and neuropathic pain development. Spinal nerve ligation injury in GFAP knockout mice resulted in neuropathic pain states with similar onset, but a shortened duration compared with that in age, and gender-matched wild-type littermates. Intrathecal GFAP antisense oligonucleotide treatment in injured rats with neuropathic pain states reversed injury-induced behavioral hypersensitivity and GFAP upregulation in DRG and spinal cord. Together, these findings indicate that injury-induced GFAP upregulation not only serves as a marker for astrocyte activation, but it may also play a critical, but yet identified, role in the maintenance of neuropathic pain states. PMID:19307059

  11. Solitary fibrous tumour of the vagus nerve.

    PubMed

    Scholsem, Martin; Scholtes, Felix

    2012-04-01

    We describe the complete removal of a foramen magnum solitary fibrous tumour in a 36-year-old woman. It originated on a caudal vagus nerve rootlet, classically described as the 'cranial' accessory nerve root. This ninth case of immunohistologically confirmed cranial or spinal nerve SFT is the first of the vagus nerve.

  12. Intraoperative monitoring of lower cranial nerves in skull base surgery: technical report and review of 123 monitored cases.

    PubMed

    Topsakal, Cahide; Al-Mefty, Ossama; Bulsara, Ketan R; Williford, Veronica S

    2008-01-01

    The fundamental goal of skull base surgery is tumor removal with preservation of neurological function. Injury to the lower cranial nerves (LCN; CN 9-12) profoundly affects a patient's quality of life. Although intraoperative cranial nerve monitoring (IOM) is widely practiced for other cranial nerves, literature addressing the LCN is scant. We examined the utility of IOM of the LCN in a large patient series. One hundred twelve patients underwent 123 skull base operations with IOM between January 1994 to December 1999. The vagus nerve (n=37), spinal accessory nerve (n=118), and the hypoglossal nerve (n=83) were monitored intraoperatively. Electromyography (EMG) and compound muscle action potentials (CMAP) were recorded from the relevant muscles after electrical stimulation. This data was evaluated retrospectively. Patients who underwent IOM tended to have larger tumors with more intricate involvement of the lower cranial nerves. Worsening of preoperative lower cranial nerve function was seen in the monitored and unmonitored groups. With the use of IOM in the high risk group, LCN injury was reduced to a rate equivalent to that of the lower risk group (p>0.05). The immediate feedback obtained with IOM may prevent injury to the LCN due to surgical manipulation. It can also help identify the course of a nerve in patients with severely distorted anatomy. These factors may facilitate gross total tumor resection with cranial nerve preservation. The incidence of high false positive and negative CMAP and the variability in CMAP amplitude and threshold can vary depending on individual and technical factors.

  13. Peroneal nerve injury with foot drop complicating ankle sprain--a series of four cases with review of the literature.

    PubMed

    Brief, James M; Brief, Rochelle; Ergas, Enrique; Brief, L Paul; Brief, Andrew A

    2009-01-01

    Foot drop has many etiologies. One rarely mentioned and often neglected reason for foot drop is an acute inversion sprain of the ankle. Over the past 14 years, a collection of 32 cases of foot drop have been compiled in our orthopaedic and physiatric practices. All cases had appropriate evaluations, including electrodiagnostic studies (electromyography and nerve conduction studies) to determine the location and type of injury. Treatment and follow-up are also discussed. Of the 32 case studies, four were caused by a straightforward acute inversion sprain of the ankle. These cases are described with the electrodiagnostic evaluations, treatments, and outcomes. Proposed mechanisms for this type of foot drop are discussed, including traction and compression of the common peroneal nerve as it winds around the neck of the fibula, and possible compression by hematoma. Surgical versus conservative treatment is described. The functional impairment associated with foot drop is detailed.

  14. Gabapentin loses efficacy over time after nerve injury in rats: role of glutamate transporter-1 in the locus coeruleus.

    PubMed

    Kimura, Masafumi; Eisenach, James C; Hayashida, Ken-Ichiro

    2016-09-01

    Despite being one of the first-choice analgesics for chronic neuropathic pain, gabapentin sometimes fails to provide analgesia, but the mechanisms for this lack of efficacy is unclear. Rats with nerve injury including L5-L6 spinal nerve ligation (SNL) respond uniformly and well to gabapentin, but many of these studies are performed within just a few weeks of injury, questioning their relevance to chronic neuropathic pain. In this study, intraperitoneal gabapentin showed a time-dependently reduction in antihypersensitivity after SNL, associated with downregulation of astroglial glutamate transporter-1 (GLT-1) in the locus coeruleus (LC). Consistently, SNL also time-dependently increased basal but masked gabapentin-induced noradrenergic neuronal activity in the LC. In rats 2 weeks after SNL, knock-down of GLT-1 in the LC reduced the antihypersensitivity effect of gabapentin. In rats 8 weeks after SNL, increasing GLT-1 expression by histone deacetylase inhibitor valproate restored the antihypersensitivity effect of gabapentin, associated with restored gabapentin-induced noradrenergic neuronal activity in the LC and subsequent spinal noradrenaline release. Knock-down of GLT-1 in the LC reversed the effect of valproate to restore gabapentin-induced antihypersensitivity. In addition, the antihypersensitivity effect of the intrathecal α2-adrenoceptor agonist clonidine also decreased with time after SNL injury. These results suggest that downregulation of GLT-1 in the LC and reduced spinal noradrenergic inhibition contribute to impaired analgesic efficacy from gabapentin in chronic neuropathic pain and that valproate can rescue this impaired efficacy.

  15. 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

  16. Hypoxia-Induced Upregulation of miR-132 Promotes Schwann Cell Migration After Sciatic Nerve Injury by Targeting PRKAG3.

    PubMed

    Yao, Chun; Shi, Xiangxiang; Zhang, Zhanhu; Zhou, Songlin; Qian, Tianmei; Wang, Yaxian; Ding, Fei; Gu, Xiaosong; Yu, Bin

    2016-10-01

    Following peripheral nerve injury, hypoxia is formed as a result of defects in blood supply at the injury site. Despite accumulating evidence on the effects of microRNAs (miRNAs) on phenotype modulation of Schwann cells (SCs) after peripheral nerve injury, the impact of hypoxia on SC behaviors through miRNAs during peripheral nerve regeneration has not been estimated. In this study, we confirmed our previous microarray data on the upregulation of miR-132 after sciatic nerve injury in rats and observed that overexpression of miR-132 significantly promoted cell migration of primary cultured SCs. Interestingly, hypoxia-increased expression of miR-132 also enhanced SC migration while inhibition of miR-132 suppressed hypoxia-induced increase in SC migration. miR-132 downregulated PRKAG3 through binding to its 3'-UTR, and PRKAG3 knockdown compromised the reducing effect of miR-132 inhibition on SC migration under normal or hypoxia condition. Moreover, in vivo injection of miR-132 agomir into rats with sciatic nerve transection accelerated SC migration from the proximal to distal stump. Overall, our results suggest that the hypoxia-induced upregulation of miR-132 could promote SC migration and facilitate peripheral nerve regeneration.

  17. Spinal autofluorescent flavoprotein imaging in a rat model of nerve injury-induced pain and the effect of spinal cord stimulation.

    PubMed

    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

  18. Platelet-rich plasma gel in combination with Schwann cells for repair of sciatic nerve injury.

    PubMed

    Ye, Fagang; Li, Haiyan; Qiao, Guangxi; Chen, Feng; Tao, Hao; Ji, Aiyu; Hu, Yanling

    2012-10-15

    Bone marrow mesenchymal stem cells were isolated from New Zealand white rabbits, culture-expanded and differentiated into Schwann cell-like cells. Autologous platelet-rich plasma and Schwann cell-like cells were mixed in suspension at a density of 1 × 10(6) cells/mL, prior to introduction into a poly (lactic-co-glycolic acid) conduit. Fabricated tissue-engineered nerves were implanted into rabbits to bridge 10 mm sciatic nerve defects (platelet-rich plasma group). Controls were established using fibrin as the seeding matrix for Schwann cell-like cells at identical density to construct tissue-engineered nerves (fibrin group). Twelve weeks after implantation, toluidine blue staining and scanning electron microscopy were used to demonstrate an increase in the number of regenerating nerve fibers and thickness of the myelin sheath in the platelet-rich plasma group compared with the fibrin group. Fluoro-gold retrograde labeling revealed that the number of Fluoro-gold-positive neurons in the dorsal root ganglion and the spinal cord anterior horn was greater in the platelet-rich plasma group than in the fibrin group. Electrophysiological examination confirmed that compound muscle action potential and nerve conduction velocity were superior in the platelet-rich plasma group compared with the fibrin group. These results indicate that autologous platelet-rich plasma gel can effectively serve as a seeding matrix for Schwann cell-like cells to construct tissue-engineered nerves to promote peripheral nerve regeneration. PMID:25538751

  19. Nuclear factor erythroid 2-related factor 2 antibody attenuates thermal hyperalgesia in the dorsal root ganglion: Neurochemical changes and behavioral studies after sciatic nerve-pinch injury.

    PubMed

    Xiang, Qiong; Yu, Chao; Zhu, Yao-Feng; Li, Chun-Yan; Tian, Rong-Bo; Li, Xian-Hui

    2016-08-01

    Oxidative stress is generated in several peripheral nerve injury models.Nuclear factor erythroid 2-related factor 2 (Nrf2) is activated to have a role in antioxidant effect. After nerve injury, the severely painful behavior is also performed. However, little has been explored regarding the function of Nrf2 in this painful process. Therefore, in this study, we compared the effects of Nrf2 antibody administration following sciatic nerve-pinch injury on painful behavior induced in young mice and neurochemical changes in dorsal root ganglion neurons. After pinch nerve injury, we found that the magnitude of the thermal allodynia was significantly decreased after application of Nrf2 antibody (5ul, 1mg/ml) in such injured animals and phosphorylated ERK(p-ERK) as well as the apoptotic protein (i.e., Bcl-6) in DRG neurons were also down-regulated in the anti-Nrf2-treated injured groups compared to the saline-treated groups. Taken collectively, these data suggested that the Nrf2 antibody reduced thermal hyperalgesia via ERK pathway and the down regulation of Bcl-6 protein from the apoptosis pathway might be protecting against the protein deletions caused by anti-Nrf2 effect and suggested the new therapeutic strategy with Nrf2 inhibitor following nerve injury. PMID:27316447

  20. Acute closed traumatic sciatic nerve injury: a complication of heterotopic ossification and prominence of the femoral nail: a case report.

    PubMed

    Niempoog, Sunyarn; Chumchuen, Sukanis

    2014-08-01

    The report of a 27-years-old man with presence of heterotopic ossification (HO) after femoral nailing 7years ago who developed foot drop afterfalling to the ground on his buttocks. Radiographs revealed a prominence ofthefemoral nail with HO in his right hip. EMG confirmedperoneal nerve injury ofthe hip region. Femoral nail and the HO were removed and external neurolysis was performed. At 9 months after surgery, he had not regain motor power thus posterior tibialis tendon transfer was performed to restore ankle dorsiflexion. Finally, at 2 years follow-up, he could ambulate well but did not regained sensation, extensor digitorum communis and peroneal muscle function. PMID:25518317

  1. Delayed radiation injury to the retrobulbar optic nerves and chiasm. Clinical syndrome and treatment with hyperbaric oxygen and corticosteroids

    SciTech Connect

    Roden, D.; Bosley, T.M.; Fowble, B.; Clark, J.; Savino, P.J.; Sergott, R.C.; Schatz, N.J. )

    1990-03-01

    Thirteen patients with delayed radiation injury to the optic nerves and chiasm were treated with hyperbaric oxygen (HBO) and corticosteroids. These patients experienced painless, abrupt loss of vision in one (6 patients) or both (7 patients) eyes between 4 and 35 months after receiving radiation doses of at least 4500 cGy to the region of the chiasm. Diagnostic evaluation including neuro-imaging and lumbar puncture showed no recurrent tumor and no other cause for visual loss. No patient's vision improved during treatment or follow-up lasting between 1 and 4 years. There were no serious complications of treatment.

  2. The Laser Accessory Market

    NASA Astrophysics Data System (ADS)

    Desai, Ashvin

    1988-09-01

    Wandering through the exhibit hall yesterday, I noticed that if you look at the laser companies and if you look at the accessory companies, there are pretty much the same number of accessory booths as well as the laser companies. There was one difference. Laser company booths are all sexy looking, very flashy, big booths. Whereas if you look at the accessories booths, they were small, not so prominent.

  3. Advantages of reusable accessories.

    PubMed

    Wolfsen, H C

    2000-04-01

    Despite scant evidence supporting the use of disposable accessories, these devices have been widely disseminated. Manufacturers and governmental regulators, the most devout proponents of one-time use accessories, have framed the issue in economic terms-parsimonious practitioners reusing disposable accessories at the risk of cross-contamination, mechanical failure and product liability. This simplistic view represents revisionist history and ignores the long tradition of reusing these devices. This article reviews the numerous studies that support the safe and cost effective reuse of disposable and reusable accessories.

  4. Systemic Simvastatin Rescues Retinal Ganglion Cells from Optic Nerve Injury Possibly through Suppression of Astroglial NF-κB Activation

    PubMed Central

    Morishita, Seita; Oku, Hidehiro; Horie, Taeko; Tonari, Masahiro; Kida, Teruyo; Okubo, Akiko; Sugiyama, Tetsuya; Takai, Shinji; Hara, Hideaki; Ikeda, Tsunehiko

    2014-01-01

    Neuroinflammation is involved in the death of retinal ganglion cells (RGCs) after optic nerve injury. The purpose of this study was to determine whether systemic simvastatin can suppress neuroinflammation in the optic nerve and rescue RGCs after the optic nerve is crushed. Simvastatin or its vehicle was given through an osmotic minipump beginning one week prior to the crushing. Immunohistochemistry and real-time PCR were used to determine the degree of neuroinflammation on day 3 after the crushing. The density of RGCs was determined in Tuj-1 stained retinal flat mounts on day 7. The effect of simvastain on the TNF-α-induced NF-κB activation was determined in cultured optic nerve astrocytes. On day 3, CD68-positive cells, most likely microglia/macrophages, were accumulated at the crushed site. Phosphorylated NF-κB was detected in some astrocytes at the border of the lesion where the immunoreactivity to MCP-1 was intensified. There was an increase in the mRNA levels of the CD68 (11.4-fold), MCP-1 (22.6-fold), ET-1 (2.3-fold), GFAP (1.6-fold), TNF-α (7.0-fold), and iNOS (14.8-fold) genes on day 3. Systemic simvastatin significantly reduced these changes. The mean ± SD number of RGCs was 1816.3±232.6/mm2 (n = 6) in the sham controls which was significantly reduced to 831.4±202.5/mm2 (n = 9) on day 7 after the optic nerve was crushed. This reduction was significantly suppressed to 1169.2±201.3/mm2 (P = 0.01, Scheffe; n = 9) after systemic simvastatin. Simvastatin (1.0 µM) significantly reduced the TNF-α-induced NF-κB activation in cultured optic nerve astrocytes. We conclude that systemic simvastatin can reduce the death of RGCs induced by crushing the optic nerve possibly by suppressing astroglial NF-κB activation. PMID:24392131

  5. The Fibular Nerve Injury Method: A Reliable Assay to Identify and Test Factors That Repair Neuromuscular Junctions.

    PubMed

    Dalkin, William; Taetzsch, Thomas; Valdez, Gregorio

    2016-01-01

    The neuromuscular junction (NMJ) undergoes deleterious structural and functional changes as a result of aging, injury and disease. Thus, it is imperative to understand the cellular and molecular changes involved in maintaining and repairing NMJs. For this purpose, we have developed a method to reliably and consistently examine regenerating NMJs in mice. This nerve injury method involves crushing the common fibular nerve as it passes over the lateral head of the gastrocnemius muscle tendon near the knee. Using 70 day old female mice, we demonstrate that motor axons begin to reinnervate previous postsynaptic targets within 7 days post-crush. They completely reoccupy their previous synaptic areas by 12 days. To determine the reliability of this injury method, we compared reinnervation rates between individual 70 day old female mice. We found that the number of reinnervated postsynaptic sites was similar between mice at 7, 9, and 12 days post-crush. To determine if this injury assay can also be used to compare molecular changes in muscles, we examined levels of the gamma-subunit of the muscle nicotinic receptor (gamma-AChR) and the muscle-specific kinase (MuSK). The gamma-AChR subunit and MuSK to are highly upregulated following denervation and return to normal levels following reinnervation of NMJs. We found a close relationship between transcript levels for these genes and innervation status of muscles. We believe that this method will accelerate our understanding of the cellular and molecular changes involved in repairing the NMJ and other synapses. PMID:27585036

  6. Sensory Neuron Downregulation of the Kv9.1 Potassium Channel Subunit Mediates Neuropathic Pain following Nerve Injury

    PubMed Central

    Tsantoulas, Christoforos; Zhu, Lan; Shaifta, Yasin; Grist, John; Ward, Jeremy P. T.; Raouf, Ramin; Michael, Gregory J.; McMahon, Stephen B.

    2013-01-01

    Chronic neuropathic pain affects millions of individuals worldwide, is typically long-lasting, and remains poorly treated with existing therapies. Neuropathic pain arising from peripheral nerve lesions is known to be dependent on the emergence of spontaneous and evoked hyperexcitability in damaged nerves. Here, we report that the potassium channel subunit Kv9.1 is expressed in myelinated sensory neurons, but is absent from small unmyelinated neurons. Kv9.1 expression was strongly and rapidly downregulated following axotomy, with a time course that matches the development of spontaneous activity and pain hypersensitivity in animal models. Interestingly, siRNA-mediated knock-down of Kv9.1 in naive rats led to neuropathic pain behaviors. Diminished Kv9.1 function also augmented myelinated sensory neuron excitability, manifested as spontaneous firing, hyper-responsiveness to stimulation, and persistent after-discharge. Intracellular recordings from ex vivo dorsal root ganglion preparations revealed that Kv9.1 knock-down was linked to lowered firing thresholds and increased firing rates under physiologically relevant conditions of extracellular potassium accumulation during prolonged activity. Similar neurophysiological changes were detected in animals subjected to traumatic nerve injury and provide an explanation for neuropathic pain symptoms, including poorly understood conditions such as hyperpathia and paresthesias. In summary, our results demonstrate that Kv9.1 dysfunction leads to spontaneous and evoked neuronal hyperexcitability in myelinated fibers, coupled with development of neuropathic pain behaviors. PMID:23197740

  7. MHC-I and PirB Upregulation in the Central and Peripheral Nervous System following Sciatic Nerve Injury.

    PubMed

    Bombeiro, André Luis; Thomé, Rodolfo; Oliveira Nunes, Sérgio Luiz; Monteiro Moreira, Bárbara; Verinaud, Liana; Oliveira, Alexandre Leite Rodrigues de

    2016-01-01

    Major histocompatibility complex class one (MHC-I) antigen-presenting molecules participate in central nervous system (CNS) synaptic plasticity, as does the paired immunoglobulin-like receptor B (PirB), an MHC-I ligand that can inhibit immune-cells and bind to myelin axon growth inhibitors. Based on the dual roles of both molecules in the immune and nervous systems, we evaluated their expression in the central and peripheral nervous system (PNS) following sciatic nerve injury in mice. Increased PirB and MHC-I protein and gene expression is present in the spinal cord one week after nerve transection, PirB being mostly expressed in the neuropile region. In the crushed nerve, MHC-I protein levels increased 2 weeks after lesion (wal) and progressively decreased over the next eight weeks. The same kinetics were observed for infiltrating cytotoxic T lymphocytes (CTLs) but not for PirB expression, which continuously increased. Both MHC-I and PirB were found in macrophages and Schwann cells but rarely in axons. Interestingly, at 8 wal, PirB was mainly restricted to the myelin sheath. Our findings reinforce the participation of MHC-I and PirB in CNS plasticity events. In contrast, opposing expression levels of these molecules were found in the PNS, so that MHC-I and PirB seem to be mostly implicated in antigen presentation to CTLs and axon myelination, respectively. PMID:27551751

  8. MHC-I and PirB Upregulation in the Central and Peripheral Nervous System following Sciatic Nerve Injury

    PubMed Central

    Bombeiro, André Luis; Thomé, Rodolfo; Oliveira Nunes, Sérgio Luiz; Monteiro Moreira, Bárbara; Verinaud, Liana; de Oliveira, Alexandre Leite Rodrigues

    2016-01-01

    Major histocompatibility complex class one (MHC-I) antigen-presenting molecules participate in central nervous system (CNS) synaptic plasticity, as does the paired immunoglobulin-like receptor B (PirB), an MHC-I ligand that can inhibit immune-cells and bind to myelin axon growth inhibitors. Based on the dual roles of both molecules in the immune and nervous systems, we evaluated their expression in the central and peripheral nervous system (PNS) following sciatic nerve injury in mice. Increased PirB and MHC-I protein and gene expression is present in the spinal cord one week after nerve transection, PirB being mostly expressed in the neuropile region. In the crushed nerve, MHC-I protein levels increased 2 weeks after lesion (wal) and progressively decreased over the next eight weeks. The same kinetics were observed for infiltrating cytotoxic T lymphocytes (CTLs) but not for PirB expression, which continuously increased. Both MHC-I and PirB were found in macrophages and Schwann cells but rarely in axons. Interestingly, at 8 wal, PirB was mainly restricted to the myelin sheath. Our findings reinforce the participation of MHC-I and PirB in CNS plasticity events. In contrast, opposing expression levels of these molecules were found in the PNS, so that MHC-I and PirB seem to be mostly implicated in antigen presentation to CTLs and axon myelination, respectively. PMID:27551751

  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. A NOVEL METHOD TO QUANTIFY HISTOCHEMICAL CHANGES THROUGHOUT THE MEDIOLATERAL AXIS OF THE SUBSTANTIA GELATINOSA AFTER SPARED NERVE INJURY: CHARACTERIZATION WITH TRPV1 AND SUBSTANCE P

    PubMed Central

    Corder, G.; Siegel, A.; Intondi, A.B.; Zhang, X.; Zadina, J.E.; Taylor, B.K.

    2010-01-01

    Nerve injury dramatically increases or decreases protein expression in the spinal cord dorsal horn. Whether the spatial distribution of these changes is restricted to the central innervation territories of injured nerves or could spread to adjacent territories in the dorsal horn is not understood. To address this question, we developed a simple computer software-assisted method to precisely distinguish and efficiently quantify immunohistochemical staining patterns across the mediolateral axis of the dorsal horn 2 wk after transection of either the tibial and common peroneal nerves (thus sparing the sural branch, spared nerve injury, SNI), the tibial nerve, or the common peroneal and sural nerves. Using thiamine monophosphatase (TMP) histochemistry, we determined that central terminals of the tibial, common peroneal, sural, and posterior cutaneous nerves occupy the medial 35%, medial-central 20%, central-lateral 20%, and lateral 25% of the substantia gelatinosa, respectively. We then used these calculations to show that SNI reduced the expression of SP and TRPV1 immunoreactivity within the tibial and peroneal innervation territories in the L4 dorsal horn, without changing expression in the uninjured, sural sector. We conclude that SNI-induced loss of SP and TRPV1 in central terminals of dorsal horn is restricted to injured fibers. Our new method enables direct comparison of injured and uninjured terminals in the dorsal horn so as to better understand their relative contributions to mechanisms of chronic pain. PMID:20350706

  11. Earthworm extracts facilitate PC12 cell differentiation and promote axonal sprouting in peripheral nerve injury.

    PubMed

    Chen, Chao-Tsung; Lin, Jaung-Geng; Lu, Tung-Wu; Tsai, Fuu-Jen; Huang, Chih-Yang; Yao, Chun-Hsu; Chen, Yueh-Sheng

    2010-01-01

    The present study provides in vitro and in vivo evaluations of earthworm (Pheretima aspergilum) on peripheral nerve regeneration. In the in vitro study, we found the earthworm (EW) water extracts caused a marked enhancement of the nerve growth factor-mediated neurite outgrowth from PC12 cells as well as the expressions of growth associated protein 43 and synapsin I. In the in vivo study, silicone rubber chambers filled with EW extracts were used to bridge a 10 mm sciatic nerve defect in rats. Eight weeks after implantation, the group receiving EW extracts had a much higher success percentage of regeneration (90%) compared to the control (60%) receiving the saline. In addition, quantitative histology of the successfully regenerated nerves revealed that myelinated axons in EW group at 31.25 microg/ml was significantly more than those in the controls (p < 0.05). These results showed that EW extracts can be a potential growth-promoting factor on regenerating peripheral nerves. PMID:20503471

  12. [METABOLIC CHANGES OF SKELETAL MUSCLES IN TRAUMATIC INJURY OF PERIPHERAL NERVE AND AUTOPLASTY IN EXPERIMENT].

    PubMed

    Gayovych, V V; Magomedov, A M; Makarenko, O M; Savohsko, S I

    2016-03-01

    The changes in metabolism of the amine acids, enzymes, electrolytes, fat acids (FA) in skeletal muscles of anterior and posterior extremities of rats in significant defects of peripheral nerve and its autoplasty were studied in experimental investigation. Metabolic changes in skeletal muscles are accompanied by significant intensity of proteolysis, lowering of the enzymes activity, energetic metabolism and in a less extent of the electrolytes balance and the FA metabolism. After autoplasty of big defects in the traumatized nerve the proteins' synthesis and restoration of activity of lactate dehydrogenase and creatine phosphokinase constitute the markers of muscular tissue restoration. Surgical restoration of the nerve is accompanied by a protein synthesis activation in muscles, but normalization of the enzyme systems indices, the lipids metabolism and the electrolytes balance was not observed. Metabolic dysbalance needs a certain pharmacological correction and prevention of a progress of pathological process in skeletal muscles. PMID:27514098

  13. Neuromuscular ultrasound of cranial nerves.

    PubMed

    Tawfik, Eman A; Walker, Francis O; Cartwright, Michael S

    2015-04-01

    Ultrasound of cranial nerves is a novel subdomain of neuromuscular ultrasound (NMUS) which may provide additional value in the assessment of cranial nerves in different neuromuscular disorders. Whilst NMUS of peripheral nerves has been studied, NMUS of cranial nerves is considered in its initial stage of research, thus, there is a need to summarize the research results achieved to date. Detailed scanning protocols, which assist in mastery of the techniques, are briefly mentioned in the few reference textbooks available in the field. This review article focuses on ultrasound scanning techniques of the 4 accessible cranial nerves: optic, facial, vagus and spinal accessory nerves. The relevant literatures and potential future applications are discussed.

  14. NT-3 modulates NPY expression in primary sensory neurons following peripheral nerve injury

    PubMed Central

    STERNE, G. D.; BROWN, R. A.; GREEN, C. J.; TERENGHI, G.

    1998-01-01

    Peripheral nerve transection induces significant changes in neuropeptide expression and content in injured primary sensory neurons, possibly due to loss of target derived neurotrophic support. This study shows that neurotrophin-3 (NT-3) delivery to the injured nerve influences neuropeptide Y (NPY) expression within dorsal root ganglia (DRG) neurons. NT-3 was delivered by grafting impregnated fibronectin (500 ng/ml; NT group) in the axotomised sciatic nerve. Animals grafted with plain fibronectin mats (FN) or nerve grafts (NG) were used as controls. L4 and L5 DRG from operated and contralateral sides were harvested between 5 and 240 d. Using immunohistochemistry and computerised image analysis the percentage, diameter and optical density of neurons expressing calcitonin gene-related peptide (CGRP), substance P (SP), vasoactive intestinal peptide (VIP) and NPY were quantified. Sciatic nerve axotomy resulted in significant reduction in expression of CGRP and SP, and significant upregulation of VIP and NPY (P<0.05 for ipsilateral vs contralateral DRG). By d 30, exogenous NT-3 and nerve graft attenuated the upregulation of NPY (P<0.05 for NT and NG vs FN). However, NT-3 administration did not influence the expression of CGRP, SP or VIP. The mean cell diameter of NPY immunoreactive neurons was significantly smaller in the NT-3 group (P<0.05 for NT vs FN and NG) suggesting a differential influence of NT-3 on larger neurons. The optical densities of NPY immunoreactive neurons of equal size were the same in each group at any time point, indicating that the neurons responding to NT-3 downregulate NPY expression to levels not detectable by immunohistochemistry. These results demonstrate that targeted administration of NT-3 regulates the phenotype of a NPY-immunoreactive neuronal subpopulation in the dorsal root ganglia, a further evidence of the trophic role of neurotrophins on primary sensory neurons. PMID:9827642

  15. Medical countermeasure against respiratory toxicity and acute lung injury following inhalation exposure to chemical warfare nerve agent VX

    SciTech Connect

    Nambiar, Madhusoodana P.; Doctor, Bhupendra P.

    2007-03-15

    To develop therapeutics against lung injury and respiratory toxicity following nerve agent VX exposure, we evaluated the protective efficacy of a number of potential pulmonary therapeutics. Guinea pigs were exposed to 27.03 mg/m{sup 3} of VX or saline using a microinstillation inhalation exposure technique for 4 min and then the toxicity was assessed. Exposure to this dose of VX resulted in a 24-h survival rate of 52%. There was a significant increase in bronchoalveolar lavage (BAL) protein, total cell number, and cell death. Surprisingly, direct pulmonary treatment with surfactant, liquivent, N-acetylcysteine, dexamethasone, or anti-sense syk oligonucleotides 2 min post-exposure did not significantly increase the survival rate of VX-exposed guinea pigs. Further blocking the nostrils, airway, and bronchioles, VX-induced viscous mucous secretions were exacerbated by these aerosolized treatments. To overcome these events, we developed a strategy to protect the animals by treatment with atropine. Atropine inhibits muscarinic stimulation and markedly reduces the copious airway secretion following nerve agent exposure. Indeed, post-exposure treatment with atropine methyl bromide, which does not cross the blood-brain barrier, resulted in 100% survival of VX-exposed animals. Bronchoalveolar lavage from VX-exposed and atropine-treated animals exhibited lower protein levels, cell number, and cell death compared to VX-exposed controls, indicating less lung injury. When pulmonary therapeutics were combined with atropine, significant protection to VX-exposure was observed. These results indicate that combinations of pulmonary therapeutics with atropine or drugs that inhibit mucous secretion are important for the treatment of respiratory toxicity and lung injury following VX exposure.

  16. Medical countermeasure against respiratory toxicity and acute lung injury following inhalation exposure to chemical warfare nerve agent VX.

    PubMed

    Nambiar, Madhusoodana P; Gordon, Richard K; Rezk, Peter E; Katos, Alexander M; Wajda, Nikolai A; Moran, Theodore S; Steele, Keith E; Doctor, Bhupendra P; Sciuto, Alfred M

    2007-03-01

    To develop therapeutics against lung injury and respiratory toxicity following nerve agent VX exposure, we evaluated the protective efficacy of a number of potential pulmonary therapeutics. Guinea pigs were exposed to 27.03 mg/m(3) of VX or saline using a microinstillation inhalation exposure technique for 4 min and then the toxicity was assessed. Exposure to this dose of VX resulted in a 24-h survival rate of 52%. There was a significant increase in bronchoalveolar lavage (BAL) protein, total cell number, and cell death. Surprisingly, direct pulmonary treatment with surfactant, liquivent, N-acetylcysteine, dexamethasone, or anti-sense syk oligonucleotides 2 min post-exposure did not significantly increase the survival rate of VX-exposed guinea pigs. Further blocking the nostrils, airway, and bronchioles, VX-induced viscous mucous secretions were exacerbated by these aerosolized treatments. To overcome these events, we developed a strategy to protect the animals by treatment with atropine. Atropine inhibits muscarinic stimulation and markedly reduces the copious airway secretion following nerve agent exposure. Indeed, post-exposure treatment with atropine methyl bromide, which does not cross the blood-brain barrier, resulted in 100% survival of VX-exposed animals. Bronchoalveolar lavage from VX-exposed and atropine-treated animals exhibited lower protein levels, cell number, and cell death compared to VX-exposed controls, indicating less lung injury. When pulmonary therapeutics were combined with atropine, significant protection to VX-exposure was observed. These results indicate that combinations of pulmonary therapeutics with atropine or drugs that inhibit mucous secretion are important for the treatment of respiratory toxicity and lung injury following VX exposure.

  17. 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

  18. Nerve injury induces glial cell line-derived neurotrophic factor (GDNF) expression in Schwann cells through purinergic signaling and the PKC-PKD pathway.

    PubMed

    Xu, Pin; Rosen, Kenneth M; Hedstrom, Kristian; Rey, Osvaldo; Guha, Sushovan; Hart, Courtney; Corfas, Gabriel

    2013-07-01

    Upon peripheral nerve injury, specific molecular events, including increases in the expression of selected neurotrophic factors, are initiated to prepare the tissue for regeneration. However, the mechanisms underlying these events and the nature of the cells involved are poorly understood. We used the injury-induced upregulation of glial cell-derived neurotrophic factor (GDNF) expression as a tool to gain insights into these processes. We found that both myelinating and nonmyelinating Schwann cells are responsible for the dramatic increase in GDNF expression after injury. We also demonstrate that the GDNF upregulation is mediated by a signaling cascade involving activation of Schwann cell purinergic receptors, followed by protein kinase C signaling which activates protein kinase D (PKD), which leads to increased GDNF transcription. Given the potent effects of GDNF on survival and repair of injured peripheral neurons, we propose that targeting these pathways may yield therapeutic tools to treat peripheral nerve injury and neuropathies.

  19. Effects of local lidocaine treatment before and after median nerve injury on mechanical hypersensitivity and microglia activation in rat cuneate nucleus.

    PubMed

    Lin, Shih-Chang; Yeh, Jiann-Horng; Chen, Chih-Li; Chou, Shiu-Huey; Tsai, Yi-Ju

    2011-04-01

    This study examined the relationship between microglia activation in the cuneate nucleus (CN) and behavioral hypersensitivity after chronic constriction injury (CCI) of the median nerve. We also investigated effects of local lidocaine pre- and post-treatment on microglia activation and development of hypersensitivity in this model. By immunohistochemistry and immunoblotting, little immunoreactivity of OX-42, a microglia activation marker, was detected in the CN of normal rats. As early as 1 day after CCI, there was a significant increase in OX-42 immunoreactivity in the lesion side of CN, which reached a maximum at 14 days. Microinjection of minocycline, a microglia activation inhibitor, into the CN 1 day after CCI attenuated injury-induced behavioral hypersensitivity in a dose-dependent manner. Furthermore, the animals received 1%, 2% or 5% lidocaine 15 min prior to median nerve CCI (pre-treatment), 5h (early post-treatment) or 1 day (late post-treatment) after median nerve CCI. Pre-treatment and early post-treatment with 2% and 5% lidocaine, but not 1% lidocaine, attenuated OX-42 immunoreactivity and behavioral hypersensitivity following median nerve injury. Late post-treatment with 1%, 2%, or 5% lidocaine failed to decrease OX-42 immunoreactivity and mechanical hypersensitivity in CCI rats. In conclusion, median nerve injury-induced microglia activation in the CN modulated development of behavioral hypersensitivity. High-concentration lidocaine was effective in decreasing microglia activation in the CN and in attenuating neuropathic pain sensations at the early stage following nerve injury, when microglia had not yet been activated.

  20. Regulation of Schwann cell proliferation and migration by miR-1 targeting brain-derived neurotrophic factor after peripheral nerve injury

    PubMed Central

    Yi, Sheng; Yuan, Ying; Chen, Qianqian; Wang, Xinghui; Gong, Leilei; Liu, Jie; Gu, Xiaosong; Li, Shiying

    2016-01-01

    Peripheral nerve injury is a global problem that causes disability and severe socioeconomic burden. Brain-derived neurotrophic factor (BDNF) benefits peripheral nerve regeneration and becomes a promising therapeutic molecule. In the current study, we found that microRNA-1 (miR-1) directly targeted BDNF by binding to its 3′-UTR and caused both mRNA degradation and translation suppression of BDNF. Moreover, miR-1 induced BDNF mRNA degradation primarily through binding to target site 3 rather than target site 1 or 2 of BDNF 3′-UTR. Following rat sciatic nerve injury, a rough inverse correlation was observed between temporal expression profiles of miR-1 and BDNF in the injured nerve. The overexpression or silencing of miR-1 in cultured Schwann cells (SCs) inhibited or enhanced BDNF secretion from the cells, respectively, and also suppressed or promoted SC proliferation and migration, respectively. Interestingly, BDNF knockdown could attenuate the enhancing effect of miR-1 inhibitor on SC proliferation and migration. These findings will contribute to the development of a novel therapeutic strategy for peripheral nerve injury, which overcomes the limitations of direct administration of exogenous BDNF by using miR-1 to regulate endogenous BDNF expression. PMID:27381812

  1. Crosstalk between p38, Hsp25 and Akt in spinal motor neurons after sciatic nerve injury

    NASA Technical Reports Server (NTRS)

    Murashov, A. K.; Ul Haq, I.; Hill, C.; Park, E.; Smith, M.; Wang, X.; Wang, X.; Goldberg, D. J.; Wolgemuth, D. J.

    2001-01-01

    The p38 stress-activated protein kinase pathway is involved in regulation of phosphorylation of Hsp25, which in turn regulates actin filament dynamic in non-neuronal cells. We report that p38, Hsp25 and Akt signaling pathways were specifically activated in spinal motor neurons after sciatic nerve axotomy. The activation of the p38 kinase was required for induction of Hsp25 expression. Furthermore, Hsp25 formed a complex with Akt, a member of PI-3 kinase pathway that prevents neuronal cell death. Together, our observations implicate Hsp25 as a central player in a complex system of signaling that may both promote regeneration of nerve fibers and prevent neuronal cell death in the injured spinal cord.

  2. Systemic administration of vitamins C and E attenuates nociception induced by chronic constriction injury of the sciatic nerve in rats.

    PubMed

    Riffel, Ana Paula K; de Souza, Jéssica A; Santos, Maria do Carmo Q; Horst, Andréa; Scheid, Taína; Kolberg, Carolina; Belló-Klein, Adriane; Partata, Wania A

    2016-03-01

    Antioxidants have been tested to treat neuropathic pain, and α-Tocopherol (vitamin E--vit. E) and ascorbic acid (vitamin C--vit. C) are potent antioxidants. We assessed the effect of intraperitoneal administration of vit. C (30 mg/kg/day) and vit. E (15 mg/kg/day), given alone or in combination, on the mechanical and thermal thresholds and the sciatic functional index (SFI) in rats with chronic constriction injury (CCI) of the sciatic nerve. We also determined the lipid hydroperoxides and total antioxidant capacity (TAC) in the injured sciatic nerve. Further, we assessed the effects of oral administration of vit. C+vit. E (vit. C+E) and of a combination of vit. C+E and gabapentin (100mg/kg/day, i.p.) on the mechanical and thermal thresholds of CCI rats. The vitamins, whether administered orally or i.p., attenuated the reductions in the mechanical and thermal thresholds induced by CCI. The antinociceptive effect was greater with a combination of vit. C+E than with each vitamin given alone. The SFI was also improved in vitamin-treated CCI rats. Co-administration of vit. C+E and gabapentin induced a greater antinociceptive effect than gabapentin alone. No significant change occurred in TAC and lipid hydroperoxide levels, but TAC increased (45%) while lipid hydroperoxides decreased (38%) in the sciatic nerve from vit. C+E-treated CCI rats. Thus, treatment with a combination of vit. C+E was more effective to treat CCI-induced neuropathic pain than vitamins alone, and the antinociceptive effect was greater with co-administration of vit. C+E and gabapentin than with gabapentin alone. PMID:26855326

  3. Differential regulation of glucocorticoid receptor expression in distinct columns of periaqueductal grey in rats with behavioural disability following nerve injury.

    PubMed

    Mor, David; Keay, Kevin A

    2013-10-01

    Neuropathic pain is diagnosed primarily by sensory dysfunction, which includes both spontaneous, and stimulus-evoked pain. Clinical evaluation highlights the disabilities which characterise this condition for most patients. Chronic constriction injury of the sciatic nerve (CCI) evokes sensory dysfunction characteristic of neuropathic pain. Approximately, 30 % of CCI rats show disabilities similar to those identified in clinical evaluation of neuropathic pain patients, these include: altered social behaviours; sleep disturbances; and endocrine dysfunction. The periaqueductal grey (PAG) is a nodal point in the brain circuits which regulate these functions, and undergoes a distinct set of neural and glial adaptations following CCI, in rats with disabilities. CCI increases corticosterone, which through its actions at the glucocorticoid receptor (GR), can trigger cellular adaptation. GR expression in PAG was quantified using qRT-PCR, Western blotting and immunohistochemical analyses and nerve-injured rats, with and without disabilities, were compared. Our data showed that the PAG of disabled rats has significantly increased expression of GR mRNA and protein. Further, this increased protein expression reflects contrasting patterns of change in GR expression in PAG subregions. The dorsolateral PAG had significant increases in the number of GR-immunoreactive (GR-IR) cells and the caudal lateral and ventrolateral PAG each had significant reductions in the number of GR-IR cells. These regional increases and decreases correlated with the degree of disability, as indicated by the degree of change in social behaviours. Our results suggest a role for altered PAG, GR-corticosterone interactions and their resultant cellular consequences in the expression of disabilities in a subpopulation of nerve-injured rats.

  4. Fatty acid binding protein is induced in neurons of the dorsal root ganglia after peripheral nerve injury.

    PubMed

    De León, M; Welcher, A A; Nahin, R H; Liu, Y; Ruda, M A; Shooter, E M; Molina, C A

    1996-05-01

    Peripheral nerve trauma induces the expression of genes presumed to be involved in the process of nerve degeneration and repair. In the present study, an in vivo paradigm was employed to identify molecules which may have important roles in these processes. A cDNA library was constructed with RNA extracted from rat dorsal root ganglia (DRG) 3 days after a sciatic nerve crush. After differential hybridization to this library, several cDNAs were identified that encoded mRNAs that were upregulated in the DRG ipsilateral to the crush injury, as opposed to the contralateral or naive DRG. Approximately 0.15% of all the clones screened were found to be induced. This report presents the types of induced sequences identified and characterizes one of them, DA11. The 0.7 kb DA11 full length cDNA clone contains a 405 nucleotide open reading frame that encodes a putative protein of 15.2 kDa (135 amino acid residues) and is a member of the family of fatty acid binding proteins (FABP). The DA11 protein differs by one amino acid residue from the sequence of the C-FAPB protein and by eight residues from the sequence of mal1, proteins found in rat and mouse skin, respectively. Northern and Western blot analyses showed that the DA11 mRNA and protein were induced in the injured DRG. Furthermore, studies using antibodies generated against DA11 found that the DA11-like immunoreactivity was more pronounced in the nuclei of neurons located in the DRG ipsilateral to the sciatic cut than those located in the contralateral DRG. The induction of DA11 mRNA and protein in DRG neurons suggests, for the first time, the involvement of a neuronal FABP in the process of degeneration and repair in the nervous system.

  5. Pain-related behavior following REM sleep deprivation in the rat: influence of peripheral nerve injury, spinal glutamatergic receptors and nitric oxide.

    PubMed

    Wei, Hong; Zhao, Wenjuan; Wang, Yong-Xiang; Pertovaara, Antti

    2007-05-01

    We assessed whether pain-related behavior in neuropathic or control rats is changed following rapid eye movement sleep deprivation (REMSD). Furthermore, we determined the contribution of spinal glutamatergic receptors and nitric oxide to sensitivity changes following REMSD versus peripheral nerve injury. Pain behavior was assessed in Sprague-Dawley (SD) and Hannover-Wistar (HW) rats with a spinal nerve ligation or a sham operation. Nerve ligation produced mechanical hypersensitivity of the injured dermatome in all animals. Baseline sensitivity to mechanical stimulation was higher in the HW than the SD group, independent of nerve injury. In both strains, mechanical sensitivity of neuropathic and sham-operated animals was increased following 48 h of REMSD. Heat sensitivity of an uninjured dermatome was not different among experimental conditions. Reversal of mechanical hypersensitivity was attempted in HW rats by spinal administration of an antagonist of the metabotropic glutamate receptor 5 (mGluR(5)) or the NMDA receptor and a nitric oxide synthase (NOS) inhibitor. Mechanical hypersensitivity induced by REMSD in unoperated rats was attenuated by all three drugs, while in neuropathic animals the mechanical anti-hypersensitive effect was most pronounced with the antagonist of the mGluR(5) or a NOS inhibitor. The results indicate that the strain of the animals markedly influences baseline withdrawal threshold to mechanical stimulation. Mechanical hypersensitivity following REMSD, however, is similarly increased in HW and SD strains, and the REMSD-associated increase in mechanical sensitivity is independent of nerve injury. Furthermore, mechanical hypersensitivities following REMSD and peripheral nerve injury share common spinal mechanisms involving, at least, the mGluR(5) and nitric oxide.

  6. 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

  7. Clinical observation of peripheral nerve injury in 2 patients with cancer after radiotherapy

    PubMed Central

    Liang, Li; Jia, Ting-zhen; Zhang, Shu-lan; Wang, Mo-pei; Ma, Li-Wen; Liu, Qiang

    2013-01-01

    Aim of the study This study aims to analyze the clinical manifestations and sequelae of peripheral nerve radiation damage of two cases of cancer patients after radiotherapy at the corresponding sites in clinical practice and to summarize experiences and lesions in order to provide a reference for future tumor radiotherapy. Material and methods Some data of two cases of patients, such as doses of radiotherapy, clinical manifestations and damage occurrence time, were collected and examinations were conducted to define diagnosis. Afterwards, therapies and follow-up were conducted. Results Case 1 (rectal cancer) was diagnosed as mild left lower extremity nerve damage. After the symptomatic treatment, the disease condition was improved, and there was no tumor recurrence sign. Case 2 (breast cancer) was diagnosed as left brachial plexus damage, and left upper extremity movement function was lost completely. While the analgesic treatment was conducted, anti-tumor relevant treatments were being carried out. Conclusions Radiotherapy can cause different extents of radioactive nerve damage. In practice, it is necessary to constantly improve the radiotherapy technology level and actively prevent the occurrence of complications. Once symptoms appear, the diagnosis and treatment should be conducted as early as possible in order to avoid aggravating damage to cause dysfunction and cause lifetime pain to patients. PMID:23788990

  8. Proteomic analysis of microdissected facial nuclei of the rat following facial nerve injury.

    PubMed

    Melle, Christian; Ernst, Günther; Grosheva, Maria; Angelov, Doychin N; Irintchev, Andrey; Guntinas-Lichius, Orlando; von Eggeling, Ferdinand

    2009-12-15

    Recent studies using molecular and genetic techniques just have started to elucidate the complex process that drives successful peripheral nerve regeneration. Introducing proteomics to this field, we unilaterally performed a facial nerve axotomy in 13 adult Wistar rats. Seven days later, a total of 40 20-microm coronary cryostat sections of the operated and contralateral unoperated nucleus facialis were microdissected. On the one hand, microdissected areas were pooled for each side, lysed and applied to ProteinChip Arrays. On the other hand, one microdissected area from the right and left facial nucleus each was directly placed on the affinity chromatographic array. Facial motoneurons were lysed in situ and released their proteins to spatially defined points. 215 laser addressable distinct positions across the surface of the spot enabled a high spatial resolution of measured protein profiles for the analysed tissue area. Protein profiles of the single positions were plotted over the used tissue section to visualize their distribution. The comparative analysis of the protein lysates from operated and normal nuclei facialis revealed, for both approaches used, differentially expressed proteins. Although by direct application of one cryostat section only a few hundred motoneurons were analysed, results comparable to these using lysates were obtained. Additionally, the applied technique revealed differences in the intensity distribution of several proteins of unknown function in the lesioned in comparison to the contralateral normal facial nucleus. This proteomic analysis with ultra high sensitivity paired with potential for a spatial resolution is a promising methodology for peripheral nerve regeneration studies. PMID:19748522

  9. 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

  10. 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

  11. Use of quantitative intra-operative electrodiagnosis during partial ulnar nerve transfer to restore elbow flexion: the treatment of eight patients following a brachial plexus injury.

    PubMed

    Suzuki, O; Sunagawa, T; Yokota, K; Nakashima, Y; Shinomiya, R; Nakanishi, K; Ochi, M

    2011-03-01

    The transfer of part of the ulnar nerve to the musculocutaneous nerve, first described by Oberlin, can restore flexion of the elbow following brachial plexus injury. In this study we evaluated the additional benefits and effectiveness of quantitative electrodiagnosis to select a donor fascicle. Eight patients who had undergone transfer of a simple fascicle of the ulnar nerve to the motor branch of the musculocutaneous nerve were evaluated. In two early patients electrodiagnosis had not been used. In the remaining six patients, however, all fascicles of the ulnar nerve were separated and electrodiagnosis was performed after stimulation with a commercially available electromyographic system. In these procedures, recording electrodes were placed in flexor carpi ulnaris and the first dorsal interosseous. A single fascicle in the flexor carpi ulnaris in which a high amplitude had been recorded was selected as a donor and transferred to the musculocutaneous nerve. In the two patients who had not undergone electrodiagnosis, the recovery of biceps proved insufficient for normal use. Conversely, in the six patients in whom quantitative electrodiagnosis was used, elbow flexion recovered to an M4 level. Quantitative intra-operative electrodiagnosis is an effective method of selecting a favourable donor fascicle during the Oberlin procedure. Moreover, fascicles showing a high-amplitude in reading flexor carpi ulnaris are donor nerves that can restore normal elbow flexion without intrinsic loss.

  12. Successful Nonoperative Management of HAGL (Humeral Avulsion of Glenohumeral Ligament) Lesion With Concurrent Axillary Nerve Injury in an Active-Duty US Navy SEAL.

    PubMed

    Ernat, Justin J; Bottoni, Craig R; Rowles, Douglas J

    2016-01-01

    Humeral avulsion of the glenohumeral ligament (HAGL) is a lesion that has been recognized as a cause of recurrent shoulder instability. To our knowledge there are no reports of successful return to full function in young, competitive athletes or return to manual labor following nonoperative management of a HAGL lesion. A 26-year-old Navy SEAL was diagnosed with a HAGL injury, and associated traction injury of the axillary nerve as well as a partial tear of the rotator cuff. Operative intervention was recommended; however, due to issues with training and with inability to properly rehab with the axillary nerve injury, surgical plans were delayed. Interestingly, the patient demonstrated both clinical and radiographic magnetic resonance imaging healing of his lesion over an 18-month period. At 18 months the patient had returned to full active duty without pain or instability as a Navy SEAL. PMID:27552458

  13. Comparison of hemihypoglossal- and accessory-facial neurorrhaphy for treating facial paralysis in rats.

    PubMed

    Li, Dezhi; Wan, Hong; Feng, Jie; Wang, Shiwei; Su, Diya; Hao, Shuyu; Schumacher, Michael; Liu, Song

    2014-12-15

    The aim of this study was to determine the effectiveness of hypoglossal-facial nerve "side"-to-end (HemiHN-FN) and accessory-facial nerve end-to-end (AN-FN) neurorrhaphy using a predegenerated nerve graft (PNG) for reanimating facial paralysis in a rat FN injury model. A total of 25 rats with complete unilateral facial paralysis resulting from section of the right FN were divided into 5 groups (n=5 each) that were submitted to immediate, delayed (3 months after FN injury) or no (control) FN reconstruction procedures involving HemiHN-FN or AN-FN neurorrhaphy. Approximately 3 months after FN reconstruction, cholera toxin subunit B conjugate Alexa 555 (CTB-Alexa 555) was injected into the ipsilateral whisker pad muscle and CTB-Alexa 555-labeled neurons were observed in the hypoglossal or accessory nuclei of all the FN reconstruction rats, but none of these neurons were found in the controls. There were numerous myelinated and nonmyelinated axons in both PNG and repaired FN of the FN reconstruction rats. No differences were found for these numbers between the two neurorrhaphy methods for each of the treatment time points, indicating the equal effectiveness of axon regeneration. However, a significantly higher number of CTB-Alexa 555-labeled neurons was observed in the hypoglossal nucleus of the immediate HemiHN-FN neurorrhaphy-treated rats when compared to that in the accessory nucleus of the immediate AN-FN neurorrhaphy-treated rats, consistent with the surface values of the recorded MAPs at the whisker pad muscle while electro-stimulating the FN. These results suggest that HemiHN-FN neurorrhaphy produces more efficient innervation of the paralyzed facial muscles than AN-FN neurorrhaphy without sacrificing ipsilateral hypoglossal function. Taking into consideration the clinical relevance of these findings for postoperative complications and functional reanimation in relation to the central plasticity, we suggest that HemiHN-FN neurorrhaphy may be the preferable facial

  14. The mGluR5 Antagonist Fenobam Induces Analgesic Conditioned Place Preference in Mice with Spared Nerve Injury

    PubMed Central

    Lax, Neil C.; George, David C.; Ignatz, Christopher; Kolber, Benedict J.

    2014-01-01

    Antagonists of metabotropic glutamate receptors (mGluRs) have the potential to act as analgesic drugs that may help alleviate chronic pain. This study was done to look at the possible rewarding properties of the mGluR5 antagonist, fenobam, in a cognitive assay. Analgesic conditioned place preference (aCPP) was used to examine the effects of fenobam (30 mg/kg) and the prototypical mGluR5 antagonist, MPEP, and these effects were compared to those of a drug with known analgesic properties, morphine (10 mg/kg). In each experiment, one group of mice received spared nerve injury (SNI) surgery to model chronic pain; the other group received a control sham surgery. Both fenobam and MPEP induced preference in the SNI mice, such that SNI mice spent significantly more time in the mGluR5 antagonist-paired chamber compared to a vehicle-paired chamber. No such preference developed for sham mice. Morphine induced preference in male and female mice in both the SNI and sham groups. The results showed that fenobam and MPEP likely reduced on-going distress in the SNI mice, causing them to prefer the chamber paired with the drug compared to the vehicle-paired chamber. Since sham animals did not prefer the drug-paired chamber, these data demonstrate that mGluR5 antagonism is non-rewarding in the absence of pain-like injury. PMID:25061818

  15. Coronectomy versus surgical removal of the lower third molars with a high risk of injury to the inferior alveolar nerve. A bibliographical review

    PubMed Central

    Moreno-Vicente, Javier; Schiavone-Mussano, Rocío; Clemente-Salas, Enrique; Marí-Roig, Antoni; Jané-Salas, Enric

    2015-01-01

    Background Coronectomy is the surgical removal of the crown of the tooth deliberately leaving part of its roots. This is done with the hope of eliminating the pathology caused, and since the roots are still intact, the integrity of the inferior alveolar nerve is preserved. Objectives The aim is to carry out a systematic review in order to be able to provide results and conclusions with the greatest scientific evidence possible. Material and Methods A literature review is carried out through the following search engines: Pubmed MEDLINE, Scielo, Cochrane library and EMI. The level of evidence criteria from the Agency for Healthcare Research and Quality was applied, and the clinical trials’ level of quality was analyzed by means of the JADAD criteria. Results The following articles were obtained which represents a total of 17: 1 systematic review, 2 randomized clinical trials and 2 non-randomized clinical trials, 3 cohort studies, 2 retrospective studies, 3 case studies and 4 literature reviews. Conclusions Coronectomy is an adequate preventative technique in protecting the inferior alveolar nerve, which is an alternative to the conventional extraction of third molars, which unlike the former technique, presents a high risk of injury to the inferior alveolar nerve. However, there is a need for new clinical studies, with a greater number of samples and with a longer follow-up period in order to detect potential adverse effects of the retained roots. Key words: Coronectomy, inferior alveolar nerve, nerve injury, wisdom tooth removal, paresthesia, and systematic review. PMID:25858081

  16. 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

  17. SHOULDER PAIN AND DYSFUNCTION SECONDARY TO NEURAL INJURY

    PubMed Central

    Stickler, Laurie

    2011-01-01

    Study Design: Resident's Case Study Background/Introduction: The reports of spinal accessory nerve injury in the literature primarily focus on injury following surgical dissection or traumatic stretch injury. There is limited literature describing the presentation and diagnosis of this injury with an unknown cause. The purpose of this case report is to describe the clinical decision-making process that guided the diagnosis and treatment of a complex patient with spinal accessory nerve palsy (SANP) whose clinical presentation and response to therapy were inconsistent with the results of multiple diagnostic tests. Case Description: The patient was a 27-year-old female triathlete with a five month history of right-sided neck, anterior shoulder, and chest pain. Outcome: Based on the physical exam, magnetic resonance imaging, radiographs, electrodiagnostic and nerve conduction testing, the patient was diagnosed by her physician with right sterno-clavicular joint strain and scapular dyskinesis and was referred to physical therapy. Care was initiated based on this initial diagnosis. Upon further examination and perusal of the literature, the physical therapist proposed a diagnosis of spinal accessory nerve injury. Intervention included manual release of soft tissue tightness, neuromuscular facilitation and sport-specific strengthening, resulting in full return to functional and sport activities. These interventions focused on neurological re-education and muscular facilitation to address SANP as opposed to a joint sprain and dysfunction, as initially diagnosed. Discussion: Proper diagnosis is imperative to effective treatment in all patients. This case illustrates the importance of a thorough examination and consideration of multiple diagnostic findings, particularly when EMG/NCV tests were negative, the cause was not apparent, and symptoms were less severe than other cases documented in the literature. Level of Evidence: Diagnosis, level 4 PMID:21904699

  18. Early increasing-intensity treadmill exercise reduces neuropathic pain by preventing nociceptor collateral sprouting and disruption of chloride cotransporters homeostasis after peripheral nerve injury.

    PubMed

    López-Álvarez, Víctor M; Modol, Laura; Navarro, Xavier; Cobianchi, Stefano

    2015-09-01

    Activity treatments, such as treadmill exercise, are used to improve functional recovery after nerve injury, parallel to an increase in neurotrophin levels. However, despite their role in neuronal survival and regeneration, neurotrophins may cause neuronal hyperexcitability that triggers neuropathic pain. In this work, we demonstrate that an early increasing-intensity treadmill exercise (iTR), performed during the first week (iTR1) or during the first 2 weeks (iTR2) after section and suture repair of the rat sciatic nerve, significantly reduced the hyperalgesia developing rapidly in the saphenous nerve territory and later in the sciatic nerve territory after regeneration. Nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) expression in sensory neurons and spinal cord was reduced in parallel. iTR prevented the extension of collateral sprouts of saphenous nociceptive calcitonin gene-related peptide fibers within the adjacent denervated skin and reduced NGF expression in the same skin and in the L3 dorsal root ganglia (DRG). Injury also induced Na⁺-K⁺-2Cl⁻ cotransporter 1 (NKCC1) upregulation in DRG, and K⁺-Cl⁻ cotransporter 2 (KCC2) downregulation in lumbar spinal cord dorsal horn. iTR normalized NKCC1 and boosted KCC2 expression, together with a significant reduction of microgliosis in L3-L5 dorsal horn, and a reduction of BDNF expression in microglia at 1 to 2 weeks postinjury. These data demonstrate that specific activity protocols, such as iTR, can modulate neurotrophins expression after peripheral nerve injury and prevent neuropathic pain by blocking early mechanisms of sensitization such as collateral sprouting and NKCC1/KCC2 disregulation. PMID:26090759

  19. Changes in the Capillarity of the Rat Extensor Digitorum Longus Muscle 4 Weeks after Nerve Injury Studied by 2D Measurement Methods.

    PubMed

    Čebašek, Vita; Ribarič, Samo

    2016-01-01

    We have previously shown by 3D study that 2 weeks after nerve injury there was no change in the length of capillaries per muscle fibre length in rat extensor digitorum longus muscle (EDL). The primary goal of the present 2D study was to determine the capillarity of rat EDL 4 weeks after various modes of nerve injury. Additionally, we wished to calculate the same capillary/fibre parameters that were used in our 3D stereological study. EDL muscles derived from denervated (4 weeks after nerve injury), re-innervated (4 weeks after two successive nerve crushes) and age-matched controls from the beginning (CON-1) and the end (CON-2) of the experiment were analysed in two ways. Global indices of capillarity, such as capillary density (CD) and capillary/fibre (C/F) ratio, were determined by automatic analysis, local indices as the number (CAF) and the length of capillaries around individual muscle fibres (Lcap) in relation to muscle fibre size were estimated manually by tracing the muscle fibre outlines and the transversally and longitudinally cut segments of capillaries seen in 5-µm-thin muscle cross sections. Four weeks after both types of nerve injury, CD increased in comparison to the CON-2 group (p < 0.001) due to atrophied muscle fibres in denervated muscles and probably proliferation of capillaries in re-innervated ones. Higher C/F, CAF (both p < 0.001) and Lcap (p < 0.01) in re-innervated than denervated EDL confirmed this assumption. Calculated capillary/fibre parameters were comparable to our previous 3D study, which strengthens the practical value to the adapted 2D method used in this study.

  20. Changes in the Capillarity of the Rat Extensor Digitorum Longus Muscle 4 Weeks after Nerve Injury Studied by 2D Measurement Methods.

    PubMed

    Čebašek, Vita; Ribarič, Samo

    2016-01-01

    We have previously shown by 3D study that 2 weeks after nerve injury there was no change in the length of capillaries per muscle fibre length in rat extensor digitorum longus muscle (EDL). The primary goal of the present 2D study was to determine the capillarity of rat EDL 4 weeks after various modes of nerve injury. Additionally, we wished to calculate the same capillary/fibre parameters that were used in our 3D stereological study. EDL muscles derived from denervated (4 weeks after nerve injury), re-innervated (4 weeks after two successive nerve crushes) and age-matched controls from the beginning (CON-1) and the end (CON-2) of the experiment were analysed in two ways. Global indices of capillarity, such as capillary density (CD) and capillary/fibre (C/F) ratio, were determined by automatic analysis, local indices as the number (CAF) and the length of capillaries around individual muscle fibres (Lcap) in relation to muscle fibre size were estimated manually by tracing the muscle fibre outlines and the transversally and longitudinally cut segments of capillaries seen in 5-µm-thin muscle cross sections. Four weeks after both types of nerve injury, CD increased in comparison to the CON-2 group (p < 0.001) due to atrophied muscle fibres in denervated muscles and probably proliferation of capillaries in re-innervated ones. Higher C/F, CAF (both p < 0.001) and Lcap (p < 0.01) in re-innervated than denervated EDL confirmed this assumption. Calculated capillary/fibre parameters were comparable to our previous 3D study, which strengthens the practical value to the adapted 2D method used in this study. PMID:27023720

  1. 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. PMID:24657809

  2. Lack of interleukin-17 leads to a modulated micro-environment and amelioration of mechanical hypersensitivity after peripheral nerve injury in mice.

    PubMed

    Day, Yuan-Ji; Liou, Jiin-Tarng; Lee, Chiou-Mei; Lin, Yi-Chiao; Mao, Chih-Chieh; Chou, An-Hsun; Liao, Chia-Chih; Lee, Hung-Chen

    2014-07-01

    Interleukin-17 (IL-17) is involved in a wide range of inflammatory disorders and in recruitment of inflammatory cells to injury sites. A recent study of IL-17 knock-out mice revealed that IL-17 contributes to neuroinflammation and neuropathic pain after peripheral nerve injury. Surprisingly, little is known of micro-environment modulation by IL-17 in injured sites and in pathologically related neuroinflammation and chronic neuropathic pain. Therefore, we investigated nociceptive sensitization, immune cell infiltration, myeloperoxidase (MPO) activity, and expression of multiple cytokines and opioid peptides in damaged nerves of wild-type (IL-17(+/+)) and IL-17 knock-out (IL-17(-/-)) mice after partial sciatic nerve ligation. Our results demonstrated that the IL-17(-/-) mice had less behavioral hypersensitivity after partial sciatic nerve ligation, and inflammatory cell infiltration and pro-inflammatory cytokine (tumor necrosis factor-α, IL-6, and interferon-γ) levels in damaged nerves were significantly decreased, with the levels of anti-inflammatory cytokines IL-10 and IL-13, and expressions of enkephalin, β-endorphin, and dynorphin were also decreased compared to those in wild-type control mice. In conclusion, we provided evidence that IL-17 modulates the micro-environment at the level of the peripheral injured nerve site and regulates progression of behavioral hypersensitivity in a murine chronic neuropathic pain model. The attenuated behavioral hypersensitivity in IL-17(-/-) mice could be a result of decreased inflammatory cell infiltration to the injured site, resulting in modulation of the pro- and anti-inflammatory cytokine milieu within the injured nerve. Therefore, IL-17 may be a critical component for neuropathic pain pathogenesis and a novel target for therapeutic intervention for this and other chronic pain states. PMID:24721689

  3. Adenoviral-mediated glial cell line-derived neurotrophic factor gene transfer has a protective effect on sciatic nerve following constriction-induced spinal cord injury.

    PubMed

    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

  4. Accessory oral cavity

    PubMed Central

    Gnaneswaran, Manica Ramamoorthy; Varadarajan, Usha; Srinivasan, Ramesh; Kamatchi, Sangeetha

    2012-01-01

    This is a rare case report of a patient around 11 years with the complaint of extra mouth who reported to the hospital for removal of that extra mouth. On examination there was accessory oral cavity with small upper and lower lips, seven teeth and saliva was drooling out. Under general anesthesia crevicular incision from 32 to 43 was put and labial gingiva with alveolar mucosa was reflected completely and bone exposed to lower border of mandible. There were seven teeth resembling lower permanent anterior teeth in the accessory mouth, which was excised with the accessory lips. 41 extracted and osteotomy carried out extending the incision from the extracted site and osteotomy carried out. Dermoid cyst both below and above the mylohyoid muscle and rudimentary tongue found and excised and the specimen sent for histopathological examination. The wound was closed and uneventful healing noted to the satisfaction of the patient. This is a rare and interesting case which has been documented. PMID:23833508

  5. Neuronal Nitric Oxide Signaling Regulates Erection Recovery after Cavernous Nerve Injury

    PubMed Central

    Sezen, Sena F.; Lagoda, Gwen; Burnett, Arthur L.

    2015-01-01

    Purpose NO is the major neuronal mediator of penile erection, but its role in EF status after CN injury is uncertain. This study aimed to determine the function of neuronal NO signaling in the pathobiology of EF recovery after partial CN injury using both genetic and pharmacologic mouse experimental paradigms. Materials and Methods EF was evaluated in WT and nNOS−/− mice (n=5–7/group) at 1, 3 and 7 days after UCI or sham injury and at day 7 in WT mice treated with the NO synthase inhibitor, L-NAME at baseline and for 6 days following UCI. Apoptosis in the penis was evaluated by Western blot analysis of p-Akt-S473, 3-NT, and caspase-3 expressions after BCI. Results ICP was significantly decreased at 1, 3 and 7 days in WT mice but only at day 1 in nNOS−/− mice after UCI compared with sham treatment values (p<0.05). L-NAME-treated WT mice had improved EF compared with the vehicle-treated group response at day 7 following UCI (p<0.05). p-Akt-S473 expression in penes was significantly decreased in vehicle-treated (p<0.05) but not L-NAME-treated WT mice. 3-NT expression in penes was significantly decreased in L-NAME-treated WT and vehicle-treated nNOS−/− mice (p<0.05). Caspase-3 expression in penes was significantly increased in vehicle-treated (p<0.05) but not L-NAME-treated WT mice and vehicle-treated nNOS−/− mice. Conclusions Neuronal NO signaling regulates EF recovery early after partial CN injury, exerting an inhibitory role via induction of apoptotic changes in penile tissue. Therapeutic strategies to improve EF recovery after RP may consider targeting pathogenic sites of NO neurobiology. PMID:22177198

  6. Exogenous Modulation of Retinoic Acid Signaling Affects Adult RGC Survival in the Frog Visual System after Optic Nerve Injury

    PubMed Central

    Duprey-Díaz, Mildred V.; Blagburn, Jonathan M.; Blanco, Rosa E.

    2016-01-01

    After lesions to the mammalian optic nerve, the great majority of retinal ganglion cells (RGCs) die before their axons have even had a chance to regenerate. Frog RGCs, on the other hand, suffer only an approximately 50% cell loss, and we have previously investigated the mechanisms by which the application of growth factors can increase their survival rate. Retinoic acid (RA) is a vitamin A-derived lipophilic molecule that plays major roles during development of the nervous system. The RA signaling pathway is also present in parts of the adult nervous system, and components of it are upregulated after injury in peripheral nerves but not in the CNS. Here we investigate whether RA signaling affects long-term RGC survival at 6 weeks after axotomy. Intraocular injection of all-trans retinoic acid (ATRA), the retinoic acid receptor (RAR) type-α agonist AM80, the RARβ agonist CD2314, or the RARγ agonist CD1530, returned axotomized RGC numbers to almost normal levels. On the other hand, inhibition of RA synthesis with disulfiram, or of RAR receptors with the pan-RAR antagonist Ro-41-5253, or the RARβ antagonist LE135E, greatly reduced the survival of the axotomized neurons. Axotomy elicited a strong activation of the MAPK, STAT3 and AKT pathways; this activation was prevented by disulfiram or by RAR antagonists. Finally, addition of exogenous ATRA stimulated the activation of the first two of these pathways. Future experiments will investigate whether these strong survival-promoting effects of RA are mediated via the upregulation of neurotrophins. PMID:27611191

  7. Analgesic effect of iridoid glycosides from Paederia scandens (LOUR.) MERRILL (Rubiaceae) on spared nerve injury rat model of neuropathic pain.

    PubMed

    Liu, Mei; Zhou, Lanlan; Chen, Zhiwu; Hu, Caibiao

    2012-09-01

    Iridoid glycosides of Paederia scandens (IGPS) is a major active component isolated from traditional Chinese herb P. scandens (LOUR.) MERRILL (Rubiaceae). The aim of the present study was to investigate the analgesic effect of IGPS on spared nerve injury (SNI) model of neuropathic pain. The SNI model in rats was established by complete transection of the common peroneal and tibial distal branches of the sciatic nerve, leaving the sural branch intact. The mechanical withdrawal threshold (MWT) in response to mechanical stimulation was measured by electronic von Frey filaments on day 1 before operation and on days 1, 3, 5, 7, 10, and 14 after operation, respectively. Nitric oxide synthase (NOS) activity and nitric oxide (NO) production of spinal cord were measured by spectrophotometry and its cyclic guanosine monophosphate (cGMP) content by radioimmunoassay, mRNA expression of inducible NOS (iNOS) and protein kinase G type I (PKG-I, including PKG Ια and PKG Iβ) of spinal cord were analyzed by RT-PCR. There was a marked mechanical hypersensitivity response observed on day 1 after operation in SNI model, which accompanied with decreased MWT. Treatment with IGPS (70, 140, 280 mg/kg) significantly alleviated SNI-induced mechanical hypersensitivity response evidenced by increased MWT; as well as markedly decreased NOS activity, NO and cGMP levels. At the same time, IGPS (70, 140, 280 mg/kg) could also inhibit mRNA expression of iNOS, PKG Ια and PKG Iβ in the spinal cord. The results suggested that IGPS possesses antinociceptive effect, which may be partly related to the inhibition of NO/cGMP/PKG signaling pathway in the rat SNI model of neuropathic pain. PMID:22698486

  8. Exogenous Modulation of Retinoic Acid Signaling Affects Adult RGC Survival in the Frog Visual System after Optic Nerve Injury.

    PubMed

    Duprey-Díaz, Mildred V; Blagburn, Jonathan M; Blanco, Rosa E

    2016-01-01

    After lesions to the mammalian optic nerve, the great majority of retinal ganglion cells (RGCs) die before their axons have even had a chance to regenerate. Frog RGCs, on the other hand, suffer only an approximately 50% cell loss, and we have previously investigated the mechanisms by which the application of growth factors can increase their survival rate. Retinoic acid (RA) is a vitamin A-derived lipophilic molecule that plays major roles during development of the nervous system. The RA signaling pathway is also present in parts of the adult nervous system, and components of it are upregulated after injury in peripheral nerves but not in the CNS. Here we investigate whether RA signaling affects long-term RGC survival at 6 weeks after axotomy. Intraocular injection of all-trans retinoic acid (ATRA), the retinoic acid receptor (RAR) type-α agonist AM80, the RARβ agonist CD2314, or the RARγ agonist CD1530, returned axotomized RGC numbers to almost normal levels. On the other hand, inhibition of RA synthesis with disulfiram, or of RAR receptors with the pan-RAR antagonist Ro-41-5253, or the RARβ antagonist LE135E, greatly reduced the survival of the axotomized neurons. Axotomy elicited a strong activation of the MAPK, STAT3 and AKT pathways; this activation was prevented by disulfiram or by RAR antagonists. Finally, addition of exogenous ATRA stimulated the activation of the first two of these pathways. Future experiments will investigate whether these strong survival-promoting effects of RA are mediated via the upregulation of neurotrophins. PMID:27611191

  9. Effects of umbilical cord tissue mesenchymal stem cells (UCX®) on rat sciatic nerve regeneration after neurotmesis injuries

    PubMed Central

    Gärtner, A; Pereira, T; Armada-da-Silva, PAS; Amado, S; Veloso, AP; Amorim, I; Ribeiro, J; Santos, JD; Bárcia, RN; Cruz, P; Cruz, H; Luís, AL; Santos, JM; Geuna, S; Maurício, AC

    2014-01-01

    Peripheral nerves have the intrinsic capacity of self-regeneration after traumatic injury but the extent of the regeneration is often very poor. Increasing evidence demonstrates that mesenchymal stem/stromal cells (MSCs) may play an important role in tissue regeneration through the secretion of soluble trophic factors that enhance and assist in repair by paracrine activation of surrounding cells. In the present study, the therapeutic value of a population of umbilical cord tissue-derived MSCs, obtained by a proprietary method (UCX®), was evaluated on end-to-end rat sciatic nerve repair. Furthermore, in order to promote both, end-to-end nerve fiber contacts and MSC cell-cell interaction, as well as reduce the flush away effect of the cells after administration, a commercially available haemostatic sealant, Floseal®, was used as vehicle. Both, functional and morphologic recoveries were evaluated along the healing period using extensor postural thrust (EPT), withdrawal reflex latency (WRL), ankle kinematics analysis, and either histological analysis or stereology, in the hyper-acute, acute and chronic phases of healing. The histological analysis of the hyper-acute and acute phase studies revealed that in the group treated with UCX® alone the Wallerian degeneration was improved for the subsequent process of regeneration, the fiber organization was higher, and the extent of fibrosis was lower. The chronic phase experimental groups revealed that treatment with UCX® induced an increased number of regenerated fibers and thickening of the myelin sheet. Kinematics analysis showed that the ankle joint angle determined for untreated animals was significantly different from any of the treated groups at the instant of initial contact (IC). At opposite toe off (OT) and heel rise (HR), differences were found between untreated animals and the groups treated with either uCx® alone or UCX® administered with Floseal®. Overall, the UCX® application presented positive effects in

  10. Effects of umbilical cord tissue mesenchymal stem cells (UCX®) on rat sciatic nerve regeneration after neurotmesis injuries.

    PubMed

    Gärtner, A; Pereira, T; Armada-da-Silva, Pas; Amado, S; Veloso, Ap; Amorim, I; Ribeiro, J; Santos, Jd; Bárcia, Rn; Cruz, P; Cruz, H; Luís, Al; Santos, Jm; Geuna, S; Maurício, Ac

    2014-01-01

    Peripheral nerves have the intrinsic capacity of self-regeneration after traumatic injury but the extent of the regeneration is often very poor. Increasing evidence demonstrates that mesenchymal stem/stromal cells (MSCs) may play an important role in tissue regeneration through the secretion of soluble trophic factors that enhance and assist in repair by paracrine activation of surrounding cells. In the present study, the therapeutic value of a population of umbilical cord tissue-derived MSCs, obtained by a proprietary method (UCX(®)), was evaluated on end-to-end rat sciatic nerve repair. Furthermore, in order to promote both, end-to-end nerve fiber contacts and MSC cell-cell interaction, as well as reduce the flush away effect of the cells after administration, a commercially available haemostatic sealant, Floseal(®), was used as vehicle. Both, functional and morphologic recoveries were evaluated along the healing period using extensor postural thrust (EPT), withdrawal reflex latency (WRL), ankle kinematics analysis, and either histological analysis or stereology, in the hyper-acute, acute and chronic phases of healing. The histological analysis of the hyper-acute and acute phase studies revealed that in the group treated with UCX(®) alone the Wallerian degeneration was improved for the subsequent process of regeneration, the fiber organization was higher, and the extent of fibrosis was lower. The chronic phase experimental groups revealed that treatment with UCX(®) induced an increased number of regenerated fibers and thickening of the myelin sheet. Kinematics analysis showed that the ankle joint angle determined for untreated animals was significantly different from any of the treated groups at the instant of initial contact (IC). At opposite toe off (OT) and heel rise (HR), differences were found between untreated animals and the groups treated with either uCx(®) alone or UCX(®) administered with Floseal(®). Overall, the UCX(®) application presented

  11. Large-area irradiated low-level laser effect in a biodegradable nerve guide conduit on neural regeneration of peripheral nerve injury in rats.

    PubMed

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

    2011-08-01

    This study used a biodegradable composite containing genipin-cross-linked gelatin annexed with β-tricalcium phosphate ceramic particles (genipin-gelatin-tricalcium phosphate, GGT), developed in a previous study, as a nerve guide conduit. The aim of this study was to analyse the influence of a large-area irradiated aluminium-gallium-indium phosphide (AlGaInP) diode laser (660 nm) on the neural regeneration of the transected sciatic nerve after bridging the GGT nerve guide conduit in rats. The animals were divided into two groups: group 1 comprised sham-irradiated controls and group 2 rats underwent low-level laser (LLL) therapy. A compact multi-cluster laser system with 20 AlGaInP laser diodes (output power, 50mW) was applied transcutaneously to the injured peripheral nerve immediately after closing the wound, which was repeated daily for 5 min for 21 consecutive days. Eight weeks after implantation, walking track analysis showed a significantly higher sciatic function index (SFI) score (P<0.05) and better toe spreading development in the laser-treated group than in the sham-irradiated control group. For electrophysiological measurement, both the mean peak amplitude and nerve conduction velocity of compound muscle action potentials (CMAPs) were higher in the laser-treated group than in the sham-irradiated group. The two groups were found to be significantly different during the experimental period (P<0.005). Histomorphometric assessments revealed that the qualitative observation and quantitative analysis of the regenerated nerve tissue in the laser-treated group were superior to those of the sham-irradiated group. Thus, the motor functional, electrophysiologic and histomorphometric assessments demonstrate that LLL therapy can accelerate neural repair of the corresponding transected peripheral nerve after bridging the GGT nerve guide conduit in rats. PMID:21397226

  12. The subdiaphragmatic part of the phrenic nerve - morphometry and connections to autonomic ganglia.

    PubMed

    Loukas, Marios; Du Plessis, Maira; Louis, Robert G; Tubbs, R Shane; Wartmann, Christopher T; Apaydin, Nihal

    2016-01-01

    Few anatomical textbooks offer much information concerning the anatomy and distribution of the phrenic nerve inferior to the diaphragm. The aim of this study was to identify the subdiaphragmatic distribution of the phrenic nerve, the presence of phrenic ganglia, and possible connections to the celiac plexus. One hundred and thirty formalin-fixed adult cadavers were studied. The right phrenic nerve was found inferior to the diaphragm in 98% with 49.1% displaying a right phrenic ganglion. In 22.8% there was an additional smaller ganglion (right accessory phrenic ganglion). The remaining 50.9% had no grossly identifiable right phrenic ganglion. Most (65.5% of specimens) exhibited plexiform communications with the celiac ganglion, aorticorenal ganglion, and suprarenal gland. The left phrenic nerve inferior to the diaphragm was observed in 60% of specimens with 19% containing a left phrenic ganglion. No accessory left phrenic ganglia were observed. The left phrenic ganglion exhibited plexiform communications to several ganglia in 71.4% of specimens. Histologically, the right phrenic and left phrenic ganglia contained large soma concentrated in their peripheries. Both phrenic nerves and ganglia were closely related to the diaphragmatic crura. Surgically, sutures to approximate the crura for repair of hiatal hernias must be placed above the ganglia in order to avoid iatrogenic injuries to the autonomic supply to the diaphragm and abdomen. These findings could also provide a better understanding of the anatomy and distribution of the fibers of that autonomic supply.

  13. Sodium channel Nav1.6 accumulates at the site of infraorbital nerve injury

    PubMed Central

    Henry, Michael A; Freking, Angelique R; Johnson, Lonnie R; Levinson, S Rock

    2007-01-01

    Background Sodium channel (NaCh) expressions change following nerve and inflammatory lesions and this change may contribute to the activation of pain pathways. In a previous study we found a dramatic increase in the size and density of NaCh accumulations, and a remodeling of NaChs at intact and altered myelinated sites at a location just proximal to a combined partial axotomy and chromic suture lesion of the rat infraorbital nerve (ION) with the use of an antibody that identifies all NaCh isoforms. Here we evaluate the contribution of the major nodal NaCh isoform, Nav1.6, to this remodeling of NaChs following the same lesion. Sections of the ION from normal and ION lesioned subjects were double-stained with antibodies against Nav1.6 and caspr (contactin-associated protein; a paranodal protein to identify nodes of Ranvier) and then z-series of optically sectioned images were captured with a confocal microscope. ImageJ (NIH) software was used to quantify the average size and density of Nav1.6 accumulations, while additional single fiber analyses measured the axial length of the nodal gap, and the immunofluorescence intensity of Nav1.6 in nodes and of caspr in the paranodal region. Results The findings showed a significant increase in the average size and density of Nav1.6 accumulations in lesioned IONs when compared to normal IONs. The results of the single fiber analyses in caspr-identified typical nodes showed an increased axial length of the nodal gap, an increased immunofluorescence intensity of nodal Nav1.6 and a decreased immunofluorescence intensity of paranodal caspr in lesioned IONs when compared to normal IONs. In the lesioned IONs, Nav1.6 accumulations were also seen in association with altered caspr-relationships, such as heminodes. Conclusion The results of the present study identify Nav1.6 as one isoform involved in the augmentation and remodeling of NaChs at nodal sites following a combined partial axotomy and chromic suture ION lesion. The

  14. Accessory fissures of the lung

    SciTech Connect

    Godwin, D.; Tarver, R.D.

    1985-01-01

    Accessory fissures of the lung are commonly observed in lung specimens, but are often unappreciated or misinterpreted in radiographs and computer tomographic (CT) scans. They usually occur at the boundaries between bronchopulmonary segments. Most common are the inferior accessory fissure, which demarcates the medial basal segment; the superior accessory fissure, which demarcates the superior segment; and the left minor fissure, which demarcates the lingula. This essay will illustrate the findings of the common accessory fissures both on plain radiographs and on CT scans.

  15. Partial nerve injury induces electrophysiological changes in conducting (uninjured) nociceptive and nonnociceptive DRG neurons: Possible relationships to aspects of peripheral neuropathic pain and paresthesias

    PubMed Central

    Djouhri, Laiche; Fang, Xin; Koutsikou, Stella; Lawson, Sally N.

    2012-01-01

    Partial nerve injury leads to peripheral neuropathic pain. This injury results in conducting/uninterrupted (also called uninjured) sensory fibres, conducting through the damaged nerve alongside axotomised/degenerating fibres. In rats seven days after L5 spinal nerve axotomy (SNA) or modified-SNA (added loose-ligation of L4 spinal nerve with neuroinflammation-inducing chromic-gut), we investigated a) neuropathic pain behaviours and b) electrophysiological changes in conducting/uninterrupted L4 dorsal root ganglion (DRG) neurons with receptive fields (called: L4-receptive-field-neurons). Compared to pretreatment, modified-SNA rats showed highly significant increases in spontaneous-foot-lifting duration, mechanical-hypersensitivity/allodynia, and heat-hypersensitivity/hyperalgesia, that were significantly greater than after SNA, especially spontaneous-foot-lifting. We recorded intracellularly in vivo from normal L4/L5 DRG neurons and ipsilateral L4-receptive-field-neurons. After SNA or modified-SNA, L4-receptive-field-neurons showed the following: a) increased percentages of C-, Ad-, and Ab-nociceptors and cutaneous Aa/b-low-threshold mechanoreceptors with ongoing/spontaneous firing; b) spontaneous firing in C-nociceptors that originated peripherally; this was at a faster rate in modified-SNA than SNA; c) decreased electrical thresholds in A-nociceptors after SNA; d) hyperpolarised membrane potentials in A-nociceptors and Aa/b-low-threshold-mechanoreceptors after SNA, but not C-nociceptors; e) decreased somatic action potential rise times in C- and A-nociceptors, not Aa/b-low-threshold-mechanoreceptors. We suggest that these changes in subtypes of conducting/uninterrupted neurons after partial nerve injury contribute to the different aspects of neuropathic pain as follows: spontaneous firing in nociceptors to ongoing/spontaneous pain; spontaneous firing in Aa/b-low-threshold-mechanoreceptors to dysesthesias/paresthesias; and lowered A-nociceptor electrical thresholds

  16. Transplantation of Cerebral Dopamine Neurotrophic Factor Transducted BMSCs in Contusion Spinal Cord Injury of Rats: Promotion of Nerve Regeneration by Alleviating Neuroinflammation.

    PubMed

    Zhao, Hua; Cheng, Lei; Du, Xinwen; Hou, Yong; Liu, Yi; Cui, Zhaoqiang; Nie, Lin

    2016-01-01

    Traumatic spinal cord injury (SCI) causes neuron death and axonal damage resulting in functional motor and sensory loss, showing limited regeneration because of adverse microenvironment such as neuroinflammation and glial scarring. Currently, there is no effective therapy to treat SCI in clinical practice. Bone marrow-derived mesenchymal stem cells (BMSCs) are candidates for cell therapies but its effect is limited by neuroinflammation and adverse microenvironment in the injured spinal cord. In this study, we developed transgenic BMSCs overexpressing cerebral dopamine neurotrophic factor (CDNF), a secretory neurotrophic factor that showed potent effects on neuron protection, anti-inflammation, and sciatic nerve regeneration in previous studies. Our results showed that the transplantation of CDNF-BMSCs suppressed neuroinflammation and decreased the production of proinflammatory cytokines after SCI, resulting in the promotion of locomotor function and nerve regeneration of the injured spinal cord. This study presents a novel promising strategy for the treatment of spinal cord injury.

  17. Repetitive magnetic stimulation affects the microenvironment of nerve regeneration and evoked potentials after spinal cord injury

    PubMed Central

    Jiang, Jin-lan; Guo, Xu-dong; Zhang, Shu-quan; Wang, Xin-gang; Wu, Shi-feng

    2016-01-01

    Repetitive magnetic stimulation has been shown to alter local blood flow of the brain, excite the corticospinal tract and muscle, and induce motor function recovery. We established a rat model of acute spinal cord injury using the modified Allen's method. After 4 hours of injury, rat models received repetitive magnetic stimulation, with a stimulus intensity of 35% maximum output intensity, 5-Hz frequency, 5 seconds for each sequence, and an interval of 2 minutes. This was repeated for a total of 10 sequences, once a day, 5 days in a week, for 2 consecutive weeks. After repetitive magnetic stimulation, the number of apoptotic cells decreased, matrix metalloproteinase 9/2 gene and protein expression decreased, nestin expression increased, somatosensory and motor-evoked potentials recovered, and motor function recovered in the injured spinal cord. These findings confirm that repetitive magnetic stimulation of the spinal cord improved the microenvironment of neural regeneration, reduced neuronal apoptosis, and induced neuroprotective and repair effects on the injured spinal cord. PMID:27335567

  18. Plasticity of recurrent inhibitory reflexes in cat spinal motoneurons following peripheral nerve injury.

    PubMed

    Havton, L; Kellerth, J O

    1990-01-01

    Chronic axotomy of a peripheral motor nerve in cat causes a gradual reduction in the number of intramedullary axon collaterals originating from the axotomized motoneurons (Havton and Kellerth 1984, 1989). This axon collateral elimination would be expected to reduce the amount of recurrent inhibitory reflex actions mediated by these cells. The aim of the present study was to investigate the recurrent inhibition originating from axotomized motoneurons and, also, to see whether the elimination of axon collaterals from the axotomized neurons might induce secondary compensatory changes in the recurrent inhibitory pathways originating from synergistic non-lesioned motoneurons. The results, which were obtained by means of intracellular recordings and monosynaptic reflex testing, indicate that postoperati