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Sample records for root nerve signals

  1. Nerve root replantation.

    PubMed

    Carlstedt, Thomas

    2009-01-01

    Traumatic avulsion of nerve roots from the spinal cord is a devastating event that usually occurs in the brachial plexus of young adults following motor vehicle or sports accidents or in newborn children during difficult childbirth. A strategy to restore motor function in the affected arm by reimplanting into the spinal cord the avulsed ventral roots or autologous nerve grafts connected distally to the avulsed roots has been developed. Surgical outcome is good and useful recovery in shoulder and proximal arm muscles occurs. Pain is alleviated with motor recovery but sensory improvement is poor when only motor conduits have been reconstructed. In experimental studies, restoration of sensory connections with general improvement in the outcome from this surgery is pursued.

  2. The roles of mechanical compression and chemical irritation in regulating spinal neuronal signaling in painful cervical nerve root injury.

    PubMed

    Zhang, Sijia; Nicholson, Kristen J; Smith, Jenell R; Gilliland, Taylor M; Syré, Peter P; Winkelstein, Beth A

    2013-11-01

    Both traumatic and slow-onset disc herniation can directly compress and/or chemically irritate cervical nerve roots, and both types of root injury elicit pain in animal models of radiculopathy. This study investigated the relative contributions of mechanical compression and chemical irritation of the nerve root to spinal regulation of neuronal activity using several outcomes. Modifications of two proteins known to regulate neurotransmission in the spinal cord, the neuropeptide calcitonin gene-related peptide (CGRP) and glutamate transporter 1 (GLT-1), were assessed in a rat model after painful cervical nerve root injuries using a mechanical compression, chemical irritation or their combination of injury. Only injuries with compression induced sustained behavioral hypersensitivity (p≤0.05) for two weeks and significant decreases (p<0.037) in CGRP and GLT-1 immunoreactivity to nearly half that of sham levels in the superficial dorsal horn. Because modification of spinal CGRP and GLT-1 is associated with enhanced excitatory signaling in the spinal cord, a second study evaluated the electrophysiological properties of neurons in the superficial and deeper dorsal horn at day 7 after a painful root compression. The evoked firing rate was significantly increased (p=0.045) after compression and only in the deeper lamina. The painful compression also induced a significant (p=0.002) shift in the percentage of neurons in the superficial lamina classified as low- threshold mechanoreceptive (sham 38%; compression 10%) to those classified as wide dynamic range neurons (sham 43%; compression 74%). Together, these studies highlight mechanical compression as a key modulator of spinal neuronal signaling in the context of radicular injury and pain.

  3. Lumbosacral nerve root avulsion.

    PubMed

    Chin, C H; Chew, K C

    1997-01-01

    Lumbosacral nerve root avulsion is a rare clinical entity. Since the first description in 1955, only 35 cases have been reported. It is often associated with pelvic fractures and may be missed in the initial clinical examination as these patients usually present with multiple injuries. We present three such cases with clinical and radiological findings. These patients were involved in road traffic accidents. Two had fractures of the sacroiliac joint with diastasis of the symphysis pubis (Tile type C 1.2) and one had fractures of the public rami (Tile type B 2.1). All three had various degrees of sensory and motor deficit of the lower limbs. Lumbar myelogram shows characteristic pseudomeningoceles in the affected lumboscral region. Magnetic resonance (MR) imaging provides an additional non-invasive modality to diagnose this condition.

  4. [Lumbosciatica and nerve root anomalies].

    PubMed

    Sacchi, A; Rouaud, J P; Caroit, M; George, B; Cophignon, J

    1982-04-01

    The authors report 3 cases of lumbar pain and sciatica where operation revealed the existence of abnormalities in the distribution of L5 and S1 roots. In one case, the L5 root was not recognised within fibrous tissue also surrounding S1 and S2 and histological examination of this "fibrosis" led to the identification of nerve structures. Development of postoperative L5 paralysis showed that the L5 root was contained within the tissue non-individualised, consisting of multiple rootlets. In the other two cases the L5 and S1 roots arose from a common trunk. There was an associated herniated disc in all three cases. A review of the literature revealed the rarity of such abnormalities, as well as the fact that they were not recognised before surgery. They are difficult to recognise, even at the time of operation. The prognosis is less good than in typical lumbar pain and sciatica, essentially because of surgical difficulties of the disc curettage.

  5. Purely extradural spinal nerve root hemangioblastomas

    PubMed Central

    Aytar, Murat Hamit; Yener, Ulaş; Ekşi, Murat Şakir; Kaya, Behram; Özgen, Serdar; Sav, Aydin; Alanay, Ahmet

    2016-01-01

    Spinal nerve root hemangioblastomas present mostly as intradural-extradurally. Purely extradural spinal nerve root hemangioblastoma is a very rare entity. In this study, we aimed to analyze epidemiological perspectives of purely extradural spinal nerve root hemangioblastomas presented in English medical literature in addition to our own exemplary case. PubMed/MEDLINE was searched using the terms “hemangioblastoma,” “extradural,” “spinal,” and “nerve root.” Demographical variables of age, gender, concomitant presence of von Hippel–Lindau (VHL) disease; spinal imaging and/or intraoperative findings for tumor location were surveyed from retrieved articles. There are 38 patients with purely extradural spinal nerve root hemangioblastoma. The median age is 45 years (range = 24–72 years). Female:male ratio is 0.6. Spinal levels for purely extradural spinal nerve root hemangioblastomas, in order of decreasing frequency, are thoracic (48.6%), cervical (13.5%), lumbar (13.5%), lumbosacral (10.8%), sacral (8.1%), and thoracolumbar (5.4%). Concomitant presence of VHL disease is 45%. Purely extradural spinal nerve root hemangioblastomas are very rare and can be confused with other more common extradural spinal cord tumors. Concomitant presence of VHL disease is observed in less than half of the patients with purely extradural spinal nerve root hemangioblastomas. Surgery is the first-line treatment in these tumors. PMID:27891027

  6. [The measurement of nerve root tensile stress].

    PubMed

    Poeată, I; Munteanu, Fl

    2008-01-01

    In the majority of the cases sciatica is caused by an intervertebral disc herniation compressing the nerve root. The compression determines an increased tension in the nerve root. We believe that the magnitude of this stress offers more information about the root impairment that the disc displacement measured on MRI images. We present in this paper an original device which allows for intraoperative root stress analysis. The device consists of a force transducer composed of an elastic element and a displacement limitation. The initial measurements were performed on silicon catheters and human cadavers in two different situations: 1. free nerve root; 2. blocked nerve root. Next step was intraoperative nerve roots tensile stress recording during lumbar disc surgery. Different force values were obtained for the same displacement (3 mm perpendicular on nervous root): F1 = 0.21 N; F2 = 0.78 N. Considering experimental values, the tensile stress inside of a nervous root is determined by using specific mechanical calculations presented in this paper. This is a simple and useful device for rapid intraoperative recording of nerve root mechanical stress.

  7. Ultrasonography Evaluation of Vulnerable Vessels Around Cervical Nerve Roots During Selective Cervical Nerve Root Block

    PubMed Central

    2017-01-01

    Objective To evaluate the prevalence of vulnerable blood vessels around cervical nerve roots before cervical nerve root block in the clinical setting. Methods This retrospective study included 74 patients with cervical radiculopathy who received an ultrasonography-guided nerve block at an outpatient clinic from July 2012 to July 2014. Before actual injection of the steroid was performed, we evaluated the vulnerable blood vessels around each C5, C6, and C7 nerve root of each patient's painful side, with Doppler ultrasound. Results Out of 74 cases, the C5 level had 2 blood vessels (2.7%), the C6 level had 4 blood vessels (5.45%), and the C7 level had 6 blood vessels (8.11%) close to each targeted nerve root. Moreover, the C5 level had 2 blood vessels (2.7%), the C6 level 5 blood vessels (6.75%), and the C7 level had 4 blood vessels (5.45%) at the site of an imaginary needle's projected pathway to the targeted nerve root, as revealed by axial transverse ultrasound imaging with color Doppler imaging. In total, the C5 level had 4 blood vessels (5.45%), the C6 level 9 blood vessels (12.16%), and the C7 level 10 had blood vessels (13.51%) either at the targeted nerve root or at the site of the imaginary needle's projected pathway to the targeted nerve root. There was an unneglectable prevalence of vulnerable blood vessels either at the targeted nerve root or at the site of the needle' projected pathway to the nerve root. Also, it shows a higher prevalence of vulnerable blood vessels either at the targeted nerve root or at the site of an imaginary needle's projected pathway to the nerve root as the spinal nerve root level gets lower. Conclusion To prevent unexpected critical complications involving vulnerable blood vessel injury during cervical nerve root block, it is recommended to routinely evaluate for the presence of vulnerable blood vessels around each cervical nerve root using Doppler ultrasound imaging before the cervical nerve root block, especially for the lower

  8. Endoscopic decompression for intraforaminal and extraforaminal nerve root compression

    PubMed Central

    2011-01-01

    Objective The purpose of this study was to evaluate the outcome of endoscopic decompression surgery for intraforaminal and extraforaminal nerve root compression in the lumbar spine. Methods The records from seventeen consecutive patients treated with endoscopic posterior decompression without fusion for intaforaminal and extraforaminal nerve root compression in the lumbar spine (7 males and 10 females, mean age: 67.9 ± 10.7 years) were retrospectively reviewed. The surgical procedures consisted of lateral or translaminal decompression with or without discectomy. The following items were investigated: 1) the preoperative clinical findings; 2) the radiologic findings including MRI and computed tomography-discography; and 3) the surgical outcome as evaluated using the Japanese Orthopaedic Association scale for lower back pain (JOA score). Results All patients had neurological findings compatible with a radiculopathy, such as muscle weakness and sensory disturbance. MRI demonstrated the obliteration of the normal increased signal intensity fat in the intervertebral foramen. Ten patients out of 14 who underwent computed tomography-discography exhibited disc protrusion or herniation. Selective nerve root block was effective in all patients. During surgery, 12 patients were found to have a protruded disc or herniation that compressed the nerve root. Sixteen patients reported pain relief immediately after surgery. Conclusions Intraforaminal and extraforaminal nerve root compression is a rare but distinct pathological condition causing severe radiculopathy. Endoscopic decompression surgery is considered to be an appropriate and less invasive surgical option. PMID:21439083

  9. Clinical and Radiological Findings of Nerve Root Herniation after Discectomy of Lumbar Disc Herniation

    PubMed Central

    Bae, Jun Seok; Pee, Yong Hun; Lee, Sang-Ho

    2012-01-01

    The authors report 2 cases of nerve root herniation after discectomy of a large lumbar disc herniation caused by an unrecognized dural tear. Patients complained of the abrupt onset of radiating pain after lumbar discectomy. Magnetic resonance imaging showed cerebrospinal fluid signal in the disc space and nerve root displacement into the disc space. Symptoms improved after the herniated nerve root was repositioned. Clinical symptoms and suggestive radiologic image findings are important for early diagnosis and treatment. PMID:22993682

  10. Characterization of a chondroitin sulfate hydrogel for nerve root regeneration

    NASA Astrophysics Data System (ADS)

    Conovaloff, Aaron; Panitch, Alyssa

    2011-10-01

    Brachial plexus injury is a serious medical problem that affects many patients annually, with most cases involving damage to the nerve roots. Therefore, a chondroitin sulfate hydrogel was designed to both serve as a scaffold for regenerating root neurons and deliver neurotrophic signals. Capillary electrophoresis showed that chondroitin sulfate has a dissociation constant in the micromolar range with several common neurotrophins, and this was determined to be approximately tenfold stronger than with heparin. It was also revealed that nerve growth factor exhibits a slightly stronger affinity for hyaluronic acid than for chondroitin sulfate. However, E8 chick dorsal root ganglia cultured in the presence of nerve growth factor revealed that ganglia cultured in chondroitin sulfate scaffolds showed more robust growth than those cultured in control gels of hyaluronic acid. It is hypothesized that, despite the stronger affinity of nerve growth factor for hyaluronic acid, chondroitin sulfate serves as a better scaffold for neurite outgrowth, possibly due to inhibition of growth by hyaluronic acid chains.

  11. Intraoperative Recording of ENG From Human Sacral Nerve Roots

    DTIC Science & Technology

    2001-10-25

    clitoris nerve [4], the pudendal nerve and the dorsal sacral nerve roots [5]. Several studies have shown that electrical stimulation of these...pressure. In addition two surface electrodes were placed next to the clitoris for stimulation of the dorsal clitoral nerve. The cuff electrodes were

  12. Reconstruction of nerve root sheaths for sacral extradural spinal meningeal cysts with spinal nerve root fibers.

    PubMed

    Sun, Jianjun; Wang, Zhenyu; Li, Zhendong; Wu, Haibo; Yen, Ruyu; Zheng, Mei; Chang, Qing; Liu, Isabelle Yisha

    2013-11-01

    This study analyzed the clinical characteristics and outcomes of sacral extradural spinal meningeal cysts with spinal nerve root fibers treated by reconstruction of the nerve root sheaths. The relationships between the cysts and spinal nerve root fibers were examined microscopically, the cysts were partially excised, and the defects were oversewn to reconstruct the nerve root sheaths. The Improved Japanese Orthopedic Association (IJOA) scoring system was used to evaluate preoperative and postoperative neurological function. Thirty-eight patients were included in this study, with a mean age of 41.4 ± 15.57 years. The mean IJOA score was 18.8 ± 1.32 preoperatively and 19.6 ± 0.65 postoperatively, which was a significant difference (t=-3.77, P=0.001). These results indicate a significant improvement in neurological function after surgery. The most significant improvement in neurological function was sensation (z=-2.86, P=0.004), followed by bowel/bladder function (z=-2.31, P=0.02).

  13. Chronic sciatic nerve compression induces fibrosis in dorsal root ganglia.

    PubMed

    Li, Qinwen; Chen, Jianghai; Chen, Yanhua; Cong, Xiaobin; Chen, Zhenbing

    2016-03-01

    In the present study, pathological alterations in neurons of the dorsal root ganglia (DRG) were investigated in a rat model of chronic sciatic nerve compression. The rat model of chronic sciatic nerve compression was established by placing a 1 cm Silastic tube around the right sciatic nerve. Histological examination was performed via Masson's trichrome staining. DRG injury was assessed using Fluoro Ruby (FR) or Fluoro Gold (FG). The expression levels of target genes were examined using reverse transcription‑quantitative polymerase chain reaction, western blot and immunohistochemical analyses. At 3 weeks post‑compression, collagen fiber accumulation was observed in the ipsilateral area and, at 8 weeks, excessive collagen formation with muscle atrophy was observed. The collagen volume fraction gradually and significantly increased following sciatic nerve compression. In the model rats, the numbers of FR‑labeled DRG neurons were significantly higher, relative to the sham‑operated group, however, the numbers of FG‑labeled neurons were similar. In the ipsilateral DRG neurons of the model group, the levels of transforming growth factor‑β1 (TGF‑β1) and connective tissue growth factor (CTGF) were elevated and, surrounding the neurons, the levels of collagen type I were increased, compared with those in the contralateral DRG. In the ipsilateral DRG, chronic nerve compression was associated with significantly higher levels of phosphorylated (p)‑extracellular signal‑regulated kinase 1/2, and significantly lower levels of p‑c‑Jun N‑terminal kinase and p‑p38, compared with those in the contralateral DRGs. Chronic sciatic nerve compression likely induced DRG pathology by upregulating the expression levels of TGF‑β1, CTGF and collagen type I, with involvement of the mitogen‑activated protein kinase signaling pathway.

  14. [EFFECTIVENESS OF CONTRALATERAL C7 NERVE ROOT AND MULTIPLE NERVES TRANSFER FOR TREATMENT OF BRACHIAL PLEXUS ROOT AVULSION].

    PubMed

    Wei, Wang; Alimujiang-Abulaiti; Tuerxunjiang-Dadihan; Meihua, Shen; Yafei, Liu; Chunxiao, Yuan; Aihemaitijiang-Yusufu

    2014-06-01

    To evaluate the methods and effectiveness of contralateral C7 nerve root and multiple nerves transfer for the treatment of brachial plexus root avulsion. Between June 2006 and June 2010, 23 patients with brachial plexus root avulsion were treated. There were 20 males and 3 females, aged 17 to 42 years (mean, 27.4 years). The time from injury to operation was 4 to 12 months (mean, 5.9 months). In 16 patients having no associated injury, the first stage procedure of contralateral C7 nerve root transfer and accessory nerve transfer to suprascapular nerve or phrenic nerve transfer to anterior upper trunk was performed, and the second stage procedure of the contralateral C7 nerve root transfer to median nerve and intercostal nerve transfer to axillary nerve was performed. In 4 patients having phrenic nerve and accessory nerve injuries, the first stage procedure of the contralateral C7 nerve root transfer and second stage procedure of the contralateral C7 nerve root transfer to median nerve and musculocutaneous nerve were performed. In 3 patients having hemothorax, pneumothorax, and rib fractures, the first stage procedure of the contralateral C7 nerve root transfer and accessory nerve transfer to suprascapular nerve, and the second stage procedure of the contralateral C7 nerve root transfer to median nerve and musculocutaneous nerve were performed. The British Medical Research Council (MRC) sensory grading (S0-S4) and modified muscle strength grading standard (M0-M5) were used for comprehensive assessment of limb and shoulder abduction, elbow/biceps muscle strength, flexor wrist and finger muscle strength and median nerve sensory recovery. Twenty-three patients were followed up 3-4.5 years (mean, 3.4 years). At abduction was more than 30° in 13 cases, and was more than 60° in 3 cases; in 3 patients having hemothorax, pneumothorax, and rib fractures, the shoulder abduction was more than 30°; and in 4 patients having phrenic nerve and accessory nerve injuries, the

  15. A practical approach to enlargement of nerves, plexuses and roots.

    PubMed

    Khadilkar, Satish V; Yadav, Rakhil S; Soni, Girish

    2015-04-01

    Detecting enlargement of accessible nerves is very helpful in assessing patients with peripheral nerve disorders, as only a few types of neuropathy lead to nerve thickening. The three leading causes are leprosy, hereditary motor and sensory neuropathies (types 1 and 3) and chronic inflammatory demyelinating neuropathies. MRI, neurography and ultrasonography allow assessment of clinically inaccessible portions of deep-seated nerves, plexuses and roots. As a result, isolated proximal segment thickenings, as found in chronic inflammatory sensory polyradiculopathy, can now be better evaluated and managed. Similarly, focal nerve enlargements due to infection, inflammation, infiltration and neoplasm are being identified and treated effectively. We present a practical approach to the diagnosis and management of patients with enlarged peripheral nerves, plexuses and roots, including cranial nerves. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

  16. Study on lumbosacral nerve root compression using DTI

    PubMed Central

    Li, Jinfeng; Wang, Yonghao; Wang, Yueyi; Lv, Yang; Ma, Lin

    2016-01-01

    Diffusion tensor imaging (DTI) can objectively describe the distribution of nerve roots in morphology, and provide a set of objective reference data on the quantitative indicators. The present study aimed to investigate the value of DTI in lumbosacral nerve root compression in patients with lumbar intervertebral disc degeneration. DTI was performed in 45 patients with lumbar intervertebral disc degeneration. Apparent diffusion coefficient (ADC) and fractional anisotropy (FA) values were measured in compressed and normal nerve roots. Fiber tracking imaging was also applied to observe the lumbosacral nerve roots. ADC value was significantly lower in the compressed group (1.314±0.14 mm2/sec) compared to in the uncompressed group (1.794±0.11 mm2/sec) (P<0.05). The FA value was significantly lower in the compressed group (0.196±0.020) compared to the uncompressed group (0.272±0.016) (P<0.05). DTI can evidently reveal the compressed nerve roots. DTI could be used to evaluate the lumbosacral nerve injury in patients with lumbar intervertebral disc degeneration to quantitatively assess nerve roots. PMID:27602215

  17. Axoplasmic importins enable retrograde injury signaling in lesioned nerve.

    PubMed

    Hanz, Shlomit; Perlson, Eran; Willis, Dianna; Zheng, Jun-Qi; Massarwa, R'ada; Huerta, Juan J; Koltzenburg, Martin; Kohler, Matthias; van-Minnen, Jan; Twiss, Jeffery L; Fainzilber, Mike

    2003-12-18

    Axoplasmic proteins containing nuclear localization signals (NLS) signal retrogradely by an unknown mechanism in injured nerve. Here we demonstrate that the importin/karyopherin alpha and beta families underlie this process. We show that importins are found in axons at significant distances from the cell body and that importin beta protein is increased after nerve lesion by local translation of axonal mRNA. This leads to formation of a high-affinity NLS binding complex that traffics retrogradely with the motor protein dynein. Trituration of synthetic NLS peptide at the injury site of axotomized dorsal root ganglion (DRG) neurons delays their regenerative outgrowth, and NLS introduction to sciatic nerve concomitantly with a crush injury suppresses the conditioning lesion induced transition from arborizing to elongating growth in L4/L5 DRG neurons. These data suggest a model whereby lesion-induced upregulation of axonal importin beta may enable retrograde transport of signals that modulate the regeneration of injured neurons.

  18. Magnetoneurography of evoked compound action currents in human cervical nerve roots.

    PubMed

    Mackert, B M; Burghoff, M; Hiss, L H; Nordahn, M; Marx, P; Trahms, L; Curio, G

    2001-02-01

    A measurement protocol for magnetoneurography (MNG) is established which allows the non-invasive localization and tracing of evoked compound action currents propagating along cervical nerve roots in man. Inside a magnetically shielded room either both median or both ulnar nerves of healthy subjects were conventionally electrostimulated in alternation. Evoked magnetic responses were recorded using a multichannel SQUID-detector with a planar measuring area centered over the neck. Simultaneously, electric surface potentials were recorded using cervical bipolar electrode montages. Upon median (ulnar) nerve stimulation somatosensory evoked magnetic fields up to 20 fT (10 fT) amplitude were detected propagating over the cervical transforaminal root entry zone, with corresponding electrical surface potentials of 1.5 microV (0.5 microV). Furthermore, the signal-to-noise ratio of the spatiotemporal magnetic field mappings in median nerve stimulation experiments allowed dipolar source reconstructions and tracing of the propagation of the compound action currents along nerve root fibers. Magnetoneurography allows tracing of the propagation of evoked compound action currents along cervical roots in healthy subjects with millisecond temporal and high spatial resolution. Thus, MNG offers a sensitivity appropriate to serve as a clinical diagnostic tool for localizing focal neuropathies of cervical nerve roots.

  19. Rare Intradural Cervical Nerve Root Metastasis of Follicular Thyroid Carcinoma

    PubMed Central

    Milosavljevic, Elena; Hanna, George; Gospodarev, Vadim; Raghavan, Ravi; Ghostine, Samer

    2016-01-01

    Intradural extramedullary nerve root metastasis is extremely unusual with only a handful of cases reported, and it presents most commonly in the thoracic and lumbosacral regions. We report the first case of metastasis to a ventral cervical nerve root in a patient with low-grade follicular thyroid carcinoma thought to be in remission for several years. Histopathology demonstrated malignant transformation and invasion of the nerve root. This case underscores that any history of malignancy regardless of staging, grading, or remission status should raise the suspicion of metastasis as it can mimic other spine and nerve sheath tumors and represent malignant transformation. Gross total resection can be safely achieved with intraoperative neuromonitoring and result in improved function; however, treatment is likely palliative. PMID:28018768

  20. Motor affliction of the L5 nerve root in lumbar nerve root compression syndromes.

    PubMed

    Jönsson, B; Strömqvist, B

    1995-09-15

    From a prospective and consecutive study on degenerative lumbar spine disorders containing 416 patients, all patients with a severely reduced or absent strength of the extensor hallucis longus muscle (n = 35) before surgery were identified. The incidence, diagnosis, and recovery after surgery of patients with L5 root compression syndromes and a severely reduced or absent power before surgery of the big toe extensor was evaluated. The L5 root is commonly involved in disc herniation and central and lateral spinal stenosis. Whether motor recovery occurs after root decompression is not fully known. All patients underwent a conventional radiologic evaluation before surgery including one or more myelography, computed tomography scan, and magnetic resonance imaging. At examination before surgery, extensor hallucis longus-power was graded as normal, reduced, or severely reduced/absent, and the latter group is presented here. Surgical findings were registered. Clinical investigation was performed after 4, 12-, and 24-month follow-up periods. A pronounced extensor hallucis longus paresis was seen in disc herniation in 20 of 187 patients, in lateral spinal stenosis in 10 of 122 patients, and central spinal stenosis 5 of 107 patients. Improvement of the paresis after surgery was equally common in disc herniation (15 of 20 patients) and lateral spinal stenosis (7 of 10 patients). Complete restitution was more common in disc herniation. None of the five patients with central spinal stenosis improved concerning paresis at the follow-up period. Improvement was most common during the first 4 months after surgery. No correlation between age or preoperative symptom duration and recovery was noted in either group. The incidence of pronounced extensor hallucis longus paresis in lumbar nerve root compression varied between 5-11%. Recovery after surgery was common in disc herniation and lateral spinal stenosis but did not occur in central stenosis. Complete recovery was most common in

  1. Intraoperative conjoined lumbosacral nerve roots associated with spondylolisthesis.

    PubMed

    Popa, Iulian; Poenaru, Dan V; Oprea, Manuel D; Andrei, Diana

    2013-07-01

    Lumbosacral nerve roots anomalies may produce low back pain. These anomalies are reported to be a cause for failed back surgery. They are usually left undiagnosed, especially in endoscopic discectomy techniques. Any surgery for entrapment disorders, performed on a patient with undiagnosed lumbosacral nerve roots anomaly, may lead to serious neural injuries because of an improper surgical technique or decompression. In this report, we describe our experience with a case of L5-S1 spondylolisthesis and associated congenital lumbosacral nerve root anomalies discovered during the surgical intervention, and the difficulties raised by such a discovery. Careful examination of coronal and axial views obtained through high-quality Magnetic Resonance Imaging may lead to a proper diagnosis of this condition leading to an adequate surgical planning, minimizing the intraoperatory complications.

  2. Calcium Signaling in Intact Dorsal Root Ganglia

    PubMed Central

    Gemes, Geza; Rigaud, Marcel; Koopmeiners, Andrew S.; Poroli, Mark J.; Zoga, Vasiliki; Hogan, Quinn H.

    2013-01-01

    Background Ca2+ is the dominant second messenger in primary sensory neurons. In addition, disrupted Ca2+ signaling is a prominent feature in pain models involving peripheral nerve injury. Standard cytoplasmic Ca2+ recording techniques use high K+ or field stimulation and dissociated neurons. To compare findings in intact dorsal root ganglia, we used a method of simultaneous electrophysiologic and microfluorimetric recording. Methods Dissociated neurons were loaded by bath-applied Fura-2-AM and subjected to field stimulation. Alternatively, we adapted a technique in which neuronal somata of intact ganglia were loaded with Fura-2 through an intracellular microelectrode that provided simultaneous membrane potential recording during activation by action potentials (APs) conducted from attached dorsal roots. Results Field stimulation at levels necessary to activate neurons generated bath pH changes through electrolysis and failed to predictably drive neurons with AP trains. In the intact ganglion technique, single APs produced measurable Ca2+ transients that were fourfold larger in presumed nociceptive C-type neurons than in nonnociceptive Aβ-type neurons. Unitary Ca2+ transients summated during AP trains, forming transients with amplitudes that were highly dependent on stimulation frequency. Each neuron was tuned to a preferred frequency at which transient amplitude was maximal. Transients predominantly exhibited monoexponential recovery and had sustained plateaus during recovery only with trains of more than 100 APs. Nerve injury decreased Ca2+ transients in C-type neurons, but increased transients in Aβ-type neurons. Conclusions Refined observation of Ca2+ signaling is possible through natural activation by conducted APs in undissociated sensory neurons and reveals features distinct to neuronal types and injury state. PMID:20526180

  3. Proposed Classification of Auriculotemporal Nerve, Based on the Root System

    PubMed Central

    Komarnitki, Iulian; Tomczyk, Jacek; Ciszek, Bogdan; Zalewska, Marta

    2015-01-01

    The topography of the auriculotemporal nerve (ATN) root system is the main criterion of this nerve classification. Previous publications indicate that ATN may have between one and five roots. Most common is a one- or two-root variant of the nerve structure. The problem of many publications is the inconsistency of nomenclature which concerns the terms “roots”, “connecting branches”, or “branches” that are used to identify the same structures. This study was performed on 80 specimens (40 adults and 40 fetuses) to propose a classification based on: (i) the number of roots, (ii) way of root division, and (iii) configuration of interradicular fibers that form the ATN trunk. This new classification is a remedy for inconsistency of nomenclature of ATN in the infratemporal fossa. This classification system has proven beneficial when organizing all ATN variants described in previous studies and could become a helpful tool for surgeons and dentists. Examination of ATN from the infratemporal fossa of fetuses (the youngest was at 18 weeks gestational age) showed that, at that stage, the nerve is fully developed. PMID:25856464

  4. [Blood circulation of cauda equina and nerve root].

    PubMed

    Kobayashi, Shigeru; Baba, Hisatoshi; Uchida, Kenzo; Kokubo, Yasuo; Yayama, Takafumi; Takeno, Kenichi; Negoro, Kohei

    2005-03-01

    It is generally considered that the genesis of radiculopathy associated with pathologic conditions of the spine, such as lumbar disc herniaton and lumbarl canal stenosis, may result from both mechanical compression and vascular problems. In this article, we have reviewed about the blood circulation of cauda equina and nerve root under normal and pathologic conditions.

  5. Conjoined lumbosacral nerve roots: current aspects of diagnosis.

    PubMed

    Böttcher, J; Petrovitch, A; Sörös, P; Malich, A; Hussein, S; Kaiser, W A

    2004-03-01

    Conjoined lumbosacral nerve roots (CLNR) are the most common anomalies involving the lumbar nerve structures which can be one of the origins of failed back syndromes. They can cause sciatica even without the presence of a additional compressive impingement (such as disc herniation, spondylolisthesis or lateral recess stenosis), and often congenital lumbosacral spine anomalies (such as bony defects) are present at the "conjoined sheaths". This congenital anomaly has been reported in 14% of cadaver studies, but myelographic or computed tomographic studies have revealed an incidence of approximately 4% only. Diagnostic methods such as magnetic resonance imaging (MRI) are helpful for determination of the exact anatomical relations in this context. We present five typical cases of conjoined nerve roots observed during a 1 year period, equivalent to 6% of our out-patients without a history of surgical treatment on the lumbar spine. In all cases with suspicious radiological findings MRI or lumbar myelography combined with CT and multiplanar reconstructions is recommended.

  6. [Electrostimulation of nerve roots in neurogenic bladder].

    PubMed

    Colombel, P; Egon, G; Isambert, J L; Ritz, M

    1994-05-15

    Thirty per cent of the patients with spinal injuries present chronical urinary problems. For these, G.S. Brindley's technique represents an important progress. It includes a section of posterior roots to control detrusor hyperexcitability and a stimulation of anterior roots to empty the bladder. The equipment is now perfectly reliable and the technique has been defined. Indications are essentially unstable bladders with incontinence and certain hypoactive bladders. The following results were obtained: continence is obtained in 90% of patients; complete bladder emptying in the majority of cases with very marked reduction of urinary infections; improvement of erection and regularization of intestinal transit. The complications of the surgery are uncommon but serious (CSF leaks, postoperative denervations, sepsis and material failure).

  7. Infrared neural stimulation of human spinal nerve roots in vivo

    PubMed Central

    Cayce, Jonathan M.; Wells, Jonathon D.; Malphrus, Jonathan D.; Kao, Chris; Thomsen, Sharon; Tulipan, Noel B.; Konrad, Peter E.; Jansen, E. Duco; Mahadevan-Jansen, Anita

    2015-01-01

    Abstract. Infrared neural stimulation (INS) is a neurostimulation modality that uses pulsed infrared light to evoke artifact-free, spatially precise neural activity with a noncontact interface; however, the technique has not been demonstrated in humans. The objective of this study is to demonstrate the safety and efficacy of INS in humans in vivo. The feasibility of INS in humans was assessed in patients (n=7) undergoing selective dorsal root rhizotomy, where hyperactive dorsal roots, identified for transection, were stimulated in vivo with INS on two to three sites per nerve with electromyogram recordings acquired throughout the stimulation. The stimulated dorsal root was removed and histology was performed to determine thermal damage thresholds of INS. Threshold activation of human dorsal rootlets occurred in 63% of nerves for radiant exposures between 0.53 and 1.23  J/cm2. In all cases, only one or two monitored muscle groups were activated from INS stimulation of a hyperactive spinal root identified by electrical stimulation. Thermal damage was first noted at 1.09  J/cm2 and a 2∶1 safety ratio was identified. These findings demonstrate the success of INS as a fresh approach for activating human nerves in vivo and providing the necessary safety data needed to pursue clinically driven therapeutic and diagnostic applications of INS in humans. PMID:26157986

  8. Infrared neural stimulation of human spinal nerve roots in vivo.

    PubMed

    Cayce, Jonathan M; Wells, Jonathon D; Malphrus, Jonathan D; Kao, Chris; Thomsen, Sharon; Tulipan, Noel B; Konrad, Peter E; Jansen, E Duco; Mahadevan-Jansen, Anita

    2015-01-01

    Infrared neural stimulation (INS) is a neurostimulation modality that uses pulsed infrared light to evoke artifact-free, spatially precise neural activity with a noncontact interface; however, the technique has not been demonstrated in humans. The objective of this study is to demonstrate the safety and efficacy of INS in humans in vivo. The feasibility of INS in humans was assessed in patients ([Formula: see text]) undergoing selective dorsal root rhizotomy, where hyperactive dorsal roots, identified for transection, were stimulated in vivo with INS on two to three sites per nerve with electromyogram recordings acquired throughout the stimulation. The stimulated dorsal root was removed and histology was performed to determine thermal damage thresholds of INS. Threshold activation of human dorsal rootlets occurred in 63% of nerves for radiant exposures between 0.53 and [Formula: see text]. In all cases, only one or two monitored muscle groups were activated from INS stimulation of a hyperactive spinal root identified by electrical stimulation. Thermal damage was first noted at [Formula: see text] and a [Formula: see text] safety ratio was identified. These findings demonstrate the success of INS as a fresh approach for activating human nerves in vivo and providing the necessary safety data needed to pursue clinically driven therapeutic and diagnostic applications of INS in humans.

  9. Ultrasound and electrical nerve stimulation-guided S1 nerve root block.

    PubMed

    Sato, Masaki; Mikawa, Yasuhito; Matuda, Akiko

    2013-10-01

    A selective lumbosacral nerve root block is generally is performed under X-ray fluoroscopy, which has the disadvantage of radiation exposure and the need for fluoroscopy equipment. In this study, we assessed the effectiveness of ultrasound and nerve stimulation-guided S1 nerve root block on 37 patients with S1 radicular syndrome. With the patient in a prone position, an ultrasound scan was performed by placing the probe parallel to the body axis. The needle was pointed slightly medial from the lateral side of the probe and advanced toward a hyperechoic area in the sacral foramina with ultrasound guidance. Contrast medium was then injected and its dispersion confirmed by fluoroscopy. The acquired contrast images were classified into intraneural, perineural, and paraneural patterns. The significance of differences in the effect of the block among the contrast image patterns was analyzed. After nerve block, decreased sensation at the S1 innervated region and pain relief was achieved in all patients. No significant difference was noted in the effect of the block between perineural and paraneural patterns. In conclusion, this technique provided reliable S1 nerve root block in patients with S1 radicular syndrome and minimized radiation exposure.

  10. Autotaxin and lysophosphatidic acid1 receptor-mediated demyelination of dorsal root fibers by sciatic nerve injury and intrathecal lysophosphatidylcholine

    PubMed Central

    2010-01-01

    Background Although neuropathic pain is frequently observed in demyelinating diseases such as Guillain-Barré syndrome and multiple sclerosis, the molecular basis for the relationship between demyelination and neuropathic pain behaviors is poorly understood. Previously, we found that lysophosphatidic acid receptor (LPA1) signaling initiates sciatic nerve injury-induced neuropathic pain and demyelination. Results In the present study, we have demonstrated that sciatic nerve injury induces marked demyelination accompanied by myelin-associated glycoprotein (MAG) down-regulation and damage of Schwann cell partitioning of C-fiber-containing Remak bundles in the sciatic nerve and dorsal root, but not in the spinal nerve. Demyelination, MAG down-regulation and Remak bundle damage in the dorsal root were abolished in LPA1 receptor-deficient (Lpar1-/-) mice, but these alterations were not observed in sciatic nerve. However, LPA-induced demyelination in ex vivo experiments was observed in the sciatic nerve, spinal nerve and dorsal root, all which express LPA1 transcript and protein. Nerve injury-induced dorsal root demyelination was markedly attenuated in mice heterozygous for autotaxin (atx+/-), which converts lysophosphatidylcholine (LPC) to LPA. Although the addition of LPC to ex vivo cultures of dorsal root fibers in the presence of recombinant ATX caused potent demyelination, it had no significant effect in the absence of ATX. On the other hand, intrathecal injection of LPC caused potent dorsal root demyelination, which was markedly attenuated or abolished in atx+/- or Lpar1-/- mice. Conclusions These results suggest that LPA, which is converted from LPC by ATX, activates LPA1 receptors and induces dorsal root demyelination following nerve injury, which causes neuropathic pain. PMID:21062487

  11. Traumatic Cervical Nerve Root Avulsion with Pseudomeningocele Formation

    PubMed Central

    Haider, Ali S; Watson, Ian T; Sulhan, Suraj; Arrey, Eliel N; Khan, Umair; Nguyen, Phu; Layton, Kennith F

    2017-01-01

    Cervical nerve root avulsion is a well-documented result of motor vehicle collision (MVC), especially when occurring at high velocities. These avulsions are commonly traction injuries of nerve roots that may be accompanied by a tear in the meninges through the vertebral foramina with associated collections of cerebrospinal fluid (CSF), thereby resulting in a pseudomeningocele. We present a case of a 19-year-old male who experienced an MVC and was brought to the emergency department (ED) with right arm paralysis and other injuries. A neurological examination demonstrated intact sensation but 0/5 muscle strength in the right upper extremity. A magnetic resonance imaging (MRI) of the spinal cord demonstrated massive epidural hematomas extending the length of the cervical spine caudally from C2. An MRI of the right brachial plexus showed C3-C7 anterior horn cell edema and associated traumatic nerve root avulsion with pseudomeningoceles on the right from C5-C8. The development of spinal cord hematoma with these injuries has rarely been documented in the literature and the multiple level avulsion described here with extensive hematoma is a rare clinical presentation. A literature review was conducted to determine the diagnostic requirements, treatment strategies, and complications of such an injury. Our patient received conservative treatment of the right brachial plexus injury and was transferred to an inpatient rehabilitation facility 13 days later.  PMID:28352498

  12. Diffusion tensor imaging with quantitative evaluation and fiber tractography of lumbar nerve roots in sciatica.

    PubMed

    Shi, Yin; Zong, Min; Xu, Xiaoquan; Zou, Yuefen; Feng, Yang; Liu, Wei; Wang, Chuanbing; Wang, Dehang

    2015-04-01

    To quantitatively evaluate nerve roots by measuring fractional anisotropy (FA) values in healthy volunteers and sciatica patients, visualize nerve roots by tractography, and compare the diagnostic efficacy between conventional magnetic resonance imaging (MRI) and DTI. Seventy-five sciatica patients and thirty-six healthy volunteers underwent MR imaging using DTI. FA values for L5-S1 lumbar nerve roots were calculated at three levels from DTI images. Tractography was performed on L3-S1 nerve roots. ROC analysis was performed for FA values. The lumbar nerve roots were visualized and FA values were calculated in all subjects. FA values decreased in compressed nerve roots and declined from proximal to distal along the compressed nerve tracts. Mean FA values were more sensitive and specific than MR imaging for differentiating compressed nerve roots, especially in the far lateral zone at distal nerves. DTI can quantitatively evaluate compressed nerve roots, and DTT enables visualization of abnormal nerve tracts, providing vivid anatomic information and localization of probable nerve compression. DTI has great potential utility for evaluating lumbar nerve compression in sciatica. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  13. Functional Reinnervation of the Canine Bladder after Spinal Root Transection and Immediate Somatic Nerve Transfer

    PubMed Central

    Ruggieri, Michael R.; Braverman, Alan S.; D’Andrea, Linda; MCCarthy, James; Barbe, Mary F.

    2013-01-01

    This study was performed to determine whether nerve transfer immediately after spinal root transection would lead to bladder reinnervation in a canine model. In one animal, the left T12 intercostal nerve was mobilized, cut and attached to the severed ends of sacral roots inducing bladder contraction using a graft from the T11 intercostal nerve. On the right side and bilaterally in two other dogs, coccygeal roots innervating tail musculature were cut and attached to the severed bladder sacral roots (coccygeal nerve transfer [CG NT]). In four other dogs, bladder sacral roots were transected in the vertebral column, and the genitofemoral nerve was transferred within the abdomen to the pelvic nerve (genitofemoral nerve transfer [GF NT]). After 14 months for CG NT and 4.5 months for GF NT, electrical stimulation of the pelvic nerve induced bladder pressure and urethral fluid flow on the intercostal nerve transfer side, in each of the five CG NT sites and bilaterally in three of the four GF NT animals. Reinnervation was further shown by retrograde labeling of spinal cord neurons following fluorogold injections into the bladder wall and by histological examination of the root/nerve suture sites. In all CG NT animals, labeled neuronal cell bodies were located in ventral horns in lamina IX of coccygeal cord segments. In the three GF NT animals in which pelvic nerve stimulation induced bladder contraction, abundant labeled cell bodies were observed in lamina IX and lateral zona intermedia of upper lumbar cord. These results clearly demonstrate that bladder reinnervation can be accomplished by immediate nerve transfer of intercostal nerves or coccygeal spinal roots to severed bladder sacral roots, or by transfer of peripheral genitofemoral nerves (L1,2 origin) to pelvic nerves. PMID:18352835

  14. Effect of the gamma knife treatment on the trigeminal nerve root in Chinese patients with primary trigeminal neuralgia.

    PubMed

    Song, Zhi-Xiu; Qian, Wei; Wu, Yu-Quan; Sun, Fang-Jie; Fei, Jun; Huang, Run-Sheng; Fang, Jing-Yu; Wu, Cai-Zhen; An, You-Ming; Wang, Daxin; Yang, Jun

    2014-01-01

    To understand the mechanism of the gamma knife treating the trigeminal neuralgia. Using the MASEP-SRRS type gamma knife treatment system, 140 Chinese patients with trigeminal neuralgia (NT) were treated in our hospital from 2002 to 2010, in which the pain relief rate reached 95% and recurrence rate was 3% only. We investigated the effect of the gamma knife treatment on the trigeminal nerve root in 20 Chinese patients with primary trigeminal neuralgia by the magnetic resonance imager (MRI) observation. 1) The cross-sectional area of trigeminal nerve root became smaller and MRI signals were lower in the treatment side than those in the non-treatment side after the gamma knife treatment of primary trigeminal neuralgia; 2) in the treatment side, the cross-sectional area of the trigeminal nerve root decreased significantly after the gamma knife treatment; 3) there was good correlation between the clinical improvement and the MRI findings; and 4) the straight distance between the trigeminal nerve root and the brainstem did not change after the gamma knife treatment. The pain relief induced the gamma knife radiosurgery might be related with the atrophy of the trigeminal nerve root in Chinese patients with primary trigeminal neuralgia.

  15. Signaling Pathways Critical for Tooth Root Formation.

    PubMed

    Wang, J; Feng, J Q

    2017-10-01

    Tooth is made of an enamel-covered crown and a cementum-covered root. Studies on crown dentin formation have been a major focus in tooth development for several decades. Interestingly, the population prevalence for genetic short root anomaly (SRA) with no apparent defects in crown is close to 1.3%. Furthermore, people with SRA itself are predisposed to root resorption during orthodontic treatment. The discovery of the unique role of Nfic (nuclear factor I C; a transcriptional factor) in controlling root but not crown dentin formation points to a new concept: tooth crown and root have different control mechanisms. Further genetic mechanism studies have identified more key molecules (including Osterix, β-catenin, and sonic hedgehog) that play a critical role in root formation. Extensive studies have also revealed the critical role of Hertwig's epithelial root sheath in tooth root formation. In addition, Wnt10a has recently been found to be linked to multirooted tooth furcation formation. These exciting findings not only fill the critical gaps in our understanding about tooth root formation but will aid future research regarding the identifying factors controlling tooth root size and the generation of a whole "bio-tooth" for therapeutic purposes. This review starts with human SRA and mainly focuses on recent progress on the roles of NFIC-dependent and NFIC-independent signaling pathways in tooth root formation. Finally, this review includes a list of the various Cre transgenic mouse lines used to achieve tooth root formation-related gene deletion or overexpression, as well as strengths and limitations of each line.

  16. Organization of peripheral nerves and spinal roots of the Atlantic stingray, Dasyatis sabina.

    PubMed

    Coggeshall, R E; Leonard, R B; Applebaum, M L; Willis, W D

    1978-01-01

    1. The sizes and numbers of axons in peripheral nerves and spinal roots were investigated in the stingray, Dasyatis sabina. 2. The axons of the dorsal and ventral roots do not mingle in peripheral nerves of this animal as they do in higher vertebrates. Thus, it was usually possible to split the peripheral nerve into two portions, one containing only dorsal root axons, the other containing only ventral root axons. This feature was useful for the analysis of certain aspects of spinal cord organization. 3. The fact that dorsal and ventral root axons were segregated in peripheral nerves enabled us to demonstrate, without experimental surgery, that the central processes of the dorsal root ganglion cells and the proximal ventral root axons were 10-20% narrower, on the average, than the distal processes of the same dorsal root ganglion cells or the distal parts of the same ventral root axons. 4. The stingray is remarkable in having very few unmyelinated axons in the dorsal roots, ventral roots, or peripheral nerves. This paucity of unmyelinated axons distinguishes the Atlantic stingrays from all other vertebrates whose roots and nerves have been examined for unmyelinated fibers. 5. Similar findings were obtained for one spotted eagle ray (Aetobatus narinari) and two cow-nose rays (Rhinoptera bonasus).

  17. Electrical stimulation threshold in chronically compressed lumbar nerve roots: Observational study.

    PubMed

    Plata-Bello, Julio; Pérez-Lorensu, Pedro Javier; Brage, Liberto; Hernández-Hernández, Vanessa; Dóniz, Ayoze; Roldán-Delgado, Héctor; Febles, Pablo; García-Conde, Mario; Pérez-Orribo, Luis; García-Marín, Víctor

    2015-12-01

    Intraoperative neuromonitoring (IONM) is a common practice in spinal surgery, mostly during pedicle screw placement. However, there is not enough information about the factors that can interfere with IONM data. One of these factors may be existing damage of the nerve root whose function must be preserved. The main purpose of the present study is to evaluate the effect of chronic compression in lumbar nerve roots in terms of stimulation thresholds during direct nerve stimulation. Direct electrical stimulation was performed in 201 lumbar nerve roots during lumbar spinal procedures under general anaesthesia in 80 patients with different lumbar spinal pathologies. Clinical and radiological data were reviewed in order to establish the presence of chronic compression. Chronically compressed nerve roots showed a higher stimulation threshold than non compressed nerve roots (11.93 mA vs. 4.33 mA). This difference was confirmed with intra-subject comparison (paired sample t test, p=0.012). No other clinical factors were associated with this higher stimulation threshold in lumbar nerve roots. A higher stimulation threshold is present in compressed lumbar nerve roots than non compressed roots. This needs to be taken into consideration during pedicle screw placement, where intraoperative neurophysiological monitoring is being used. Copyright © 2015 Elsevier B.V. All rights reserved.

  18. New insights into root gravitropic signalling

    PubMed Central

    Sato, Ethel Mendocilla; Hijazi, Hussein; Bennett, Malcolm J.; Vissenberg, Kris; Swarup, Ranjan

    2015-01-01

    An important feature of plants is the ability to adapt their growth towards or away from external stimuli such as light, water, temperature, and gravity. These responsive plant growth movements are called tropisms and they contribute to the plant’s survival and reproduction. Roots modulate their growth towards gravity to exploit the soil for water and nutrient uptake, and to provide anchorage. The physiological process of root gravitropism comprises gravity perception, signal transmission, growth response, and the re-establishment of normal growth. Gravity perception is best explained by the starch–statolith hypothesis that states that dense starch-filled amyloplasts or statoliths within columella cells sediment in the direction of gravity, resulting in the generation of a signal that causes asymmetric growth. Though little is known about the gravity receptor(s), the role of auxin linking gravity sensing to the response is well established. Auxin influx and efflux carriers facilitate creation of a differential auxin gradient between the upper and lower side of gravistimulated roots. This asymmetric auxin gradient causes differential growth responses in the graviresponding tissue of the elongation zone, leading to root curvature. Cell biological and mathematical modelling approaches suggest that the root gravitropic response begins within minutes of a gravity stimulus, triggering genomic and non-genomic responses. This review discusses recent advances in our understanding of root gravitropism in Arabidopsis thaliana and identifies current challenges and future perspectives. PMID:25547917

  19. Spinal cord infarction following therapeutic computed tomography-guided left L2 nerve root injection.

    PubMed

    Somayaji, H S; Saifuddin, A; Casey, A T H; Briggs, T W R

    2005-02-15

    Case report. To report a rare case of spinal cord infarction following therapeutic computed tomography-guided nerve root injection. Diagnostic and therapeutic image-guided nerve root injection is commonly performed in the management of low back pain and sciatica. The severe complication of spinal cord infarction has been reported in only 3 cases previously. Retrospective review of case records and imaging. A 71-year-old woman presented with symptoms and signs of left L2 nerve root compression. She was managed with computed tomography-guided left L2 nerve root injection using bupivacaine and triamcinolone and developed immediate bilateral sensory loss and paraplegia. Magnetic resonance imaging demonstrated diffuse hyperintensity within the distal thoracic cord and conus on T2-weighted images, consistent with spinal cord infarction. We report the fourth case of spinal cord infarction following nerve root injection. The severity of this complication warrants that it should be considered during patient consent for this procedure.

  20. 3.0T MRI tractography of lumbar nerve roots in disc herniation.

    PubMed

    Chuanting, Li; Qingzheng, Wang; Wenfeng, Xiao; Yiyi, Hui; Bin, Zhao

    2014-10-01

    Diffusion tensor imaging (DTI) with fiber tracking (FT) has found clinical applications in the evaluation of the central nervous system and has been extensively used to image white matter tract. The feasibility of FT of the lumbar nerve roots in disc herniation is unclear. To demonstrate the feasibility of FT in the lumbar nerve roots, and to assess potential differences in fractional anisotropy (FA) and apparent diffusion coefficient (ADC) of L4, L5, and S1 nerves between healthy disc and disc herniation. Twenty patients with unilateral sciatica related to posterolateral or foraminal disc herniation and 20 healthy volunteers were enrolled in our study. Anatomical fusion with the axial T2 sequences was used to estimate the relevance of reconstructions. DTI with tractography of the L4, L5, and S1 nerves was performed. Mean FA and ADC values were calculated from tractography images. Lumbosacral root compression sites could be clearly identified on the tractography images. There was no significant difference in FA or ADC between left and right nerve roots at the same level (P > 0.05) in healthy volunteers. The mean FA value of the compressed spinal nerve roots was significantly lower than that of FA of the contralateral nerve roots (P = 0.0001). ADC was significantly higher in compressed nerve roots than that in the contralateral nerve root (P = 0.0002). 3 T magnetic resonance imaging (MRI) DTI and FT of the lumbosacral region nerve is possible. There are significant changes in FA and ADC values in the compressed L4, L5, and S1 nerves. © The Foundation Acta Radiologica 2013 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

  1. Prolonged electrical stimulation causes no damage to sacral nerve roots in rabbits.

    PubMed

    Yan, Peng; Yang, Xiaohong; Yang, Xiaoyu; Zheng, Weidong; Tan, Yunbing

    2014-06-15

    Previous studies have shown that, anode block electrical stimulation of the sacral nerve root can produce physiological urination and reconstruct urinary bladder function in rabbits. However, whether long-term anode block electrical stimulation causes damage to the sacral nerve root remains unclear, and needs further investigation. In this study, a complete spinal cord injury model was established in New Zealand white rabbits through T9-10 segment transection. Rabbits were given continuous electrical stimulation for a short period and then chronic stimulation for a longer period. Results showed that compared with normal rabbits, the structure of nerve cells in the anterior sacral nerve roots was unchanged in spinal cord injury rabbits after electrical stimulation. There was no significant difference in the expression of apoptosis-related proteins such as Bax, Caspase-3, and Bcl-2. Experimental findings indicate that neurons in the rabbit sacral nerve roots tolerate electrical stimulation, even after long-term anode block electrical stimulation.

  2. Prolonged electrical stimulation causes no damage to sacral nerve roots in rabbits

    PubMed Central

    Yan, Peng; Yang, Xiaohong; Yang, Xiaoyu; Zheng, Weidong; Tan, Yunbing

    2014-01-01

    Previous studies have shown that, anode block electrical stimulation of the sacral nerve root can produce physiological urination and reconstruct urinary bladder function in rabbits. However, whether long-term anode block electrical stimulation causes damage to the sacral nerve root remains unclear, and needs further investigation. In this study, a complete spinal cord injury model was established in New Zealand white rabbits through T9–10 segment transection. Rabbits were given continuous electrical stimulation for a short period and then chronic stimulation for a longer period. Results showed that compared with normal rabbits, the structure of nerve cells in the anterior sacral nerve roots was unchanged in spinal cord injury rabbits after electrical stimulation. There was no significant difference in the expression of apoptosis-related proteins such as Bax, Caspase-3, and Bcl-2. Experimental findings indicate that neurons in the rabbit sacral nerve roots tolerate electrical stimulation, even after long-term anode block electrical stimulation. PMID:25206785

  3. Changes in lumbosacral spinal nerve roots on diffusion tensor imaging in spinal stenosis

    PubMed Central

    Hou, Zhong-jun; Huang, Yong; Fan, Zi-wen; Li, Xin-chun; Cao, Bing-yi

    2015-01-01

    Lumbosacral degenerative disc disease is a common cause of lower back and leg pain. Conventional T1-weighted imaging (T1WI) and T2-weighted imaging (T2WI) scans are commonly used to image spinal cord degeneration. However, these modalities are unable to image the entire lumbosacral spinal nerve roots. Thus, in the present study, we assessed the potential of diffusion tensor imaging (DTI) for quantitative assessment of compressed lumbosacral spinal nerve roots. Subjects were 20 young healthy volunteers and 31 patients with lumbosacral stenosis. T2WI showed that the residual dural sac area was less than two-thirds that of the corresponding normal area in patients from L3 to S1 stenosis. On T1WI and T2WI, 74 lumbosacral spinal nerve roots from 31 patients showed compression changes. DTI showed thinning and distortion in 36 lumbosacral spinal nerve roots (49%) and abruption in 17 lumbosacral spinal nerve roots (23%). Moreover, fractional anisotropy values were reduced in the lumbosacral spinal nerve roots of patients with lumbosacral stenosis. These findings suggest that DTI can objectively and quantitatively evaluate the severity of lumbosacral spinal nerve root compression. PMID:26807125

  4. Inhibitory Injury Signaling Represses Axon Regeneration After Dorsal Root Injury.

    PubMed

    Mar, Fernando M; Simões, Anabel R; Rodrigo, Inês S; Sousa, Mónica M

    2016-09-01

    Following injury to peripheral axons, besides increased cyclic adenosine monophosphate (cAMP), the positive injury signals extracellular-signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK), and signal transducer and activator of transcription 3 (STAT-3) are locally activated and retrogradely transported to the cell body, where they induce a pro-regenerative program. Here, to further understand the importance of injury signaling for successful axon regeneration, we used dorsal root ganglia (DRG) neurons that have a central branch without regenerative capacity and a peripheral branch that regrows after lesion. Although injury to the DRG central branch (dorsal root injury (DRI)) activated ERK, JNK, and STAT-3 and increased cAMP levels, it did not elicit gain of intrinsic growth capacity nor the ability to overcome myelin inhibition, as occurred after peripheral branch injury (sciatic nerve injury (SNI)). Besides, gain of growth capacity after SNI was independent of ERK and cAMP. Antibody microarrays of dynein-immunoprecipitated axoplasm from rats with either DRI or SNI revealed a broad differential activation and transport of signals after each injury type and further supported that ERK, JNK, STAT-3, and cAMP signaling pathways are minor contributors to the differential intrinsic axon growth capacity of both injury models. Increased levels of inhibitory injury signals including GSK3β and ROCKII were identified after DRI, not only in axons but also in DRG cell bodies. In summary, our work shows that activation and transport of positive injury signals are not sufficient to promote increased axon growth capacity and that differential modulation of inhibitory molecules may contribute to limited regenerative response.

  5. Role of NINJA in root jasmonate signaling.

    PubMed

    Acosta, Iván F; Gasperini, Debora; Chételat, Aurore; Stolz, Stéphanie; Santuari, Luca; Farmer, Edward E

    2013-09-17

    Wound responses in plants have to be coordinated between organs so that locally reduced growth in a wounded tissue is balanced by appropriate growth elsewhere in the body. We used a JASMONATE ZIM DOMAIN 10 (JAZ10) reporter to screen for mutants affected in the organ-specific activation of jasmonate (JA) signaling in Arabidopsis thaliana seedlings. Wounding one cotyledon activated the reporter in both aerial and root tissues, and this was either disrupted or restricted to certain organs in mutant alleles of core components of the JA pathway including COI1, OPR3, and JAR1. In contrast, three other mutants showed constitutive activation of the reporter in the roots and hypocotyls of unwounded seedlings. All three lines harbored mutations in Novel Interactor of JAZ (NINJA), which encodes part of a repressor complex that negatively regulates JA signaling. These ninja mutants displayed shorter roots mimicking JA-mediated growth inhibition, and this was due to reduced cell elongation. Remarkably, this phenotype and the constitutive JAZ10 expression were still observed in backgrounds lacking the ability to synthesize JA or the key transcriptional activator MYC2. Therefore, JA-like responses can be recapitulated in specific tissues without changing a plant's ability to make or perceive JA, and MYC2 either has no role or is not the only derepressed transcription factor in ninja mutants. Our results show that the role of NINJA in the root is to repress JA signaling and allow normal cell elongation. Furthermore, the regulation of the JA pathway differs between roots and aerial tissues at all levels, from JA biosynthesis to transcriptional activation.

  6. Role of NINJA in root jasmonate signaling

    PubMed Central

    Acosta, Iván F.; Gasperini, Debora; Chételat, Aurore; Stolz, Stéphanie; Santuari, Luca; Farmer, Edward E.

    2013-01-01

    Wound responses in plants have to be coordinated between organs so that locally reduced growth in a wounded tissue is balanced by appropriate growth elsewhere in the body. We used a JASMONATE ZIM DOMAIN 10 (JAZ10) reporter to screen for mutants affected in the organ-specific activation of jasmonate (JA) signaling in Arabidopsis thaliana seedlings. Wounding one cotyledon activated the reporter in both aerial and root tissues, and this was either disrupted or restricted to certain organs in mutant alleles of core components of the JA pathway including COI1, OPR3, and JAR1. In contrast, three other mutants showed constitutive activation of the reporter in the roots and hypocotyls of unwounded seedlings. All three lines harbored mutations in Novel Interactor of JAZ (NINJA), which encodes part of a repressor complex that negatively regulates JA signaling. These ninja mutants displayed shorter roots mimicking JA-mediated growth inhibition, and this was due to reduced cell elongation. Remarkably, this phenotype and the constitutive JAZ10 expression were still observed in backgrounds lacking the ability to synthesize JA or the key transcriptional activator MYC2. Therefore, JA-like responses can be recapitulated in specific tissues without changing a plant’s ability to make or perceive JA, and MYC2 either has no role or is not the only derepressed transcription factor in ninja mutants. Our results show that the role of NINJA in the root is to repress JA signaling and allow normal cell elongation. Furthermore, the regulation of the JA pathway differs between roots and aerial tissues at all levels, from JA biosynthesis to transcriptional activation. PMID:24003128

  7. Repair of multiple cervical root avulsion with sural nerve graft.

    PubMed

    Hsu, Sanford P C; Shih, Yang-Hsin; Huang, Ming-Chao; Chuang, Tien-Yow; Huang, Wen-Cheng; Wu, Hsiu-Mei; Lin, Pei-Hsin; Lee, Liang-Shong; Cheng, Henrich

    2004-09-01

    To obtain easier access to avulsed roots in the intradural space for patients suffering cervical root avulsion, the authors of this study developed a novel repair method. This involves using nerve grafts to bridge corresponding segments of the spinal cord and the trunk or cord level of the plexus, respectively, in two surgical stages. All eight patients admitted to this study received pre- and post-operative workups of electrophysiological evaluations and muscle power grading through Medical Research Council (MRC) scores. The degrees of impairment were also graded according to a modified version of Dumitru's and Wilbourn's scale (mild = 1; moderate = 2; severe = 3). The preoperative versus post-operative differences in the severity of the injuries and in the grading of the target muscle power were calculated according to the Wilcoxon signed-rank test. The preoperative degree of the severity of the injuries, as measured by electromyography (EMG), was 3.00 +/- 0.00 (mean +/- S.D.). The post-operative result was 2.125 +/- 0.641. Significant change took place after repair (P = 0.0313). Moreover, although little improvement was observed in the triceps, brachioradialis (BR), extensor carpi radialis (ECR), flexor digitorum profundus (FDP) and intrinsic hand muscles, the MRC grading showed significant yet not prominent motor recovery in the deltoid and biceps brachii (both P = 0.0313). We were impressed that the initial significant statistical results of differences in pre- and post-operative severity of the injuries and muscle power grading, demonstrated that regeneration does occur with this repair strategy.

  8. Activation of neurotrophins in lumbar dorsal root probably contributes to neuropathic pain after spinal nerve ligation

    PubMed Central

    Kazemi, Abdolreza; Rahmati, Masoud; Eslami, Rasoul; Sheibani, Vahid

    2017-01-01

    Objective(s): Neurotrophins (NTs) exert various effects on neuronal system. Growing evidence indicates that NTs are involved in the pathophysiology of neuropathic pain. However, the exact role of these proteins in modulating nociceptive signaling requires being defined. Thus, the aim of this study was to evaluate the effects of spinal nerve ligation (SNL) on NTs activation in the lumbar dorsal root. Materials and Methods: Ten male Wistar rats were randomly assigned to two groups: tight ligation of the L5 spinal nerve (SNL: n=5) and Sham (n=5). In order to produce neuropathic pain, the L5 spinal nerve was tightly ligated (SNL). Then, allodynia and hyperalgesia tests were conducted weekly. After 4 weeks, tissue samples were taken from the two groups for laboratory evaluations. Here, Real-Time PCR quantity method was used for measuring NTs gene expression levels. Results: SNL resulted in a significant weight loss in the soleus muscle (P<0.05), mechanical allodynia and thermal hyperalgesia thresholds (respectively, P<0.05; P<0.05). Also, NGF, NT-4, NT-3, TrkA, TrkB and TrkC expression were up-regulated following spinal nerve ligation group (respectively, P=0.025, P=0.013, P=0.001, P=0.002, P<0.001, P=001) (respectively, 4.7, 5.2, 7.5, 5.1, 7.2, 6.2 folds). Conclusion: The present study provides new evidence that neuropathic pain induced by spinal nerve ligation probably activates NTs and Trk receptors expression in DRG. However, further studies are needed to better elucidate the role of NTs in a neuropathic pain. PMID:28133521

  9. Heterogeneity of root and nerve ultrasound pattern in CIDP patients.

    PubMed

    Padua, L; Granata, G; Sabatelli, M; Inghilleri, M; Lucchetta, M; Luigetti, M; Coraci, D; Martinoli, C; Briani, C

    2014-01-01

    The few published ultrasound (US) studies on chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) report diffusely increased cross-sectional area (CSA) of nerves. The data are, however, heterogeneous and correlations with clinical history or disease severity are lacking. Thirty-four patients with CIDP underwent US nerve evaluation by two neurologists blinded to clinical data. US nerve pattern for each patient was defined by a third neurologist blinded to clinical data. Three US classes were identified based on CSA and echogenicity: large nerves with hypoechoic nerves/fascicles (class 1); large nerves with heterogeneous hypo- and hyperechoic fascicles (class 2); normal size nerve but abnormal hyperechoic array (class 3). In all patients, US nerve changes were observed: in most of the cases, enlarged nerves or nerve segments were observed. The three 'classes' of US nerve changes significantly correlated (R: 0.68, p<0.001) with disease duration, but not with age or Inflammatory Neuropathy Cause and Treatment (INCAT) disability score. US may be of adjunctive diagnostic value in CIDP assessment. Nerve morphological changes may mirror the underlying pathophysiological mechanisms and seem to correlate with disease duration. These results offer the possibility of exploring the use of US to assess CIDP disease activity and treatment. Copyright © 2013 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

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

    PubMed Central

    EVERILL, B.; KOCSIS, J. D.

    2008-01-01

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

  11. Transient nerve root compression load and duration differentially mediate behavioral sensitivity and associated spinal astrocyte activation and mGLuR5 expression.

    PubMed

    Nicholson, K J; Guarino, B B; Winkelstein, B A

    2012-05-03

    Injury to the cervical nerve roots is a common source of neck pain. Animal models of nerve root compression have previously established the role of compression magnitude and duration in nerve root-mediated pain and spinal inflammation; yet, the response of the spinal glutamatergic system to transient nerve root compression and its relationship to compression mechanics have not been studied. The glutamate receptor, mGluR5, has a central role in pain, and its expression by neurons and astrocytes in the spinal cord may be pivotal for neuronal-glial signaling. This study quantified spinal GFAP and mGluR5 expression following nerve root compressions of different magnitudes and durations in the rat. Compression to the C7 nerve root was applied for a duration that was either above (10 min) or below (3 min) the critical duration for mediating afferent discharge rates during compression. To also test for the effect of the magnitude of the compression load, either a 10 gf or a 60 gf was applied to the nerve root for each duration. Mechanical allodynia was assessed, and the C7 spinal cord was harvested on day 7 for immunofluorescent analysis. Double labeling was used to localize the expression of mGluR5 on astrocytes (GFAP) and neurons (MAP2). Seven days after injury, 10 min of compression produced significantly greater behavioral sensitivity (P<0.001) and spinal GFAP expression (P=0.002) than 3 min of compression, regardless of the compression magnitude. Nerve root compression at 60 gf produced a significant increase (P<0.001) in spinal mGluR5 for both of the durations studied. There was no difference in the distribution of mGluR5 between astrocytes and neurons following nerve root compression of any type. The glutamatergic and glial systems are differentially modulated by the mechanics of nerve root compression despite the known contribution of glia to pain through glutamatergic signaling. Copyright © 2012 IBRO. Published by Elsevier Ltd. All rights reserved.

  12. Recording nerve signals in canine sciatic nerves with a flexible penetrating microelectrode array

    NASA Astrophysics Data System (ADS)

    Byun, Donghak; Cho, Sung-Joon; Lee, Byeong Han; Min, Joongkee; Lee, Jong-Hyun; Kim, Sohee

    2017-08-01

    Objective. Previously, we presented the fabrication and characterization of a flexible penetrating microelectrode array (FPMA) as a neural interface device. In the present study, we aim to prove the feasibility of the developed FPMA as a chronic intrafascicular recording tool for peripheral applications. Approach. For recording from the peripheral nerves of medium-sized animals, the FPMA was integrated with an interconnection cable and other parts that were designed to fit canine sciatic nerves. The uniformity of tip exposure and in vitro electrochemical properties of the electrodes were characterized. The capability of the device to acquire in vivo electrophysiological signals was evaluated by implanting the FPMA assembly in canine sciatic nerves acutely as well as chronically for 4 weeks. We also examined the histology of implanted tissues to evaluate the damage caused by the device. Main results. Throughout recording sessions, we observed successful multi-channel recordings (up to 73% of viable electrode channels) of evoked afferent and spontaneous nerve unit spikes with high signal quality (SNR  >  4.9). Also, minor influences of the device implantation on the morphology of nerve tissues were found. Significance. The presented results demonstrate the viability of the developed FPMA device in the peripheral nerves of medium-sized animals, thereby bringing us a step closer to human applications. Furthermore, the obtained data provide a driving force toward a further study for device improvements to be used as a bidirectional neural interface in humans.

  13. The Relation Between Rotation Deformity and Nerve Root Stress in Lumbar Scoliosis

    NASA Astrophysics Data System (ADS)

    Kim, Ho-Joong; Lee, Hwan-Mo; Moon, Seong-Hwan; Chun, Heoung-Jae; Kang, Kyoung-Tak

    Even though several finite element models of lumbar spine were introduced, there has been no model including the neural structure. Therefore, the authors made the novel lumbar spine finite element model including neural structure. Using this model, we investigated the relation between the deformity pattern and nerve root stress. Two lumbar models with different types of curve pattern (lateral bending and lateral bending with rotation curve) were made. In the model of lateral bending curves without rotation, the principal compressive nerve root stress on the concave side was greater than the principal tensile stress on the convex side at the apex vertebra. Contrarily, in the lateral bending curve with rotational deformity, the nerve stress on the convex side was higher than that on the concave side. Therefore, this study elicit that deformity pattern could have significantly influence on the nerve root stress in the lumbar spine.

  14. Implantable electrode for recording nerve signals in awake animals

    NASA Technical Reports Server (NTRS)

    Ninomiya, I.; Yonezawa, Y.; Wilson, M. F.

    1976-01-01

    An implantable electrode assembly consisting of collagen and metallic electrodes was constructed to measure simultaneously neural signals from the intact nerve and bioelectrical noises in awake animals. Mechanical artifacts, due to bodily movement, were negligibly small. The impedance of the collagen electrodes, measured in awake cats 6-7 days after implantation surgery, ranged from 39.8-11.5 k ohms at a frequency range of 20-5 kHz. Aortic nerve activity and renal nerve activity, measured in awake conditions using the collagen electrode, showed grouped activity synchronous with the cardiac cycle. Results indicate that most of the renal nerve activity was from postganglionic sympathetic fibers and was inhibited by the baroceptor reflex in the same cardiac cycle.

  15. Return of function after spinal cord implantation of avulsed spinal nerve roots.

    PubMed

    Carlstedt, T; Grane, P; Hallin, R G; Norén, G

    1995-11-18

    Avulsion of nerve roots from the spinal cord is widely regarded as an untreatable injury. However, a series of experiments in animals has shown that, if continuity is restored between spinal cord and ventral roots, axons from spinal motor neurons can regrow into the peripheral nerves with recovery of motor function. These observations were applied in the treatment of a man with avulsion of the 6th cervical (C6) to 1st thoracic roots due to brachial plexus injury. Two ventral roots were implanted into the spinal cord through slits in the pia mater, C6 directly and C7 via sural nerve grafts. Voluntary activity in proximal arm muscles was detected electromyographically after nine months and clinically after one year. After three years the patient had voluntary activity (with some co-contraction) in the deltoid, biceps, and triceps muscles. To determine whether the improvement was due to spontaneous recovery from C5, the C5 root was blocked pharmacologically, and the results indicated that the repaired roots were contributing substantially to motor function. Repair of spinal nerve roots deserves further exploration in management of brachial plexus injury.

  16. Deficient FGF signaling causes optic nerve dysgenesis and ocular coloboma.

    PubMed

    Cai, Zhigang; Tao, Chenqi; Li, Hongge; Ladher, Raj; Gotoh, Noriko; Feng, Gen-Sheng; Wang, Fen; Zhang, Xin

    2013-07-01

    FGF signaling plays a pivotal role in eye development. Previous studies using in vitro chick models and systemic zebrafish mutants have suggested that FGF signaling is required for the patterning and specification of the optic vesicle, but due to a lack of genetic models, its role in mammalian retinal development remains elusive. In this study, we show that specific deletion of Fgfr1 and Fgfr2 in the optic vesicle disrupts ERK signaling, which results in optic disc and nerve dysgenesis and, ultimately, ocular coloboma. Defective FGF signaling does not abrogate Shh or BMP signaling, nor does it affect axial patterning of the optic vesicle. Instead, FGF signaling regulates Mitf and Pax2 in coordinating the closure of the optic fissure and optic disc specification, which is necessary for the outgrowth of the optic nerve. Genetic evidence further supports that the formation of an Frs2α-Shp2 complex and its recruitment to FGF receptors are crucial for downstream ERK signaling in this process, whereas constitutively active Ras signaling can rescue ocular coloboma in the FGF signaling mutants. Our results thus reveal a previously unappreciated role of FGF-Frs2α-Shp2-Ras-ERK signaling axis in preventing ocular coloboma. These findings suggest that components of FGF signaling pathway may be novel targets in the diagnosis of and the therapeutic interventions for congenital ocular anomalies.

  17. Implantation of cauda equina nerve roots through a biodegradable scaffold at the conus medullaris in rat.

    PubMed

    Grahn, Peter J; Vaishya, Sandeep; Knight, Andrew M; Chen, Bingkun K; Schmeichel, Ann M; Currier, Bradford L; Spinner, Robert J; Yaszemski, Michael J; Windebank, Anthony J

    2014-09-01

    Traumatic injuries occurring at the conus medullaris of the spinal cord cause permanent damage both to the central nervous system and to the cauda equina nerve roots. This proof-of-concept study was to determine whether implanting the nerve roots into a biodegradable scaffold would improve regeneration after injury. All experimental works involving rats were performed according to the approved guidelines by the Mayo Clinic Institutional Animal Care and Use Committee. Surgical procedures were performed on 32 Sprague-Dawley rats. Four ventral cauda equina nerve roots were reimplanted either directly into the ventral cord stump or through a poly(lactic-co-glycolic acid) (PLGA) scaffold. These experimental groups were compared with a control group in which the nerves were inserted into a muscle fascia barrier that was placed between the spinal cord and the nerve roots. Animals were sacrificed at 4 weeks. There was no difference in motor neuron counts in the spinal cord rostral to the injury in all treatment groups, implying equal potential for the regeneration into implanted nerve roots. One-way analysis of variance testing, with Tukey post hoc test, showed a statistically significant improvement in axon regeneration through the injury in the PLGA scaffold treatment group compared with the control (p<.05, scaffold n=11, control n=11). This pilot study demonstrated that a PLGA scaffold improved regeneration of axons into peripheral nerve roots. However, the number of regenerating axons observed was limited and did not lead to functional recovery. Future experiments will employ a different scaffold material and possible growth factors or enzymes to increase axon populations. Copyright © 2014 Elsevier Inc. All rights reserved.

  18. Reduction in nerve root compression by the nucleus pulposus after Feng's Spinal Manipulation.

    PubMed

    Feng, Yu; Gao, Yan; Yang, Wendong; Feng, Tianyou

    2013-04-25

    Ninety-four patients with lumbar intervertebral disc herniation were enrolled in this study. Of these, 48 were treated with Feng's Spinal Manipulation, hot fomentation, and bed rest (treatment group). The remaining 46 patients were treated with hot fomentation and bed rest only (control group). After 3 weeks of treatment, clinical parameters including the angle of straight-leg raising, visual analogue scale pain score, and Japanese Orthopaedic Association score for low back pain were improved. The treatment group had significantly better improvement in scores than the control group. Magnetic resonance myelography three-dimensional reconstruction imaging of the vertebral canal demonstrated that filling of the compressed nerve root sleeve with cerebrospinal fluid increased significantly in the treatment group. The diameter of the nerve root sleeve was significantly larger in the treatment group than in the control group. However, the sagittal diameter index of the herniated nucleus pulposus and the angle between the nerve root sleeve and the thecal sac did not change significantly in either the treatment or control groups. The effectiveness of Feng's Spinal Manipulation for the treatment of symptoms associated with lumbar intervertebral disc herniation may be attributable to the relief of nerve root compression, without affecting the herniated nucleus pulposus or changing the morphology or position of the nerve root.

  19. 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

  20. [Sciatica due to unusual causes: Tarlov cysts and nerve roots anomalies].

    PubMed

    Younes, M; Korbaa, W; Zrour, S; Bejia, I; Touzi, M; Bergaoui, N

    2009-03-01

    Tarlov cysts and nerve roots anomalies usually involve lumbosacral roots and are often asymptomatic. MRI has enabled recognition of many conditions that used to be missed by CT or myelography investigations performed for back and leg pain. However, even without additional compressive impingement (disc hernia, spondylolisthesis or lumbar canal stenosis) these anomalies can be responsible for sciatica, motor deficit and bladder sphincter dysfunction. Tarlov cysts are perinervous dilatations of the dorsal root ganglion. CT and especially MRI can reveal these cysts and their precise relations with the neighboring structures. Delayed filling of the cysts can be visualized on the myelogram. MRI is more sensitive than CT myelography for a positive diagnosis of nerve root anomalies, a differential diagnosis with disc hernia and classification of these anomalies. Surgical treatment is indicated for symptomatic Tarlov cysts and nerve root anomalies resistant to conservative treatment. Better outcome is observed in patients with an additional compressive impingement component. We report two cases of sciatica: one caused by Tarlov cysts diagnosed by MRI and the other by nerve root anomalies diagnosed by CT myelography. In both cases, conservative treatment was undertaken. The clinical, radiological and therapeutic aspects of these disorders are discussed.

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

    PubMed

    Flores, Leandro Pretto

    2012-01-01

    Extension of the elbow is required to oppose gravity; however, activation of the triceps brachii is frequently underestimated during the surgical planning for brachial plexus injuries. This report aims to describe a novel technique of distal nerve transfer designed for elbow extension reconstruction in patients sustaining a C5-C7 nerve root injury. We report a patient sustaining a brachial plexus injury with triceps palsy and preserved finger extension motion; after careful intraneural dissection of the radial nerve, a fascicle innervating the extensor digitorum communis muscle was sectioned, derouted and connected to a motor branch to the lateral head of the triceps. Eleven months after surgery, elbow extension strength scored MRC M4. No deficits on finger extension were observed. Copyright © 2011 Wiley-Liss, Inc.

  2. 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

  3. Cerebrospinal fluid infection after lumbar nerve root steroid injection: a case report

    PubMed Central

    Kim, Seong-Su; Shim, Sung Min; Cho, Hae Jun

    2017-01-01

    A 45-year-old woman was admitted due to severe headache and neck stiffness. She had visited a local clinic for back pain and received a lumbar nerve root steroid injection 10 days before admission. Computed tomography and magnetic resonance imaging showed psoas abscess, pneumocephalus, and subdural hygroma. She was diagnosed with psoas abscess and meningitis. The abscess and external ventricle were drained, and antibiotics were administered. Unfortunately, the patient died on hospital day 19 due to diffuse leptomeningitis. Lumbar nerve root steroid injections are commonly used to control back pain. Vigilance to "red flag signs" and a rapid diagnosis can prevent lethal outcomes produced by rare and unexpected complications related to infection. Here, we report a case of fatal meningitis after infection of the cerebrospinal fluid following a lumbar nerve root steroid injection. PMID:28184274

  4. Spinal nerve root β-APP staining in infants is not a reliable indicator of trauma.

    PubMed

    Squier, W; Scheimberg, I; Smith, C

    2011-10-10

    This preliminary communication describes seven babies with β-amyloid precursor protein (βAPP) positive axonal swellings in nerve roots at multiple levels of the spinal cord. All seven babies died of natural causes. Two died in utero providing evidence for nerve root injury in the absence of trauma, two died within one day of birth and the possibility of birth related injury has to be considered. Three babies were over one month of age and had no history or pathological evidence of trauma. These findings show that if axonal injury is carefully sought in every infant death, not just in babies where trauma is suspected, it will be found in a proportion of babies dying from natural diseases. While spinal nerve root axonal injury in infants may suggest trauma, it is not, in itself, diagnostic of trauma. Copyright © 2011. Published by Elsevier Ireland Ltd.

  5. Slit-Robo GTPase-activating proteins are differentially expressed in murine dorsal root ganglia: modulation by peripheral nerve injury.

    PubMed

    Chen, Zhi-Bing; Zhang, Hai-Ying; Zhao, Jiu-Hong; Zhao, Wei; Zhao, Dan; Zheng, Lin-Feng; Zhang, Xian-Fang; Liao, Xiao-Ping; Yi, Xi-Nan

    2012-04-01

    The Slit-Robo GTPase-activating proteins (srGAPs) play an important role in neurite outgrowth and axon guidance; however, little is known about its role in nerve regeneration after injury. Here, we studied the expression of srGAPs in mouse dorsal root ganglia (DRG) following sciatic nerve transection (SNT) using morphometric and immunohistochemical techniques. Reverse transcriptase polymerase chain reaction and Western blot analysis indicated that srGAP1 and srGAP3, but not srGAP2, were expressed in normal adult DRG. Following unilateral SNT, elevated mRNA and protein levels of srGAP1 and srGAP3 were detected in the ipsilateral relative to contralateral L(3-4) DRGs from day 3 to day 14. Immunohistochemical results showed that srGAP1 and srGAP3 were largely expressed in subpopulations of DRG neurons in naïve DRGs. However, after SNT, srGAP3 in neurons was significantly increased in the ipsilateral relative to contralateral DRGs, which peaked at day 7 to day 14. Interestingly, DRG neurons with strong srGAP3 labeling also coexpressed Robo2 after peripheral nerve injury. These results suggest that srGAPs are differentially expressed in murine DRG and srGAP3 are the predominant form. Moreover, srGAP3 may participate in Slit-Robo signaling in response to peripheral nerve injury or the course of nerve regeneration.

  6. [Physiological approach to peripheral neuropathy. Conventional nerve conduction studies and magnetic motor root stimulation].

    PubMed

    Ugawa, Yoshikazu

    2004-11-01

    In this communication, I first show some points we should mind in the conventional peripheral nerve conduction studies and later present clinical usefulness of motor root stimulation for peripheral neuropathy. CONVENTIONAL NERVE CONDUCTION STUDIES (NCS): The most important point revealed by the conventional NCSs is whether neuropathy is due to axonal degeneration or demyelinating process. Precise clinical examination with this neurophysiological information leads us to a diagnosis and treatment. Poor clinical examination makes these findings useless. Long standing axonal degeneration sometimes induces secondary demyelination at the most distal part of involved nerves. On the other hand, severe segmental demyelination often provokes secondary axonal degeneration at distal parts to the site of demyelination. These secondary changes show the same abnormal neurophysiological findings as those of the primary involvement. We should be careful of this possibility when interpreting the results of NCS. NCS of sensory nerves is not good at revealing demyelinating process. Mild temporal dispersion of potentials often reduces an amplitude of SNAP or loss of responses, which usually suggests axonal degeneration, because of short duration of sensory nerve potentials. MOTOR ROOT STIMULATION IN PERIPHERAL NEUROPATHY: Magnetic stimulation with a coil placed over the spine activates motor roots and evokes EMG responses from upper and lower limb muscles. The site of activation with this method was determined to be where the motor roots exit from the spinal canal (intervertebral foramina) (J Neurol Neurosurg Psychiatry 52 (9): 1025-1032, 1989) because induced currents are very dense at such a foramen made by electric resistant bones. In several kinds of peripheral neuropathy, this method has been used to detect a lesion at a proximal part of the peripheral nerves which can not be detected by the conventional NCSs. I present a few cases in whom motor root stimulation had a clinical

  7. Role of Netrin-1 Signaling in Nerve Regeneration

    PubMed Central

    Dun, Xin-Peng; Parkinson, David B.

    2017-01-01

    Netrin-1 was the first axon guidance molecule to be discovered in vertebrates and has a strong chemotropic function for axonal guidance, cell migration, morphogenesis and angiogenesis. It is a secreted axon guidance cue that can trigger attraction by binding to its canonical receptors Deleted in Colorectal Cancer (DCC) and Neogenin or repulsion through binding the DCC/Uncoordinated (Unc5) A–D receptor complex. The crystal structures of Netrin-1/receptor complexes have recently been revealed. These studies have provided a structure based explanation of Netrin-1 bi-functionality. Netrin-1 and its receptor are continuously expressed in the adult nervous system and are differentially regulated after nerve injury. In the adult spinal cord and optic nerve, Netrin-1 has been considered as an inhibitor that contributes to axon regeneration failure after injury. In the peripheral nervous system, Netrin-1 receptors are expressed in Schwann cells, the cell bodies of sensory neurons and the axons of both motor and sensory neurons. Netrin-1 is expressed in Schwann cells and its expression is up-regulated after peripheral nerve transection injury. Recent studies indicated that Netrin-1 plays a positive role in promoting peripheral nerve regeneration, Schwann cell proliferation and migration. Targeting of the Netrin-1 signaling pathway could develop novel therapeutic strategies to promote peripheral nerve regeneration and functional recovery. PMID:28245592

  8. GFRα1 released by nerves enhances cancer cell perineural invasion through GDNF-RET signaling.

    PubMed

    He, Shuangba; Chen, Chun-Hao; Chernichenko, Natalya; He, Shizhi; Bakst, Richard L; Barajas, Fernando; Deborde, Sylvie; Allen, Peter J; Vakiani, Efsevia; Yu, Zhenkun; Wong, Richard J

    2014-05-13

    The ability of cancer cells to invade along nerves is associated with aggressive disease and diminished patient survival rates. Perineural invasion (PNI) may be mediated by nerve secretion of glial cell line-derived neurotrophic factor (GDNF) attracting cancer cell migration through activation of cell surface Ret proto-oncogene (RET) receptors. GDNF family receptor (GFR)α1 acts as coreceptor with RET, with both required for response to GDNF. We demonstrate that GFRα1 released by nerves enhances PNI, even in the absence of cancer cell GFRα1 expression. Cancer cell migration toward GDNF, RET phosphorylation, and MAPK pathway activity are increased with exposure to soluble GFRα1 in a dose-dependent fashion. Dorsal root ganglia (DRG) release soluble GFRα1, which potentiates RET activation and cancer cell migration. In vitro DRG coculture assays of PNI show diminished PNI with DRG from GFRα1(+/-) mice compared with GFRα1(+/+) mice. An in vivo murine model of PNI demonstrates that cancer cells lacking GFRα1 maintain an ability to invade nerves and impair nerve function, whereas those lacking RET lose this ability. A tissue microarray of human pancreatic ductal adenocarcinomas demonstrates wide variance of cancer cell GFRα1 expression, suggesting an alternate source of GFRα1 in PNI. These findings collectively demonstrate that GFRα1 released by nerves enhances PNI through GDNF-RET signaling and that GFRα1 expression by cancer cells enhances but is not required for PNI. These results advance a mechanistic understanding of PNI and implicate the nerve itself as a key facilitator of this adverse cancer cell behavior.

  9. Multiple Routes of Light Signaling during Root Photomorphogenesis.

    PubMed

    Lee, Hyo-Jun; Park, Young-Joon; Ha, Jun-Ho; Baldwin, Ian T; Park, Chung-Mo

    2017-09-01

    Plants dynamically adjust their architecture to optimize growth and performance under fluctuating light environments, a process termed photomorphogenesis. A variety of photomorphogenic responses have been studied extensively in the shoots, where diverse photoreceptors and signaling molecules have been functionally characterized. Notably, accumulating evidence demonstrates that the underground roots also undergo photomorphogenesis, raising the question of how roots perceive and respond to aboveground light. Recent findings indicate that root photomorphogenesis is mediated by multiple signaling routes, including shoot-to-root transmission of mobile signaling molecules, direct sensing of light by the roots, and light channeling through the plant body. In this review we discuss recent advances in how light signals are transmitted to the roots to trigger photomorphogenic responses. Copyright © 2017 Elsevier Ltd. All rights reserved.

  10. Method of the nerve root selection in diagnostic and therapeutic process in patients with multilevel nerves entrapment in lumbar spine due to the degenerative process.

    PubMed

    Kubaszewski, Łukasz; Nowakowski, Andrzej; Gasik, Robert

    2011-01-01

    This paper presents a method for determining the proper diagnostic techniques and the respective therapy in patients affected with nerve root compression in the lumbar region of the spine based on developing an algorithm that attempts to assess the level of compression and determine the afflicted nerve root. The clinical picture of degenerative disease of the lumbar spine is characterized by symptoms related to the affected nerve root. The diagnosis and respective therapy benefits from the use of minimally invasive techniques, such as selective root blocks or use of the radiofrequency. For instance, with changes on many levels it is necessary to comply with the rules for the selection of the correct nerve roots so there can be referral for proper treatment. The method of selection is dependent on the correlation of the results of the clinical examination, as well as secondary diagnostic studies, of which the gold standard is the MRI. In clinical practice we rely on the results of magnetic resonance imaging to determine the nerve root level in the lumbar spine. This allows the classification of the roots in relation to the frequency of compression occurrence along its course. The morphologic changes resulting in a similar clinical picture may indirectly suggest a degree of exacerbated risk. In addition, we suggest a system of describing the MRI scans, which allows us to retrospectively obtain information on the locations of potential compression of nerve roots.

  11. Unmyelinated tactile cutaneous nerves signal erotic sensations.

    PubMed

    Jönsson, Emma H; Backlund Wasling, Helena; Wagnbeck, Vicktoria; Dimitriadis, Menelaos; Georgiadis, Janniko R; Olausson, Håkan; Croy, Ilona

    2015-06-01

    Intrapersonal touch is a powerful tool for communicating emotions and can among many things evoke feelings of eroticism and sexual arousal. The peripheral neural mechanisms of erotic touch signaling have been less studied. C tactile afferents (unmyelinated low-threshold mechanoreceptors), known to underpin pleasant aspects of touch processing, have been posited to play an important role. In two studies, we investigated the relationship between C tactile activation and the perception of erotic and pleasant touch, using tactile brushing stimulation. In total, 66 healthy subjects (37 women, age range 19-51 years) were examined. In study 1 (n = 20), five different stroking velocities were applied to the forearm and the inner thigh. The participants answered questions about partnership, mood, and touch. In study 2 (n = 46), the same five stroking velocities were applied to the forearm. The participants answered questions about partnership, touch, and sexuality. Both touch eroticism and pleasantness were rated significantly higher for C tactile optimal velocities compared with suboptimal velocities. No difference was found between the ratings of the thigh and the forearm. The velocity-dependent rating curves of pleasantness, intensity, and eroticism differed from each other. Pleasantness was best explained by a quadratic fit, intensity by a linear fit, and eroticism by both. A linear transformation of pleasantness and intensity predicted the observed eroticism ratings reliably. Eroticism ratings were negatively correlated with length of relationship. Touch was rated most erotic when perceived as pleasant and weak. In human hairy skin, perception of pleasantness is correlated with the firing rate of C tactile afferents, and perception of intensity is correlated with the firing rate of Aβ afferents. Accordingly, eroticism may be perceived most readily for touch stimuli that induce high activity in C tactile fibers and low activity in Aβ fibers. © 2015 International

  12. An Nfic-hedgehog signaling cascade regulates tooth root development

    PubMed Central

    Liu, Yang; Feng, Jifan; Li, Jingyuan; Zhao, Hu; Ho, Thach-Vu; Chai, Yang

    2015-01-01

    Coordination between the Hertwig's epithelial root sheath (HERS) and apical papilla (AP) is crucial for proper tooth root development. The hedgehog (Hh) signaling pathway and Nfic are both involved in tooth root development; however, their relationship has yet to be elucidated. Here, we establish a timecourse of mouse molar root development by histological staining of sections, and we demonstrate that Hh signaling is active before and during root development in the AP and HERS using Gli1 reporter mice. The proper pattern of Hh signaling activity in the AP is crucial for the proliferation of dental mesenchymal cells, because either inhibition with Hh inhibitors or constitutive activation of Hh signaling activity in transgenic mice leads to decreased proliferation in the AP and shorter roots. Moreover, Hh activity is elevated in Nfic−/− mice, a root defect model, whereas RNA sequencing and in situ hybridization show that the Hh attenuator Hhip is downregulated. ChIP and RNAscope analyses suggest that Nfic binds to the promoter region of Hhip. Treatment of Nfic−/− mice with Hh inhibitor partially restores cell proliferation, AP growth and root development. Taken together, our results demonstrate that an Nfic-Hhip-Hh signaling pathway is crucial for apical papilla growth and proper root formation. This discovery provides insight into the molecular mechanisms regulating tooth root development. PMID:26293299

  13. Scanning pattern of diffusion tensor tractography and an analysis of the morphology and function of spinal nerve roots.

    PubMed

    Tian, Xin; Liu, Huaijun; Geng, Zuojun; Yang, Hua; Wang, Guoshi; Yang, Jiping; Wang, Chunxia; Li, Cuining; Li, Ying

    2013-11-25

    Radiculopathy, commonly induced by intervertebral disk bulging or protrusion, is presently diagnosed in accordance with clinical symptoms because there is no objective quantitative diagnostic criterion. Diffusion tensor magnetic resonance imaging and diffusion tensor tractography revealed the characterization of anisotropic diffusion and displayed the anatomic form of nerve root fibers. This study included 18 cases with intervertebral disc degeneration-induced unilateral radiculopathy. Magnetic resonance diffusion tensor imaging was creatively used to reveal the scanning pattern of fiber tracking of the spinal nerve root. A scoring system of nerve root morphology was used to quantitatively assess nerve root morphology and functional alteration after intervertebral disc degeneration. Results showed that after fiber tracking, compared with unaffected nerve root, fiber bundles gathered together and interrupted at the affected side. No significant alteration was detected in the number of fiber bundles, but the cross-sectional area of nerve root fibers was reduced. These results suggest that diffusion tensor magnetic resonance imaging-based tractography can be used to quantitatively evaluate nerve root function according to the area and morphology of fiber bundles of nerve roots.

  14. Microanatomy and histological features of central myelin in the root exit zone of facial nerve.

    PubMed

    Yee, Gi-Taek; Yoo, Chan-Jong; Han, Seong-Rok; Choi, Chan-Young

    2014-05-01

    The aim of this study was to evaluate the microanatomy and histological features of the central myelin in the root exit zone of facial nerve. Forty facial nerves with brain stem were obtained from 20 formalin fixed cadavers. Among them 17 facial nerves were ruined during preparation and 23 root entry zone (REZ) of facial nerves could be examined. The length of medial REZ, from detach point of facial nerve at the brain stem to transitional area, and the thickness of glial membrane of central myelin was measured. We cut brain stem along the facial nerve and made a tissue block of facial nerve REZ. Each tissue block was embedded with paraffin and serially sectioned. Slices were stained with hematoxylin and eosin (H&E), periodic acid-Schiff, and glial fibrillary acid protein. Microscopy was used to measure the extent of central myelin and thickness of outer glial membrane of central myelin. Thickness of glial membrane was examined at two different points, the thickest area of proximal and distal REZ. Special stain with PAS and GFAP could be differentiated the central and peripheral myelin of facial nerve. The length of medial REZ was mean 2.6 mm (1.6-3.5 mm). The glial limiting membrane of brain stem is continued to the end of central myelin. We called it glial sheath of REZ. The thickness of glial sheath was mean 66.5 µm (40-110 µm) at proximal REZ and 7.4 µm (5-10 µm) at distal REZ. Medial REZ of facial nerve is mean 2.6 mm in length and covered by glial sheath continued from glial limiting membrane of brain stem. Glial sheath of central myelin tends to become thin toward transitional zone.

  15. Differences between Cervical Schwannomas of the Anterior and Posterior Nerve Roots in Relation to the Incidence of Postoperative Radicular Dysfunction

    PubMed Central

    Ohnishi, Yu-Ichiro; Ohkawa, Toshika; Ninomiya, Koshi; Moriwaki, Takashi; Yoshimine, Toshiki

    2015-01-01

    Study Design A retrospective study. Purpose To assess the case files of patients who underwent surgery for cervical dumbbell schwannoma for determining the differences between schwannomas of the anterior and posterior nerve roots with respect to the incidence of postoperative radicular dysfunction. Overview of Literature The spinal roots giving origin to schwannoma are frequently nonfunctional, but there is a risk of postoperative neurological deficit once these roots are resected during surgery. Methods Fifteen patients with cervical dumbbell schwannomas were treated surgically. Ten men and 5 women, who were 35-79 years old (mean age, 61.5 years), presented with neck pain (n=6), radiculopathy (n=10), and myelopathy (n=11). Results Fourteen patients underwent gross total resection and exhibited no recurrence. Follow-ups were performed for a period of 6-66 months (mean, 28 months). Preoperative symptoms resolved in 11 patients (73.3%) but they persisted partially in 4 patients (26.7%). Six patients had tumors of anterior nerve root origin, and 9 patients had tumors of posterior nerve root origin. Two patients who underwent total resection of anterior nerve root tumors (33.3%) displayed minor postoperative motor weakness. One patient who underwent total resection of a posterior nerve root tumor (11.1%) showed postoperative numbness. Conclusions Appropriate tumor removal improved the neurological symptoms. In this study, the incidence of radicular dysfunction was higher in patients who underwent resection of anterior nerve root tumors than in patients who underwent resection of posterior nerve root tumors. PMID:25901239

  16. Surgical Excision of a Symptomatic Thoracic Nerve Root Perineural Cyst Resulting in Complete Resolution of Symptoms: A Case Report.

    PubMed

    Aljuboori, Zaid; Yaseen, Alae; Simpson, Jessica; Boakye, Maxwell

    2017-06-12

    Tarlov (perineural) cysts of the nerve root are common and usually incidental findings during magnetic resonance imaging (MRI) of the lumbosacral spine. There are a few case reports where symptomatic thoracic perineural cysts have been described in the literature. We report a case of a high thoracic nerve root perineural cyst that failed conservative therapy, requiring surgical intervention. Our patient presented with radicular symptoms involving the left hand. Imaging workup revealed a cystic lesion of the left T1 nerve root at the level of the foramen. Surgical resection resulted in significant improvement in patient symptoms, and pathology revealed a perineural cyst. We conclude that a thoracic perineural (Tarlov) cyst can be symptomatic by causing nerve root compression and can be mistaken as a nerve root sheath tumor on imaging. Surgical treatment can be curative.

  17. Surgical Excision of a Symptomatic Thoracic Nerve Root Perineural Cyst Resulting in Complete Resolution of Symptoms: A Case Report

    PubMed Central

    Yaseen, Alae; Simpson, Jessica; Boakye, Maxwell

    2017-01-01

    Tarlov (perineural) cysts of the nerve root are common and usually incidental findings during magnetic resonance imaging (MRI) of the lumbosacral spine. There are a few case reports where symptomatic thoracic perineural cysts have been described in the literature. We report a case of a high thoracic nerve root perineural cyst that failed conservative therapy, requiring surgical intervention. Our patient presented with radicular symptoms involving the left hand. Imaging workup revealed a cystic lesion of the left T1 nerve root at the level of the foramen. Surgical resection resulted in significant improvement in patient symptoms, and pathology revealed a perineural cyst. We conclude that a thoracic perineural (Tarlov) cyst can be symptomatic by causing nerve root compression and can be mistaken as a nerve root sheath tumor on imaging. Surgical treatment can be curative. PMID:28706767

  18. Ethylene signaling pathway modulates attractiveness of host roots to the root-knot nematode Meloidogyne hapla.

    PubMed

    Fudali, Sylwia L; Wang, Congli; Williamson, Valerie M

    2013-01-01

    Infective juveniles of the root-knot nematode Meloidogyne hapla are attracted to the zone of elongation of roots where they invade the host but little is known about what directs the nematode to this region of the root. We found that Arabidopsis roots exposed to an ethylene (ET)-synthesis inhibitor attracted significantly more nematodes than control roots and that ET-overproducing mutants were less attractive. Arabidopsis seedlings with ET-insensitive mutations were generally more attractive whereas mutations resulting in constitutive signaling were less attractive. Roots of the ET-insensitive tomato mutant Never ripe (Nr) were also more attractive, indicating that ET signaling also modulated attraction of root-knot nematodes to this host. ET-insensitive mutants have longer roots due to reduced basipetal auxin transport. However, assessments of Arabidopsis mutants that differ in various aspects of the ET response suggest that components of the ET-signaling pathway directly affecting root length are not responsible for modulating root attractiveness and that other components of downstream signaling result in changes in levels of attractants or repellents for M. hapla. These signals may aid in directing this pathogen to an appropriate host and invasion site for completing its life cycle.

  19. 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

  20. Bony spinal canal changes that differentiate conjoined nerve roots from herniated nucleus pulposus

    SciTech Connect

    Hoddick, W.K.; Helms, C.A.

    1985-01-01

    CT examinations of the lumbar spine in 12 consecutive patients with conjoined nerve roots were reviewed. Asymmetry of the bony spinal canal, seen as slight dilatation of the ipsilateral lateral recess, was present in all cases. This finding, which is not typically associated with extruded free intervertebral disk fragments, should serve to distinguish these two entities.

  1. Mechanical properties of nerve roots and rami radiculares isolated from fresh pig spinal cords

    PubMed Central

    Nishida, Norihiro; Kanchiku, Tsukasa; Ohgi, Junji; Ichihara, Kazuhiko; Chen, Xian; Taguchi, Toshihiko

    2015-01-01

    No reports have described experiments designed to determine the strength characteristics of spinal nerve roots and rami radiculares for the purpose of explaining the complexity of symptoms of medullary cone lesions and cauda equina syndrome. In this study, to explain the pathogenesis of cauda equina syndrome, monoaxial tensile tests were performed to determine the strength characteristics of spinal nerve roots and rami radiculares, and analysis was conducted to evaluate the stress-strain relationship and strength characteristics. Using the same tensile test device, the nerve root and ramus radiculares isolated from the spinal cords of pigs were subjected to the tensile test and stress relaxation test at load strain rates of 0.1, 1, 10, and 100 s-1 under identical settings. The tensile strength of the nerve root was not rate dependent, while the ramus radiculares tensile strength tended to decrease as the strain rate increased. These findings provide important insights into cauda equina symptoms, radiculopathy, and clinical symptoms of the medullary cone. PMID:26807127

  2. Mechanical properties of nerve roots and rami radiculares isolated from fresh pig spinal cords.

    PubMed

    Nishida, Norihiro; Kanchiku, Tsukasa; Ohgi, Junji; Ichihara, Kazuhiko; Chen, Xian; Taguchi, Toshihiko

    2015-11-01

    No reports have described experiments designed to determine the strength characteristics of spinal nerve roots and rami radiculares for the purpose of explaining the complexity of symptoms of medullary cone lesions and cauda equina syndrome. In this study, to explain the pathogenesis of cauda equina syndrome, monoaxial tensile tests were performed to determine the strength characteristics of spinal nerve roots and rami radiculares, and analysis was conducted to evaluate the stress-strain relationship and strength characteristics. Using the same tensile test device, the nerve root and ramus radiculares isolated from the spinal cords of pigs were subjected to the tensile test and stress relaxation test at load strain rates of 0.1, 1, 10, and 100 s(-1) under identical settings. The tensile strength of the nerve root was not rate dependent, while the ramus radiculares tensile strength tended to decrease as the strain rate increased. These findings provide important insights into cauda equina symptoms, radiculopathy, and clinical symptoms of the medullary cone.

  3. Gas-filled intradural cyst with migration into the nerve root of the cauda equina.

    PubMed

    Kudo, Yohei; Nishijima, Yoji; Mochida, Kiyoshi; Sekido, Yasutomo; Tachibana, Shigekuni

    2008-05-01

    Only 4 cases of gas-filled intradural cysts of the spine have been reported previously. All cysts were due to intradural herniation of a gas-containing disc. The authors report 2 additional patients with gas-filled intradural cysts that migrated into the nerve root of the cauda equina. After surgical treatment their severe leg pain completely resolved.

  4. Glial hyperpolarization upon nerve root stimulation in the leech Hirudo medicinalis.

    PubMed

    Schmidt, J; Prinz, P; Deitmer, J W

    1999-07-01

    Hyperpolarizing responses in neuropil glial cells evoked by nerve root stimulation were studied in the central nervous system of the leech Hirudo medicinalis using intracellular recording and extracellular stimulation techniques. From a mean resting potential of -60.5 +/- 1.0, the glial membrane was hyperpolarized by -8.6 +/- 0.8 mV, via stimulation of the dorsal posterior nerve root in an isolated ganglion. Nerve root stimulation evoked biphasic or depolarizing responses in glial cells with resting potentials around -70 mV (Rose CR, Deitmer JW. J. Neurophysiol. 73:125-131, 1995). The hyperpolarizing response was reduced by the ionotropic glutamate receptor antagonist CNQX (50 microM) to 58% of its initial amplitude. In 15 mM Ca2+/15 mM Mg(2+)-saline the hyperpolarization was reduced by 44%. The hyperpolarization that persisted in high-divalent cation saline was not affected by CNQX. Bath-applied glutamate (500 microM) and kainate (2 microM) elicited glial hyperpolarizations that were sensitive to CNQX and 10 mM Mg2+/1 mM Ca(2+)-saline. The 5-HT-antagonist methysergide did not affect the hyperpolarizations evoked by nerve root stimulation. The results show that in the leech glial membrane responses to neuronal activity include not only depolarizations, as shown previously, but also hyperpolarizations, which are mediated by direct and indirect neuron-glial communication pathways. In the indirect pathway, glutamate is a transmitter between neurons.

  5. A conduction block in sciatic nerves can be detected by magnetic motor root stimulation.

    PubMed

    Matsumoto, Hideyuki; Konoma, Yuko; Fujii, Kengo; Hanajima, Ritsuko; Terao, Yasuo; Ugawa, Yoshikazu

    2013-08-15

    Useful diagnostic techniques for the acute phase of sciatic nerve palsy, an entrapment neuropathy, are not well established. The aim of this paper is to demonstrate the diagnostic utility of magnetic sacral motor root stimulation for sciatic nerve palsy. We analyzed the peripheral nerves innervating the abductor hallucis muscle using both electrical stimulations at the ankle and knee and magnetic stimulations at the neuro-foramina and conus medullaris levels in a patient with sciatic nerve palsy at the level of the piriformis muscle due to gluteal compression related to alcohol consumption. On the fourth day after onset, magnetic sacral motor root stimulation using a MATS coil (the MATS coil stimulation method) clearly revealed a conduction block between the knee and the sacral neuro-foramina. Two weeks after onset, needle electromyography supported the existence of the focal lesion. The MATS coil stimulation method clearly revealed a conduction block in the sciatic nerve and is therefore a useful diagnostic tool for the abnormal neurophysiological findings associated with sciatic nerve palsy even at the acute phase.

  6. Use of Posterior Root-Muscle Reflexes in Peripheral Nerve Surgery: A Case Report.

    PubMed

    Mandeville, Ross M; Brown, Justin M; Gertsch, Jeffrey H; Allison, David W

    2016-01-01

    It is well established that a mixed-agent general anesthetic regimen of volatile gas and intravenous anesthetic or total intravenous anesthetic (TIVA) is required to obtain adequate transcranial motor-evoked potentials (TcMEPs) to detect and hopefully prevent injury during brain, spinal cord, and peripheral nerve surgery. But even under ideal general anesthetic conditions, TcMEPs are not always detectable in every muscle monitored, and are prone to anesthetic fade, especially when neuropathic or injured tissue is monitored. TcMEP sensitivity to general anesthesia can be especially problematic during peripheral nerve surgery where there is often only one or a few essential muscles required to provide adequate monitoring; thus, maximum fidelity is essential. However, there is an anesthetic-resistant high-fidelity modality available to successfully monitor the motor component of distant peripheral nerves originating from the cauda equina. Percutaneus transabdominal electrical stimulation elicits a relatively anesthetic-resistant, robust motor response in muscles innervated by cauda equina nerve roots. We report the successful use of posterior root-muscle (PRM) reflex to monitor the decompression of the sciatic nerve at its bifurcation in a 22-year-old female with a history of severe sciatic nerve neuropathic pain and muscle weakness following benign thigh tumor resection.

  7. The action of prostaglandin E2 and triamcinolone acetonide on the firing activity of lumbar nerve roots.

    PubMed

    Muramoto, T; Atsuta, Y; Iwahara, T; Sato, M; Takemitsu, Y

    1997-01-01

    Sciatica, due to lumbar disc herniation, is understood electrophysiogically to be an ectopic firing originating from a nerve root. The recent concept of chemical radiculitis implies the involvement, not only of mechanical compression, but also of chemical mediators which contribute to the generation of ectopic firing. The present study demonstrates that prostaglandin E2, a chemical mediator of inflammation, provoked the ectopic firing of nerve roots in a canine in vitro model which indicates that it may play a part in the irritation of nerve roots. In contrast, triamcinolone acetonide suppressed the firing induced by prostaglandin suggesting that steroids may be effective in the treatment of root symptoms.

  8. An animal model for trigeminal neuralgia by compression of the trigeminal nerve root.

    PubMed

    Luo, Dao-Shu; Zhang, Ting; Zuo, Chang-Xu; Zuo, Zhong-Fu; Li, Hui; Wu, Sheng-Xi; Wang, Wei; Li, Yun-Qing

    2012-01-01

    Microvascular compression of the trigeminal nerve root is a major cause of most trigeminal neuralgia (TN) in patients; however, no reliable animal model to further study the pathogenesis of TN currently exists. Our objective was to establish a novel and practical animal model for TN by chronic compression of the trigeminal (CCT) nerve root in rats, which would provide a better animal model to mimic the clinical feature of TN on the research of the pathogenesis of TN. A randomized, double blind, controlled animal trial. Sixteen adult male Sprague-Dawley rats (200-220 g) were randomly divided into 2 groups: one group that received chronic compression of the trigeminal nerve root (the CCT group, n=8) and another group that received sham operation without compression (the sham operation group, n=8). A small plastic filament was retrogressively inserted into the intracalvarium from the inferior orbital fissure until it reached the trigeminal nerve root for compression in CCT group. Animal behaviors were observed for 4 weeks after operation. Immunohistochemistry of glial fibrillary acidic protein (GFAP), isolectin B4 (IB4), substance P (SP) and calcitonin gene-related peptide (CGRP) were performed in the trigeminal root entry zone (TREZ) and medullary dorsal horn (MDH). The orofacial mechanical allodynia and heat hyperalgesia in the CCT rats were obviously increased after the operation and lasted for 28 days. Increased face-grooming behavior was also observed in the CCT rats and continued for over 21 days, returning to baseline by day 28. Immunohistochemistry for GFAP in the TREZ revealed a progressive extension of astrocytic processes in the ipsilateral TREZ of rats in the CCT group. Furthermore, the IB4 positive immunoreactive nonpeptidergic C-fiber terminals in the MDH were reduced for 4 weeks after the operation. Both SP and CGRP, expressed in the peptidergic C-fiber terminals, were found to be decreased in the ipsilateral MDH of CCT animals after the trigeminal

  9. MRI-guided and CT-guided cervical nerve root infiltration therapy: a cost comparison.

    PubMed

    Maurer, M H; Froeling, V; Röttgen, R; Bretschneider, T; Hartwig, T; Disch, A C; de Bucourt, M; Hamm, B; Streitparth, F

    2014-06-01

    To evaluate and compare the costs of MRI-guided and CT-guided cervical nerve root infiltration for the minimally invasive treatment of radicular neck pain. Between September 2009 and April 2012, 22 patients (9 men, 13 women; mean age: 48.2 years) underwent MRI-guided (1.0 Tesla, Panorama HFO, Philips) single-site periradicular cervical nerve root infiltration with 40 mg triamcinolone acetonide. A further 64 patients (34 men, 30 women; mean age: 50.3 years) were treated under CT fluoroscopic guidance (Somatom Definition 64, Siemens). The mean overall costs were calculated as the sum of the prorated costs of equipment use (purchase, depreciation, maintenance, and energy costs), personnel costs and expenditure for disposables that were identified for MRI- and CT-guided procedures. Additionally, the cost of ultrasound guidance was calculated. The mean intervention time was 24.9 min. (range: 12 - 36 min.) for MRI-guided infiltration and 19.7 min. (range: 5 - 54 min.) for CT-guided infiltration. The average total costs per patient were EUR 240 for MRI-guided interventions and EUR 124 for CT-guided interventions. These were (MRI/CT guidance) EUR 150/60 for equipment use, EUR 46/40 for personnel, and EUR 44/25 for disposables. The mean overall cost of ultrasound guidance was EUR 76. Cervical nerve root infiltration using MRI guidance is still about twice as expensive as infiltration using CT guidance. However, since it does not involve radiation exposure for patients and personnel, MRI-guided nerve root infiltration may become a promising alternative to the CT-guided procedure, especially since a further price decrease is expected for MRI devices and MR-compatible disposables. In contrast, ultrasound remains the less expensive method for nerve root infiltration guidance. © Georg Thieme Verlag KG Stuttgart · New York.

  10. Lack of effectiveness of laser therapy applied to the nerve course and the correspondent medullary roots

    PubMed Central

    Sousa, Fausto Fernandes de Almeida; Ribeiro, Thaís Lopes; Fazan, Valéria Paula Sassoli; Barbieri, Claudio Henrique

    2013-01-01

    OBJECTIVE: To investigate the influence of low intensity laser irradiation on the regeneration of the fibular nerve of rats after crush injury. METHODS: Twenty-five rats were used, divided into three groups: 1) intact nerve, no treatment; 2) crushed nerve, no treatment; 3) crush injury, laser irradiation applied on the medullary region corresponding to the roots of the sciatic nerve and subsequently on the course of the damaged nerve. Laser irradiation was carried out for 14 consecutive days. RESULTS: Animals were evaluated by functional gait analysis with the peroneal functional index and by histomorphometric analysis using the total number of myelinated nerve fibers and their density, total number of Schwann cells, total number of blood vessels and the occupied area, minimum diameter of the fiber diameter and G-quotient. CONCLUSION: According to the statistical analysis there was no significant difference among groups and the authors conclude that low intensity laser irradiation has little or no influence on nerve regeneration and functional recovery. Laboratory investigation. PMID:24453650

  11. Gene profiling of the red light signalling pathways in roots.

    PubMed

    Molas, Maria Lia; Kiss, John Z; Correll, Melanie J

    2006-01-01

    Red light, acting through the phytochromes, controls numerous aspects of plant development. Many of the signal transduction elements downstream of the phytochromes have been identified in the aerial portions of the plant; however, very few elements in red-light signalling have been identified specifically for roots. Gene profiling studies using microarrays and quantitative Real-Time PCR were performed to characterize gene expression changes in roots of Arabidopsis seedlings exposed to 1 h of red light. Several factors acting downstream of phytochromes in red-light signalling in roots were identified. Some of the genes found to be differentially expressed in this study have already been characterized in the red-light-signalling pathway for whole plants. For example, PHYTOCHROME KINASE 1 (PKS1), LONG HYPOCOTYL 5 (HY5), EARLY FLOWERING 4 (ELF4), and GIGANTEA (GI) were all significantly up-regulated in roots of seedlings exposed to 1 h of red light. The up-regulation of SUPPRESSOR OF PHYTOCHROME A RESPONSES 1 (SPA1) and CONSTITUTIVE PHOTOMORPHOGENIC 1-like (COP1-like) genes suggests that the PHYA-mediated pathway was attenuated by red light. In addition, genes involved in lateral root and root hair formation, root plastid development, phenylpropanoid metabolism, and hormone signalling were also regulated by exposure to red light. Interestingly, members of the RPT2/NPH3 (ROOT PHOTOTROPIC 2/NON PHOTOTROPIC HYPOCOTYL 3) family, which have been shown to mediate blue-light-induced phototropism, were also differentially regulated in roots in red light. Therefore, these results suggest that red and blue light pathways interact in roots of seedlings and that many elements involved in red-light-signalling found in the aerial portions of the plant are differentially expressed in roots within 1 h of red light exposure.

  12. Nerve root degeneration and regeneration by intrathecal phenol in rats: a morphologic approach.

    PubMed

    Romero-Figueroa, Socorro; Aldrete, J Antonio; Martínez-Cruz, Angelina; Orozco, Sandra; Castillo, Sebastian; Castillo-Henkel, Carlos; Guízar-Sahagún, Gabriel

    2006-12-01

    Intrathecal injection of phenol (ITP) has been used to control intractable pain and spasticity. Direct caustic nerve damage has been postulated as the mechanism of analgesia. Sensation is commonly recovered, suggesting that a spontaneous regeneration process takes place. There is, however, a lack of mechanistic information on ITP therapy. To define morphologically the neurolysis and regeneration phenomena produced by ITP, anesthetized rats were subjected to laminectomy at L5; 5 microl of 22% phenol in saline solution or vehicle (control) was injected. Light and electron microscopy studies of nerve roots were performed at 2, 14, and 60 days after injection. Rats given ITP showed at the early stage a variable amount of roots with signs of infarction characterized by loss of axon-myelin units and thrombosis of intra-root vessels. At 14 days, abundance of macrophages removing debris, open vessels, and nerve sprouts was identified in damaged roots. At this time, non-myelinating glial fibrillary acidic protein-positive Schwann cells were observed in both damaged and apparently undamaged roots. At 60 days, abundance of 2',3'-cyclic nucleotide 3'-phosphodiesterase-positive Schwann cells myelinating newly formed axons was observed in damaged roots. Control rats did not show signs of neural or vascular pathology. Attempting to prevent thrombosis, another group of rats received heparin before ITP; these anti-coagulated rats developed radicular thrombosis, neurolysis, and hemorrhage. In conclusion, neurolysis produced by ITP is associated with acute ischemia (not prevented by heparin) and is followed by vascular, nerve, and myelin regeneration. Our results help understand the lack of efficacy of and some complications by ITP clinical therapy.

  13. Model-based Bayesian signal extraction algorithm for peripheral nerves

    NASA Astrophysics Data System (ADS)

    Eggers, Thomas E.; Dweiri, Yazan M.; McCallum, Grant A.; Durand, Dominique M.

    2017-10-01

    Objective. Multi-channel cuff electrodes have recently been investigated for extracting fascicular-level motor commands from mixed neural recordings. Such signals could provide volitional, intuitive control over a robotic prosthesis for amputee patients. Recent work has demonstrated success in extracting these signals in acute and chronic preparations using spatial filtering techniques. These extracted signals, however, had low signal-to-noise ratios and thus limited their utility to binary classification. In this work a new algorithm is proposed which combines previous source localization approaches to create a model based method which operates in real time. Approach. To validate this algorithm, a saline benchtop setup was created to allow the precise placement of artificial sources within a cuff and interference sources outside the cuff. The artificial source was taken from five seconds of chronic neural activity to replicate realistic recordings. The proposed algorithm, hybrid Bayesian signal extraction (HBSE), is then compared to previous algorithms, beamforming and a Bayesian spatial filtering method, on this test data. An example chronic neural recording is also analyzed with all three algorithms. Main results. The proposed algorithm improved the signal to noise and signal to interference ratio of extracted test signals two to three fold, as well as increased the correlation coefficient between the original and recovered signals by 10-20%. These improvements translated to the chronic recording example and increased the calculated bit rate between the recovered signals and the recorded motor activity. Significance. HBSE significantly outperforms previous algorithms in extracting realistic neural signals, even in the presence of external noise sources. These results demonstrate the feasibility of extracting dynamic motor signals from a multi-fascicled intact nerve trunk, which in turn could extract motor command signals from an amputee for the end goal of

  14. Root apex transition zone: a signalling-response nexus in the root.

    PubMed

    Baluska, Frantisek; Mancuso, Stefano; Volkmann, Dieter; Barlow, Peter W

    2010-07-01

    Longitudinal zonation, as well as a simple and regular anatomy, are hallmarks of the root apex. Here we focus on one particular root-apex zone, the transition zone, which is located between the apical meristem and basal elongation region. This zone has a unique role as the determiner of cell fate and root growth; this is accomplished by means of the complex system of a polar auxin transport circuit. The transition zone also integrates diverse inputs from endogenous (hormonal) and exogenous (sensorial) stimuli and translates them into signalling and motoric outputs as adaptive differential growth responses. These underlie the root-apex tropisms and other aspects of adaptive root behaviour.

  15. Concurrent spinal nerve root schwannoma and meningioma mimicking single-component schwannoma.

    PubMed

    Nakamizo, Akira; Suzuki, Satoshi O; Shimogawa, Takafumi; Amano, Toshiyuki; Mizoguchi, Masahiro; Yoshimoto, Koji; Sasaki, Tomio

    2012-04-01

    We present a first case of concurrent tumors consisting of schwannoma and meningioma arising at the same spinal level in a patient without neurofibromatosis. A 49-year-old man without clinical evidence of neurofibromatosis presented with a 5-month history of right neck pain. MRI demonstrated an extradural tumor involving the right-sided C2 nerve root with a small intradural component. T1- and T2-weighted and contrast-enhanced MRI could not differentiate the intradural tumor as different from the extradural tumor. Total removal of the tumors was performed. No contiguity of the extradural tumor with the intradural tumor was seen. The intradural tumor attached strongly to the dura mater around the C2 nerve root exits. Intraoperative pathological diagnosis confirmed the extradural tumor as schwannoma and the intradural tumor as meningioma. We therefore thoroughly coagulated the dura mater adjacent to the intradural tumor and resected the dura mater around the nerve root exits together with the tumor. Pathological examination revealed that the resection edge of the extradural component consisted of a spinal nerve with thickened epineurium and was free of neoplastic cells. No schwannoma component was evident in the intradural tumor. No obvious transition thus existed between the extra- and intradural tumors. Distinguishing these tumors prior to surgery is critical for determining an optimal surgical plan, as schwannoma and meningioma require different surgical procedures. We therefore recommend a careful review of preoperative imaging with the possibility of concurrent tumors in mind. © 2011 Japanese Society of Neuropathology.

  16. Microstructural changes in compressed nerve roots treated by percutaneous transforaminal endoscopic discectomy in patients with lumbar disc herniation

    PubMed Central

    Wu, Weifei; Liang, Jie; Chen, Ying; Chen, Aihua; Wu, Bin; Yang, Zong

    2016-01-01

    Abstract To investigate the microstructural changes in compressed nerves using diffusion tensor imaging (DTI) of herniated disc treated with percutaneous transforaminal endoscopic discectomy. Diffusion tensor imaging has been widely used to visualize peripheral nerves, and the microstructure of compressed nerve roots can be assessed using DTI. However, the microstructural changes after surgery are not well-understood in patients with lumbar disc herniation. Thirty-four consecutive patients with foraminal disc herniation affecting unilateral sacral 1 (S1) nerve roots were enrolled in this study. DTI with tractography was performed on S1 nerve roots before and after surgery. The mean fractional anisotropy (FA) and apparent diffusion coefficient values were calculated from tractography images. In compressed nerve roots, the FA value before surgery was significantly lower than that after surgery (P = 0.000). A significant difference in FA values was found between the compressed and normal sides before surgery (P = 0.000). However, no significant difference was found between the compressed and normal sides after surgery (P = 0.057). A significant difference in apparent diffusion coefficient values was found before and after surgery at the compressed side (P = 0.023). However, no significant difference was found between the compressed and normal sides after surgery (P = 0.203). We show that the diffusion parameters of compressed nerve roots were not significantly different before and after percutaneous transforaminal endoscopic discectomy, indicating that the microstructure of the nerve root recovered after surgery. PMID:27749591

  17. Effects of peripheral nerve injury on parvalbumin expression in adult rat dorsal root ganglion neurons.

    PubMed

    Medici, Tom; Shortland, Peter J

    2015-12-16

    Parvalbumin (PV) is a calcium binding protein that identifies a subpopulation of proprioceptive dorsal root ganglion (DRG) neurons. Calcitonin gene-related peptide (CGRP) is also expressed in a high proportion of muscle afferents but its relationship to PV is unclear. Little is known of the phenotypic responses of muscle afferents to nerve injury. Sciatic nerve axotomy or L5 spinal nerve ligation and section (SNL) lesions were used to explore these issues in adult rats using immunocytochemistry. In naive animals, the mean PV expression was 25 % of L4 or L5 dorsal root ganglion (DRG) neurons, and this was unchanged 2 weeks after sciatic nerve axotomy. Colocalization studies with the injury marker activating transcription factor 3 (ATF3) showed that approximately 24 % of PV neurons expressed ATF3 after sciatic nerve axotomy suggesting that PV may show a phenotypic switch from injured to uninjured neurons. This possibility was further assessed using the spinal nerve ligation (SNL) injury model where injured and uninjured neurons are located in different DRGs. Two weeks after L5 SNL there was no change in total PV staining and essentially all L5 PV neurons expressed ATF3. Additionally, there was no increase in PV-ir in the adjacent uninjured L4 DRG cells. Co-labelling of DRG neurons revealed that less than 2 % of PV neurons normally expressed CGRP and no colocalization was seen after injury. These experiments clearly show that axotomy does not produce down regulation of PV protein in the DRG. Moreover, this lack of change is not due to a phenotypic switch in PV immunoreactive (ir) neurons, or de novo expression of PV-ir in uninjured neurons after nerve injury. These results further illustrate differences that occur when muscle afferents are injured as compared to cutaneous afferents.

  18. Intracerebroventricular administration of nerve growth factor induces gliogenesis in sensory ganglia, dorsal root, and within the dorsal root entry zone.

    PubMed

    Schlachetzki, Johannes C M; Pizzo, Donald P; Morrissette, Debbi A; Winkler, Jürgen

    2014-01-01

    Previous studies indicated that intracerebroventricular administration of nerve growth factor (NGF) leads to massive Schwann cell hyperplasia surrounding the medulla oblongata and spinal cord. This study was designed to characterize the proliferation of peripheral glial cells, that is, Schwann and satellite cells, in the trigeminal ganglia and dorsal root ganglia (DRG) of adult rats during two weeks of NGF infusion using bromodeoxyuridine (BrdU) to label dividing cells. The trigeminal ganglia as well as the cervical and lumbar DRG were analyzed. Along the entire neuraxis a small number of dividing cells were observed within these regions under physiological condition. NGF infusion has dramatically increased the generation of new cells in the neuronal soma and axonal compartments of sensory ganglia and along the dorsal root and the dorsal root entry zone. Quantification of BrdU positive cells within sensory ganglia revealed a 2.3- to 3-fold increase in glial cells compared to controls with a similar response to NGF for the different peripheral ganglia examined. Immunofluorescent labeling with S100β revealed that Schwann and satellite cells underwent mitosis after NGF administration. These data indicate that intracerebroventricular NGF infusion significantly induces gliogenesis in trigeminal ganglia and the spinal sensory ganglia and along the dorsal root entry zone as well as the dorsal root.

  19. [Electrostimulation of the anterior sacral nerve roots. An International Congress--Le Mans--24-25 November 1989].

    PubMed

    Colombel, P; Egon, G

    1991-01-01

    Electrostimulation of the anterior sacral nerve roots in patients with spinal injuries according to the technique described by G. S. Brindley was the subject of an International conference held in Le Mans on 24th and 25th November, 1989. The equipment is now perfectly reliable and the technique has been well defined. Section of the posterior nerve roots increases bladder capacity and promotes continence. Stimulation of the anterior nerve roots contributes to correct bladder emptying. Two other benefits can be expected: improved defecation and erection. Complications are uncommon, but this technique must be reserved for failures of rehabilitation and uroneuropharmacoloical techniques.

  20. Calcium-Mediated Abiotic Stress Signaling in Roots

    PubMed Central

    Wilkins, Katie A.; Matthus, Elsa; Swarbreck, Stéphanie M.; Davies, Julia M.

    2016-01-01

    Roots are subjected to a range of abiotic stresses as they forage for water and nutrients. Cytosolic free calcium is a common second messenger in the signaling of abiotic stress. In addition, roots take up calcium both as a nutrient and to stimulate exocytosis in growth. For calcium to fulfill its multiple roles must require strict spatio-temporal regulation of its uptake and efflux across the plasma membrane, its buffering in the cytosol and its sequestration or release from internal stores. This prompts the question of how specificity of signaling output can be achieved against the background of calcium’s other uses. Threats to agriculture such as salinity, water availability and hypoxia are signaled through calcium. Nutrient deficiency is also emerging as a stress that is signaled through cytosolic free calcium, with progress in potassium, nitrate and boron deficiency signaling now being made. Heavy metals have the capacity to trigger or modulate root calcium signaling depending on their dose and their capacity to catalyze production of hydroxyl radicals. Mechanical stress and cold stress can both trigger an increase in root cytosolic free calcium, with the possibility of membrane deformation playing a part in initiating the calcium signal. This review addresses progress in identifying the calcium transporting proteins (particularly channels such as annexins and cyclic nucleotide-gated channels) that effect stress-induced calcium increases in roots and explores links to reactive oxygen species, lipid signaling, and the unfolded protein response. PMID:27621742

  1. Anatomical evidence for the absence of a morphologically distinct cranial root of the accessory nerve in man.

    PubMed

    Lachman, Nirusha; Acland, Robert D; Rosse, Cornelius

    2002-01-01

    The accessory nerve is conventionally described as having a cranial and spinal root. According to standard descriptions the cranial root (or part) is formed by rootlets that emerge from the medulla between the olive and the inferior cerebellar peduncle. These rootlets are considered to join the spinal root, travel with it briefly, then separate within the jugular foramen to become part of the vagus nerve. In 15 fresh specimens we exposed the posterior cranial fossa with a coronal cut through the foramen magnum and explored the course of each posterior medullary rootlet (PMR) arising from within the retro-olivary groove. We chose the caudal end of the olive as the landmark for the caudal end of the medulla. In all specimens every PMR that did not contribute to the glossopharyngeal nerve joined the vagus nerve at the jugular foramen. The distance between the caudal limit of the olive and the origin of the most caudal PMR that contributed to the vagus nerve ranged from 1-21 mm (mean = 8.8 mm). All rootlets that joined the accessory nerve arose caudal to the olive. The distance from the caudal limit of the olive and the most rostral accessory rootlet ranged from 1-15 mm (mean = 5.4 mm). We were unable to demonstrate any connection between the accessory and vagus nerves within the jugular foramen. Our findings indicate that the accessory nerve has no cranial root; it consists only of the structure hitherto referred to as its spinal root.

  2. Diffusion-tensor imaging of small nerve bundles: cranial nerves, peripheral nerves, distal spinal cord, and lumbar nerve roots--clinical applications.

    PubMed

    Cauley, Keith A; Filippi, Christopher G

    2013-08-01

    The purpose of this article is to review recent advances in diffusion-tensor imaging (DTI) and tractography of the cranial and peripheral nerves. Advances in MR data acquisition and postprocessing methods are permitting high-resolution DTI of the cranial and peripheral nerves in the clinical setting. DTI offers information beyond routine clinical MRI, and DTI findings have implications for the diagnosis and treatment of nerve disease.

  3. A Whitacre-type spinal needle does not prevent intravascular injection during cervical nerve root injections.

    PubMed

    Candido, Kenneth D; Ghaly, Ramsis F; Mackerley, Sara; Knezevic, Nebojsa Nick

    2010-07-01

    We present a case of intravascular injection in a 41-year-old female during cervical selective nerve root injection using a 22-gauge 3.5-inch Whitacre-type pencil-point subarachnoid needle with a curve placed at the distal tip positioned using continual live fluoroscopic guidance. After negative aspiration for blood and cerebrospinal fluid and no elicited paresthesias during the procedure, 1 mL of contrast was injected. Initial imaging at C6 captured the outline of the nerve root along with a significant amount of transient vascular runoff. This case report demonstrates that Whitacre-type spinal needles do not prevent vascular injection, and that aspiration of the needle is not a reliable sign of intravascular injection.

  4. Neurotoxicity of various root canal sealers on rat sciatic nerve: an electrophysiologic and histopathologic study.

    PubMed

    Tuğ Kılkış, Buket; Er, Kürşat; Taşdemir, Tamer; Yildirim, Mehmet; Taskesen, Fatih; Tümkaya, Levent; Kalkan, Yıldıray; Serper, Ahmet

    2015-11-01

    The aim of this study was to compare the neurotoxicity of various root canal sealers on rat sciatic nerve by electrophysiologic and histopathologic analyses. A total of 40 male rats were randomly divided into five groups: Control, AH Plus, GuttaFlow, Sealapex and Smartpastebio. Sciatic nerves of the rats were uncovered using the surgical procedures, and the prepared sealers were then applied on nerves with a polyethylene tube vehicle for 15 days. Nerve potentials were recorded at initial exposure, 5, 30 and 120 min (early phase), and 15 days (late phase) by an electrophysiologic analysis system for all groups. The obtained measurements were then used to calculate the nerve conduction velocities (NCV). Subsequently, all rats were sacrificed, and their sciatic nerves were removed for histopathologic analysis. Statistical analysis was performed using the Kruskal-Wallis and Mann-Whitney U tests for intergroup variables and the Friedman and Wilcoxon test for intragroup variables. Statistical significance was set at P < 0.05. There was no significant difference between early and late phase results in the control group. This group showed little or no lasting damage to nerve tissue. All sealers decreased the NCV in the early phase time periods, but this decrease was only statistically significant in the AH Plus group at 120-min time period (P < 0.0125). During the late phase, the AH Plus and GuttaFlow groups almost reached initial NCV values, and it was lower than the initial values in the Sealapex and Smartpastebio groups. However, this decrease was not statistically significant. When intergroup comparisons were performed, statistically significant differences occurred at 30 min in the Sealapex group and 120 min in the AH Plus group compared with the control group (P < 0.0125). All sealers induced neurotoxicity as a result of degenerative and inflammatory responses of nerve tissue in histologic analysis. Histologic analysis revealed Sealapex and GuttaFlow to

  5. [Nerve root compression by gas containing lumbar disc herniation--case report].

    PubMed

    Yasuoka, Hiroki; Nemoto, Osamu; Kawaguchi, Masahisa; Naitou, Satoko; Yamamoto, Kouji; Ukegawa, You

    2009-06-01

    The radiographic appearance of gas collection in the intervertebral disc represents the so-called "vacuum phenomenon." Incidence of the vacuum phenomenon on plain radiographs is reported to be 1-20%, whereas gas-containing disc herniations are rarely observed. We present a case report involving a patient with L4/5 gas-containing disc herniation, which was demonstrated by CT and MRI scans and was also surgically documented. A 48-year-old man with no previous back trauma presented with a 14-day history of left leg pain. On neurologic examination, the straight leg raising test was positive at 60degrees. Leg muscle strength was weak on the extensor hallucis longus. Sensory disturbances and abnormalities in deep-tendon reflexes were not observed. Lumbar roentogenograms showed "vacuum phenomenon" at L2/3, L4/5 and the L5/S disc space. MRI indicated a herniated disc at L4/5 displacing the dural sac and a focal low intensity in the lesion. Administration of an epidural block relieved the patient's symptoms. Ten months later, the patient reported a gradual return of similar left leg pain. His symptoms did not respond to conservative management. Lumbar spine films indicated abnormalities identical to the original results. MRI showed an enlarged area of low intensity with compression of the left L5 nerve root. In addition to recurrent pain, discography with metrizamide injections confirmed the presence of intradiscal gas and compression of the left L5 nerve root. During surgery, a gray-bluish air mass compressing the L5 nerve root was identified. Manipulation of the mass resulted in rupture and the release of gas. The displaced nerve root immediately relaxed to its normal position. Seven months after the operation, the patient remains free of pain.

  6. CNS-derived glia ensheath peripheral nerves and mediate motor root development.

    PubMed

    Kucenas, Sarah; Takada, Norio; Park, Hae-Chul; Woodruff, Elvin; Broadie, Kendal; Appel, Bruce

    2008-02-01

    Motor function requires that motor axons extend from the spinal cord at regular intervals and that they are myelinated by Schwann cells. Little attention has been given to another cellular structure, the perineurium, which ensheaths the motor nerve, forming a flexible, protective barrier. Consequently, the origin of perineurial cells and their roles in motor nerve formation are poorly understood. Using time-lapse imaging in zebrafish, we show that perineurial cells are born in the CNS, arising as ventral spinal-cord glia before migrating into the periphery. In embryos lacking perineurial glia, motor neurons inappropriately migrated outside of the spinal cord and had aberrant axonal projections, indicating that perineurial glia carry out barrier and guidance functions at motor axon exit points. Additionally, reciprocal signaling between perineurial glia and Schwann cells was necessary for motor nerve ensheathment by both cell types. These insights reveal a new class of CNS-born glia that critically contributes to motor nerve development.

  7. Diffusion-weighted magnetic resonance imaging for the diagnosis of patients with lumbar nerve root entrapment syndromes: results from a pilot study.

    PubMed

    Reinhold, Maximilian; Ederer, Christian; Henninger, Benjamin; Eberwein, Alexandra; Kremser, Christian

    2015-02-01

    Lumbar nerve root entrapment syndromes cause radicular signs and symptoms in the affected leg. The applicability of diffusion-weighted imaging (DWI) for the assessment of lower lumbar nerves (L4-S1) has been demonstrated. The purpose of this pilot study was to establish DWI reference data for the all lumbosacral nerve roots (L1-S1) in a healthy, asymptomatic study population and to determine its potential as a diagnostic tool for patients with lumbar radicular syndromes. 20 asymptomatic healthy volunteers were included (average age 39 years (24-59 years; n = 10 female, n = 10 male). The lumbosacral spine was scanned twice in a standardized fashion (1.5 T Magnetom Avanto and 3 T Magnetom Skyra, Siemens AG Healthcare, Erlangen, Germany). A spin-echo type echo-planar (SE-EPI) sequence was used to determine axial ADC maps and measurements (length, width, and angulation) of the dorsal root ganglion (DRG) and distal spinal nerves (DSN). Disc pathology, lumbar foraminal stenosis and nerve root compromise were classified. Using 3 T images 218 (91%) lumbar nerve roots had no pathologic finding [1.5 T: 226 (94%)]. All DRG and DSN could be visualized and identified on axial apparent diffusion coefficient (ADC). On average we measured ADC values of 1,231 mm(2)/s (SD 308 mm(2)/s) at the DRG for the 1.5 T scanner and 1,756 mm(2)/s (SD 465 mm(2)/s) for the 3 T scanner. There were no statistically significant gender or side differences in the 1.5 and 3 T images (p > 0.05). We noted an increase of the ADC values starting from cranial (L1: 1,444 mm(2)/s) to caudal (S1: 1,918 mm(2)/s). The average ADC value at the DSN was 1,018 mm(2)/s for the 1.5 T scanner compared to 1,589 mm(2)/s for the 3 T scanner (p < 0.001). For the first time, we have established data for the DRG and DSN in human lumbosacral spinal nerves (L1-S1), using diffusion-weighted magnetic resonance imaging techniques. 3 T ADC maps have a higher signal to noise ratio, thus offering better image quality. Results from

  8. Accuracy of cone-beam computed tomography in defining spatial relationships between third molar roots and inferior alveolar nerve

    PubMed Central

    Pippi, Roberto; Santoro, Marcello; D’Ambrosio, Ferdinando

    2016-01-01

    Objective: Cone-beam computed tomography (CBCT) has been proposed in surgical planning of lower third molar extraction. The aim of the present study was to assess the reliability of CBCT in defining third molar root morphology and its spatial relationships with the inferior alveolar nerve (IAN). Materials and Methods: Intraoperative and radiographic variables of 74 lower third molars were retrospectively analyzed. Intraoperative variables included IAN exposure, number of roots, root morphology of extracted third molars, and presence/absence of IAN impression on the root surface. Radiographic variables included presence/absence of the cortex separating IAN from the third molar roots on CBCT examination, number of roots and root morphology on both orthopantomography (OPG) and CBCT. The statistical association between variables was evaluated using the Fisher's exact test. Results: In all cases of intraoperative IAN exposure, the cortex appeared discontinuous on CBCT images. All cases, in which the cortical bone was continuous on CBCT images, showed no association with nerve exposure. In all cases in which nerve impression was identified on the root surface, the IAN cortex showed interruptions on CBCT images. No nerve impression was identified in any of the cases, in which the cortex appeared continuous on CBCT images. CBCT also highlighted accessory roots and apical anomalies/curvatures, not visible on the OPG. Conclusions: CBCT seems to provide reliable and accurate information about the third molar root morphology and its relationship with the IAN. PMID:28042257

  9. Does pain relief by CT-guided indirect cervical nerve root injection with local anesthetics and steroids predict pain relief after decompression surgery for cervical nerve root compression?

    PubMed

    Antoniadis, Alexander; Dietrich, Tobias J; Farshad, Mazda

    2016-10-01

    The relationship of pain relief from a recently presented CT-guided indirect cervical nerve root injection with local anesthetics and steroids to surgical decompression as a treatment for single-level cervical radiculopathy is not clear. This retrospective study aimed to compare the immediate and 6-week post-injection effects to the short- and long-term outcomes after surgical decompression, specifically in regard to pain relief. Patients (n = 39, age 47 ± 10 years) who had undergone CT-guided indirect injection with local anesthetics and steroids as an initial treatment for single cervical nerve root radiculopathy and who subsequently needed surgical decompression were included retrospectively. Pain levels (VAS scores) were monitored before, immediately after, and 6 weeks after injection (n = 34), as well as 6 weeks (n = 38) and a mean of 25 months (SD ± 12) after surgical decompression (n = 36). Correlation analysis was performed to find potential associations of pain relief after injection and after surgery to investigate the predictive value of post-injection pain relief. There was no correlation between immediate pain relief after injection (-32 ± 27 %) and 6 weeks later (-7 ± 19 %), (r = -0.023, p = 0.900). There was an association by tendency between immediate pain relief after injection and post-surgical pain relief at 6 weeks (-82 ± 27 %), (r = 0.28, p = 0.08). Pain relief at follow-up remained high at -70 ± 21 % and was correlated with the immediate pain amelioration effect of the injection (r = 0.37, p = 0.032). Five out of seven patients who reported no pain relief from injection had a pain relief from surgery in excess of 50 %. The amount of immediate radiculopathic pain relief after indirect cervical nerve root injection is associated with the amount of pain relief achieved at long-term follow-up after surgical decompression of single-level cervical radiculopathy

  10. GDNF-treated acellular nerve graft promotes motoneuron axon regeneration after implantation into cervical root avulsed spinal cord.

    PubMed

    Chu, T-H; Wang, L; Guo, A; Chan, V W-K; Wong, C W-M; Wu, W

    2012-12-01

    It is well known that glial cell line-derived neurotrophic factor (GDNF) is a potent neurotrophic factor for motoneurons. We have previously shown that it greatly enhanced motoneuron survival and axon regeneration after implantation of peripheral nerve graft following spinal root avulsion. In the current study, we explore whether injection of GDNF promotes axon regeneration in decellularized nerve induced by repeated freeze-thaw cycles. We injected saline or GDNF into the decellularized nerve after root avulsion in adult Sprague-Dawley rats and assessed motoneuron axon regeneration and Schwann cell migration by retrograde labelling and immunohistochemistry. We found that no axons were present in saline-treated acellular nerve whereas Schwann cells migrated into GDNF-treated acellular nerve grafts. We also found that Schwann cells migrated into the nerve grafts as early as 4 days after implantation, coinciding with the first appearance of regenerating axons in the grafts. Application of GDNF outside the graft did not induce Schwann cell infiltration nor axon regeneration into the graft. Application of pleiotrophin, a trophic factor which promotes axon regeneration but not Schwann cell migration, did not promote axon infiltration into acellular nerve graft. We conclude that GDNF induced Schwann cell migration and axon regeneration into the acellular nerve graft. Our findings can be of potential clinical value to develop acellular nerve grafting for use in spinal root avulsion injuries. © 2012 The Authors. Neuropathology and Applied Neurobiology © 2012 British Neuropathological Society.

  11. Volatile signalling by sesquiterpenes from ectomycorrhizal fungi reprogrammes root architecture

    PubMed Central

    Ditengou, Franck A.; Müller, Anna; Rosenkranz, Maaria; Felten, Judith; Lasok, Hanna; van Doorn, Maja Miloradovic; Legué, Valerie; Palme, Klaus; Schnitzler, Jörg-Peter; Polle, Andrea

    2015-01-01

    The mutualistic association of roots with ectomycorrhizal fungi promotes plant health and is a hallmark of boreal and temperate forests worldwide. In the pre-colonization phase, before direct contact, lateral root (LR) production is massively stimulated, yet little is known about the signals exchanged during this step. Here, we identify sesquiterpenes (SQTs) as biologically active agents emitted by Laccaria bicolor while interacting with Populus or Arabidopsis. We show that inhibition of fungal SQT production by lovastatin strongly reduces LR proliferation and that (–)-thujopsene, a low-abundance SQT, is sufficient to stimulate LR formation in the absence of the fungus. Further, we show that the ectomycorrhizal ascomycote, Cenococcum geophilum, which cannot synthesize SQTs, does not promote LRs. We propose that the LR-promoting SQT signal creates a win-win situation by enhancing the root surface area for plant nutrient uptake and by improving fungal access to plant-derived carbon via root exudates. PMID:25703994

  12. Rapid identification of anterior and posterior root of cauda equina nerves by near-infrared diffuse reflectance spectroscopy.

    PubMed

    Xie, Shaofei; Xiang, Bingren; Bu, Shoushan; Cao, Xiaojian; Ye, Ye; Lu, Jun; Deng, Haishan

    2009-01-01

    A new rapid chemometric method has been developed to identify the anterior and posterior roots of cauda equina nerves by near-infrared (NIR) diffuse reflectance spectroscopy. NIR spectra of nerves were measured using a Fourier transform NIR spectrometer equipped with a fiber-optic probe. The result revealed no observable difference in the spectra between the anterior and posterior root samples, but the two roots could be identified by cluster analysis based on the differences of their spectral features. The overall accuracy of the cluster analysis model was 87.5%, and the accuracy for the actual anterior root and actual posterior root were 95% and 80%, respectively. The result suggested that NIR spectroscopy in combination with the chemometrics method (cluster analysis) could be used to classify the anterior and posterior roots of cauda equina nerves. The proposed method required only a few minutes, while classical methods commonly required at least one hour. It was demonstrated that the new method could provide a rapid, correct, nondestructive and low-cost potential means to quickly differentiate anterior and posterior roots in mixed cauda equina nerves, which would be helpful for surgeons to align nerve stumps correctly.

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

    PubMed

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

    2014-12-01

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

  14. Comparison with Magnetic Resonance Three-Dimensional Sequence for Lumbar Nerve Root with Intervertebral Foramen

    PubMed Central

    Takashima, Hiroyuki; Shishido, Hiroki; Yoshimoto, Mitsunori; Imamura, Rui; Akatsuka, Yoshihiro; Terashima, Yoshinori; Fujiwara, Hiroyoshi; Nagae, Masateru; Kubo, Toshikazu; Yamashita, Toshihiko

    2016-01-01

    Study Design Prospective study based on magnetic resonance (MR) imaging of the lumbar spinal root of the intervertebral foramen. Purpose This study was to compare MR three-dimensional (3D) sequences for the evaluation of the lumbar spinal root of the intervertebral foramen. Overview of Literature The diagnosis of spinal disorders by MR imaging is commonly performed using two-dimensional T1- and T2-weighted images, whereas 3D MR images can be used for acquiring further detailed data using thin slices with multi-planar reconstruction. Methods On twenty healthy volunteers, we investigated the contrast-to-noise ratio (CNR) of the lumbar spinal root of the intervertebral foramen with a 3D balanced sequence. The sequences used were the fast imaging employing steady state acquisition and the coherent oscillatory state acquisition for the manipulation of image contrast (COSMIC). COSMIC can be used with or without fat suppression (FS). We compared these sequence to determine the optimized visualization sequence for the lumbar spinal root of the intervertebral foramen. Results For the CNR between the nerve root and the peripheral tissue, these were no significant differences between the sequences at the entry of foramen. There was a significant difference and the highest CNR was seen with COSMIC-FS for the intra- and extra-foramen. Conclusions In this study, the findings suggest that the COSMIC-FS sequences should be used for the internal or external foramen for spinal root disorders. PMID:26949459

  15. Impaired endolysosomal function disrupts Notch signaling in optic nerve astrocytes

    PubMed Central

    Valapala, Mallika; Hose, Stacey; Gongora, Celine; Dong, Lijin; Wawrousek, Eric F.; Zigler, J. Samuel; Sinha, Debasish

    2013-01-01

    Astrocytes migrate from the optic nerve into the inner retina, forming a template upon which retinal vessels develop. In the Nuc1 rat, mutation in the gene encoding βA3/A1-crystallin disrupts both Notch signaling in astrocytes and formation of the astrocyte template. Here we show that loss of βA3/A1-crystallin in astrocytes does not impede Notch ligand binding or extracellular cleavages. However, it affects V-ATPase activity, thereby compromising acidification of the endolysosomal compartments, leading to reduced γ-secretase-mediated processing and release of the Notch intracellular domain (NICD). Lysosomal-mediated degradation of Notch is also impaired. These defects decrease the level of NICD in the nucleus, inhibiting expression of Notch target genes. Overexpression of βA3/A1-crystallin in those same astrocytes restored V-ATPase activity and normal endolysosomal acidification, thereby increasing the levels of γ-secretase to facilitate optimal Notch signaling. We postulate that βA3/A1-crystallin is essential for normal endolysosomal acidification, and thereby, normal activation of Notch signaling in astrocytes. PMID:23535650

  16. Correlation between muscular and nerve signals responsible for hand grasping in non-human primates.

    PubMed

    Sheshadri, Swathi; Kortelainen, Jukka; Nag, Sudip; Ng, Kian Ann; Bazley, Faith A; Michoud, Frederic; Patil, Anoop; Orellana, Josue; Libedinsky, Camilo; Lahiri, Amitabha; Chan, Louiza; Chng, Keefe; Cutrone, Annarita; Bossi, Silvia; Thakor, Nitish V; Delgado-Martinez, Ignacio; Yen, Shih-Cheng

    2014-01-01

    Neuroprosthetic devices that interface with the nervous system to restore functional motor activity offer a viable alternative to nerve regeneration, especially in proximal nerve injuries like brachial plexus injuries where muscle atrophy may set in before nerve re-innervation occurs. Prior studies have used control signals from muscle or cortical activity. However, nerve signals are preferred in many cases since they permit more natural and precise control when compared to muscle activity, and can be accessed with much lower risk than cortical activity. Identification of nerve signals that control the appropriate muscles is essential for the development of such a `bionic link'. Here we examine the correlation between muscle and nerve signals responsible for hand grasping in the M. fascicularis. Simultaneous recordings were performed using a 4-channel thin-film longitudinal intra-fascicular electrode (tf-LIFE) and 9 bipolar endomysial muscle electrodes while the animal performed grasping movements. We were able to identify a high degree of correlation (r > 0.6) between nerve signals from the median nerve and movement-dependent muscle activity from the flexor muscles of the forearm, with a delay that corresponded to 25 m/s nerve conduction velocity. The phase of the flexion could be identified using a wavelet approximation of the ENG. This result confirms this approach for a future neuroprosthetic device for the treatment of peripheral nerve injuries.

  17. Pulsed electrical stimulation protects neurons in the dorsal root and anterior horn of the spinal cord after peripheral nerve injury.

    PubMed

    Pei, Bao-An; Zi, Jin-Hua; Wu, Li-Sheng; Zhang, Cun-Hua; Chen, Yun-Zhen

    2015-10-01

    Most studies on peripheral nerve injury have focused on repair at the site of injury, but very few have examined the effects of repair strategies on the more proximal neuronal cell bodies. In this study, an approximately 10-mm-long nerve segment from the ischial tuberosity in the rat was transected and its proximal and distal ends were inverted and sutured. The spinal cord was subjected to pulsed electrical stimulation at T10 and L3, at a current of 6.5 mA and a stimulation frequency of 15 Hz, 15 minutes per session, twice a day for 56 days. After pulsed electrical stimulation, the number of neurons in the dorsal root ganglion and anterior horn was increased in rats with sciatic nerve injury. The number of myelinated nerve fibers was increased in the sciatic nerve. The ultrastructure of neurons in the dorsal root ganglion and spinal cord was noticeably improved. Conduction velocity of the sciatic nerve was also increased. These results show that pulsed electrical stimulation protects sensory neurons in the dorsal root ganglia as well as motor neurons in the anterior horn of the spinal cord after peripheral nerve injury, and that it promotes the regeneration of peripheral nerve fibers.

  18. Pulsed electrical stimulation protects neurons in the dorsal root and anterior horn of the spinal cord after peripheral nerve injury

    PubMed Central

    Pei, Bao-an; Zi, Jin-hua; Wu, Li-sheng; Zhang, Cun-hua; Chen, Yun-zhen

    2015-01-01

    Most studies on peripheral nerve injury have focused on repair at the site of injury, but very few have examined the effects of repair strategies on the more proximal neuronal cell bodies. In this study, an approximately 10-mm-long nerve segment from the ischial tuberosity in the rat was transected and its proximal and distal ends were inverted and sutured. The spinal cord was subjected to pulsed electrical stimulation at T10 and L3, at a current of 6.5 mA and a stimulation frequency of 15 Hz, 15 minutes per session, twice a day for 56 days. After pulsed electrical stimulation, the number of neurons in the dorsal root ganglion and anterior horn was increased in rats with sciatic nerve injury. The number of myelinated nerve fibers was increased in the sciatic nerve. The ultrastructure of neurons in the dorsal root ganglion and spinal cord was noticeably improved. Conduction velocity of the sciatic nerve was also increased. These results show that pulsed electrical stimulation protects sensory neurons in the dorsal root ganglia as well as motor neurons in the anterior horn of the spinal cord after peripheral nerve injury, and that it promotes the regeneration of peripheral nerve fibers. PMID:26692864

  19. Experimental studies on the effect of chymopapain on nerve root compression caused by intervertebral disk material.

    PubMed

    Krempen, J F; Minnig, D I; Smith, B S

    1975-01-01

    Chymopapain degrades the nucleus pulposus portion of the intervertebral disk of rabbits. The degradation is not grossly visible until 15 days post-injection. Depolymerization of the chondromucoprotein and decreases in the ability of a disk to imbibe fluid, is, in effect, a "chemical decompression" of the nucleur pulposus. The enzyme must come into direct contact with the chondromucoprotein complex of the disk material, and to a significant extent also must reach the area of disk material adjacent to the herniated annulus. Rapid depolymerization of the chondromucoprotein complex on a biomechanical level, and "decompression" of disk material on a biomechanical level can be correlated with relief of pain in all types of disk herniation in human beings. A primary biochemical change in the disk material would lead to a secondary decrease in inflammation if the change led to a "decompression" of the chondromucoprotein. Since the primary effect of chymopapain is on the chondromucoprotein of the disk, beneficial results would not be expected if nerve root compression is due to bony impingement or scar tissue following previous surgery. Chymopapain did not seem to possess any anti-inflammatory properties when bone was used as an irritant under a nerve root. However, this was technically difficult to evaluate and the possibility that chymopapain may also interfere with a chemical mediator of pain or interfere directly with an inflammatory reaction secondary to root compression can not be excluded.

  20. Microvascular decompression of trigeminal nerve root for treatment of a patient with hemimasticatory spasm.

    PubMed

    Dou, Ning-Ning; Zhong, Jun; Zhou, Qiu-Meng; Zhu, Jin; Wang, Yong-Nan; Li, Shi-Ting

    2014-05-01

    Hemimasticatory spasm is a rare disease; with little knowledge of the pathogenesis, it has still been intractable today. We presented a 56-year-old woman with involuntary painful spasm in her left masseter muscle for 11 years. The patient was successfully treated with microvascular decompression surgery. An offending superior cerebellar artery was found to contact with the motor branch of the trigeminal nerve root, which was then removed away and pieces of soft wadding were interposed between the nerve and the vessel to assure the separation. Postoperatively, the symptom totally disappeared and no recurrence was observed during the 7 months' follow-up. The treatment as well as the pathogenesis of the disease was reviewed, and we put forward a new hypothesis.

  1. Gas-containing disc herniations: dual nerve root compression at a single disc level.

    PubMed

    Ryu, Kyeong-Sik; Rathi, Nitesh Kumar; Shin, Myung-Hoon; Park, Chun-Kun

    2012-01-01

    A 72-year-old man presented with gas-containing disc herniations resulting in dual nerve root (exiting and traversing root) compression at the single level manifesting as lower back pain with the right anterolateral thigh and medial calf pain and no response to 4 weeks of conservative treatment. Physical examination revealed positive Lasegue's sign at 40°, but the patient had no evidence of neurological deficit. Magnetic resonance imaging showed two separate disc herniations, a posterocentral herniated disc that had migrated inferiorly at the L3-4 level and compressed the L4 traversing root, and another that had compressed the L3 exiting root in the extraforaminal area at the same level. Coronal computed tomography demonstrated the presence of gas in the spinal canal and extraforaminal area at the L3-4 level, and the vacuum phenomenon was also noted at the L3-4 intervertebral disc. Microscopic discectomy was performed using midline and paramedian approaches, and the presence of gas was confirmed by bubbles after pouring saline into the area intraoperatively. Histological examination revealed fibrous tissue. The patient was discharged with complete relief of pain. This is a rare case of symptomatic gas-containing disc herniations causing dual compression of exiting and traversing roots at a single disc level.

  2. TNFa/TNFR2 signaling is required for glial ensheathment at the dorsal root entry zone.

    PubMed

    Smith, Cody J; Wheeler, Michael A; Marjoram, Lindsay; Bagnat, Michel; Deppmann, Christopher D; Kucenas, Sarah

    2017-04-05

    Somatosensory information from the periphery is routed to the spinal cord through centrally-projecting sensory axons that cross into the central nervous system (CNS) via the dorsal root entry zone (DREZ). The glial cells that ensheath these axons ensure rapid propagation of this information. Despite the importance of this glial-axon arrangement, how this afferent nerve is assembled during development is unknown. Using in vivo, time-lapse imaging we show that as centrally-projecting pioneer axons from dorsal root ganglia (DRG) enter the spinal cord, they initiate expression of the cytokine TNFalpha. This induction coincides with ensheathment of these axons by associated glia via a TNF receptor 2 (TNFR2)-mediated process. This work identifies a signaling cascade that mediates peripheral glial-axon interactions and it functions to ensure that DRG afferent projections are ensheathed after pioneer axons complete their navigation, which promotes efficient somatosensory neural function.

  3. TNFa/TNFR2 signaling is required for glial ensheathment at the dorsal root entry zone

    PubMed Central

    Smith, Cody J.; Bagnat, Michel; Deppmann, Christopher D.

    2017-01-01

    Somatosensory information from the periphery is routed to the spinal cord through centrally-projecting sensory axons that cross into the central nervous system (CNS) via the dorsal root entry zone (DREZ). The glial cells that ensheath these axons ensure rapid propagation of this information. Despite the importance of this glial-axon arrangement, how this afferent nerve is assembled during development is unknown. Using in vivo, time-lapse imaging we show that as centrally-projecting pioneer axons from dorsal root ganglia (DRG) enter the spinal cord, they initiate expression of the cytokine TNFalpha. This induction coincides with ensheathment of these axons by associated glia via a TNF receptor 2 (TNFR2)-mediated process. This work identifies a signaling cascade that mediates peripheral glial-axon interactions and it functions to ensure that DRG afferent projections are ensheathed after pioneer axons complete their navigation, which promotes efficient somatosensory neural function. PMID:28379965

  4. [Acupuncture combined with moxibustion plaster for nerve-root type cervical spondylosis].

    PubMed

    Liu, Li-an; Zhang, Shu; Wang, Hajying; Tang Lixin

    2016-02-01

    To compare the clinical efficacy differences between acupuncture combined with moxi-bustion plaster and electroacupuncture (EA) for nerve-root type cervical spondylosis. A total of 60 casesof nerve-root type cervical spondylosis were randomly divided into a plaster group and an EA group, 30 cases ineach one. Patients in the plaster group were treated with regular acupuncture at Jiaji(EX-B 2) points and ashipoints, combined with moxibustion plaster at Gaohuang (BL 43); patients in the EA group were treated with EAat identical acupoints as plaster group. The treatment was given once a day, and 5 days were taken as one course;there was an interval of 2 days between courses and totally 2 courses were performed. The pain questionnaires andquantitative score of signs and symptoms were observed before and after treatment in the two groups. The clinicalefficacy of the two groups was compared. The total effective rate was 96. 7% (29/30) in the plastergroup, which was not significantly different from 93. 3% (28/30) in the EA group (P>0. 05). After treatment,PRI, VAS and PPI were all reduced in the two groups (all Pnerve-root type cervical spondylosis; EA issuperior to acupuncture combined with moxibustion plaster on relieving pain, while acupuncture combined withmoxibustion plaster is superior to EA on improving life quality, muscle strength and feeling.

  5. MicroRNA Signatures of Drought Signaling in Rice Root

    PubMed Central

    Nikpay, Nava; Ebrahimi, Mohammad Ali; Bihamta, Mohammad Reza; Mardi, Mohsen; Salekdeh, Ghasem Hosseini

    2016-01-01

    Background Drought stress is one of the most important abiotic stresses and the main constraint to rice agriculture. MicroRNA-mediated post-transcriptional gene regulation is one of the ways to establish drought stress tolerance in plants. MiRNAs are 20–24-nt regulatory RNAs that play an important role in regulating plant gene expression upon exposure to biotic and abiotic stresses. Methodology/Principal Findings In this study, we applied a partial root drying system as well as a complete root drying system to identify miRNAs involved in conditions of drought stress, drought signaling and wet signaling using high-throughput sequencing. To this end, we produced four small RNA libraries: (1) fully-watered (WW), (2) fully-droughted (WD), and split-root systems where (3) one-half was well watered (SpWW) and (4) the other half was water-deprived (SpWD). Our analysis revealed 10,671 and 783 unique known and novel miRNA reads in all libraries, respectively. We identified, 65 (52 known + 13 novel), 72 (61 known + 11 novel) and 51 (38 known + 13 novel) miRNAs that showed differential expression under conditions of drought stress, drought signaling and wet signaling, respectively. The results of quantitative real-time PCR showed expression patterns similar to the high-throughput sequencing results. Furthermore, our target prediction led to the identification of 244, 341 and 239 unique target genes for drought-stress-, drought-signaling- and wet-signaling-responsive miRNAs, respectively. Conclusions/Significance Our results suggest that miRNAs that are responsive under different conditions could play different roles in the regulation of abscisic acid signaling, calcium signaling, detoxification and lateral root formation. PMID:27276090

  6. Cranial Nerve Development Requires Co-Ordinated Shh and Canonical Wnt Signaling

    PubMed Central

    Kurosaka, Hiroshi; Trainor, Paul A.; Leroux-Berger, Margot; Iulianella, Angelo

    2015-01-01

    Cranial nerves govern sensory and motor information exchange between the brain and tissues of the head and neck. The cranial nerves are derived from two specialized populations of cells, cranial neural crest cells and ectodermal placode cells. Defects in either cell type can result in cranial nerve developmental defects. Although several signaling pathways are known to regulate cranial nerve formation our understanding of how intercellular signaling between neural crest cells and placode cells is coordinated during cranial ganglia morphogenesis is poorly understood. Sonic Hedgehog (Shh) signaling is one key pathway that regulates multiple aspects of craniofacial development, but whether it co-ordinates cranial neural crest cell and placodal cell interactions during cranial ganglia formation remains unclear. In this study we examined a new Patched1 (Ptch1) loss-of-function mouse mutant and characterized the role of Ptch1 in regulating Shh signaling during cranial ganglia development. Ptch1Wig/ Wig mutants exhibit elevated Shh signaling in concert with disorganization of the trigeminal and facial nerves. Importantly, we discovered that enhanced Shh signaling suppressed canonical Wnt signaling in the cranial nerve region. This critically affected the survival and migration of cranial neural crest cells and the development of placodal cells as well as the integration between neural crest and placodes. Collectively, our findings highlight a novel and critical role for Shh signaling in cranial nerve development via the cross regulation of canonical Wnt signaling. PMID:25799573

  7. [Lumbar nerve root pain with fever in tropical area: posterior spinal tuberculosis].

    PubMed

    Ouédraogo, D D; Daboiko, J C; Eti, E; Ouali, B; Ouattara, B; Gbané, M; Gbazi, C; Kouakou, N M

    2008-12-01

    The purpose of this report is to describe the case of tuberculosis osteitis of the posterior vertebral arch in a 35-year-old man with recent history of pulmonary tuberculosis. Clinical findings were pain due to bilateral inflammation of the lumbar nerve roots, fistulised cold abcess and motor deficit in both lower extremities. The tomodensitometry demonstrated a lytic bone lesion involving the spinous process of the second lumbar vertebra in association with spondylitis and a large paravertebral abscess with calcification typical of tuberculosis. Cure was achieved by a single 12-month course of appropriate treatment.

  8. Sector computed tomographic spine scanning in the diagnosis of lumbar nerve root entrapment

    SciTech Connect

    Risius, B.; Modic, M.T.; Hardy, R.W. Jr.; Duchesneau, P.M.; Weinstein, M.A.

    1982-04-01

    The diagnosis of lumbar nerve root entrapment was made by sector computed tomography (CT) scanning in 25 patients whose myelograms were normal at the site of the CT scan abnormalities. Sector CT scanning demonstrates preoperatively which neural foramina are narrow. This information, correlated with the patient's history and physical examination, indicates which foramina should be operated on and prevents unnecessary exploration of normal neutral foramina. CT findings were confirmed surgically in 14 patients. Eleven of these 14 patients had excellent postoperative results and remain pain free.

  9. Dorsal root ganglion myeloid zinc finger protein 1 contributes to neuropathic pain after peripheral nerve trauma.

    PubMed

    Li, Zhisong; Gu, Xiyao; Sun, Linlin; Wu, Shaogen; Liang, Lingli; Cao, Jing; Lutz, Brianna Marie; Bekker, Alex; Zhang, Wei; Tao, Yuan-Xiang

    2015-04-01

    Peripheral nerve injury-induced changes in gene transcription and translation in primary sensory neurons of the dorsal root ganglion (DRG) are considered to contribute to neuropathic pain genesis. Transcription factors control gene expression. Peripheral nerve injury increases the expression of myeloid zinc finger protein 1 (MZF1), a transcription factor, and promotes its binding to the voltage-gated potassium 1.2 (Kv1.2) antisense (AS) RNA gene in the injured DRG. However, whether DRG MZF1 participates in neuropathic pain is still unknown. Here, we report that blocking the nerve injury-induced increase of DRG MZF1 through microinjection of MZF1 siRNA into the injured DRG attenuated the initiation and maintenance of mechanical, cold, and thermal pain hypersensitivities in rats with chronic constriction injury (CCI) of the sciatic nerve, without affecting locomotor functions and basal responses to acute mechanical, heat, and cold stimuli. Mimicking the nerve injury-induced increase of DRG MZF1 through microinjection of recombinant adeno-associated virus 5 expressing full-length MZF1 into the DRG produced significant mechanical, cold, and thermal pain hypersensitivities in naive rats. Mechanistically, MZF1 participated in CCI-induced reductions in Kv1.2 mRNA and protein and total Kv current and the CCI-induced increase in neuronal excitability through MZF1-triggered Kv1.2 AS RNA expression in the injured DRG neurons. MZF1 is likely an endogenous trigger of neuropathic pain and might serve as a potential target for preventing and treating this disorder.

  10. A hydraulic signal in root-to-shoot signalling of water shortage.

    PubMed

    Christmann, Alexander; Weiler, Elmar W; Steudle, Ernst; Grill, Erwin

    2007-10-01

    Photosynthesis and biomass production of plants are controlled by the water status of the soil. Upon soil drying, plants can reduce water consumption by minimizing transpiration through stomata, the closable pores of the leaf. The phytohormone abscisic acid (ABA) mediates stomatal closure, and is the assigned signal for communicating water deficit from the root to the shoot. However, our study does not support ABA as the proposed long-distance signal. The shoot response to limited soil water supply is not affected by the capacity to generate ABA in the root; however, the response does require ABA biosynthesis and signalling in the shoot. Soil water stress elicits a hydraulic response in the shoot, which precedes ABA signalling and stomatal closure. Attenuation of the hydraulic response in various plants prevented long-distance signalling of water stress, consistent with root-to-shoot communication by a hydraulic signal.

  11. Activating transcription factor 3, a useful marker for regenerative response after nerve root injury.

    PubMed

    Lindå, Hans; Sköld, Mattias K; Ochsmann, Thomas

    2011-01-01

    Activating transcription factor 3 (ATF3) is induced in various tissues in response to stress. In this experiment, ATF3 expression was studied in adult rats subjected either to a dorsal or ventral root avulsion (VRA; L4-6), or sciatic nerve transection (SNT). Post-operative survival times varied between 1.5 h and 3 weeks. In additional experiments an avulsed ventral root was directly replanted to the spinal cord. Dorsal root ganglias (DRGs) from humans exposed to traumatic dorsal root avulsions were also examined. After SNT ATF3 immunoreactivity (ATF3 IR) was detected in a few DRG neurons already 6 h after the lesion. After 24 h the number had clearly increased and still at 3 weeks DRG neurons remained labeled. In the ventral horn, ATF3 IR in motoneurons (MN) was first detected 24 h after the SNT, and still 3 weeks post-operatively lesioned MN showed ATF3 labeling. After a VRA many spinal MN showed ATF3 IR already after 3 h, and after 6 h all MN were labeled. At 3 weeks a majority of the lesioned MN had died, but all the remaining ones were labeled. When an avulsed ventral root was directly replanted, MN survived and were still labeled at 5 weeks. In DRG, a few neurons were labeled already at 1.5 h after a dorsal root avulsion. At 24 h the number had increased but still only a minority of the neurons were labeled. At 3 days the number of labeled neurons was reduced, and a further reduction was at hand at 7 days and 3 weeks. In parallel, in humans, 3 days after a traumatic dorsal root avulsion, only a few DRG neurons showed ATF3 IR. At 6 weeks no labeled neurons could be detected. These facts imply that ATF3 response to axotomy involves a distance-dependent mechanism. ATF3 also appears to be a useful and reliable neuronal marker of nerve lesions even in humans. In addition, ATF3 up-regulation in both motor and sensory neurons seems to be linked to regenerative competence.

  12. Nerve growth factor signaling in prostate health and disease.

    PubMed

    Arrighi, Nicola; Bodei, Serena; Zani, Danilo; Simeone, Claudio; Cunico, Sergio Cosciani; Missale, Cristina; Spano, Pierfranco; Sigala, Sandra

    2010-06-01

    The prostate is one of the most abundant sources of nerve growth factor (NGF) in different species, including humans. NGF and its receptors are implicated in the control of prostate cell proliferation and apoptosis and it can either support or suppress cell growth. The co-expression of both NGF receptors, p75(NGFR) and tropomyosin-related kinase A (trkA), represents a crucial condition for the antiproliferative effect of NGF; indeed, p75(NGFR) is progressively lost during prostate tumorigenesis and its disappearance represents a malignancy marker of prostate adenocarcinoma (PCa). Interestingly, a dysregulation of NGF signal transduction was found in a number of human tumors. This review summarizes the current knowledge on the role of NGF and its receptors in prostate and in PCa. Conclusions bring to the hypothesis that the NGF network could be a candidate for future pharmacological manipulation in the PCa therapy: in particular the re-expression of p75(NTR) and/or the negative modulation of trkA could represent a target to induce apoptosis and to reduce proliferation and invasiveness of PCa.

  13. Striking the Right Chord: Signaling Enigma during Root Gravitropism.

    PubMed

    Singh, Manjul; Gupta, Aditi; Laxmi, Ashverya

    2017-01-01

    Plants being sessile can often be judged as passive acceptors of their environment. However, plants are actually even more active in responding to the factors from their surroundings. Plants do not have eyes, ears or vestibular system like animals, still they "know" which way is up and which way is down? This is facilitated by receptor molecules within plant which perceive changes in internal and external conditions such as light, touch, obstacles; and initiate signaling pathways that enable the plant to react. Plant responses that involve a definite and specific movement are called "tropic" responses. Perhaps the best known and studied tropisms are phototropism, i.e., response to light, and geotropism, i.e., response to gravity. A robust root system is vital for plant growth as it can provide physical anchorage to soil as well as absorb water, nutrients and essential minerals from soil efficiently. Gravitropic responses of both primary as well as lateral root thus become critical for plant growth and development. The molecular mechanisms of root gravitropism has been delved intensively, however, the mechanism behind how the potential energy of gravity stimulus converts into a biochemical signal in vascular plants is still unknown, due to which gravity sensing in plants still remains one of the most fascinating questions in molecular biology. Communications within plants occur through phytohormones and other chemical substances produced in plants which have a developmental or physiological effect on growth. Here, we review current knowledge of various intrinsic signaling mechanisms that modulate root gravitropism in order to point out the questions and emerging developments in plant directional growth responses. We are also discussing the roles of sugar signals and their interaction with phytohormone machinery, specifically in context of root directional responses.

  14. Striking the Right Chord: Signaling Enigma during Root Gravitropism

    PubMed Central

    Singh, Manjul; Gupta, Aditi; Laxmi, Ashverya

    2017-01-01

    Plants being sessile can often be judged as passive acceptors of their environment. However, plants are actually even more active in responding to the factors from their surroundings. Plants do not have eyes, ears or vestibular system like animals, still they “know” which way is up and which way is down? This is facilitated by receptor molecules within plant which perceive changes in internal and external conditions such as light, touch, obstacles; and initiate signaling pathways that enable the plant to react. Plant responses that involve a definite and specific movement are called “tropic” responses. Perhaps the best known and studied tropisms are phototropism, i.e., response to light, and geotropism, i.e., response to gravity. A robust root system is vital for plant growth as it can provide physical anchorage to soil as well as absorb water, nutrients and essential minerals from soil efficiently. Gravitropic responses of both primary as well as lateral root thus become critical for plant growth and development. The molecular mechanisms of root gravitropism has been delved intensively, however, the mechanism behind how the potential energy of gravity stimulus converts into a biochemical signal in vascular plants is still unknown, due to which gravity sensing in plants still remains one of the most fascinating questions in molecular biology. Communications within plants occur through phytohormones and other chemical substances produced in plants which have a developmental or physiological effect on growth. Here, we review current knowledge of various intrinsic signaling mechanisms that modulate root gravitropism in order to point out the questions and emerging developments in plant directional growth responses. We are also discussing the roles of sugar signals and their interaction with phytohormone machinery, specifically in context of root directional responses. PMID:28798760

  15. Imaging of dynamic ion signaling during root gravitropism.

    PubMed

    Monshausen, Gabriele B

    2015-01-01

    Gravitropic signaling is a complex process that requires the coordinated action of multiple cell types and tissues. Ca(2+) and pH signaling are key components of gravitropic signaling cascades and can serve as useful markers to dissect the molecular machinery mediating plant gravitropism. To monitor dynamic ion signaling, imaging approaches combining fluorescent ion sensors and confocal fluorescence microscopy are employed, which allow the visualization of pH and Ca(2+) changes at the level of entire tissues, while also providing high spatiotemporal resolution. Here, I describe procedures to prepare Arabidopsis seedlings for live cell imaging and to convert a microscope for vertical stage fluorescence microscopy. With this imaging system, ion signaling can be monitored during all phases of the root gravitropic response.

  16. Calretinin-immunoreactive nerves in the uterus, pelvic autonomic ganglia, lumbosacral dorsal root ganglia and lumbosacral spinal cord.

    PubMed

    Papka, R E; Collins, J; Copelin, T; Wilson, K

    1999-10-01

    Nerves containing the calcium-binding protein calretinin have been reported in several organs but not in female reproductive organs and associated ganglia. This study was undertaken to determine if nerves associated with the uterus contain calretinin and the source(s) of calretinin-synthesizing nerves in the rat (are they sensory, efferent, or both?). Calretinin-immunoreactive nerves were present in the uterine horns and cervix where they were associated with arteries, uterine smooth muscle, glands, and the epithelium. Calretinin-immunoreactive terminals were apposed to neurons in the paracervical ganglia; in addition, some postganglionic neurons in this ganglion were calretinin positive. Calretinin perikarya were present in the lumbosacral dorsal root ganglia, no-dose ganglia, and lumbosacral spinal cord. Retrograde axonal tracing, utilizing Fluorogold injected into the uterus or paracervical parasympathetic ganglia, revealed calretinin-positive/Fluorogold-labeled neurons in the dorsal root and nodose ganglia. Also, capsaicin treatment substantially reduced the calretinin-positive fibers in the uterus and pelvic ganglia, thus indicating the sensory nature of these fibers. The presence of calretinin immunoreactivity identifies a subset of nerves that are involved in innervation of the pelvic viscera and have origins from lumbosacral dorsal root ganglia and vagal nodose ganglia. Though the exact function of calretinin in these nerves is not currently known, calretinin is likely to play a role in calcium regulation and their function.

  17. Case report: successful epiradicular peripheral nerve stimulation of the C2 dorsal root ganglion for postherpetic neuralgia.

    PubMed

    Lynch, Paul J; McJunkin, Tory; Eross, Eric; Gooch, Stacie; Maloney, Jillian

    2011-01-01

    Postherpetic neuralgia (PHN) is the most common complication following an acute varicella zoster virus infection. PHN often results in a chronic severe pain condition refractory to conservative pain management treatments. Peripheral nerve stimulation over the affected spinal nerve root may be an effective treatment option for patients with intractable PHN. To describe a successful case of peripheral nerve stimulation of the second cervical dorsal root ganglion for the treatment of intractable PHN. An 80-year-old man with a 15-month history of severe PHN was referred to our clinic for pain management. His pain was localized to the left side in the distribution of the C2 dermatome. The patient's pain was unresponsive to comprehensive conventional treatments for PHN including physical therapy, membrane stabilizing medications, opioids, anti-inflammatories, cervical epidural steroid injections, cervical facet joint injections, and dorsal root ganglion blockade with pulsed radiofrequency. After failing to respond to conservative and interventional therapies, a peripheral nerve stimulator trial was conducted for a period of seven days. The lead was placed within the epidural space over the atlanto-axial joint under fluoroscopy to stimulate the left C2 nerve root. This trial resulted in a significant decrease of the patient's pain, and discontinuation of all pain medications. We describe a case of successful electrode placement at the C2 spinal level for the treatment of refractory PHN. © 2010 International Neuromodulation Society.

  18. C5 Nerve root palsies following cervical spine surgery: A review

    PubMed Central

    Epstein, Nancy E.; Hollingsworth, Renee

    2015-01-01

    Background: Cervical C5 nerve root palsies may occur in between 0% and 30% of routine anterior or posterior cervical spine operations. They are largely attributed to traction injuries/increased cord migration following anterior/posterior decompressions. Of interest, almost all studies cite spontaneous resolution of these deficits without surgery with 3–24 postoperative months. Methods: Different studies cite various frequencies for C5 root palsies following anterior or posterior cervical spine surgery. In their combined anterior/posterior series involving C4-C5 level decompressions, Libelski et al. cited up to a 12% incidence of C5 palsies. In Gu et al. series, C5 root palsies occurred in 3.1% of double-door laminoplasty, 4.5% of open-door laminoplasty, and 11.3% of laminectomy. Miller et al. observed an intermediate 6.9% frequency of C5 palsies followed by posterior cervical decompressions and fusions (PCDF). Results: Gu et al. also identified multiple risk factors for developing C5 palsies following posterior surgery; male gender, ossification of the posterior longitudinal ligament (OPLL), narrower foramina, laminectomy, and marked dorsal spinal cord drift. Miller et al. also identified an average $1918 increased cost for physical/occupational therapy for patients with C5 palsies. Conclusions: The incidence of C5 root deficits for anterior/posterior cervical surgery at C4-C5 was 12% in one series, and ranged up to 11.3% for laminectomies, while others cited 0–30%. Although identification of preoperative risk factors for C5 root deficits may help educate patients regarding these risks, there is no clear method for their avoidance at this time. PMID:26005577

  19. Hindlimb spasticity after unilateral motor cortex lesion in rats is reduced by contralateral nerve root transfer

    PubMed Central

    Zong, Haiyang; Ma, Fenfen; Zhang, Laiyin; Lu, Huiping; Gong, Jingru; Cai, Min; Lin, Haodong; Zhu, Yizhun; Hou, Chunlin

    2016-01-01

    Lower extremity spasticity is a common sequela among patients with acquired brain injury. The optimum treatment remains controversial. The aim of our study was to test the feasibility and effectiveness of contralateral nerve root transfer in reducing post stroke spasticity of the affected hindlimb muscles in rats. In our study, we for the first time created a novel animal hindlimb spastic hemiplegia model in rats with photothrombotic lesion of unilateral motor cortex and we established a novel surgical procedure in reducing motor cortex lesion-induced hindlimb spastic hemiplegia in rats. Thirty six rats were randomized into three groups. In group A, rats received sham operation. In group B, rats underwent unilateral hindlimb motor cortex lesion. In group C, rats underwent unilateral hindlimb cortex lesion followed by contralateral L4 ventral root transfer to L5 ventral root of the affected side. Footprint analysis, Hoffmann reflex (H-reflex), cholera toxin subunit B (CTB) retrograde tracing of gastrocnemius muscle (GM) motoneurons and immunofluorescent staining of vesicle glutamate transporter 1 (VGLUT1) on CTB-labelled motoneurons were used to assess spasticity of the affected hindlimb. Sixteen weeks postoperatively, toe spread and stride length recovered significantly in group C compared with group B (P<0.001). Hmax (H-wave maximum amplitude)/Mmax (M-wave maximum amplitude) ratio of gastrocnemius and plantaris muscles (PMs) significantly reduced in group C (P<0.01). Average VGLUT1 positive boutons per CTB-labelled motoneurons significantly reduced in group C (P<0.001). We demonstrated for the first time that contralateral L4 ventral root transfer to L5 ventral root of the affected side was effective in relieving unilateral motor cortex lesion-induced hindlimb spasticity in rats. Our data indicated that this could be an alternative treatment for unilateral lower extremity spasticity after brain injury. Therefore, contralateral neurotization may exert a potential

  20. Preservation and Tissue Handling Technique on Iatrogenic Dural Tear with Herniated Nerve Root at Cauda Equina Level

    PubMed Central

    Djaja, Yoshi Pratama; Saleh, Ifran; Safri, Ahmad Yanuar

    2016-01-01

    Iatrogenic or incidental dural tear is a relatively common complication in lumbar decompression surgery. Although mostly there are no changes that occurred in long-term result following an incidental durotomy, the sequelae are not always benign especially when the herniated nerve root is involved. Preservation and tissue handling is paramount in order to prevent further injury. Two cases of dural tear with herniated nerve root complicating the lumbar decompression surgery are presented. Direct watertight repair was performed using the preservation and tissue handling concept. Assessing the relative size between the dural tear and the root mass is the key in determining whether enlargement of tear is needed. Whenever feasible, the tear will not be enlarged. Opening the vent by using a suture anchor and manually repositioning the nerve root with a fine instrument is the key for an atraumatic handling of the herniated nerve root. Clinical and neurophysiology examination was performed postoperatively and no further neurologic deficit occurred despite the iatrogenic injury. Although some debate on a few intraoperative and postoperative details still persists, tissue handling and preservation concept should be applied in all cases. PMID:28127488

  1. Generation of New Neurons in Dorsal Root Ganglia in Adult Rats after Peripheral Nerve Crush Injury

    PubMed Central

    2015-01-01

    The evidence of neurons generated ex novo in sensory ganglia of adult animals is still debated. In the present study, we investigated, using high resolution light microscopy and stereological analysis, the changes in the number of neurons in dorsal root ganglia after 30 days from a crush lesion of the rat brachial plexus terminal branches. Results showed, as expected, a relevant hypertrophy of dorsal root ganglion neurons. In addition, we reported, for the first time in the literature, that neuronal hypertrophy was accompanied by massive neuronal hyperplasia leading to a 42% increase of the number of primary sensory neurons. Moreover, ultrastructural analyses on sensory neurons showed that there was not a relevant neuronal loss as a consequence of the nerve injury. The evidence of BrdU-immunopositive neurons and neural progenitors labeled with Ki67, nanog, nestin, and sox-2 confirmed the stereological evidence of posttraumatic neurogenesis in dorsal root ganglia. Analysis of morphological changes following axonal damage in addition to immunofluorescence characterization of cell phenotype suggested that the neuronal precursors which give rise to the newly generated neurons could be represented by satellite glial cells that actively proliferate after the lesion and are able to differentiate toward the neuronal lineage. PMID:25722894

  2. 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

  3. Macrophages related to leptomeninges and ventral nerve roots. An ultrastructural study.

    PubMed Central

    Fraher, J P; McDougall, R D

    1975-01-01

    In immature rats active macrophages were frequently seen projecting into the subarachnoid space from the surface of the leptomeninges. They also occurred between the layers of the pia and within the nerve roots. They were most frequent during the first two weeks after birth, which is a period of rapid neural growth and myelination in ventral roots. In contrast, they were much fewer at later stages. The ultrastructural characteristics of these cells are described. It is suggested that these cells take part in tissue growth and remodelling by the removal of material which degenerates or becomes redundant during development. For example, they may ingest effete leptomeningeal cells or fragments of them. Those within the ventral roots may phagocytose abnormal Schwann cells, or the myelin of sheaths which have failed to develop normally. It is also suggested that macrophages may be involved in the excavation of the subarachnoid space. Another possible function in which they may be involved is the ingestion of material, possibly of a protein nature, from the cerebrospinal fluid. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 Fig. 5 Fig. 6 PMID:1213953

  4. Cyclic AMP Signaling: A Molecular Determinant of Peripheral Nerve Regeneration

    PubMed Central

    Knott, Eric P.; Assi, Mazen; Pearse, Damien D.

    2014-01-01

    Disruption of axonal integrity during injury to the peripheral nerve system (PNS) sets into motion a cascade of responses that includes inflammation, Schwann cell mobilization, and the degeneration of the nerve fibers distal to the injury site. Yet, the injured PNS differentiates itself from the injured central nervous system (CNS) in its remarkable capacity for self-recovery, which, depending upon the length and type of nerve injury, involves a series of molecular events in both the injured neuron and associated Schwann cells that leads to axon regeneration, remyelination repair, and functional restitution. Herein we discuss the essential function of the second messenger, cyclic adenosine monophosphate (cyclic AMP), in the PNS repair process, highlighting the important role the conditioning lesion paradigm has played in understanding the mechanism(s) by which cyclic AMP exerts its proregenerative action. Furthermore, we review the studies that have therapeutically targeted cyclic AMP to enhance endogenous nerve repair. PMID:25177696

  5. Spectral and spatial dependence of
diffuse optical signals in response to
peripheral nerve stimulation

    PubMed Central

    Chen, Debbie K.; Erb, M. Kelley; Tong, Yunjie; Yu, Yang; Sassaroli, Angelo; Bergethon, Peter R.; Fantini, Sergio

    2010-01-01

    Using non-invasive, near-infrared spectroscopy we have previously reported optical signals measured at or around peripheral nerves in response to their stimulation. Such optical signals featured amplitudes on the order of 0.1% and peaked about 100 ms after peripheral nerve stimulation in human subjects. Here, we report a study of the spatial and spectral dependence of the optical signals induced by stimulation of the human median and sural nerves, and observe that these optical signals are: (1) unlikely due to either dilation or constriction of blood vessels, (2) not associated with capillary bed hemoglobin, (3) likely due to blood vessel(s) displacement, and (4) unlikely due to fiber-skin optical coupling effects. We conclude that the most probable origin of the optical response to peripheral nerve stimulation is from displacement of blood vessels within the optically probed volume, as a result of muscle twitch in adjacent areas. PMID:21258519

  6. Nerve growth factor (NGF) and diabetic neuropathy in the rat: morphological investigations of the sural nerve, dorsal root ganglion, and spinal cord.

    PubMed

    Unger, J W; Klitzsch, T; Pera, S; Reiter, R

    1998-09-01

    A number of functions for nerve growth factor (NGF) have been described over the past years, including its role for neuronal function and regeneration during toxic or metabolic neuropathies. In order to further assess the effects of NGF on the somatosensory system in diabetic neuropathy, the sural nerve, dorsal root ganglia (DRG), and dorsal horn of the spinal cord were investigated by morphological and quantitative methods in rats after 12 weeks of uncontrolled streptozotocin-induced diabetes mellitus. The results from our study suggest a twofold effect of NGF: (1) In sural nerve treatment with NGF (0.1 or 0.5 mg/kg) for 12 weeks was able to reverse distinct diabetes-related alterations in myelinated nerve fiber morphology, such as myelin thickness. These changes occurred in the entire myelinated population of sensory nerves and were not restricted to nociceptive nerve fibers. (2) The NGF effect on neurotransmitters of the sensory, nociceptive system was reflected by increased CGRP and substance P content in the DRG and in the dorsal horn of the spinal cord. No change of trkA receptor immunostaining was seen in DRGs of diabetic rats; however, a reduction of trkA immunoreactivity of DRG neurons was noted after long-term NGF treatment of healthy controls. The data demonstrate that NGF regulates a number of neuronal parameters along peripheral and central parts of the somatosensory pathway in the adult. This neurotrophic support may be essential for inducing functionally significant regenerative mechanisms in diabetic neuropathy.

  7. 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

  8. Confocal imaging reveals three-dimensional fine structure difference between ventral and dorsal nerve roots

    NASA Astrophysics Data System (ADS)

    Wu, Yuxiang; Sui, Tao; Cao, Xiaojian; Lv, Xiaohua; Zeng, Shaoqun; Sun, Peng

    2011-05-01

    Peripheral nerve injury repair is one of the most challenging problems in neurosurgery, partially due to lack of knowledge of three-dimensional (3-D) fine structure and organization of peripheral nerves. In this paper, we explored the structures of nerve fibers in ventral and dorsal nerves with a laser scanning confocal microscopy. Thick tissue staining results suggested that nerve fibers have a different 3-D structure in ventral and dorsal nerves, and reconstruction from serial sectioning images showed that in ventral nerves the nerve fibers travel in a winding form, while in dorsal nerves, the nerve fibers form in a parallel cable pattern. These structural differences could help surgeons to differentiate ventral and dorsal nerves in peripheral nerve injury repair, and also facilitate scientists to get a deeper understanding about nerve fiber organization.

  9. Confocal imaging reveals three-dimensional fine structure difference between ventral and dorsal nerve roots.

    PubMed

    Wu, Yuxiang; Sui, Tao; Cao, Xiaojian; Lv, Xiaohua; Zeng, Shaoqun; Sun, Peng

    2011-05-01

    Peripheral nerve injury repair is one of the most challenging problems in neurosurgery, partially due to lack of knowledge of three-dimensional (3-D) fine structure and organization of peripheral nerves. In this paper, we explored the structures of nerve fibers in ventral and dorsal nerves with a laser scanning confocal microscopy. Thick tissue staining results suggested that nerve fibers have a different 3-D structure in ventral and dorsal nerves, and reconstruction from serial sectioning images showed that in ventral nerves the nerve fibers travel in a winding form, while in dorsal nerves, the nerve fibers form in a parallel cable pattern. These structural differences could help surgeons to differentiate ventral and dorsal nerves in peripheral nerve injury repair, and also facilitate scientists to get a deeper understanding about nerve fiber organization.

  10. Ultrasonographic nerve enlargement of the median and ulnar nerves and the cervical nerve roots in patients with demyelinating Charcot-Marie-Tooth disease: distinction from patients with chronic inflammatory demyelinating polyneuropathy.

    PubMed

    Sugimoto, Takamichi; Ochi, Kazuhide; Hosomi, Naohisa; Takahashi, Tetsuya; Ueno, Hiroki; Nakamura, Takeshi; Nagano, Yoshito; Maruyama, Hirofumi; Kohriyama, Tatsuo; Matsumoto, Masayasu

    2013-10-01

    Demyelinating Charcot-Marie-Tooth disease (CMT) and chronic inflammatory demyelinating polyneuropathy (CIDP) are both demyelinating polyneuropathies. The differences in nerve enlargement degree and pattern at multiple evaluation sites/levels are not well known. We investigated the differences in nerve enlargement degree and the distribution pattern of nerve enlargement in patients with demyelinating CMT and CIDP, and verified the appropriate combination of sites/levels to differentiate between these diseases. Ten patients (aged 23-84 years, three females) with demyelinating CMT and 16 patients (aged 30-85 years, five females) with CIDP were evaluated in this study. The nerve sizes were measured at 24 predetermined sites/levels from the median and ulnar nerves and the cervical nerve roots (CNR) using ultrasonography. The evaluation sites/levels were classified into three regions: distal, intermediate and cervical. The number of sites/levels that exhibited nerve enlargement (enlargement site number, ESN) in each region was determined from the 24 sites/levels and from the selected eight screening sites/levels, respectively. The cross-sectional areas of the peripheral nerves were markedly larger at all evaluation sites in patients with demyelinating CMT than in patients with CIDP (p < 0.01). However, the nerve sizes of CNR were not significantly different between patients with either disease. When we evaluated ESN of four selected sites for screening from the intermediate region, the sensitivity and specificity to distinguish between demyelinating CMT and CIDP were 0.90 and 0.94, respectively, with the cut-off value set at four. Nerve ultrasonography is useful to detect nerve enlargement and can clarify morphological differences in nerves between patients with demyelinating CMT and CIDP.

  11. The statistical mechanics of complex signaling networks: nerve growth factor signaling

    NASA Astrophysics Data System (ADS)

    Brown, K. S.; Hill, C. C.; Calero, G. A.; Myers, C. R.; Lee, K. H.; Sethna, J. P.; Cerione, R. A.

    2004-10-01

    The inherent complexity of cellular signaling networks and their importance to a wide range of cellular functions necessitates the development of modeling methods that can be applied toward making predictions and highlighting the appropriate experiments to test our understanding of how these systems are designed and function. We use methods of statistical mechanics to extract useful predictions for complex cellular signaling networks. A key difficulty with signaling models is that, while significant effort is being made to experimentally measure the rate constants for individual steps in these networks, many of the parameters required to describe their behavior remain unknown or at best represent estimates. To establish the usefulness of our approach, we have applied our methods toward modeling the nerve growth factor (NGF)-induced differentiation of neuronal cells. In particular, we study the actions of NGF and mitogenic epidermal growth factor (EGF) in rat pheochromocytoma (PC12) cells. Through a network of intermediate signaling proteins, each of these growth factors stimulates extracellular regulated kinase (Erk) phosphorylation with distinct dynamical profiles. Using our modeling approach, we are able to predict the influence of specific signaling modules in determining the integrated cellular response to the two growth factors. Our methods also raise some interesting insights into the design and possible evolution of cellular systems, highlighting an inherent property of these systems that we call 'sloppiness.'

  12. The Accuracy of the Physical Examination for the Diagnosis of Midlumbar and Low Lumbar Nerve Root Impingement

    PubMed Central

    Suri, Pradeep; Rainville, James; Katz, Jeffrey N.; Jouve, Cristin; Hartigan, Carol; Limke, Janet; Pena, Enrique; Li, Ling; Swaim, Bryan; Hunter, David J

    2010-01-01

    Study Design Cross-sectional study with prospective recruitment. Objective To determine the accuracy of the physical examination for the diagnosis of midlumbar nerve root impingement (L2, L3, or L4), low lumbar nerve root impingement (L5 or S1) and level-specific lumbar nerve root impingement on magnetic resonance imaging (MRI), using individual tests and combinations of tests. Summary of Background Data The sensitivity and specificity of the physical examination for the localization of nerve root impingement has not been previously studied. Methods Sensitivities, specificities and LRs were calculated for the ability of individual tests and test combinations to predict the presence or absence of nerve root impingement at midlumbar, low lumbar, and specific nerve root levels. Results LRs ≥5.0 indicate moderate to large changes from pre-test probability of nerve root impingement to post-test probability. For the diagnosis of midlumbar impingement, the femoral stretch test (FST), crossed femoral stretch test (CFST), medial ankle pinprick sensation, and patellar reflex testing demonstrated LRs ≥5.0 (LR ∞). LRs ≥5.0 were seen with the combinations of FST and either patellar reflex testing (LR 7.0; 95% CI 2.3–21), or the sit-to-stand test (LR ∞). For the diagnosis of low lumbar impingement, the Achilles reflex test demonstrated a LR ≥5.0 (LR 7.1; CI 0.96–53); test combinations did not increase LRs. For the diagnosis of level-specific impingement, LRs ≥5.0 were seen for anterior thigh sensation at L2 (LR 13; 95% CI 1.8–87); FST at L3 (LR 5.7 ; 95% CI 2.3–4.4); patellar reflex testing (LR 7.7; 95% CI 1.7–35), medial ankle sensation (LR ∞), or CFST (LR 13; 95% CI 1.8–87) at L4; and hip abductor strength at L5(LR 11; 95% CI 1.3–84). Test combinations increased LRs for level-specific root impingement at the L4 level only. Conclusions Individual physical examination tests may provide clinical information which substantially alters the likelihood

  13. Secreted phosphoprotein 24 kD inhibits nerve root inflammation induced by bone morphogenetic protein-2.

    PubMed

    Tian, Haijun; Li, Chen-Shuang; Scott, Trevor P; Montgomery, Scott R; Phan, Kevin; Lao, Lifeng; Zhang, Wei; Li, Yawei; Hayashi, Tetsuo; Takahashi, Shinji; Alobaidaan, Raed; Ruangchainikom, Monchai; Zhao, Ke-Wei; Brochmann, Elsa J; Murray, Samuel S; Wang, Jeffrey C; Daubs, Michael D

    2015-02-01

    Bone morphogenetic protein-2 (BMP-2) has been used to successfully promote spine fusion, but side-effects including nerve inflammation have been observed. To investigate the direct neurotoxic effects of BMP-2 and test the hypotheses that the use of BMP binding proteins, such as secreted phosphoprotein 24 kD (Spp24), can reduce or eliminate these effects. In vitro experiments and in vivo analysis in a rodent model. In vitro, dorsal root ganglion cells were cultured in the presence of BMP-2 with and without Spp24 and calcitonin gene-related peptide and Substance P, markers of neuroinflammation, were measured by immunohistochemistry. In vivo, rats underwent a left-sided laminotomy at L5 to expose the S1 nerve root and were randomized into four different groups according to the intervention at the laminotomy site: collagen sponge only (no BMP-2 or Spp24), BMP-2 in a collagen sponge only, BMP-2 in a collagen sponge+an empty collagen sponge to act as a barrier, and BMP-2 in a collagen sponge+Spp24 in a collagen sponge to act as a barrier. Functional evaluation was done using the Basso, Beattie, and Bresnahan scale and immunohistochemical analyses were performed using calcitonin gene-related peptide and Substance P staining. The neuroinflammatory effects of BMP-2 in vitro were ameliorated by the addition of Spp24. Similarly, in vivo, Spp24 reduced the expression of markers on neuroinflammation in animals treated with BMP-2 and also improved the function after BMP-2 administration. These results confirm that BMP binding proteins have great potential as adjuvant therapies to limit BMP-2 related side-effects in spine surgery. Copyright © 2015 Elsevier Inc. All rights reserved.

  14. Chronic nerve injury-induced Mas receptor expression in dorsal root ganglion neurons alleviates neuropathic pain.

    PubMed

    Zhao, Yuanting; Qin, Yue; Liu, Tuanjiang; Hao, Dingjun

    2015-12-01

    Neuropathic pain, which is characterized by hyperalgesia, allodynia and spontaneous pain, is one of the most painful symptoms that can be experienced in the clinic. It often occurs as a result of injury to the peripheral nerves, dorsal root ganglion (DRG), spinal cord or brain. The renin-angiotensin system (RAS) plays an important role in nociception. As an essential component of the RAS, the angiotensin (Ang)-(1-7)/Mas axis may be involved in antinociception. The aim of the present study was to explore the expression pattern of Mas in DRG neurons following chronic nerve injury and examine the effects of Mas inhibition and activation on neuropathic pain in a chronic constriction injury (CCI) rat model. The results showed, that compared with the sham group, CCI caused a time-dependent induction of Mas expression at both the mRNA and the protein levels in DRG neurons. Consistent with the results, isolated DRG neurons showed a time-dependent increase in Ang-(1-7) binding on the cell membrane following the CCI surgery, but not the sham surgery. Compared with the sham control groups, CCI significantly decreased the paw withdrawal latency and threshold, and this was markedly improved and aggravated by intrathecal injection of the selective Mas agonist Ang-(1-7) and the selective Mas inhibitor D-Pro7-Ang-(1-7), respectively. In conclusion, this study has provided the first evidence, to the best of our knowledge, that the Mas expression in DRG neurons is time-dependently induced by chronic nerve injury and that the intrathecal activation and inhibition of Mas can improve and aggravate CCI-induced neuropathic pain, respectively. This study has provided novel insights into the pathophysiological process of neuropathic pain and suggests that the Ang-(1-7)/Mas axis could be an effective therapeutic target for neuropathic pain, warranting further study.

  15. Increased response to glutamate in small diameter dorsal root ganglion neurons after sciatic nerve injury.

    PubMed

    Gong, Kerui; Kung, Ling-Hsuan; Magni, Giulia; Bhargava, Aditi; Jasmin, Luc

    2014-01-01

    Glutamate in the peripheral nervous system is involved in neuropathic pain, yet we know little how nerve injury alters responses to this neurotransmitter in primary sensory neurons. We recorded neuronal responses from the ex-vivo preparations of the dorsal root ganglia (DRG) one week following a chronic constriction injury (CCI) of the sciatic nerve in adult rats. We found that small diameter DRG neurons (<30 µm) exhibited increased excitability that was associated with decreased membrane threshold and rheobase, whereas responses in large diameter neurons (>30 µm) were unaffected. Puff application of either glutamate, or the selective ionotropic glutamate receptor agonists alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) and kainic acid (KA), or the group I metabotropic receptor (mGluR) agonist (S)-3,5-dihydroxyphenylglycine (DHPG), induced larger inward currents in CCI DRGs compared to those from uninjured rats. N-methyl-D-aspartate (NMDA)-induced currents were unchanged. In addition to larger inward currents following CCI, a greater number of neurons responded to glutamate, AMPA, NMDA, and DHPG, but not to KA. Western blot analysis of the DRGs revealed that CCI resulted in a 35% increase in GluA1 and a 60% decrease in GluA2, the AMPA receptor subunits, compared to uninjured controls. mGluR1 receptor expression increased by 60% in the membrane fraction, whereas mGluR5 receptor subunit expression remained unchanged after CCI. These results show that following nerve injury, small diameter DRG neurons, many of which are nociceptive, have increased excitability and an increased response to glutamate that is associated with changes in receptor expression at the neuronal membrane. Our findings provide further evidence that glutamatergic transmission in the periphery plays a role in nociception.

  16. Meralgia paresthetica-like syndrome may be caused by transient lumbar nerve root injury without definite compression: a case report.

    PubMed

    Dharmasaroja, Pornpatr; Dharmasaroja, Permphan

    2010-12-01

    Meralgia paresthetica is a well-known sensory syndrome describing paresthesia and/or anesthesia in the anterolateral aspect of the thigh that is supplied by the lateral femoral cutaneous nerve. Compression of the nerve usually occurs at the point where it passes between the anterior superior iliac spine and the inguinal ligament. Proximal lesions such as lumbar radiculopathy, lumbar disc herniation, and spinal stenosis have been reported to cause meralgia paresthetica-like syndrome. These proximal lesions directly injure L2 and L3 spinal nerve roots and cause a constant compression of the nerve roots. The presented paper introduces a hypothesis that this syndrome can be caused by transient injury to the L2 and L3 nerve roots by the upper adjacent disc bulge without definite compression. This hypothesis is supported by lumbar spine magnetic resonance imaging of a patient presenting with a meralgia paresthetica-like symptom during bending forward and twisting of the body, showing no L2/L3 herniated disc but mildly posterior bulging of T12/L1 disc. This hypothesis emphasizes an importance of appropriate postures in patients with meralgia paresthetica-like symptoms in order to prevent long-term morbidity.

  17. Microstructural changes are coincident with the improvement of clinical symptoms in surgically treated compressed nerve roots

    PubMed Central

    Wu, Weifei; Liang, Jie; Chen, Ying; Chen, Aihua; Wu, Yongde; Yang, Zong

    2017-01-01

    Diffusion tensor imaging (DTI) has been widely used to visualize peripheral nerves, but the microstructure of compressed nerve roots can be assessed using DTI. However, there are no data regarding the association among microstructural changes evaluated using DTI, the symptoms assessed using the Oswestry Disability Index (ODI) and the duration of symptoms after surgery in patients with lumbar disc herniation (LDH). Thirty patients with unilateral radiculopathy were investigated using DTI. The changes in the mean fractional anisotropy (FA) and the apparent diffusion coefficient (ADC) values as well as the correlation between these changes and the severity and duration of the clinical symptoms were investigated before and at least one month after surgery. The FA values were significantly increased after surgical treatment (p < 0.0001). Both the ADC and ODI values were noticeably decreased (p < 0.0001). A strong positive correlation between the preoperative and postoperative DTI parameters (p < 0.0001) as well as between the preoperative ODI and postoperative ODI/ODI changes (p < 0.0001) were found. In addition, there was a significant positive correlation between the changes in the DTI parameters and changes in the ODI (p < 0.0001). This preliminary study suggests it may be possible to use DTI to diagnose, quantitatively evaluate and follow-up patients with LDH. PMID:28294192

  18. Genetic Analysis of Gravity Signal Transduction in Arabidopsis Roots

    NASA Astrophysics Data System (ADS)

    Masson, Patrick; Strohm, Allison; Barker, Richard; Su, Shih-Heng

    Like most other plant organs, roots use gravity as a directional guide for growth. Specialized cells within the columella region of the root cap (the statocytes) sense the direction of gravity through the sedimentation of starch-filled plastids (amyloplasts). Amyloplast movement and/or pressure on sensitive membranes triggers a gravity signal transduction pathway within these cells, which leads to a fast transcytotic relocalization of plasma-membrane associated auxin-efflux carrier proteins of the PIN family (PIN3 and PIN7) toward the bottom membrane. This leads to a polar transport of auxin toward the bottom flank of the cap. The resulting lateral auxin gradient is then transmitted toward the elongation zones where it triggers a curvature that ultimately leads to a restoration of vertical downward growth. Our laboratory is using strategies derived from genetics and systems biology to elucidate the molecular mechanisms that modulate gravity sensing and signal transduction in the columella cells of the root cap. Our previous research uncovered two J-domain-containing proteins, ARG1 and ARL2, as contributing to this process. Mutations in the corresponding paralogous genes led to alterations of root and hypocotyl gravitropism accompanied by an inability for the statocytes to develop a cytoplasmic alkalinization, relocalize PIN3, and transport auxin laterally, in response to gravistimulation. Both proteins are associated peripherally to membranes belonging to various compartments of the vesicular trafficking pathway, potentially modulating the trafficking of defined proteins between plasma membrane and endosomes. MAR1 and MAR2, on the other end, are distinct proteins of the plastidic outer envelope protein import TOC complex (the transmembrane channel TOC75 and the receptor TOC132, respectively). Mutations in the corresponding genes enhance the gravitropic defects of arg1. Using transformation-rescue experiments with truncated versions of TOC132 (MAR2), we have shown

  19. Regenerative peripheral nerve interface viability and signal transduction with an implanted electrode.

    PubMed

    Kung, Theodore A; Langhals, Nicholas B; Martin, David C; Johnson, Philip J; Cederna, Paul S; Urbanchek, Melanie G

    2014-06-01

    The regenerative peripheral nerve interface is an internal interface for signal transduction with external electronics of prosthetic limbs; it consists of an electrode and a unit of free muscle that is neurotized by a transected residual peripheral nerve. Adding a conductive polymer coating on electrodes improves electrode conductivity. This study examines regenerative peripheral nerve interface tissue viability and signal fidelity in the presence of an implanted electrode coated or uncoated with a conductive polymer. In a rat model, the extensor digitorum longus muscle was moved as a nonvascularized free tissue transfer and neurotized by the divided peroneal nerve. Either a stainless steel pad electrode (n = 8) or a pad electrode coated with poly(3,4-ethylenedioxythiophene) conductive polymer (PEDOT) (n = 8) was implanted on the muscle transfer and secured with an encircling acellular extracellular matrix. The contralateral muscle served as the control. The free muscle transfers were successfully revascularized and over time reinnervated as evidenced by serial insertional needle electromyography. Compound muscle action potentials were successfully transduced through the regenerative peripheral nerve interface. The conductive polymer coating on the implanted electrode resulted in increased recorded signal amplitude that was observed throughout the course of the study. Histologic examination confirmed axonal sprouting, elongation, and synaptogenesis within regenerative peripheral nerve interface regardless of electrode type. The regenerative peripheral nerve interface remains viable over seven months in the presence of an implanted electrode. Electrodes with and without conductive polymer reliably transduced signals from the regenerative peripheral nerve interface. Electrodes with a conductive polymer coating resulted in recording more of the regenerative peripheral nerve interface signal.

  20. Grafting the C5 root to the musculocutaneous nerve partially restores hand sensation in complete palsies of the brachial plexus.

    PubMed

    Bertelli, Jayme Augusto; Ghizoni, Marcos Flávio

    2012-08-01

    In complete brachial plexus palsy, we have hypothesized that grafting to the musculocutaneous nerve should restore some hand sensation because the musculocutaneous nerve can drive hand sensation directly or via communication with the radial and median nerves. To investigate sensory recovery in the hand and forearm after C5 root grafting to the musculocutaneous nerve in patients with a total brachial plexus injury. Eleven patients who had recovered elbow flexion after musculocutaneous nerve grafting from a preserved C5 root and who had been followed for a minimum of 3 years were screened for sensory recovery in the hand and forearm. Six matched patients who had not undergone surgery served as controls. Methods of assessment included testing for pain sensation using Adson forceps, cutaneous pressure threshold measurements using Semmes-Weinstein monofilaments, and the static 2-point discrimination test. Deep sensation was evaluated by squeezing the first web space, and thermal sensation was assessed using warm and cold water. All grafted patients recovered sensation in a variable territory extending from just over the thenar eminence to the entire lateral forearm and hand. Seven patients were capable of perceiving 2-0 monofilament pressure on the thenar eminence, palm, and dorsoradial aspect of the hand. All could differentiate warm and cold water. None recovered 2-point discrimination. None of the patients in the control group recovered any kind of sensation in the affected limb. Grafting the musculocutaneous nerve can restore nociceptive sensation on the radial side of the hand.

  1. A valid model for predicting responsible nerve roots in lumbar degenerative disease with diagnostic doubt.

    PubMed

    Li, Xiaochuan; Bai, Xuedong; Wu, Yaohong; Ruan, Dike

    2016-03-15

    To construct and validate a model to predict responsible nerve roots in lumbar degenerative disease with diagnostic doubt (DD). From January 2009-January 2013, 163 patients with DD were assigned to the construction (n = 106) or validation sample (n = 57) according to different admission times to hospital. Outcome was assessed according to the Japanese Orthopedic Association (JOA) recovery rate as excellent, good, fair, and poor. The first two results were considered as effective clinical outcome (ECO). Baseline patient and clinical characteristics were considered as secondary variables. A multivariate logistic regression model was used to construct a model with the ECO as a dependent variable and other factors as explanatory variables. The odds ratios (ORs) of each risk factor were adjusted and transformed into a scoring system. Area under the curve (AUC) was calculated and validated in both internal and external samples. Moreover, calibration plot and predictive ability of this scoring system were also tested for further validation. Patients with DD with ECOs in both construction and validation models were around 76 % (76.4 and 75.5 % respectively). more preoperative visual analog pain scale (VAS) score (OR = 1.56, p < 0.01), stenosis levels of L4/5 or L5/S1 (OR = 1.44, p = 0.04), stenosis locations with neuroforamen (OR = 1.95, p = 0.01), neurological deficit (OR = 1.62, p = 0.01), and more VAS improvement of selective nerve route block (SNRB) (OR = 3.42, p = 0.02). the internal area under the curve (AUC) was 0.85, and the external AUC was 0.72, with a good calibration plot of prediction accuracy. Besides, the predictive ability of ECOs was not different from the actual results (p = 0.532). We have constructed and validated a predictive model for confirming responsible nerve roots in patients with DD. The associated risk factors were preoperative VAS score, stenosis levels of L4/5 or L5/S1, stenosis locations

  2. Near-infrared signals associated with electrical stimulation of peripheral nerves

    PubMed Central

    Fantini, Sergio; Chen, Debbie K.; Martin, Jeffrey M.; Sassaroli, Angelo; Bergethon, Peter R.

    2011-01-01

    We report our studies on the optical signals measured non-invasively on electrically stimulated peripheral nerves. The stimulation consists of the delivery of 0.1 ms current pulses, below the threshold for triggering any visible motion, to a peripheral nerve in human subjects (we have studied the sural nerve and the median nerve). In response to electrical stimulation, we observe an optical signal that peaks at about 100 ms post-stimulus, on a much longer time scale than the few milliseconds duration of the electrical response, or sensory nerve action potential (SNAP). While the 100 ms optical signal we measured is not a direct optical signature of neural activation, it is nevertheless indicative of a mediated response to neural activation. We argue that this may provide information useful for understanding the origin of the fast optical signal (also on a 100 ms time scale) that has been measured non-invasively in the brain in response to cerebral activation. Furthermore, the optical response to peripheral nerve activation may be developed into a diagnostic tool for peripheral neuropathies, as suggested by the delayed optical signals (average peak time: 230 ms) measured in patients with diabetic neuropathy with respect to normal subjects (average peak time: 160 ms). PMID:22399834

  3. Near-infrared signals associated with electrical stimulation of peripheral nerves

    NASA Astrophysics Data System (ADS)

    Fantini, Sergio; Chen, Debbie K.; Martin, Jeffrey M.; Sassaroli, Angelo; Bergethon, Peter R.

    2009-02-01

    We report our studies on the optical signals measured non-invasively on electrically stimulated peripheral nerves. The stimulation consists of the delivery of 0.1 ms current pulses, below the threshold for triggering any visible motion, to a peripheral nerve in human subjects (we have studied the sural nerve and the median nerve). In response to electrical stimulation, we observe an optical signal that peaks at about 100 ms post-stimulus, on a much longer time scale than the few milliseconds duration of the electrical response, or sensory nerve action potential (SNAP). While the 100 ms optical signal we measured is not a direct optical signature of neural activation, it is nevertheless indicative of a mediated response to neural activation. We argue that this may provide information useful for understanding the origin of the fast optical signal (also on a 100 ms time scale) that has been measured non-invasively in the brain in response to cerebral activation. Furthermore, the optical response to peripheral nerve activation may be developed into a diagnostic tool for peripheral neuropathies, as suggested by the delayed optical signals (average peak time: 230 ms) measured in patients with diabetic neuropathy with respect to normal subjects (average peak time: 160 ms).

  4. Adjacent regenerative peripheral nerve interfaces produce phase-antagonist signals during voluntary walking in rats.

    PubMed

    Ursu, Daniel; Nedic, Andrej; Urbanchek, Melanie; Cederna, Paul; Gillespie, R Brent

    2017-04-24

    Regenerative Peripheral Nerve Interfaces (RPNIs) are neurotized muscle grafts intended to produce electromyographic signals suitable for motorized prosthesis control. Two RPNIs producing independent agonist/antagonist signals are required for each control axis; however, it is unknown whether signals from adjacent RPNIs are independent. The purpose of this work was to determine signaling characteristics from two adjacent RPNIs, the first neurotized by a foot dorsi-flexor nerve and the second neurotized by a foot plantar-flexor nerve in a rodent model. Two Control group rats had electrodes implanted onto the soleus (tibial nerve) and extensor digitorum longus (peroneal nerve) muscles in the left hind limb. Two Dual-RPNI group rats had two separate muscles grafted to the left thigh and each implanted with electrodes: the extensor digitorum longus was neurotized with a transected fascicle from the tibial nerve, and the tibialis anterior was implanted with a transected peroneal nerve. Four months post-surgery, rats walked on a treadmill, were videographed, and electromyographic signals were recorded. Amplitude and periodicity of all signals relative to gait period were quantified. To facilitate comparisons across groups, electromyographic signals were expressed as a percent of total stepping cycle activity for each stance and swing gait phase. Independence between peroneal and tibial nerve activations were assessed by statistical comparisons between groups during stance and swing. Electromyographic activity for Control and Dual-RPNI rats displayed alternating activation patterns coinciding with stance and swing. Significant signal amplitude differences between the peroneal and tibial nerves were found in both the Control and Dual-RPNI groups. Non-inferiority tests performed on Dual-RPNI group signal confidence intervals showed that activation was equivalent to the Control group in all but the peroneal RPNI construct during stance. The similar electromyographic activity

  5. Enhanced adenoviral gene delivery to motor and dorsal root ganglion neurons following injection into demyelinated peripheral nerves.

    PubMed

    Zhang, Yongjie; Zheng, Yiyan; Zhang, Yi Ping; Shields, Lisa B E; Hu, Xiaoling; Yu, Panpan; Burke, Darlene A; Wang, Heming; Jun, Cai; Byers, Jonathan; Whittemore, Scott R; Shields, Christopher B

    2010-08-15

    Injection of viral vectors into peripheral nerves may transfer specific genes into their dorsal root ganglion (DRG) neurons and motoneurons. However, myelin sheaths of peripheral axons block the entry of viral particles into nerves. We studied whether mild, transient peripheral nerve demyelination prior to intraneural viral vector injection would enhance gene transfer to target DRG neurons and motoneurons. The right sciatic nerve of C57BL/6 mice was focally demyelinated with 1% lysolecithin, and the left sciatic nerve was similarly injected with saline (control). Five days after demyelination, 0.5 microl of Ad5-GFP was injected into both sciatic nerves at the site of previous injection. The effectiveness of gene transfer was evaluated by counting GFP(+) neurons in the DRGs and ventral horns. After peripheral nerve demyelination, there was a fivefold increase in the number of infected DRG neurons and almost a 15-fold increase in the number of infected motoneurons compared with the control, nondemyelinated side. Focal demyelination reduced the myelin sheath barrier, allowing greater virus-axon contact. Increased CXADR expression on the demyelinated axons facilitated axoplasmic viral entry. No animals sustained any prolonged neurological deficits. Increased gene delivery into DRG neurons and motoneurons may provide effective treatment for amyotrophic lateral sclerosis, pain, and spinal cord injury.

  6. Genetic analysis of gravity signal transduction in roots

    NASA Astrophysics Data System (ADS)

    Masson, Patrick; Strohm, Allison; Baldwin, Katherine

    To grow downward into the soil, roots use gravity as a guide. Specialized cells, named stato-cytes, enable this directional growth response by perceiving gravity. Located in the columella region of the cap, these cells sense a reorientation of the root within the gravity field through the sedimentation of, and/or tension/pressure exerted by, dense amyloplasts. This process trig-gers a gravity signal transduction pathway that leads to a fast alkalinization of the cytoplasm and a change in the distribution of the plasma membrane-associated auxin-efflux carrier PIN3. The latter protein is uniformly distributed within the plasma membrane on all sides of the cell in vertically oriented roots. However, it quickly accumulates at the bottom side upon gravis-timulation. This process correlates with a preferential transport of auxin to the bottom side of the root cap, resulting in a lateral gradient across the tip. This gradient is then transported to the elongation zone where it promotes differential cellular elongation, resulting in downward curvature. We isolated mutations that affect gravity signal transduction at a step that pre-cedes cytoplasmic alkalinization and/or PIN3 relocalization and lateral auxin transport across the cap. arg1 and arl2 mutations identify a common genetic pathway that is needed for all three gravity-induced processes in the cap statocytes, indicating these genes function early in the pathway. On the other hand, adk1 affects gravity-induced PIN3 relocalization and lateral auxin transport, but it does not interfere with cytoplasmic alkalinization. ARG1 and ARL2 encode J-domain proteins that are associated with membranes of the vesicular trafficking path-way whereas ADK1 encodes adenosine kinase, an enzyme that converts adenosine derived from nucleic acid metabolism and the AdoMet cycle into AMP, thereby alleviating feedback inhibi-tion of this important methyl-donor cycle. Because mutations in ARG1 (and ARL2) do not completely eliminate

  7. Effects of lower limb neurodynamic mobilization on intraneural fluid dispersion of the fourth lumbar nerve root: an unembalmed cadaveric investigation

    PubMed Central

    Gilbert, Kerry K.; Smith, Michael P.; Sobczak, Stéphane; James, C. Roger; Sizer, Phillip S.; Brismée, Jean-Michel

    2015-01-01

    Objectives Manual and physical therapists incorporate neurodynamic mobilisation (NDM) to improve function and decrease pain. Little is known about the mechanisms by which these interventions affect neural tissue. The objective of this research was to assess the effects of repetitive straight leg raise (SLR) NDM on the fluid dynamics within the fourth lumbar nerve root in unembalmed cadavers. Methods A biomimetic solution (Toluidine Blue Stock 1% and Plasma) was injected intraneurally, deep to the epineurium, into the L4 nerve roots of seven unembalmed cadavers. The initial dye spread was allowed to stabilise and measured with a digital calliper. Once the initial longitudinal dye spread stabilised, an intervention strategy (repetitive SLR) was applied incorporating NDMs (stretch/relax cycles) at a rate of 30 repetitions per minute for 5 minutes. Post-intervention calliper measurements of the longitudinal dye spread were measured. Results The mean experimental posttest longitudinal dye spread measurement (1.1 ± 0.9 mm) was significantly greater (P = 0.02) than the initial stabilised pretest longitudinal dye spread measurement. Increases ranged from 0.0 to 2.6 mm and represented an average of 7.9% and up to an 18.1% increase in longitudinal dye spread. Discussion Passive NDM in the form of repetitive SLR induced a significant increase in longitudinal fluid dispersion in the L4 nerve root of human cadaveric specimen. Lower limb NDM may be beneficial in promoting nerve function by limiting or altering intraneural fluid accumulation within the nerve root, thus preventing the adverse effects of intraneural oedema. PMID:26955255

  8. Movements elicited by electrical stimulation of muscles, nerves, intermediate spinal cord, and spinal roots in anesthetized and decerebrate cats.

    PubMed

    Aoyagi, Yoichiro; Mushahwar, Vivian K; Stein, Richard B; Prochazka, Arthur

    2004-03-01

    Electrical stimulation offers the possibility of restoring motor function of paralyzed limbs after spinal-cord injury or stroke, but few data are available to compare possible sites of stimulation, such as muscle, nerve, spinal roots, or spinal cord. The aim of this study was to establish some characteristics of stimulation at these sites in the anesthetized and midcollicular decerebrate cat. The hind limb was constrained to move in the sagittal plane against a spring load. Ventral-root stimulation only produced movements down and back; the direction moved systematically backward the more caudal the stimulated roots. In contrast, dorsal-root stimulation only produced movements up and forward. Thus, neither method alone could produce the full range of normal movements. Muscle, nerve, and intraspinal stimulation within the intermediate regions of the gray matter generated discrete, selective movements in a wide range of directions. Muscle stimulation required an order of magnitude more current. Single microwire electrodes located in the spinal gray matter could activate a synergistic group of muscles, and generally had graded recruitment curves, but the direction of movement occasionally changed abruptly as stimulus strength increased. Nerve stimulation produced the largest movements against the spring load (>80% of the passive range of motion) and was the most reproducible from animal to animal. However, recruitment curves with nerve stimulation were quite steep, so fine control of movement might be difficult. The muscle, nerve, and spinal cord all seem to be feasible sites to restore motor function. The pros and cons from this study may be helpful in deciding the best site for a particular application, but further tests are needed in the chronically transected spinal cord to assess the applicability of these results to human patients.

  9. The BMP coreceptor RGMb promotes while the endogenous BMP antagonist noggin reduces neurite outgrowth and peripheral nerve regeneration by modulating BMP signaling.

    PubMed

    Ma, Chi H E; Brenner, Gary J; Omura, Takao; Samad, Omar A; Costigan, Michael; Inquimbert, Perrine; Niederkofler, Vera; Salie, Rishard; Sun, Chia Chi; Lin, Herbert Y; Arber, Silvia; Coppola, Giovanni; Woolf, Clifford J; Samad, Tarek A

    2011-12-14

    Repulsive guidance molecule b (RGMb) is a bone morphogenetic protein (BMP) coreceptor and sensitizer of BMP signaling, highly expressed in adult dorsal root ganglion (DRG) sensory neurons. We used a murine RGMb knock-out to gain insight into the physiological role of RGMb in the DRG, and address whether RGMb-mediated modulation of BMP signaling influences sensory axon regeneration. No evidence for altered development of the PNS and CNS was detected in RGMb(-/-) mice. However, both cultured neonatal whole DRG explants and dissociated DRG neurons from RGMb(-/-) mice exhibited significantly fewer and shorter neurites than those from wild-type littermates, a phenomenon that could be fully rescued by BMP-2. Moreover, Noggin, an endogenous BMP signaling antagonist, inhibited neurite outgrowth in wild-type DRG explants from naive as well as nerve injury-preconditioned mice. Noggin is downregulated in the DRG after nerve injury, and its expression is highly correlated and inversely associated with the known regeneration-associated genes, which are induced in the DRG by peripheral axonal injury. We show that diminished BMP signaling in vivo, achieved either through RGMb deletion or BMP inhibition with Noggin, retarded early axonal regeneration after sciatic nerve crush injury. Our data suggest a positive modulatory contribution of RGMb and BMP signaling to neurite extension in vitro and early axonal regrowth after nerve injury in vivo and a negative effect of Noggin.

  10. Apical control, gravitropic signaling, and the growth of lateral roots in Arabidopsis

    NASA Astrophysics Data System (ADS)

    Mullen, Jack L.; Wolverton, Chris; Hangarter, Roger P.

    Most research on gravity responses in plants has focused on primary roots and shoots, which typically grow in a vertical orientation. However, the patterns of lateral organ growth, which generally have large effects on overall plant architecture, are such that the organs are typically not vertical. In lateral roots of Arabidopsis, growth is initially in a nearly horizontal orientation but changes to a near-vertical orientation as the lateral root develops. Although the non-vertical lateral roots are gravitropically competent, following gravitropic reorientation of seedlings, the lateral roots on the upper flank of the primary root have different growth patterns from those on the lower side of the primary root. The differences are in part dependent on reorientation of the primary root, suggesting that gravitropic signaling from the primary root also contributes to the control of lateral root growth. The hormone auxin appears to play a role in this signaling between the primary and lateral roots, as auxin transport inhibitors applied to the primary root affect lateral root growth. Also, lateral roots of pin3 mutants, which are impaired in polar auxin transport, have altered lateral root orientations. However, other signals from the primary root tip also play an important role in regulating lateral root growth.

  11. T1-nerve root neuroma presenting with apical mass and Horner's syndrome

    PubMed Central

    2007-01-01

    Background The appearance of dumbbell neuroma of the first thoracic root is extremely rare. The extradural component of a T1-dumbbell neuroma may present as an apical mass. The diagnosis of hand weakness is complex and may be delayed in T1-neuroma because of absence of the palpable cervical mass. One-stage removal of a T1-root neuroma and its intrathoracic extension demanded an extended posterior midline approach in the sitting position. Case presentation A 51-year old man had suffered a traumatic partial tendon rupture of his wrist flexor muscles 6 years ago. Since the incident he occasionally felt fullness and tenderness in the affected forearm with some tingling in his fingers bilaterally. During the last two years the hand weakness was continuous and hypotrophy of the medial flexor and intrinsic hand muscles had become apparent. Electrophysiological studies revealed an ulnar neuropathy in addition to mild median and radial nerve dysfunction, including a mild contralateral carpal tunnel syndrome. The diagnostic work-up for multiple mononeuropathy in the upper extremity was negative. Repeated electrophysiological studies revealed fibrillations in the C7 paravertebral muscles on the affected side. Chest x-ray revealed a large round apical mass on the affected side. A Horner's syndrome was noted at this point of diagnostic work-up. MRI of the cervical and thoracic spine revealed a dumbbell T1 neuroma enlarging the intervertebral foramen at T1-2 and a 5 cm large extradural tumor with extension into the apex of the ipsilateral lung. The patient underwent surgery in sitting position using a left dorsal midline approach. Although the T1 root could not be preserved, the patient's neurological condition was unchanged after the surgery. Conclusion Extended posterior midline exposure described here using hemilaminectomy, unilateral facetectomy and costo-transversectomy is efficient and safe for one-stage removal of dumbbell tumors at the T1 level with a predominantly

  12. Role of neurotrophin signalling in the differentiation of neurons from dorsal root ganglia and sympathetic ganglia.

    PubMed

    Ernsberger, Uwe

    2009-06-01

    Manipulation of neurotrophin (NT) signalling by administration or depletion of NTs, by transgenic overexpression or by deletion of genes coding for NTs and their receptors has demonstrated the importance of NT signalling for the survival and differentiation of neurons in sympathetic and dorsal root ganglia (DRG). Combination with mutation of the proapoptotic Bax gene allows the separation of survival and differentiation effects. These studies together with cell culture analysis suggest that NT signalling directly regulates the differentiation of neuron subpopulations and their integration into neural networks. The high-affinity NT receptors trkA, trkB and trkC are restricted to subpopulations of mature neurons, whereas their expression at early developmental stages largely overlaps. trkC is expressed throughout sympathetic ganglia and DRG early after ganglion formation but becomes restricted to small neuron subpopulations during embryogenesis when trkA is turned on. The temporal relationship between trkA and trkC expression is conserved between sympathetic ganglia and DRG. In DRG, NGF signalling is required not only for survival, but also for the differentiation of nociceptors. Expression of neuropeptides calcitonin gene-related peptide and substance P, which specify peptidergic nociceptors, depends on nerve growth factor (NGF) signalling. ret expression indicative of non-peptidergic nociceptors is also promoted by the NGF-signalling pathway. Regulation of TRP channels by NGF signalling might specify the temperature sensitivity of afferent neurons embryonically. The manipulation of NGF levels "tunes" heat sensitivity in nociceptors at postnatal and adult stages. Brain-derived neurotrophic factor signalling is required for subpopulations of DRG neurons that are not fully characterized; it affects mechanical sensitivity in slowly adapting, low-threshold mechanoreceptors and might involve the regulation of DEG/ENaC ion channels. NT3 signalling is required for the

  13. Cyclic programmed cell death stimulates hormone signaling and root development in Arabidopsis.

    PubMed

    Xuan, Wei; Band, Leah R; Kumpf, Robert P; Van Damme, Daniël; Parizot, Boris; De Rop, Gieljan; Opdenacker, Davy; Möller, Barbara K; Skorzinski, Noemi; Njo, Maria F; De Rybel, Bert; Audenaert, Dominique; Nowack, Moritz K; Vanneste, Steffen; Beeckman, Tom

    2016-01-22

    The plant root cap, surrounding the very tip of the growing root, perceives and transmits environmental signals to the inner root tissues. In Arabidopsis thaliana, auxin released by the root cap contributes to the regular spacing of lateral organs along the primary root axis. Here, we show that the periodicity of lateral organ induction is driven by recurrent programmed cell death at the most distal edge of the root cap. We suggest that synchronous bursts of cell death in lateral root cap cells release pulses of auxin to surrounding root tissues, establishing the pattern for lateral root formation. The dynamics of root cap turnover may therefore coordinate primary root growth with root branching in order to optimize the uptake of water and nutrients from the soil.

  14. Chromate induces adventitious root formation via auxin signalling and SOLITARY-ROOT/IAA14 gene function in Arabidopsis thaliana.

    PubMed

    López-Bucio, José; Ortiz-Castro, Randy; Ruíz-Herrera, León Francisco; Juárez, Consuelo Vargas; Hernández-Madrigal, Fátima; Carreón-Abud, Yazmín; Martínez-Trujillo, Miguel

    2015-04-01

    Morphological root plasticity optimizes nutrient and water uptake by plants and is a promising target to improve tolerance to metal toxicity. Exposure to sublethal chromate [Cr(VI)] concentrations inhibits root growth, decreases photosynthesis and compromises plant development and productivity. Despite the increasing environmental problem that Cr(VI) represents, to date, the Cr tolerance mechanisms of plants are not well understood, and it remains to be investigated whether root architecture remodelling is important for plant adaptation to Cr(VI) stress. In this report, we analysed the growth response of Arabidopsis thaliana seedlings to concentrations of Cr(VI) that strongly repress primary and lateral root growth. Interestingly, adventitious roots started developing, branched and allowed seedlings to grow under highly growth-repressing Cr(VI) concentrations. Cr(VI) negatively regulates auxin transport and response gene expression in the primary root tip, as evidenced by decreased expression of auxin-related reporters DR5::GFP, DR5::uidA and PIN1::PIN1::GFP, and then, another auxin maximum is established at the site of adventitious root initiation that drives adventitious root organogenesis. Both primary root growth inhibition and adventitious root formation induced by high Cr(VI) levels are blocked by a gain-of-function mutation in the SOLITARY-ROOT/IAA14 gene of Arabidopsis. These data provide evidence that suggests a critical role for auxin transport and signalling via IAA14/SLR1 in the developmental program linking Cr(VI) to root architecture remodelling.

  15. Yiqi Huayu recipe relieves nerve root constriction induced radicular neuralgia by down-regulating TRPV4 expression in dorsal root ganglion

    PubMed Central

    Tang, Zhanying; Cui, Xuejun; Hu, Zhijun; Xiao, Jing; Li, Weiwei; Yang, Qiangling; Liu, Dan; Lin, Jie; Wang, Yongjun; Shi, Qi

    2015-01-01

    The aim of this study was to observe the effects of Yiqi Huayu recipe on TRPV4 expression in radicular neuralgia model induced by chronic constriction to the rat lumber nerve root. Healthy male SD rats were divided into 3 groups for radicular neuralgia (RN) model construction: the sham operation group, model groups (day 3, 7, 14 and 28), and medication groups (day 3, 7, 14 and 28). Von-Frey hairs test was performed to detect the 50% with drawal threshold (50% TPW) for rats of each group. The expression of TRPV4 in dorsal root ganglion was detected at both mRNA and protein level. Rats from all model groups displayed hyperalgesia with significantly reduced 50% TPW values compared with sham-operation group (P<0.01); Yiqi Huayu recipe medication groups showed higher 50% TPW than model group since 7 days post medication (P<0.01); the medication groups showed decreased TRPV4 expression than that of model groups (P<0.01). In conclusion, Yiqi Huayu recipe alleviates nerve root constriction induced radicular neuralgia by repressing TRPV4 expression in dorsal root ganglion. PMID:26770465

  16. Nerves Control Redox Levels in Mature Tissues Through Schwann Cells and Hedgehog Signaling

    PubMed Central

    Meda, Francesca; Gauron, Carole; Rampon, Christine; Teillon, Jérémie; Volovitch, Michel

    2016-01-01

    Abstract Aims: Recent advances in redox biology have emphasized the role of hydrogen peroxide (H2O2) in the modulation of signaling pathways and revealed that H2O2 plays a role in cellular remodeling in adults. Thus, an understanding of the mechanisms that control H2O2 levels in mature tissue would be of great interest. Results: We used a denervation strategy to demonstrate that sensory neurons are responsible for controlling H2O2 levels under normal conditions and after being lesioned. Moreover, we demonstrate that severed nerves respond to appendage amputation via the induction of Hedgehog signaling and that this signaling is responsible for H2O2 production in the wounded epidermis. Finally, we show that H2O2 and nerve growth are regulated via reciprocal action in adults. Innovation and Conclusion: These data support a new paradigm for the regulation of tissue homeostasis: H2O2 attracts nerves and nerves control H2O2 levels in a positive feedback loop. This finding suggests that the peripheral nerve redox environment could be a target for manipulating cell plasticity in adults. Antioxid. Redox Signal. 24, 299–311. PMID:26442784

  17. Charcot-Marie-Tooth syndrome and neurofibromatosis type 1 with multiple neurofibromas of the entire spinal nerve roots

    PubMed Central

    Onu, David O; Hunn, Andrew W; Peters-Willke, Jens

    2013-01-01

    The coexistence of polyneuropathy which has the definite clinical and electromyographical findings consistent with Charcot-Marie-Tooth (CMT) syndrome and neurofibromatosis type 1 (NF1) has infrequently been reported. We describe a patient with both CMT and NF1, who had multiple neurofibromas involving the entire spinal neural axis. In addition, he had multiple neurofibromas distributed within the ileopsoas and gluteus muscles and subcutaneous tissues. These lesions were detected readily by MRI and the patient underwent successful surgical resection of the largest tumours compressing bilateral C2 nerve roots. To our knowledge, this is the first reported case of CMT syndrome coexisting with NF1 in which multiple neurofibromas involved the entire spinal nerve roots. We discuss the diagnostic and therapeutic challenges, emphasising the role of MRI and electrophysiology in such cases and provide a literature review. PMID:23853192

  18. Charcot-Marie-Tooth syndrome and neurofibromatosis type 1 with multiple neurofibromas of the entire spinal nerve roots.

    PubMed

    Onu, David O; Hunn, Andrew W; Peters-Willke, Jens

    2013-07-13

    The coexistence of polyneuropathy which has the definite clinical and electromyographical findings consistent with Charcot-Marie-Tooth (CMT) syndrome and neurofibromatosis type 1 (NF1) has infrequently been reported. We describe a patient with both CMT and NF1, who had multiple neurofibromas involving the entire spinal neural axis. In addition, he had multiple neurofibromas distributed within the ileopsoas and gluteus muscles and subcutaneous tissues. These lesions were detected readily by MRI and the patient underwent successful surgical resection of the largest tumours compressing bilateral C2 nerve roots. To our knowledge, this is the first reported case of CMT syndrome coexisting with NF1 in which multiple neurofibromas involved the entire spinal nerve roots. We discuss the diagnostic and therapeutic challenges, emphasising the role of MRI and electrophysiology in such cases and provide a literature review.

  19. [Electrostimulation of anterior sacral nerve roots in spinal cord injury patients (evaluation of the 1st 25 cases)].

    PubMed

    Colombel, P; Egon, G; Isambert, J L

    1992-02-01

    The authors analyse the first 25 patients with spinal cord injuries treated by G. Brindley's technique based on section of the posterior sacral nerve roots to control detrusor hyperexcitability and electrostimulation of the anterior sacral nerve roots to ensure bladder emptying and to facilitate erection and defecation. The indications for this technique are essentially unstable bladders with incontinence and certain hypoactive bladders. The following results were obtained: Acquisition of continence in 90% of cases. Bladder capacity was always greatly increased. Almost complete bladder emptying in the majority of cases. Very marked reduction in urinary tract infection. Regularization of intestinal transit. The complications of this surgery were uncommon but serious: C.S.F. leaks, Postoperative denervations. Sepsis. Material or cable failure.

  20. Neurosurgical procedures, spinal nerve roots - one stage removal of thoracic dumb-bell tumor: role of spinal evoked potential.

    PubMed

    Srivastava, Dharmendra Kumar; Singh, Deepak; Tiwari, Bhuwan Chandra; Awasthi, Namarata; Hussain, Nuzhat

    2014-02-01

    We report a rare case of benign thoracic dumb-bell tumor in the upper posterior mediastinum, which was successfully removed by posterolateral thoracotomy and foraminotomy, using intraoperative monitoring of spinal motor-evoked potentials. This technique has many advantages including minimal morbidity and mortality, a single incision, one-step complete resection with adequate exposure, spinal stabilization, avoidance of laminectomy, nerve root identification, and good predicted postoperative function.

  1. [Teflon granuloma after microvascular decompression of the trigeminal nerve root in a patient with recurrent trigeminal neuralgia].

    PubMed

    Rzaev, D A; Kulikova, E V; Moysak, G I; Voronina, E I; Ageeva, T A

    2016-01-01

    The use of a Teflon implant for Jannetta surgery in patients with trigeminal neuralgia is complicated in rare cases by the development of a Teflon granuloma and can cause recurrent facial pain. The article presents a clinical case of a Teflon granuloma developed after microvascular decompression of the trigeminal nerve root, describes the surgical findings and histological picture, and analyzes the literature, causes of granuloma development, and recommendations for treatment of these patients.

  2. Assessment on selectivity of multi-contact cuff electrode for recording peripheral nerve signals using Fitzhugh-Nagumo model of nerve excitation.

    PubMed

    Taghipour-Farshi, Hamed; Frounchi, Javad; Ahmadiasl, Nasser; Shahabi, Parviz; Salekzamani, Yaghoub

    2016-11-21

    Nerve cuff electrodes provide a safe technique for recording nerve signals. Defining a more realized modeling to investigate the selectivity of a cuff electrode in recording from peripheral nervous system is an interesting field of research. A four-contact cuff electrode was modeled to evaluate selective recording from a peripheral nerve. Fitzhugh-Nagumo equations were used to model the electromagnetic fields generated by active nerves and electrodes and the ``selectivity index'' used to quantify the selective property of the cuff electrode. The action potentials amplitude and impulse velocity generated by Fitzhugh-Nagumo model are similar to real-life nerve measurements according to the literature. The electrical field distribution caused by the impulse propagation along a specific nerve was the maximum near the corresponding contact. Also, the selectivity was increased with increasing the distance between the active sources and the number of contacts. The results of this research showed that Fitzhugh-Nagumo equations could model the nerve excitation accurately and could be used in computer simulation for studying nervous systems. Also, using these equations indicated that multi-contact cuff electrodes could be used in recording peripheral nerve signals in order to discriminate active fascicles in a nerve bundle.

  3. A purely extradural lumbar nerve root cavernoma mimicking acute myeloid leukemia recurrence: Case report and literature review

    PubMed Central

    Oliveira, Edson; Lavrador, José Pedro; Teixeira, Joaquim; Pignatelli, Alexandra; Livraghi, Sérgio

    2016-01-01

    Background: Myeloid sarcoma (MS) is a malignant tumor that usually occurs concomitantly with or following acute myeloid leukemia (AML). Cavernomas are benign congenital malformations that are unusual in the spine and exceedingly rare in pure extradural locations. Case Description: We report a 73-year-old female with a previous medical history of AML in remission for 3 years who presented with symptoms of low back pain and right lower extremity radiculopathy. A magnetic resonance scan showed an extradural, foraminal lesion centered at the L2 level involving the right L2 nerve root. In view of the history of AML, this lesion was potentially considered MS, a form of AML relapse. Surgery consisting of a right L1 and L2 hemilaminectomy facilitated gross total resection of the purely extradural lesion the proved histologically to be a cavernoma. Conclusion: In patients with a history of leukemia, MS must be considered in the differential diagnosis for any epidural or nerve root lesion that appears following treatment. Although rare, cavernomas must be considered among the differential diagnoses for epidural nerve root lesions in the setting of AML. PMID:28028446

  4. Coding of signals in noise by amphibian auditory nerve fibers.

    PubMed

    Narins, P M

    1987-01-01

    Rate-level (R-L) functions derived for pure-tones and pure-tones in broadband noise were obtained for auditory nerve fibers in the treefrog, Eleutherodactylus coqui. Normalized R-L functions for low-frequency, low-threshold fibers exhibit a horizontal rightward shift in the presence of broadband background noise. The magnitude of this shift is directly proportional to the noise spectrum level, and inversely proportional to the fiber's threshold. R-L functions for mid- and high-frequency fibers also show a horizontal shift, but to a lesser degree, consistent with their elevated thresholds relative to the low-frequency fibers. The implications of these findings for the processing of biologically significant sounds in the high levels of background noise in the animal's natural habitat are considered.

  5. Microelectronic neural bridge for signal regeneration and function rebuilding over two separate nerves

    NASA Astrophysics Data System (ADS)

    Xiaoyan, Shen; Zhigong, Wang; Xiaoying, Lü; Shushan, Xie; Zonghao, Huang

    2011-06-01

    According to the feature of neural signals, a micro-electronic neural bridge (MENB) has been designed. It consists of two electrode arrays for neural signal detection and functional electrical stimulation (FES), and a microelectronic circuit for signal amplifying, processing, and FES driving. The core of the system is realized in 0.5-μm CMOS technology and used in animal experiments. A special experimental strategy has been designed to demonstrate the feasibility of the system. With the help of the MENB, the withdrawal reflex function of the left/right leg of one spinal toad has been rebuilt in the corresponding leg of another spinal toad. According to the coherence analysis between the source and regenerated neural signals, the controlled spinal toad's sciatic nerve signal is delayed by 0.72 ms in relation to the sciatic nerve signal of the source spinal toad and the cross-correlation function reaches a value of 0.73. This shows that the regenerated signal is correlated with the source sciatic signal significantly and the neural activities involved in reflex function have been regenerated. The experiment demonstrates that the MENB is useful in rebuilding the neural function between nerves of different bodies.

  6. Sympathetic nerve stimulation induces local endothelial Ca2+ signals to oppose vasoconstriction of mouse mesenteric arteries.

    PubMed

    Nausch, Lydia W M; Bonev, Adrian D; Heppner, Thomas J; Tallini, Yvonne; Kotlikoff, Michael I; Nelson, Mark T

    2012-02-01

    It is generally accepted that the endothelium regulates vascular tone independent of the activity of the sympathetic nervous system. Here, we tested the hypothesis that the activation of sympathetic nerves engages the endothelium to oppose vasoconstriction. Local inositol 1,4,5-trisphosphate (IP(3))-mediated Ca(2+) signals ("pulsars") in or near endothelial projections to vascular smooth muscle (VSM) were measured in an en face mouse mesenteric artery preparation. Electrical field stimulation of sympathetic nerves induced an increase in endothelial cell (EC) Ca(2+) pulsars, recruiting new pulsar sites without affecting activity at existing sites. This increase in Ca(2+) pulsars was blocked by bath application of the α-adrenergic receptor antagonist prazosin or by TTX but was unaffected by directly picospritzing the α-adrenergic receptor agonist phenylephrine onto the vascular endothelium, indicating that nerve-derived norepinephrine acted through α-adrenergic receptors on smooth muscle cells. Moreover, EC Ca(2+) signaling was not blocked by inhibitors of purinergic receptors, ryanodine receptors, or voltage-dependent Ca(2+) channels, suggesting a role for IP(3), rather than Ca(2+), in VSM-to-endothelium communication. Block of intermediate-conductance Ca(2+)-sensitive K(+) channels, which have been shown to colocalize with IP(3) receptors in endothelial projections to VSM, enhanced nerve-evoked constriction. Collectively, our results support the concept of a transcellular negative feedback module whereby sympathetic nerve stimulation elevates EC Ca(2+) signals to oppose vasoconstriction.

  7. Sympathetic nerve stimulation induces local endothelial Ca2+ signals to oppose vasoconstriction of mouse mesenteric arteries

    PubMed Central

    Nausch, Lydia W. M.; Bonev, Adrian D.; Heppner, Thomas J.; Tallini, Yvonne; Kotlikoff, Michael I.

    2012-01-01

    It is generally accepted that the endothelium regulates vascular tone independent of the activity of the sympathetic nervous system. Here, we tested the hypothesis that the activation of sympathetic nerves engages the endothelium to oppose vasoconstriction. Local inositol 1,4,5-trisphosphate (IP3)-mediated Ca2+ signals (“pulsars”) in or near endothelial projections to vascular smooth muscle (VSM) were measured in an en face mouse mesenteric artery preparation. Electrical field stimulation of sympathetic nerves induced an increase in endothelial cell (EC) Ca2+ pulsars, recruiting new pulsar sites without affecting activity at existing sites. This increase in Ca2+ pulsars was blocked by bath application of the α-adrenergic receptor antagonist prazosin or by TTX but was unaffected by directly picospritzing the α-adrenergic receptor agonist phenylephrine onto the vascular endothelium, indicating that nerve-derived norepinephrine acted through α-adrenergic receptors on smooth muscle cells. Moreover, EC Ca2+ signaling was not blocked by inhibitors of purinergic receptors, ryanodine receptors, or voltage-dependent Ca2+ channels, suggesting a role for IP3, rather than Ca2+, in VSM-to-endothelium communication. Block of intermediate-conductance Ca2+-sensitive K+ channels, which have been shown to colocalize with IP3 receptors in endothelial projections to VSM, enhanced nerve-evoked constriction. Collectively, our results support the concept of a transcellular negative feedback module whereby sympathetic nerve stimulation elevates EC Ca2+ signals to oppose vasoconstriction. PMID:22140050

  8. Surgical treatment for total root avulsion type brachial plexus injuries by neurotization: A prospective comparison study between total and hemicontralateral C7 nerve root transfer

    PubMed Central

    Tu, Yuan-Kun; Tsai, Yi-Jung; Chang, Chih-Han; Su, Fong-Chin; Hsiao, Chih-Kun; Tan, Jacqueline Siau-Woon

    2014-01-01

    Purpose: We conducted a clinical study to evaluate the effects of neurotization, especially comparing the total contralateral C7 (CC7) root transfer to hemi-CC7 transfer, on total root avulsion brachial plexus injuries (BPI). Methods: Forty patients who received neurotization for BPI were enrolled in this prospective study. Group 1 (n = 20) received hemi-CC7 transfer for hand function, while group 2 (n = 20) received total-CC7 transfer. Additional neurotization included spinal accessory, phrenic, and intercostal nerve transfer for shoulder and elbow function. The results were evaluated with an average of 6 years follow-up. Results: Group 1 had fewer donor site complications (15%) than group 2 (45%); group 2 had significantly better hand M3 and M4 motor function (65%) than group 1 (30%; P = 0.02). There was no difference in sensory recovery. Significantly, better shoulder function was obtained by simultaneous neurotization on both suprascapular and axillary nerves. Conclusions: Total-CC7 transfer had better hand recovery but more donor complications than hemi-CC7. Neurotization on both supra-scapular and axillary nerves improved shoulder recovery. © 2013 The Authors. Microsurgery published by Wiley Periodicals, Inc. Microsurgery 34:91–101, 2014. PMID:23913440

  9. Purinergic signalling underlies transforming growth factor‐β‐mediated bladder afferent nerve hyperexcitability

    PubMed Central

    Gonzalez, Eric J.; Heppner, Thomas J.; Nelson, Mark T.

    2016-01-01

    Key points The sensory components of the urinary bladder are responsible for the transduction of bladder filling and are often impaired with neurological injury or disease.Elevated extracellular ATP contributes, in part, to bladder afferent nerve hyperexcitability during urinary bladder inflammation or irritation.Transforming growth factor‐β1 (TGF‐β1) may stimulate ATP release from the urothelium through vesicular exocytosis mechanisms with minimal contribution from pannexin‐1 channels to increase bladder afferent nerve discharge.Bladder afferent nerve hyperexcitability and urothelial ATP release with CYP‐induced cystitis is decreased with TGF‐β inhibition.These results establish a causal link between an inflammatory mediator, TGF‐β, and intrinsic signalling mechanisms of the urothelium that may contribute to the altered sensory processing of bladder filling. Abstract The afferent limb of the micturition reflex is often compromised following bladder injury, disease and inflammatory conditions. We have previously demonstrated that transforming growth factor‐β (TGF‐β) signalling contributes to increased voiding frequency and decreased bladder capacity with cystitis. Despite the functional presence of TGF‐β in bladder inflammation, the precise mechanisms of TGF‐β mediating bladder dysfunction are not yet known. Thus, the present studies investigated the sensory components of the urinary bladder that may underlie the pathophysiology of aberrant TGF‐β activation. We utilized bladder–pelvic nerve preparations to characterize bladder afferent nerve discharge and the mechanisms of urothelial ATP release with distention. Our findings indicate that bladder afferent nerve discharge is sensitive to elevated extracellular ATP during pathological conditions of urinary bladder inflammation or irritation. We determined that TGF‐β1 may increase bladder afferent nerve excitability by stimulating ATP release from the urothelium via vesicular

  10. Glucose and auxin signaling interaction in controlling Arabidopsis thaliana seedlings root growth and development.

    PubMed

    Mishra, Bhuwaneshwar S; Singh, Manjul; Aggrawal, Priyanka; Laxmi, Ashverya

    2009-01-01

    Plant root growth and development is highly plastic and can adapt to many environmental conditions. Sugar signaling has been shown to affect root growth and development by interacting with phytohormones such as gibberellins, cytokinin and abscisic acid. Auxin signaling and transport has been earlier shown to be controlling plant root length, number of lateral roots, root hair and root growth direction. Increasing concentration of glucose not only controls root length, root hair and number of lateral roots but can also modulate root growth direction. Since root growth and development is also controlled by auxin, whole genome transcript profiling was done to find out the extent of interaction between glucose and auxin response pathways. Glucose alone could transcriptionally regulate 376 (62%) genes out of 604 genes affected by IAA. Presence of glucose could also modulate the extent of regulation 2 fold or more of almost 63% genes induced or repressed by IAA. Interestingly, glucose could affect induction or repression of IAA affected genes (35%) even if glucose alone had no significant effect on the transcription of these genes itself. Glucose could affect auxin biosynthetic YUCCA genes family members, auxin transporter PIN proteins, receptor TIR1 and members of a number of gene families including AUX/IAA, GH3 and SAUR involved in auxin signaling. Arabidopsis auxin receptor tir1 and response mutants, axr2, axr3 and slr1 not only display a defect in glucose induced change in root length, root hair elongation and lateral root production but also accentuate glucose induced increase in root growth randomization from vertical suggesting glucose effects on plant root growth and development are mediated by auxin signaling components. Our findings implicate an important role of the glucose interacting with auxin signaling and transport machinery to control seedling root growth and development in changing nutrient conditions.

  11. Glucose and Auxin Signaling Interaction in Controlling Arabidopsis thaliana Seedlings Root Growth and Development

    PubMed Central

    Aggrawal, Priyanka; Laxmi, Ashverya

    2009-01-01

    Background Plant root growth and development is highly plastic and can adapt to many environmental conditions. Sugar signaling has been shown to affect root growth and development by interacting with phytohormones such as gibberellins, cytokinin and abscisic acid. Auxin signaling and transport has been earlier shown to be controlling plant root length, number of lateral roots, root hair and root growth direction. Principal Findings Increasing concentration of glucose not only controls root length, root hair and number of lateral roots but can also modulate root growth direction. Since root growth and development is also controlled by auxin, whole genome transcript profiling was done to find out the extent of interaction between glucose and auxin response pathways. Glucose alone could transcriptionally regulate 376 (62%) genes out of 604 genes affected by IAA. Presence of glucose could also modulate the extent of regulation 2 fold or more of almost 63% genes induced or repressed by IAA. Interestingly, glucose could affect induction or repression of IAA affected genes (35%) even if glucose alone had no significant effect on the transcription of these genes itself. Glucose could affect auxin biosynthetic YUCCA genes family members, auxin transporter PIN proteins, receptor TIR1 and members of a number of gene families including AUX/IAA, GH3 and SAUR involved in auxin signaling. Arabidopsis auxin receptor tir1 and response mutants, axr2, axr3 and slr1 not only display a defect in glucose induced change in root length, root hair elongation and lateral root production but also accentuate glucose induced increase in root growth randomization from vertical suggesting glucose effects on plant root growth and development are mediated by auxin signaling components. Conclusion Our findings implicate an important role of the glucose interacting with auxin signaling and transport machinery to control seedling root growth and development in changing nutrient conditions. PMID

  12. Neuromuscular nicotinic receptors mediate bladder contractions following bladder reinnervation with somatic to autonomic nerve transfer after decentralization by spinal root transection

    PubMed Central

    Gomez-Amaya, Sandra M.; Barbe, Mary F.; Lamarre, Neil S.; Brown, Justin M.; Braverman, Alan S.; Ruggieri, Michael R.

    2015-01-01

    This study investigates whether the reinnervated neuronal pathway mediates contraction via the same neurotransmitter and receptor mechanisms as the original pathway. Following bladder decentralization by transection of sacral roots, peripheral nerve transfer was performed with bilateral genitofemoral to pelvic nerve transfer (GFNT) and unilateral (left) femoral nerve to bilateral pelvic nerve transfer (FNT). Reinnervation was assessed 7.5 months post operatively by monitoring bladder pressure during electrical stimulation of the transferred nerves, spinal ventral roots, and spinal cord. Of the 17 animals with GFNT, 14 (82%) demonstrated functional bladder reinnervation as evidenced by increased bladder pressure during stimulation of the transferred GFN or the L3 or L4 spinal ventral roots. Lumbar spinal cord stimulation caused increased bladder pressure in 9 of 10 (90%) animals with FNT. Succinylcholine (SCh) virtually eliminated bladder pressure increases induced by electrical stimulation of the transferred somatic nerves or the lumbar spinal segments that contribute axons to these donor nerves. In control animals (either un-operated or sham-operated) SCh had no effect on nerve evoked bladder pressure increases but substantially reduced urethra and anal sphincter pressure induced by stimulation of either the lumbosacral spinal cord or the S2-3 spinal ventral roots. The reinnervated detrusor muscles of GFNT and FNT animals also contained increased alpha1 nicotinic receptor subunit immunoreactivity in punctate dots on detrusor muscle fascicles and in neuronal cell bodies, staining not observed in control animals. PMID:25444958

  13. Bayesian spatial filters for the extraction of source signals, a study in the peripheral nerve

    PubMed Central

    Tang, Yuang; Durand, Dominique M.

    2015-01-01

    The ability to extract physiological source signals to control various prosthetics offer tremendous therapeutic potential to improve the quality of life for patients suffering from motor disabilities. Regardless of the modality, recordings of physiological source signals are contaminated with noise and interference along with crosstalk between the sources. These impediments render the task of isolating potential physiological source signals for control difficult. In this paper, a novel Bayesian Source Filter for signal Extraction (BSFE) algorithm for extracting physiological source signals for control is presented. The BSFE algorithm is based on the source localization method Champagne and constructs spatial filters using Bayesian methods that simultaneously maximize the signal to noise ratio of the recovered source signal of interest while minimizing crosstalk interference between sources. When evaluated over peripheral nerve recordings obtained in-vivo, the algorithm achieved the highest signal to noise interference ratio (>7.00±3.45dB) amongst the group of methodologies compared with average correlation between the extracted source signal and the original source signal > 0.93. The results support the efficacy of the BSFE algorithm for extracting source signals from the peripheral nerve or as a pre-filtering stage for BCI methods. PMID:24608686

  14. Effect of FGF-2 and sciatic nerve grafting on ChAT expression in dorsal root ganglia neurons of spinal cord transected rats.

    PubMed

    Guzen, Fausto Pierdoná; de Araújo, Dayane Pessoa; Lucena, Eudes Euler de Souza; de Morais, Hécio Henrique Araújo; Cavalcanti, José Rodolfo Lopes de Paiva; do Nascimento, Expedito Silva; Costa, Miriam Stela Maris de Oliveira; Cavalcante, Jeferson Sousa

    2016-03-11

    Neurotrophic factors and peripheral nerves are known to be good substrates for bridging CNS trauma. The involvement of fibroblast growth factor-2 (FGF-2) activation in the dorsal root ganglion (DRG) was examined following spinal cord injury in the rat. We evaluated whether FGF-2 increases the ability of a sciatic nerve graft to enhance neuronal plasticity, in a gap promoted by complete transection of the spinal cord. The rats were subjected to a 4mm-long gap at low thoracic level and were repaired with saline (Saline or control group, n=10), or fragment of the sciatic nerve (Nerve group, n=10), or fragment of the sciatic nerve to which FGF-2 (Nerve+FGF-2 group, n=10) had been added immediately after lesion. The effects of the FGF-2 and fragment of the sciatic nerve grafts on neuronal plasticity were investigated using choline acetyl transferase (ChAT)-immunoreactivity of neurons in the dorsal root ganglion after 8 weeks. Preservation of the area and diameter of neuronal cell bodies in dorsal root ganglion (DRG) was seen in animals treated with the sciatic nerve, an effect enhanced by the addition of FGF-2. Thus, the addition of exogenous FGF-2 to a sciatic nerve fragment grafted in a gap of the rat spinal cord submitted to complete transection was able to improve neuroprotection in the DRG. The results emphasized that the manipulation of the microenvironment in the wound might amplify the regenerative capacity of peripheral neurons.

  15. Nerve growth factor signal transduction in mature pig oligodendrocytes.

    PubMed

    Althaus, H H; Hempel, R; Klöppner, S; Engel, J; Schmidt-Schultz, T; Kruska, L; Heumann, R

    1997-12-01

    It has previously been shown that nerve growth factor (NGF) is of functional significance for mature pig oligodendrocytes (OLs) in culture. The present data give evidence for the expression of TrkA, the so-called high-affinity NGF receptor, and of p75NTR, the so-called low-affinity NGF receptor. TrkA is upregulated during culturing, in contrast to the p75 receptor. Exposure of OLs to NGF induces an autophosphorylation of TrkA via its intrinsic tyrosine kinase. K-252a inhibits the TrkA autophosphorylation, which reduces the OL process formation to control levels. To the tyrosine-phosphorylated sites of TrkA several proteins, such as phospholipase C-gamma1, the adaptor protein SHC, the phosphotyrosine phosphatase SH-PTP2 (SYP) associate via their SH2 phosphotase SH-PTP2 domain. The association of SHC to TrkA is shown by co-immunoprecipitation. Indirect evidence for a possible activation of PLC-gamma1 is given by an NGF-induced increase of oligodendroglial [Ca2+]i. Downstream from TrkA, a mitogen-activated protein kinase cascade, which includes Erk1 and Erk2, is operating. An in-gel myelin basic protein kinase assay revealed that NGF activates predominantly Erk1. Finally, it is shown that NGF stimulates expression of c-fos.

  16. Assessment of Anteroposterior Subpedicular Approach and Oblique Scotty Dog Subpedicular Approach for Selective Nerve Root Block

    PubMed Central

    Yeh, Yu-Cheng; Luo, Chi-An; Joey-Tan, Kit-Yang

    2017-01-01

    Background The technique used to administer a selective nerve root block (SNRB) varies depending on individual expertise. Both the anteroposterior (AP) subpedicular approach and oblique Scotty dog subpedicular approach are widely practiced. However, the literature does not provide a clear consensus regarding which approach is more suitable. Hence, we decided to analyse the procedural parameters and clinical outcomes following SNRBs using these two approaches. Methods Patients diagnosed with a single lumbar herniated intervertebral disc (HIVD) refractory to conservative management but not willing for immediate surgery were selected for a prospective nonrandomized comparative study. An SNRB was administered as a therapeutic alternative using the AP subpedicular approach in one group (n = 25; mean age, 45 ± 5.4 years) and the oblique Scotty dog subpedicular approach in the other group (n = 22; mean age, 43.8 ± 4.7 years). Results were compared in terms of the duration of the procedure, the number of C-arm exposures, accuracy, pain relief, functional outcome and the duration of relief. Results Our results suggest that the oblique Scotty dog subpedicular approach took a significantly longer duration (p = 0.02) and a greater number of C-arm exposures (p = 0.001). But, its accuracy of needle placement was 95.5% compared to only 72% using the AP subpedicular approach (p = 0.03). There was no significant difference in terms of clinical outcomes between these approaches. Conclusions The AP subpedicular approach was simple and facile, but the oblique Scotty dog subpedicular approach was more accurate. However, a brief window period of pain relief was achieved irrespective of the approaching technique used. PMID:28261430

  17. The role of vascular damage and fibrosis in the pathogenesis of nerve root damage.

    PubMed

    Jayson, M I

    1992-06-01

    Vascular damage and fibrosis are common within the vertebral canal and intervertebral foramen. The grossest examples occur in patients who have previously undergone oil-based myelography or spinal surgery. The mechanisms of fibrosis in the latter instance may be related to persisting cotton debris from sponges used during the operation. This debris may act as a fibrogenic stimulus. However, in cadaveric studies of nonoperated spines, the author and his colleagues have found clear evidence of vascular damage and fibrosis within the spines, and this vascular damage is significantly related to the severity of degenerative disk disease. Degenerative disk disease with osteophytic proliferation and disk protrusion may lead to compression of epidural veins with dilation of noncompressed veins. There is a significant statistical relationship between the extent of the disk degeneration and prolapse and the evidence of venous compression and dilatation. The dilatated veins may contain antemortem thromboses. In turn, there is a significant statistical relationship between the evidence for venous obstruction and perineural fibrosis. Such a relationship also exists between perineural fibrosis and neuronal atrophy. If therefore appears likely that venous obstruction with resultant hypoxia is an important mechanism leading to nerve root damage. In the peripheral blood, significant defects in the fibrinolytic system correlate with the severity of the symptoms. However, it was not possible to correlate these changes with individual clinical or imaging features. These fibrinolytic changes are recognized as markers of vascular damage and may reflect the pathologic processes that the author and his colleagues have demonstrated. It is uncertain whether they play any secondary pathogenic role in the chronicity of these back problems.(ABSTRACT TRUNCATED AT 250 WORDS)

  18. Blood-nerve barrier: distribution of anionic sites on the endothelial plasma membrane and basal lamina of dorsal root ganglia.

    PubMed

    Bush, M S; Reid, A R; Allt, G

    1991-09-01

    Previous investigations of the blood-nerve barrier have correlated the greater permeability of ganglionic endoneurial vessels, compared to those of nerve trunks, with the presence of fenestrations and open intercellular junctions. Recent studies have demonstrated reduced endothelial cell surface charge in blood vessels showing greater permeability. To determine the distribution of anionic sites on the plasma membranes and basal laminae of endothelial cells in dorsal root ganglia, cationic colloidal gold and cationic ferritin were used. Electron microscopy revealed the existence of endothelial microdomains with differing labelling densities. Labelling indicated that caveolar and fenestral diaphragms and basal laminae are highly anionic at physiological pH, luminal plasma membranes and endothelial processes are moderately charged and abluminal plasma membranes are weakly anionic. Tracers did not occur in caveolae or cytoplasmic vesicles. In vitro tracer experiments at pH values of 7.3, 5.0, 3.5 and 2.0 indicated that the anionic charge on the various endothelial domains was contributed by chemical groups with differing pKa values. In summary, the labelling of ganglionic and sciatic nerve vessels was similar except for the heavy labelling of diaphragms in a minority of endoneurial vessels in ganglia. This difference is likely to account in part for the greater permeability of ganglionic endoneurial vessels. The results are discussed with regard to the blood-nerve and -brain barriers and vascular permeability in other tissues and a comparison made between the ultrastructure and anionic microdomains of epi-, peri- and endoneurial vessels of dorsal root ganglia and sciatic nerves.

  19. Root jasmonates signaling regulates folivore-induced shoot metabolites and increases Nicotiana attenuata resistance

    PubMed Central

    Fragoso, Variluska; Rothe, Eva; Baldwin, Ian T.; Kim, Sang-Gyu

    2016-01-01

    Summary While JA signaling is widely accepted as mediating plant resistance to herbivores, and the importance of the roots in plant defenses is recently being recognized, the function of root-JA production or perception in aboveground plant defense remains unstudied. To restrain JA impairment to the roots, we micrografted wild type Nicotiana attenuata shoots to the roots of transgenic plants impaired in JA signaling, and evaluated ecological relevant traits under glasshouse and field conditions. Root-JA synthesis, conjugation, and perception are involved in regulating nicotine production in roots. Strikingly, roots regulated leaf JA and ABA levels, which in turn, explain differences in nicotine transport from the roots to the shoot via the transpiration stream. Root-JA signaling also regulates the accumulation of other shoot metabolites; these account for plant resistance against a generalist, Spodoptera littoralis, and a specialist herbivore, Manduca sexta. In N. attenuata’s native habitat, silencing root-JA synthesis increased the shoot damage inflicted by Empoasca leafhoppers, which are able to select natural jasmonate mutants. Silencing JA perception in roots also increased damage by Tupiocoris notatus. Thus, the whole is greater than the sum of its parts: root jasmonate signaling profoundly tailors leaf defense responses to aboveground attack. PMID:24580101

  20. The role of graded nerve root compression on axonal damage, neuropeptide changes, and pain-related behaviors.

    PubMed

    Hubbard, Raymond D; Quinn, Kyle P; Martínez, Joan J; Winkelstein, Beth A

    2008-11-01

    Rapid neck motions can load cervical nerve roots and produce persistent pain. This study investigated the cellular basis of radicular pain and mechanical implications of tissue loading rate. A range of peak loads was applied in an in vivo rat model of dorsal root compression, and mechanical allodynia (i.e. pain) was measured. Axonal damage and nociceptive mediators were assessed in the axons and cell bodies of compressed dorsal roots in separate groups of rats at days 1 and 7 after injury. In the day 7 group, damage in the compressed axons, evaluated by decreased heavy chain neurofilament immunoreactivity, was increased for compressions above a load of 34.08 mN, which is similar to the load-threshold for producing persistent pain in that model. Also, the neuropeptide substance P and glial cell line-derived neurotrophic factor and its receptor significantly decreased (p < 0.02) with increasing load in the small nociceptive neurons of the dorsal root ganglion, suggesting that axonal damage may also decrease neurotrophic support in injured nociceptive afferent fibers. In a separate study, roots were compressed at 2mm/s, and held, to develop a quasi-linear viscoelastic model that was validated through comparisons to quasistatic loading. The model demonstrated that nearly 23% less displacement was required to reach the axonal injury load threshold during dynamic loading than for quasistatic rates. Together, these studies demonstrate that nerve root compressions that produce pain symptoms are sufficient to mediate nociceptive cellular changes, and that thresholds for pain and nociceptive pathophysiology may be lower for dynamic loading scenarios.

  1. Transfer of a fascicle from the posterior cord to the suprascapular nerve after injury of the upper roots of the brachial plexus: technical case report.

    PubMed

    Martins, Roberto Sergio; Siqueira, Mario Gilberto; Heise, Carlos Otto; Teixeira, Manoel Jacobsen

    2009-10-01

    A new nerve transfer technique using a healthy fascicle of the posterior cord for suprascapular nerve reconstruction is presented. This technique was used in a patient with posttraumatic brachial plexopathy resulting in upper trunk injury with proximal root stumps that were unavailable for grafting associated with multiple nerve dysfunction. A 45-year-old man sustained a right brachial plexus injury after a bicycle accident. Clinical evaluation and electromyography indicated upper trunk involvement. Trapezius muscle function and triceps strength were normal on physical examination. The patient underwent a combined supra- and infraclavicular approach to the brachial plexus. A neuroma-in-continuity of the upper trunk and fibrotic C5 and C6 roots were identified. Electrical stimulation of the phrenic and spinal accessory nerves produced no response. The suprascapular nerve was dissected from the upper trunk, transected, and rerouted to the infraclavicular fossa. A healthy fascicle of the posterior cord to the triceps muscle was transferred to the suprascapular nerve. At the time of the 1-year follow-up evaluation, arm abduction against gravity and external rotation reached 40 and 34 degrees, respectively. The posterior cord can be used as a source of donor fascicle to the suprascapular nerve after its infraclavicular relocation. This new intraplexal nerve transfer could be applied in patients with isolated injury of the upper trunk and concomitant lesion of the extraplexal nerve donors usually used for reinnervation of the suprascapular nerve.

  2. S3 Dorsal Root Ganglion/Nerve Root Stimulation for Refractory Postsurgical Perineal Pain: Technical Aspects of Anchorless Sacral Transforaminal Lead Placement

    PubMed Central

    Zuidema, X.; Breel, J.; Wille, F.

    2016-01-01

    Chronic perineal pain limits patients in physical and sexual activities, leading to social and psychological distress. In most cases, this pain develops after surgery in the urogenital area or as a consequence of trauma. Neuromodulation is one of the options in chronic postsurgical perineal pain treatment. We present a case of refractory perineal pain after right sided surgical resection of a Bartholin's cyst which was treated with third sacral nerve root/dorsal root ganglion stimulation using the transforaminal approach. We describe a new anchorless lead placement technique using a unique curved lead delivery sheath. We postulate that this new posterior foraminal technique of lead placement is simple, safe, and reversible and may lower the occurrence of lead related complications. PMID:27123351

  3. Light-modulated seminal wavy roots in rice mediated by nitric oxide-dependent signaling.

    PubMed

    Chen, Hsiang-Wen; Shao, Ko-Hsuan; Wang, Shu-Jen

    2015-09-01

    Rice (Oryza sativa L.) seminal roots from germinated seeds help establish seedlings, but the seminal root growth and morphology are sensitive to environmental factors. Our previous research showed that several indica-type rice varieties such as Taichung native 1 (TCN1) showed light-induced wavy roots. Also, auxin and oxylipins are two signaling factors regulating the wavy root photomorphology. To investigate the signaling pathway, here, we found that nitric oxide (NO) was a second messenger triggering the signal transduction of light stimuli to induce the wavy morphology of seminal roots in rice. Moreover, interactions between oxylipins and phytohormones such as ethylene and auxin participating in the NO-dependent regulatory pathway of light-induced wavy roots were examined. The order of action of signaling components in the pathway was NO, oxylipins, ethylene, and auxin.

  4. Intradural extramedullary hemangiopericytoma of the thoracic spine infiltrating a nerve root: a case report and literature review.

    PubMed

    Moscovici, Samuel; Ramirez-DeNoriega, Fernando; Fellig, Yakov; Rosenthal, Guy; Cohen, José E; Itshayek, Eyal

    2011-11-01

    Review the presentation and diagnosis of an intradural extramedullary hemangiopericytoma of the thoracic spine. To present a rare case of intradural, subpial hemangiopericytoma in the thoracic spine, with a brief overview of the literature. Spinal intradural extramedullary hemangiopericytoma is rare entity that radiographically mimics nerve-sheath tumors. These lesions are typically diagnosed at surgery performed due to suspicion of tumor. A 20-year-old man who presented with back pain, leg weakness, and sphincter incontinence. MR imaging demonstrated an intradural extramedullary lesion at the T9-T10 level that was isointense on T1- and T2-weighted images and homogeneously enhancing after administration of gadolinium, with cystic components seen on T2-weighted images. The preoperative diagnosis was meningioma or schwannoma. At surgery, the lesion was bluish and completely subpial, with apparent nerve root invasion. Pathological examination revealed a neoplasm adjacent to a nerve root with possible focal infiltration. Abundant reticulin fibers and widened, branching vascular channels imparting a staghorn appearance were seen. Up to five mitotic figures were counted in one high-power field. On immunostaining, the neoplastic cells were diffusely immunoreactive for CD99 and immunonegative for EMA, CD34, and S-100 protein. The pathological diagnosis was consistent with anaplastic hemangiopericytoma, WHO grade III. This is the ninth report of spinal intradural hemangiopericytoma. The location of the neoplasm supports the hypothesis that hemangiopericytoma may arise from the spinal pial capillaries.

  5. Ventilator waveforms on anesthesia machine: a simple tool for intraoperative mapping of phrenic nerve and mid-cervical roots.

    PubMed

    Georgoulis, George; Papagrigoriou, Eirini; Sindou, Marc

    2015-12-01

    A crucial aspect of surgery on the supraclavicular region, lateral neck, and mid-cervical vertebral region is the identification and sparing of the phrenic nerve and cervical (C4) root that are responsible for diaphragmatic innervation. Therefore intraoperative mapping of these nerve structures can be useful for difficult cases. Electrical stimulation with simultaneous observation of the ventilator waveforms of the anesthesia machine provides an effective method for the precise intraoperative mapping of these structures. In the literature, there is only one publication reporting the use of one of the waveforms (capnography) for this purpose. Capnography and pressure-time waveforms, two mandatory curves in anesthesiological monitoring, were studied under electrical stimulation of the phrenic nerve (one patient) and the C4 root (eight patients). The aim was to detect changes that would verify diaphragmatic contraction. No modifications in anesthesia or surgery and no additional maneuvers were required. In all patients, stimulation was followed by identifiable changes in the two waveforms, compatible with diaphragmatic contraction: acute reduction in amplitude on capnography and repetitive saw-like elevations on pressure-time curve. Frequency of patterns on pressure-time curve coincided with the frequency of stimulation; therefore the two recordings were complementary. This simple method proved effective in identifying the neural structures responsible for diaphragmatic function. We therefore suggest that it should be employed in the various types of surgery where these structures are at risk.

  6. The incidence of nerve root injury by high-speed drill can be reduced by chilled saline irrigation in a rabbit model.

    PubMed

    Tamai, K; Suzuki, A; Takahashi, S; Akhgar, J; Rahmani, M S; Hayashi, K; Ohyama, S; Nakamura, H

    2017-04-01

    We aimed to evaluate the temperature around the nerve root during drilling of the lamina and to determine whether irrigation during drilling can reduce the chance of nerve root injury. Lumbar nerve roots were exposed to frictional heat by high-speed drilling of the lamina in a live rabbit model, with saline (room temperature (RT) or chilled saline) or without saline (control) irrigation. We measured temperatures surrounding the nerve root and made histological evaluations. In the control group, the mean temperature around the nerve root was 52.0°C (38.0°C to 75.5°C) after 60 seconds of drilling, and nerve root injuries were found in one out of 13 (7.7%) immediately, three out of 14 (21.4%) at three days, and 11 out of 25 (44.0%) at seven days post-operatively. While the RT group showed a significantly lower temperature around the nerve root compared with the control group (mean 46.5°C; 34.5°C to 66.9°C, p < 0.001), RT saline failed to significantly reduce the incidence of nerve root injury (ten out of 26; 38.5%; odds ratio (OR) 0.96; 95% confidence interval (CI) 0.516 to 1.785; p = 0.563). However, chilled saline irrigation resulted in a significantly lower temperature than the control group (mean 39.0°C; 35.3°C to 52.3°C; p < 0.001) and a lower rate of nerve root injury (two out of 21; 9.5%, OR 0.13; 95% CI 0.02 to 0.703, p = 0.010). Frictional heat caused by a high-speed drill can cause histological nerve root injury. Chilled saline irrigation had a more prominent effect than RT in reducing the incidence of the thermal injury during extended drilling. Cite this article: Bone Joint J 2017;99-B:554-60. ©2017 The British Editorial Society of Bone & Joint Surgery.

  7. The role of Gd-enhanced three-dimensional MRI fast low-angle shot (FLASH) in the evaluation of symptomatic lumbosacral nerve roots.

    PubMed

    Kikkawa, I; Sugimoto, H; Saita, K; Ookami, H; Nakama, S; Hoshino, Y

    2001-01-01

    In the field of lumbar spine disorders, three-dimensional (3-D) magnetic resonance imaging (MRI) can clearly depict a lumbar nerve root from the distal region to the dorsal root ganglion. In this study, we used a gadolinium-diethylenetriaminepentaacetic acid (Gd-DTPA) enhanced-three-dimensional (3-D) fast low-angle shot (FLASH) sequence when examining lumbosacral disorders. The subjects were 33 patients (14 men and 19 women) in whom lumbosacral neural compression had been diagnosed clinically. Twenty-one patients had lumbar disc herniation, 11 had lumbar spinal stenosis, and 1 had lumbar radiculopathy caused by rheumatoid arthritis. Five subjects with low back pain were also studied as a control group. In all patients and in all 5 of the controls, the dorsal root ganglion of every root was enhanced clearly. There was no root enhancement in the 5 controls. Enhancement of the symptomatic nerve roots, caused by compression, was found in 11 of the 33 patients. All 11 patients had radiculopathy, and muscle weakness was more frequent in patients with enhanced nerve roots than in those without enhancement. There was no enhancement of the cauda equina, even in the patients with cauda syndrome. The enhancement effect may reflect some pathological condition of the compressed nerve root and needs to be studied further.

  8. Novel Immunohistochemical Techniques Using Discrete Signal Amplification Systems for Human Cutaneous Peripheral Nerve Fiber Imaging

    PubMed Central

    Wang, Ningshan; Gibbons, Christopher H.; Freeman, Roy

    2011-01-01

    Confocal imaging uses immunohistochemical binding of specific antibodies to visualize tissues, but technical obstacles limit more widespread use of this technique in the imaging of peripheral nerve tissue. These obstacles include same-species antibody cross-reactivity and weak fluorescent signals of individual and co-localized antigens. The aims of this study were to develop new immunohistochemical techniques for imaging of peripheral nerve fibers. Three-millimeter punch skin biopsies of healthy individuals were fixed, frozen, and cut into 50-µm sections. Tissues were stained with a variety of antibody combinations with two signal amplification systems, streptavidin-biotin-fluorochrome (sABC) and tyramide-horseradish peroxidase-fluorochrome (TSA), used simultaneously to augment immunohistochemical signals. The combination of the TSA and sABC amplification systems provided the first successful co-localization of sympathetic adrenergic and sympathetic cholinergic nerve fibers in cutaneous human sweat glands and vasomotor and pilomotor systems. Primary antibodies from the same species were amplified individually without cross-reactivity or elevated background interference. The confocal fluorescent signal-to-noise ratio increased, and image clarity improved. These modifications to signal amplification systems have the potential for widespread use in the study of human neural tissues. PMID:21411809

  9. Effective gene expression in the rat dorsal root ganglia with a non-viral vector delivered via spinal nerve injection

    PubMed Central

    Chang, Ming-Fong; Hsieh, Jung-Hsien; Chiang, Hao; Kan, Hung-Wei; Huang, Cho-Min; Chellis, Luke; Lin, Bo-Shiou; Miaw, Shi-Chuen; Pan, Chun-Liang; Chao, Chi-Chao; Hsieh, Sung-Tsang

    2016-01-01

    Delivering gene constructs into the dorsal root ganglia (DRG) is a powerful but challenging therapeutic strategy for sensory disorders affecting the DRG and their peripheral processes. The current delivery methods of direct intra-DRG injection and intrathecal injection have several disadvantages, including potential injury to DRG neurons and low transfection efficiency, respectively. This study aimed to develop a spinal nerve injection strategy to deliver polyethylenimine mixed with plasmid (PEI/DNA polyplexes) containing green fluorescent protein (GFP). Using this spinal nerve injection approach, PEI/DNA polyplexes were delivered to DRG neurons without nerve injury. Within one week of the delivery, GFP expression was detected in 82.8% ± 1.70% of DRG neurons, comparable to the levels obtained by intra-DRG injection (81.3% ± 5.1%, p = 0.82) but much higher than those obtained by intrathecal injection. The degree of GFP expression by neurofilament(+) and peripherin(+) DRG neurons was similar. The safety of this approach was documented by the absence of injury marker expression, including activation transcription factor 3 and ionized calcium binding adaptor molecule 1 for neurons and glia, respectively, as well as the absence of behavioral changes. These results demonstrated the efficacy and safety of delivering PEI/DNA polyplexes to DRG neurons via spinal nerve injection. PMID:27748450

  10. Heterogeneous responses of dorsal root ganglion neurons in neuropathies induced by peripheral nerve trauma and the antiretroviral drug stavudine

    PubMed Central

    Boateng, EK; Novejarque, A; Pheby, T; Rice, ASC; Huang, W

    2015-01-01

    Background Heterogeneity is increasingly recognized in clinical presentation of neuropathic pain (NP), but less often recognized in animal models. Neurochemical dysregulation in rodent dorsal root ganglia (DRG) is associated with peripheral nerve trauma, but poorly studied in non-traumatic NP conditions. Methods This study aimed to investigate the temporal expressions of activating transcription factor-3 (ATF-3), growth-associated protein-43 (GAP-43), neuropeptide Y (NPY) and galanin in traumatic and non-traumatic rat models of neuropathies associated with NP. Expressions of these markers were examined in the DRG at different time points following tibial nerve transection (TNT) injury and antiretroviral drug stavudine (d4T) administration using immunohistochemistry. The development of sensory gain following these insults was assessed by measuring limb withdrawal to a punctate mechanical stimulus. Results Both TNT-injured and d4T-treated rats developed hindpaw mechanical hypersensitivity. Robust expressions of ATF-3, GAP-43, NPY and galanin in both small- and large-sized L5 DRG neurons were observed in the DRG from TNT-injured rats. In contrast, d4T-treated rats did not exhibit any significant neurochemical changes in the DRG. Conclusions Taken together, the results suggest that ATF-3, GAP-43, NPY and galanin are likely indicators of nerve trauma-associated processes and not generic markers for NP. These experiments also demonstrate distinct expression patterns of neurochemical markers in the DRG and emphasize the mechanistic difference between nerve trauma and antiretroviral drug-associated NP. PMID:25070481

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

    PubMed

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

    2015-01-01

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

  12. Do you have the nerves to regenerate? The importance of neural signalling in the regeneration process.

    PubMed

    Pirotte, Nicky; Leynen, Nathalie; Artois, Tom; Smeets, Karen

    2016-01-01

    The importance of nerve-derived signalling for correct regeneration has been the topic of research for more than a hundred years, but we are just beginning to identify the underlying molecular pathways of this process. Within the current review, we attempt to provide an extensive overview of the neural influences during early and late phases of both vertebrate and invertebrate regeneration. In general, denervation impairs limb regeneration, but the presence of nerves is not essential for the regeneration of aneurogenic extremities. This observation led to the "neurotrophic factor(s) hypothesis", which states that certain trophic factors produced by the nerves are necessary for proper regeneration. Possible neuron-derived factors which regulate regeneration as well as the denervation-affected processes are discussed. Copyright © 2015. Published by Elsevier Inc.

  13. Modeling the response of small myelinated axons in a compound nerve to kilohertz frequency signals

    NASA Astrophysics Data System (ADS)

    Pelot, N. A.; Behrend, C. E.; Grill, W. M.

    2017-08-01

    Objective. There is growing interest in electrical neuromodulation of peripheral nerves, particularly autonomic nerves, to treat various diseases. Electrical signals in the kilohertz frequency (KHF) range can produce different responses, including conduction block. For example, EnteroMedics’ vBloc® therapy for obesity delivers 5 kHz stimulation to block the abdominal vagus nerves, but the mechanisms of action are unclear. Approach. We developed a two-part computational model, coupling a 3D finite element model of a cuff electrode around the human abdominal vagus nerve with biophysically-realistic electrical circuit equivalent (cable) model axons (1, 2, and 5.7 µm in diameter). We developed an automated algorithm to classify conduction responses as subthreshold (transmission), KHF-evoked activity (excitation), or block. We quantified neural responses across kilohertz frequencies (5-20 kHz), amplitudes (1-8 mA), and electrode designs. Main results. We found heterogeneous conduction responses across the modeled nerve trunk, both for a given parameter set and across parameter sets, although most suprathreshold responses were excitation, rather than block. The firing patterns were irregular near transmission and block boundaries, but otherwise regular, and mean firing rates varied with electrode-fibre distance. Further, we identified excitation responses at amplitudes above block threshold, termed ‘re-excitation’, arising from action potentials initiated at virtual cathodes. Excitation and block thresholds decreased with smaller electrode-fibre distances, larger fibre diameters, and lower kilohertz frequencies. A point source model predicted a larger fraction of blocked fibres and greater change of threshold with distance as compared to the realistic cuff and nerve model. Significance. Our findings of widespread asynchronous KHF-evoked activity suggest that conduction block in the abdominal vagus nerves is unlikely with current clinical parameters. Our

  14. Modeling the response of small myelinated axons in a compound nerve to kilohertz frequency signals.

    PubMed

    Pelot, N A; Behrend, C E; Grill, W M

    2017-03-31

    There is growing interest in electrical neuromodulation of peripheral nerves, particularly autonomic nerves, to treat various diseases. Electrical signals in the kilohertz frequency (KHF) range can produce different responses, including conduction block. For example, EnteroMedics' vBloc(®) therapy for obesity delivers 5 kHz stimulation to block the abdominal vagus nerves, but the mechanisms of action are unclear. We developed a two-part computational model, coupling a 3D finite element model of a cuff electrode around the human abdominal vagus nerve with biophysically-realistic electrical circuit equivalent (cable) model axons (1, 2, and 5.7 µm in diameter). We developed an automated algorithm to classify conduction responses as subthreshold (transmission), KHF-evoked activity (excitation), or block. We quantified neural responses across kilohertz frequencies (5-20 kHz), amplitudes (1-8 mA), and electrode designs. We found heterogeneous conduction responses across the modeled nerve trunk, both for a given parameter set and across parameter sets, although most suprathreshold responses were excitation, rather than block. The firing patterns were irregular near transmission and block boundaries, but otherwise regular, and mean firing rates varied with electrode-fibre distance. Further, we identified excitation responses at amplitudes above block threshold, termed 're-excitation', arising from action potentials initiated at virtual cathodes. Excitation and block thresholds decreased with smaller electrode-fibre distances, larger fibre diameters, and lower kilohertz frequencies. A point source model predicted a larger fraction of blocked fibres and greater change of threshold with distance as compared to the realistic cuff and nerve model. Our findings of widespread asynchronous KHF-evoked activity suggest that conduction block in the abdominal vagus nerves is unlikely with current clinical parameters. Our results indicate that compound neural or downstream muscle

  15. Root phonotropism: Early signalling events following sound perception in Arabidopsis roots.

    PubMed

    Rodrigo-Moreno, Ana; Bazihizina, Nadia; Azzarello, Elisa; Masi, Elisa; Tran, Daniel; Bouteau, François; Baluska, Frantisek; Mancuso, Stefano

    2017-11-01

    Sound is a fundamental form of energy and it has been suggested that plants can make use of acoustic cues to obtain information regarding their environments and alter and fine-tune their growth and development. Despite an increasing body of evidence indicating that it can influence plant growth and physiology, many questions concerning the effect of sound waves on plant growth and the underlying signalling mechanisms remains unknown. Here we show that in Arabidopsis thaliana, exposure to sound waves (200Hz) for 2 weeks induced positive phonotropism in roots, which grew towards to sound source. We found that sound waves triggered very quickly (within  minutes) an increase in cytosolic Ca(2+), possibly mediated by an influx through plasma membrane and a release from internal stock. Sound waves likewise elicited rapid reactive oxygen species (ROS) production and K(+) efflux. Taken together these results suggest that changes in ion fluxes (Ca(2+) and K(+)) and an increase in superoxide production are involved in sound perception in plants, as previously established in animals. Copyright © 2017 Elsevier B.V. All rights reserved.

  16. Neuregulin-1 signaling is essential for nerve-dependent axolotl limb regeneration.

    PubMed

    Farkas, Johanna E; Freitas, Polina D; Bryant, Donald M; Whited, Jessica L; Monaghan, James R

    2016-08-01

    The Mexican axolotl (Ambystoma mexicanum) is capable of fully regenerating amputated limbs, but denervation of the limb inhibits the formation of the post-injury proliferative mass called the blastema. The molecular basis behind this phenomenon remains poorly understood, but previous studies have suggested that nerves support regeneration via the secretion of essential growth-promoting factors. An essential nerve-derived factor must be found in the blastema, capable of rescuing regeneration in denervated limbs, and its inhibition must prevent regeneration. Here, we show that the neuronally secreted protein Neuregulin-1 (NRG1) fulfills all these criteria in the axolotl. Immunohistochemistry and in situ hybridization of NRG1 and its active receptor ErbB2 revealed that they are expressed in regenerating blastemas but lost upon denervation. NRG1 was localized to the wound epithelium prior to blastema formation and was later strongly expressed in proliferating blastemal cells. Supplementation by implantation of NRG1-soaked beads rescued regeneration to digits in denervated limbs, and pharmacological inhibition of NRG1 signaling reduced cell proliferation, blocked blastema formation and induced aberrant collagen deposition in fully innervated limbs. Taken together, our results show that nerve-dependent NRG1/ErbB2 signaling promotes blastemal proliferation in the regenerating limb and may play an essential role in blastema formation, thus providing insight into the longstanding question of why nerves are required for axolotl limb regeneration. © 2016. Published by The Company of Biologists Ltd.

  17. Roles of proteome dynamics and cytokinin signaling in root to hypocotyl ratio changes induced by shading roots of Arabidopsis seedlings.

    PubMed

    Novák, Jan; Černý, Martin; Pavlů, Jaroslav; Zemánková, Jana; Skalák, Jan; Plačková, Lenka; Brzobohatý, Břetislav

    2015-05-01

    In nature, root systems of most terrestrial plants are protected from light exposure by growing in a dark soil environment. Hence, in vitro cultivation in transparent Petri dishes leads to physiological perturbations, but the mechanisms underlying root-mediated light perception and responses have not been fully elucidated. Thus, we compared Arabidopsis thaliana seedling development in transparent and darkened Petri dishes at low light intensity (20 µmol m(-2) s(-1)), allowing us to follow (inter alia) hypocotyl elongation, which is an excellent process for studying interactions of signals involved in the regulation of growth and developmental responses. To obtain insights into molecular events underlying differences in seedling growth under these two conditions, we employed liquid chromatography-mass spectrometry (LC-MS) shotgun proteomics (available via the PRIDE deposit PXD001612). In total, we quantified the relative abundances of peptides representing 1,209 proteins detected in all sample replicates of LC-MS analyses. Comparison of MS spectra after manual validation revealed 48 differentially expressed proteins. Functional classification, analysis of available gene expression data and literature searches revealed alterations associated with root illumination (inter alia) in autotrophic CO2 fixation, C compound and carbohydrate metabolism, and nitrogen metabolism. The results also indicate a previously unreported role for cytokinin plant hormones in the escape-tropism response to root illumination. We complemented these results with reverse transcription followed by quantitative PCR (RT-qPCR), chlorophyll fluorescence and detailed cytokinin signaling analyses, detecting in the latter a significant increase in the activity of the cytokinin two-component signaling cascade in roots and implicating the cytokinin receptor AHK3 as the major mediator of root to hypocotyl signaling in responses to root illumination. © The Author 2015. Published by Oxford University

  18. Thyroid hormone reduces the loss of axotomized sensory neurons in dorsal root ganglia after sciatic nerve transection in adult rat.

    PubMed

    Schenker, Michel; Kraftsik, Rudolf; Glauser, Liliane; Kuntzer, Thierry; Bogousslavsky, Julien; Barakat-Walter, Ibtissam

    2003-11-01

    We have shown that a local administration of thyroid hormones (T3) at the level of transected rat sciatic nerve induced a significant increase in the number of regenerated axons. To address the question of whether local administration of T3 rescues the axotomized sensory neurons from death, in the present study we estimated the total number of surviving neurons per dorsal root ganglion (DRG) in three experimental group animals. Forty-five days following rat sciatic nerve transection, the lumbar (L4 and L5) DRG were removed from PBS-control, T3-treated as well as from unoperated rats, and serial sections (1 microm) were cut. The physical dissector method was used to estimate the total number of sensory neurons in the DRGs. Our results revealed that in PBS-control rats transection of sciatic nerve leads to a significant (P < 0.001) decrease in the mean number of sensory neurons (8743.8 +/- 748.6) compared with the number of neurons in nontransected ganglion (mean 13,293.7 +/- 1368.4). However, administration of T3 immediately after sciatic nerve transection rescues a great number of axotomized neurons so that their mean neuron number (12,045.8 +/- 929.8) is not significantly different from the mean number of neurons in the nontransected ganglion. In addition, the volume of ganglia showed a similar tendency. These results suggest that T3 rescues a high number of axotomized sensory neurons from death and allows these cells to grow new axons. We believe that the relative preservation of neurons is important in considering future therapeutic approaches of human peripheral nerve lesion and sensory neuropathy.

  19. How do roots alter signals of molecular proxies in terrestrial archives?

    NASA Astrophysics Data System (ADS)

    Wiesenberg, G. L.; Gocke, M. I.

    2016-12-01

    Terrestrial archives such as sediment-paleosol sequences and recent soil profiles have been frequently used for environmental and paleoenvironmental studies. One prominent tool is the use of molecular proxies from the lipid fraction due to their relative persistence and their well known suitability to trace paleoenvironmental developments as well as human activities. However, excavations of sediment-paleosol sequences often reveal the presence of roots or biopores that might have been formed during any later stage of pedogenesis or sediment accumulation, potentially altering the signal of molecular proxies. In the current study, we compile recent soils and paleosols as well as several meter thick sediment-paleosol sequences in order to trace the influence by post-pedogenic/sedimentary root penetration on molecular composition. Therefore, we documented root frequencies during field sampling campaigns and collected root (remains) with their surrounding material to assess the extension of root-derived overprint. While only suberin analysis enables identification of root-derived biomass in the vicinity of living or ancient roots, other biomarkers such as alkanes and fatty acids can derive from the primary vegetation and are commonly assumed to be only aboveground litter-derived. Further, miroorganisms and root-derived biomass contribute to lipid assemblage in soils and sediments. Therefore, their source identification and attribution to root-origin is more difficult, as also promoted degradation in the vicinity of roots can alter the biomarker signal. In the surrounding of visible root remains, we could identify root-derived overprint of up to >8cm distance, whereas this is mainly attributed to finer side roots around visible root remains. Furthermore, alteration can strongly overprint the sedimentary signal due to long-lasting overprint, especially in nutrient-rich horizons, such as paleosols. To enable proper paleoenvironmental reconstructions in terrestrial

  20. Root gravitropism in response to a signal originating outside of the cap

    NASA Technical Reports Server (NTRS)

    Wolverton, Chris; Mullen, Jack L.; Ishikawa, Hideo; Evans, Michael L.

    2002-01-01

    We have developed image analysis software linked to a rotating stage, allowing constraint of any user-selected region of a root at a prescribed angle during root gravitropism. This device allows the cap of a graviresponding root to reach vertical while maintaining a selected region within the elongation zone at a gravistimulated angle. Under these conditions gravitropic curvature of roots of Zea mays L. continues long after the root cap reaches vertical, indicating that a signal from outside of the cap can contribute to the curvature response.

  1. Root gravitropism in response to a signal originating outside of the cap

    NASA Technical Reports Server (NTRS)

    Wolverton, Chris; Mullen, Jack L.; Ishikawa, Hideo; Evans, Michael L.

    2002-01-01

    We have developed image analysis software linked to a rotating stage, allowing constraint of any user-selected region of a root at a prescribed angle during root gravitropism. This device allows the cap of a graviresponding root to reach vertical while maintaining a selected region within the elongation zone at a gravistimulated angle. Under these conditions gravitropic curvature of roots of Zea mays L. continues long after the root cap reaches vertical, indicating that a signal from outside of the cap can contribute to the curvature response.

  2. Emerging roots alter epidermal cell fate through mechanical and reactive oxygen species signaling.

    PubMed

    Steffens, Bianka; Kovalev, Alexander; Gorb, Stanislav N; Sauter, Margret

    2012-08-01

    A central question in biology is how spatial information is conveyed to locally establish a developmental program. Rice (Oryza sativa) can survive flash floods by the emergence of adventitious roots from the stem. Epidermal cells that overlie adventitious root primordia undergo cell death to facilitate root emergence. Root growth and epidermal cell death are both controlled by ethylene. This study aimed to identify the signal responsible for the spatial control of cell death. Epidermal cell death correlated with the proximity to root primordia in wild-type and ADVENTITIOUS ROOTLESS1 plants, indicating that the root emits a spatial signal. Ethylene-induced root growth generated a mechanical force of ~18 millinewtons within 1 h. Force application to epidermal cells above root primordia caused cell death in a dose-dependent manner and was inhibited by 1-methylcyclopropene or diphenylene iodonium, an inhibitor of NADPH oxidase. Exposure of epidermal cells not overlying a root to either force and ethylene or force and the catalase inhibitor aminotriazole induced ectopic cell death. Genetic downregulation of the reactive oxygen species (ROS) scavenger METALLOTHIONEIN2b likewise promoted force-induced ectopic cell death. Hence, reprogramming of epidermal cell fate by the volatile plant hormone ethylene requires two signals: mechanosensing for spatial resolution and ROS for cell death signaling.

  3. De novo expression of Nav1.7 in injured putative proprioceptive afferents: Multiple tetrodotoxin-sensitive sodium channels are retained in the rat dorsal root after spinal nerve ligation.

    PubMed

    Fukuoka, T; Miyoshi, K; Noguchi, K

    2015-01-22

    Tetrodotoxin-sensitive (TTX-s) spontaneous activity is recorded from the dorsal roots after peripheral nerve injury. Primary sensory neurons in the dorsal root ganglion (DRG) express multiple TTX-s voltage-gated sodium channel α-subunits (Navs). Since Nav1.3 increases, whereas all other Navs decrease, in the DRG neurons after peripheral nerve lesion, Nav1.3 is proposed to be critical for the generation of these spontaneous discharges and the contributions of other Navs have been ignored. Here, we re-evaluate the changes in expression of three other TTX-s Navs, Nav1.1, Nav1.6 and Nav1.7, in the injured 5th lumbar (L5) primary afferent components following L5 spinal nerve ligation (SNL) using in situ hybridization histochemistry and immunohistochemistry. While the overall signal intensities for these Nav mRNAs decreased, many injured DRG neurons still expressed these transcripts at clearly detectable levels. All these Nav proteins accumulated at the proximal stump of the ligated L5 spinal nerve. The immunostaining patterns of Nav1.6 and Nav1.7 associated with the nodes of Ranvier were maintained in the ipsilateral L5 dorsal root. Interestingly, putative proprioceptive neurons characterized by α3 Na+/K+ ATPase-immunostaining specifically lacked Nav1.7 mRNA in naïve DRG but displayed de novo expression of this transcript following SNL. Nav1.7-immunoreactive fibers were significantly increased in the ipsilateral gracile nucleus where central axonal branches of the injured A-fiber afferents terminated. These data indicate that multiple TTX-s channel subunits could contribute to the generation and propagation of the spontaneous discharges in the injured primary afferents. Specifically, Nav1.7 may cause some functional changes in sensory processing in the gracile nucleus after peripheral nerve injury.

  4. Monitoring of immune cell response to B cell depletion therapy and nerve root injury using SPIO enhanced MRI

    NASA Astrophysics Data System (ADS)

    Thorek, Daniel L.

    2009-12-01

    Magnetic resonance (MR) is a robust platform for non-invasive, high-resolution anatomical imaging. However, MR imaging lacks the requisite sensitivity and contrast for imaging at the cellular level. This represents a clinical impediment to greater diagnostic accuracy. Recent advances have allowed for the in vivo visualization of populations and even of individual cells using superparamagnetic iron oxide (SPIO) MR contrast agents. These nanoparticles, commonly manifested as a core of a single iron oxide crystal or cluster of crystals coated in a biocompatible shell, function to shorten proton relaxation times. In MR imaging these constructs locally dephase protons, resulting in a decrease in signal (hypointensity) localized to the region of accumulation of SPIO. In the context of immune cell imaging, SPIO can provide insight into the cellular migration patterns, trafficking, temporal dynamics and progression of diseases and their related pathological states. Furthermore, by visualizing the presence and activity of immune cells, SPIO-enabled cellular imaging can help evaluate the efficacy of therapy in immune disorders. This thesis examines the production, modification and application of SPIO in a range of in vitro and in vivo immune-response-relevant cellular systems. The role of different nanoparticle characteristics including diameter, surface charge and concentration are investigated in the labeling of T cells in culture. Following optimization of SPIO loading conditions for lymphocytes, the effect these particles have on the activation of primary B cells are elucidated. B cells are tracked using a variety of modalities, with and without the application of B cell depleting therapy. This is to evaluate the efficacy of SPIO as in vivo marker for B cell distribution. Unmodified SPIO were applied to monitor macrophage infiltration in a transient nerve root compression model, with implications for neck pain diagnosis and treatment. Nanoparticle accumulation and MR

  5. A manual therapy approach to evaluation and treatment of a patient with a chronic lumbar nerve root irritation.

    PubMed

    Koury, M J; Scarpelli, E

    1994-06-01

    The purpose of this case report is to familiarize the reader with the basic principles of the approach to manual therapy evaluation and treatment pioneered by Maitland, an Australian physical therapist. This approach involves a complete subjective examination to determine the severity, irritability, nature, and stage of the patient's complaints. In this way, the therapist may reach conclusions as to the amount and vigor of the physical examination and proceed with treatment in an analytical manner. Methodical reassessment is used to justify treatment progression. Comprehensive treatment and the rationale for this approach are discussed. Though most physical therapists are familiar with the straight-leg-raising test as a means of assessing low back pain and chronic lumbar nerve root irritation, they are often not familiar with other tests that examine neural tissues, such as the slump test. The proposed anatomical and biomechanical bases for these tests are discussed. The patient in this case study was a 50-year-old man with a physician's diagnosis of a chronic lumbar nerve root irritation. The patient was evaluated and treated in eight visits using techniques designed to evaluate neural tissues. Reassessment indicated significant symptom reduction, and the treatment was modified accordingly. Patient management, including home exercises, is discussed.

  6. 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.

  7. Role of dorsal root ganglion K2P1.1 in peripheral nerve injury-induced neuropathic pain

    PubMed Central

    Mao, Qingxiang; Yuan, Jingjing; Xiong, Ming; Wu, Shaogen; Chen, Liyong; Bekker, Alex; Yang, Tiande

    2017-01-01

    Peripheral nerve injury-caused hyperexcitability and abnormal ectopic discharges in the primary sensory neurons of dorsal root ganglion (DRG) play a key role in neuropathic pain development and maintenance. The two-pore domain background potassium (K2P) channels have been identified as key determinants of the resting membrane potential and neuronal excitability. However, whether K2P channels contribute to neuropathic pain is still elusive. We reported here that K2P1.1, the first identified mammalian K2P channel, was highly expressed in mouse DRG and distributed in small-, medium-, and large-sized DRG neurons. Unilateral lumbar (L) 4 spinal nerve ligation led to a significant and time-dependent reduction of K2P1.1 mRNA and protein in the ipsilateral L4 DRG, but not in the contralateral L4 or ipsilateral L3 DRG. Rescuing this reduction through microinjection of adeno-associated virus-DJ expressing full-length K2P1.1 mRNA into the ipsilateral L4 DRG blocked spinal nerve ligation-induced mechanical, thermal, and cold pain hypersensitivities during the development and maintenance periods. This DRG viral microinjection did not affect acute pain and locomotor function. Our findings suggest that K2P1.1 participates in neuropathic pain development and maintenance and may be a potential target in the management of this disorder. PMID:28326939

  8. Injury of the inferior alveolar nerve after overfilling of the root canal with endodontic cement: a case report.

    PubMed

    Scarano, Antonio; Di Carlo, Fabio; Quaranta, Alessandro; Piattelli, Adriano

    2007-07-01

    The inferior alveolar nerve (IAN) contains mainly sensory fibers. Within the mandibular canal, the IAN runs forward in company of the inferior alveolar artery, and together they are called the inferior alveolar neurovascular bundle. Disturbances of the IAN and mental nerve will predominantly give sensitivity symptoms in the soft tissue of the lower lip and chin. We present a case report of endodontic overfilling involving the mandibular canal. A 52-year-old woman was seen in our outpatient clinic for pain and numbness in the left lower lip and chin, which developed following an endodontic treatment for her mandibular left second premolar. The panoramic radiograph showed radiopaque material in the inferior alveolar canal region, with an extension from the left canine to the second premolar. This case report shows an unusual complication of mandibular second premolar root canal overfilling. The patient underwent treatment with corticosteroids, and after 2 months, the clinical examination revealed an improved clinical situation with a disappearance of the hypoesthesia but with a persistence of the pain. After 4 months, the pain had almost entirely disappeared. In conclusion, even if in our case no surgical treatment was used and although spontaneous resorption has been described for some materials, early surgical exploration with removal of the material and decompression of the IAN is suggested, irrespective of the material used, because the severity of nerve damage can increase with the duration of the injury.

  9. The Role of 5-HT3 Receptors in Signaling from Taste Buds to Nerves

    PubMed Central

    Vandenbeuch, Aurelie; Voigt, Anja; Meyerhof, Wolfgang; Kinnamon, Sue C.; Finger, Thomas E.

    2015-01-01

    5-HT3 receptors that play a significant role in the neurotransmission of taste information from taste buds to nerves. In addition, we show that the anesthetic pentobarbital, widely used in taste nerve recordings, blocks 5-HT3 signaling. Therefore, many conclusions drawn from those data need to be reexamined in light of this anesthetic effect. PMID:26631478

  10. Fluoroscopically guided extraforaminal cervical nerve root blocks: analysis of epidural flow of the injectate with respect to needle tip position.

    PubMed

    Shipley, Kyle; Riew, K Daniel; Gilula, Louis A

    2014-02-01

    Study Design Retrospective evaluation of consecutively performed fluoroscopically guided cervical nerve root blocks. Objective To describe the incidence of injectate central epidural flow with respect to needle tip position during fluoroscopically guided extraforaminal cervical nerve root blocks (ECNRBs). Methods Between February 19, 2003 and June 11, 2003, 132 consecutive fluoroscopically guided ECNRBs performed with contrast media in the final injected material (injectate) were reviewed on 95 patients with average of 1.3 injections per patient. Fluoroscopic spot images documenting the procedure were obtained as part of standard quality assurance. An independent observer not directly involved in the procedures retrospectively reviewed the images, and the data were placed into a database. Image review was performed to determine optimal needle tip positioning for injectate epidural flow. Results Central epidural injectate flow was obtained in only 28.9% of injections with the needle tip lateral to midline of the lateral mass (zone 2). 83.8% of injectate went into epidural space when the needle tip was medial to midline of the lateral mass (zone 3). 100% of injectate flowed epidurally when the needle tip was medial to or at the medial cortex of the lateral mass (zone 4). There was no statistically significant difference with regards to central epidural flow and the needle tip position on lateral view. Conclusion To ensure central epidural flow with ECNRBs one must be prepared to pass the needle tip medial to midplane of the lateral mass or to medial cortex of the lateral mass. Approximately 16% of ECNRBs with needle tip medial to midline of the lateral mass did not flow into epidural space. One cannot claim a nerve block is an epidural block unless epidural flow of injectate is observed.

  11. Parathyroid hormone receptor signalling in osterix-expressing mesenchymal progenitors is essential for tooth root formation.

    PubMed

    Ono, Wanida; Sakagami, Naoko; Nishimori, Shigeki; Ono, Noriaki; Kronenberg, Henry M

    2016-04-12

    Dental root formation is a dynamic process in which mesenchymal cells migrate toward the site of the future root, differentiate and secrete dentin and cementum. However, the identities of dental mesenchymal progenitors are largely unknown. Here we show that cells expressing osterix are mesenchymal progenitors contributing to all relevant cell types during morphogenesis. The majority of cells expressing parathyroid hormone-related peptide (PTHrP) are in the dental follicle and on the root surface, and deletion of its receptor (PPR) in these progenitors leads to failure of eruption and significantly truncated roots lacking periodontal ligaments. The PPR-deficient progenitors exhibit accelerated cementoblast differentiation with upregulation of nuclear factor I/C (Nfic). Deletion of histone deacetylase-4 (HDAC4) partially recapitulates the PPR deletion root phenotype. These findings indicate that PPR signalling in dental mesenchymal progenitors is essential for tooth root formation, underscoring importance of the PTHrP-PPR system during root morphogenesis and tooth eruption.

  12. Parathyroid hormone receptor signalling in osterix-expressing mesenchymal progenitors is essential for tooth root formation

    PubMed Central

    Ono, Wanida; Sakagami, Naoko; Nishimori, Shigeki; Ono, Noriaki; Kronenberg, Henry M.

    2016-01-01

    Dental root formation is a dynamic process in which mesenchymal cells migrate toward the site of the future root, differentiate and secrete dentin and cementum. However, the identities of dental mesenchymal progenitors are largely unknown. Here we show that cells expressing osterix are mesenchymal progenitors contributing to all relevant cell types during morphogenesis. The majority of cells expressing parathyroid hormone-related peptide (PTHrP) are in the dental follicle and on the root surface, and deletion of its receptor (PPR) in these progenitors leads to failure of eruption and significantly truncated roots lacking periodontal ligaments. The PPR-deficient progenitors exhibit accelerated cementoblast differentiation with upregulation of nuclear factor I/C (Nfic). Deletion of histone deacetylase-4 (HDAC4) partially recapitulates the PPR deletion root phenotype. These findings indicate that PPR signalling in dental mesenchymal progenitors is essential for tooth root formation, underscoring importance of the PTHrP–PPR system during root morphogenesis and tooth eruption. PMID:27068606

  13. Cytokinin interplay with ethylene, auxin, and glucose signaling controls Arabidopsis seedling root directional growth.

    PubMed

    Kushwah, Sunita; Jones, Alan M; Laxmi, Ashverya

    2011-08-01

    Optimal root architecture is established by multiple intrinsic (e.g. hormones) and extrinsic (e.g. gravity and touch) signals and is established, in part, by directed root growth. We show that asymmetrical exposure of cytokinin (CK) at the root tip in Arabidopsis (Arabidopsis thaliana) promotes cell elongation that is potentiated by glucose in a hexokinase-influenced, G protein-independent manner. This mode of CK signaling requires the CK receptor, ARABIDOPSIS HISTIDINE KINASE4 and, at a minimum, its cognate type B ARABIDOPSIS RESPONSE REGULATORS ARR1, ARR10, and ARR11 for full responsiveness, while type A response regulators act redundantly to attenuate this CK response. Ethylene signaling through the ethylene receptor ETHYLENE RESISTANT1 and its downstream signaling element ETHYLENE INSENSITIVE2 are required for CK-induced root cell elongation. Negative and positive feedback loops are reinforced by CK regulation of the expression of the genes encoding these elements in both the CK and ethylene signaling pathways. Auxin transport facilitated by PIN-FORMED2 as well as auxin signaling through control of the steady-state level of transcriptional repressors INDOLE-3-ACETIC ACID7 (IAA7), IAA14, and IAA17 via TRANSPORT INHIBITOR RESPONSE1/AUXIN SIGNALING F-BOX PROTEIN are involved in CK-induced root cell elongation. This action lies downstream of ethylene and CK induction. Intrinsic signaling in this response operates independently of the extrinsic signal touch, although actin filament organization, which is important in the touch response, may be important for this response, since latrunculin B can induce similar growth. This root growth response may have adaptive significance, since CK responsiveness is inversely related to root coiling and waving, two root behaviors known to be important for fitness.

  14. It's time to make changes: modulation of root system architecture by nutrient signals.

    PubMed

    Giehl, Ricardo F H; Gruber, Benjamin D; von Wirén, Nicolaus

    2014-03-01

    Root growth and development are of outstanding importance for the plant's ability to acquire water and nutrients from different soil horizons. To cope with fluctuating nutrient availabilities, plants integrate systemic signals pertaining to their nutritional status into developmental pathways that regulate the spatial arrangement of roots. Changes in the plant nutritional status and external nutrient supply modulate root system architecture (RSA) over time and determine the degree of root plasticity which is based on variations in the number, extension, placement, and growth direction of individual components of the root system. Roots also sense the local availability of some nutrients, thereby leading to nutrient-specific modifications in RSA, that result from the integration of systemic and local signals into the root developmental programme at specific steps. An in silico analysis of nutrient-responsive genes involved in root development showed that the majority of these specifically responded to the deficiency of individual nutrients while a minority responded to more than one nutrient deficiency. Such an analysis provides an interesting starting point for the identification of the molecular players underlying the sensing and transduction of the nutrient signals that mediate changes in the development and architecture of root systems.

  15. Different types of spinal afferent nerve endings in stomach and esophagus identified by anterograde tracing from dorsal root ganglia.

    PubMed

    Spencer, Nick J; Kyloh, Melinda; Beckett, Elizabeth A; Brookes, Simon; Hibberd, Tim

    2016-10-15

    In visceral organs of mammals, most noxious (painful) stimuli as well as innocuous stimuli are detected by spinal afferent neurons, whose cell bodies lie in dorsal root ganglia (DRGs). One of the major unresolved questions is the location, morphology, and neurochemistry of the nerve endings of spinal afferents that actually detect these stimuli in the viscera. In the upper gastrointestinal (GI) tract, there have been many anterograde tracing studies of vagal afferent endings, but none on spinal afferent endings. Recently, we developed a technique that now provides selective labeling of only spinal afferents. We used this approach to identify spinal afferent nerve endings in the upper GI tract of mice. Animals were anesthetized, and injections of dextran-amine were made into thoracic DRGs (T8-T12). Seven days post surgery, mice were euthanized, and the stomach and esophagus were removed, fixed, and stained for calcitonin gene-related peptide (CGRP). Spinal afferent axons were identified that ramified extensively through many rows of myenteric ganglia and formed nerve endings in discrete anatomical layers. Most commonly, intraganglionic varicose endings (IGVEs) were identified in myenteric ganglia of the stomach and varicose simple-type endings in the circular muscle and mucosa. Less commonly, nerve endings were identified in internodal strands, blood vessels, submucosal ganglia, and longitudinal muscle. In the esophagus, only IGVEs were identified in myenteric ganglia. No intraganglionic lamellar endings (IGLEs) were identified in the stomach or esophagus. We present the first identification of spinal afferent endings in the upper GI tract. Eight distinct types of spinal afferent endings were identified in the stomach, and most of them were CGRP immunoreactive. J. Comp. Neurol. 524:3064-3083, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  16. Implementation of linear sensory signaling via multiple coordinated mechanisms at central vestibular nerve synapses.

    PubMed

    McElvain, Lauren E; Faulstich, Michael; Jeanne, James M; Moore, Jeffrey D; du Lac, Sascha

    2015-03-04

    Signal transfer in neural circuits is dynamically modified by the recent history of neuronal activity. Short-term plasticity endows synapses with nonlinear transmission properties, yet synapses in sensory and motor circuits are capable of signaling linearly over a wide range of presynaptic firing rates. How do such synapses achieve rate-invariant transmission despite history-dependent nonlinearities? Here, ultrastructural, biophysical, and computational analyses demonstrate that concerted molecular, anatomical, and physiological refinements are required for central vestibular nerve synapses to linearly transmit rate-coded sensory signals. Vestibular synapses operate in a physiological regime of steady-state depression imposed by tonic firing. Rate-invariant transmission relies on brief presynaptic action potentials that delimit calcium influx, large pools of rapidly mobilized vesicles, multiple low-probability release sites, robust postsynaptic receptor sensitivity, and efficient transmitter clearance. Broadband linear synaptic filtering of head motion signals is thus achieved by coordinately tuned synaptic machinery that maintains physiological operation within inherent cell biological limitations.

  17. Development of the Poplar-Laccaria bicolor Ectomycorrhiza Modifies Root Auxin Metabolism, Signaling, and Response.

    PubMed

    Vayssières, Alice; Pěnčík, Ales; Felten, Judith; Kohler, Annegret; Ljung, Karin; Martin, Francis; Legué, Valérie

    2015-09-01

    Root systems of host trees are known to establish ectomycorrhizae (ECM) interactions with rhizospheric fungi. This mutualistic association leads to dramatic developmental modifications in root architecture, with the formation of numerous short and swollen lateral roots ensheathed by a fungal mantle. Knowing that auxin plays a crucial role in root development, we investigated how auxin metabolism, signaling, and response are affected in poplar (Populus spp.)-Laccaria bicolor ECM roots. The plant-fungus interaction leads to the arrest of lateral root growth with simultaneous attenuation of the synthetic auxin response element DR5. Measurement of auxin-related metabolites in the free-living partners revealed that the mycelium of L. bicolor produces high concentrations of the auxin indole-3-acetic acid (IAA). Metabolic profiling showed an accumulation of IAA and changes in the indol-3-pyruvic acid-dependent IAA biosynthesis and IAA conjugation and degradation pathways during ECM formation. The global analysis of auxin response gene expression and the regulation of AUXIN SIGNALING F-BOX PROTEIN5, AUXIN/IAA, and AUXIN RESPONSE FACTOR expression in ECM roots suggested that symbiosis-dependent auxin signaling is activated during the colonization by L. bicolor. Taking all this evidence into account, we propose a model in which auxin signaling plays a crucial role in the modification of root growth during ECM formation.

  18. Development of the Poplar-Laccaria bicolor Ectomycorrhiza Modifies Root Auxin Metabolism, Signaling, and Response1

    PubMed Central

    Vayssières, Alice; Pěnčík, Ales; Felten, Judith; Kohler, Annegret; Ljung, Karin; Martin, Francis; Legué, Valérie

    2015-01-01

    Root systems of host trees are known to establish ectomycorrhizae (ECM) interactions with rhizospheric fungi. This mutualistic association leads to dramatic developmental modifications in root architecture, with the formation of numerous short and swollen lateral roots ensheathed by a fungal mantle. Knowing that auxin plays a crucial role in root development, we investigated how auxin metabolism, signaling, and response are affected in poplar (Populus spp.)-Laccaria bicolor ECM roots. The plant-fungus interaction leads to the arrest of lateral root growth with simultaneous attenuation of the synthetic auxin response element DR5. Measurement of auxin-related metabolites in the free-living partners revealed that the mycelium of L. bicolor produces high concentrations of the auxin indole-3-acetic acid (IAA). Metabolic profiling showed an accumulation of IAA and changes in the indol-3-pyruvic acid-dependent IAA biosynthesis and IAA conjugation and degradation pathways during ECM formation. The global analysis of auxin response gene expression and the regulation of AUXIN SIGNALING F-BOX PROTEIN5, AUXIN/IAA, and AUXIN RESPONSE FACTOR expression in ECM roots suggested that symbiosis-dependent auxin signaling is activated during the colonization by L. bicolor. Taking all this evidence into account, we propose a model in which auxin signaling plays a crucial role in the modification of root growth during ECM formation. PMID:26084921

  19. A literature review reveals that trials evaluating treatment of non-specific low back pain use inconsistent criteria to identify serious pathologies and nerve root involvement

    PubMed Central

    Williams, Ciaran; Hancock, Mark J; Ferreira, Manuela; Ferreira, Paulo; Maher, Chris G

    2012-01-01

    Objectives The broad aim of this study was to assess the homogeneity of patients included in trials of non-specific low back pain (NSLBP). To do this, we investigated the consistency and clarity of criteria used to identify and exclude participants with serious pathologies and nerve root compromise in randomized controlled trials, investigating interventions for NSLBP. Methods We searched Medline database for randomized controlled trials of low back pain (LBP). published between 2000 and 2009. We then randomly selected and screened trials for inclusion until we had 50 eligible trials. Data were extracted on the criteria used to identify cases of serious conditions (e.g. cancer, fracture) and nerve root involvement. Results The majority of papers (35/50) explicitly excluded patients with serious pathology. However, the terminology used and examples given were highly variable. Nerve root involvement was an exclusion criterion in the majority but not all studies. The criteria used for excluding patients with nerve root involvement varied greatly between studies. The most common criteria were ‘motor, sensory or reflex changes’ (nine studies), followed by ‘pain radiating below the knee’ (five studies) and ‘reduced straight leg raise which reproduces leg pain’ (five studies). In half of the included studies, the criteria used, while alluding to nerve root involvement, were not explained adequately for us to determine the types of patients included or excluded. Discussion The inconsistent and unclear criteria used to identify cases of serious pathology and nerve root compromise means that published trials of LBP likely include heterogeneous patient populations. This trait limits our ability to make comparisons across trials or pool studies. Standardization and consensus is important for future research. PMID:23633884

  20. Different gymnosperm outgroups have (mostly) congruent signal regarding the root of flowering plant phylogeny.

    PubMed

    Graham, Sean W; Iles, William J D

    2009-01-01

    We examined multiple plastid genes from a diversity of gymnosperm lineages to explore the consistency of signal among different outgroups for rooting flowering plant phylogeny. For maximum parsimony (MP), most outgroups attach on a branch of the underlying ingroup tree that leads to Amborella. Maximum likelihood (ML) analyses either root angiosperms on a nearby branch or find split support for these neighboring root placements, depending on the outgroup. The inclusion of two species of Hydatellaceae, recently recognized as an ancient line of angiosperms, does not aid in inference of the root. Cost profiles for placing the root in suboptimal locations are highly correlated across most outgroup comparisons, even comparing MP and ML profiles. Those for Gnetales are the most deviant of all those considered. This divergent outgroup either attaches on a long eudicot branch with moderate bootstrap support in MP analyses or supports no particular root location in ML analysis. Removing the most rapidly evolving sites in rate classifications based on two divergent angiosperm root placements with Gnetales yields strongly conflicting root placements in MP analysis, despite substantial overlap in the estimated sets of conservative sites. However, the generally high consistency in rooting signal among distantly related gymnosperm clades suggests that the long branch connecting angiosperms to their extant relatives may not interfere substantially with inference of the angiosperm root.

  1. The Emerging Role of Reactive Oxygen Species Signaling during Lateral Root Development1[C][W

    PubMed Central

    Manzano, Concepción; Pallero-Baena, Mercedes; Casimiro, Ilda; De Rybel, Bert; Orman-Ligeza, Beata; Van Isterdael, Gert; Beeckman, Tom; Draye, Xavier; Casero, Pedro; del Pozo, Juan C.

    2014-01-01

    Overall root architecture is the combined result of primary and lateral root growth and is influenced by both intrinsic genetic programs and external signals. One of the main questions for root biologists is how plants control the number of lateral root primordia and their emergence through the main root. We recently identified S-phase kinase-associated protein2 (SKP2B) as a new early marker for lateral root development. Here, we took advantage of its specific expression pattern in Arabidopsis (Arabidopsis thaliana) in a cell-sorting and transcriptomic approach to generate a lateral root-specific cell sorting SKP2B data set that represents the endogenous genetic developmental program. We first validated this data set by showing that many of the identified genes have a function during root growth or lateral root development. Importantly, genes encoding peroxidases were highly represented in our data set. Thus, we next focused on this class of enzymes and showed, using genetic and chemical inhibitor studies, that peroxidase activity and reactive oxygen species signaling are specifically required during lateral root emergence but, intriguingly, not for primordium specification itself. PMID:24879433

  2. The Emerging Role of Reactive Oxygen Species Signaling during Lateral Root Development.

    PubMed

    Manzano, Concepción; Pallero-Baena, Mercedes; Casimiro, Ilda; De Rybel, Bert; Orman-Ligeza, Beata; Van Isterdael, Gert; Beeckman, Tom; Draye, Xavier; Casero, Pedro; Del Pozo, Juan C

    2014-07-01

    Overall root architecture is the combined result of primary and lateral root growth and is influenced by both intrinsic genetic programs and external signals. One of the main questions for root biologists is how plants control the number of lateral root primordia and their emergence through the main root. We recently identified S-phase kinase-associated protein2 (SKP2B) as a new early marker for lateral root development. Here, we took advantage of its specific expression pattern in Arabidopsis (Arabidopsis thaliana) in a cell-sorting and transcriptomic approach to generate a lateral root-specific cell sorting SKP2B data set that represents the endogenous genetic developmental program. We first validated this data set by showing that many of the identified genes have a function during root growth or lateral root development. Importantly, genes encoding peroxidases were highly represented in our data set. Thus, we next focused on this class of enzymes and showed, using genetic and chemical inhibitor studies, that peroxidase activity and reactive oxygen species signaling are specifically required during lateral root emergence but, intriguingly, not for primordium specification itself.

  3. Perineurial glia require Notch signaling during motor nerve development but not regeneration

    PubMed Central

    Binari, Laura A.; Lewis, Gwendolyn M.; Kucenas, Sarah

    2013-01-01

    Motor nerves play the critical role of shunting information out of the CNS to targets in the periphery. Their formation requires the coordinated development of distinct cellular components, including motor axons and the Schwann cells and perineurial glia that ensheath them. During nervous system assembly, these glial cells must migrate long distances and terminally differentiate, ensuring the efficient propagation of action potentials. Although we know quite a bit about the mechanisms that control Schwann cell development during this process, nothing is known about the mechanisms that mediate the migration and differentiation of perineurial glia. Using in vivo imaging in zebrafish, we demonstrate that Notch signaling is required for both perineurial migration and differentiation during nerve formation, but not regeneration. Interestingly, loss of Notch signaling in perineurial cells also causes a failure of Schwann cell differentiation, demonstrating that Schwann cells require perineurial glia for aspects of their own development. These studies describe a novel mechanism that mediates multiple aspects of perineurial development and reveal the critical importance of perineurial glia for Schwann cell maturation and nerve formation. PMID:23467342

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

    PubMed Central

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

    2014-01-01

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

  5. Postoperative occipital neuralgia with and without C2 nerve root transection during atlantoaxial screw fixation: a post-hoc comparative outcome study of prospectively collected data.

    PubMed

    Yeom, Jin S; Buchowski, Jacob M; Kim, Ho-Joong; Chang, Bong-Soon; Lee, Choon-Ki; Riew, K Daniel

    2013-07-01

    Although routine transection of the C2 nerve root during atlantoaxial segmental screw fixation has been recommended by some surgeons, it remains controversial and to our knowledge no comparative studies have been performed to determine whether transection or preservation of the C2 nerve root affects patient-derived sensory outcomes. The purpose of this study is to specifically analyze patient-derived sensory outcomes over time in patients with intentional C2 nerve root transection during atlantoaxial segmental screw fixation compared with those without transection. This is a post-hoc comparative analysis of prospectively collected patient-derived outcome data. The sample consists of 24 consecutive patients who underwent intentional bilateral transection of the C2 nerve root during posterior atlantoaxial segmental screw fixation (transection group) and subsequent 41 consecutive patients without transection (preservation group). A visual analog scale (VAS) score was used for occipital neuralgia as the primary outcome measure and VAS score for neck pain, neck disability index score and Japanese Orthopedic Association score for cervical myelopathy and recovery rate, with bone union rate as the secondary outcome measure. Patient-derived outcomes including change in VAS score for occipital neuralgia over time were statistically compared between the two groups. This study was not supported by any financial sources and there is no topic-specific conflict of interest related to the authors of this study. Seven (29%) of the 24 patients in the transection group experienced increased neuralgic pain at 1 month after surgery either because of newly developed occipital neuralgia or aggravation of preexisting occipital neuralgia. Four of the seven patients required almost daily medication even at the final follow-up (44 and 80 months). On the other hand, only four (10%) of 41 patients in the preservation group had increased neuralgic pain at 1 month after surgery, and at ≥ 1

  6. Pincher, a pinocytic chaperone for nerve growth factor/TrkA signaling endosomes

    PubMed Central

    Shao, Yufang; Akmentin, Wendy; Toledo-Aral, Juan Jose; Rosenbaum, Julie; Valdez, Gregorio; Cabot, John B.; Hilbush, Brian S.; Halegoua, Simon

    2002-01-01

    Acentral tenet of nerve growth factor (NGF) action that is poorly understood is its ability to mediate cytoplasmic signaling, through its receptor TrkA, that is initiated at the nerve terminal and conveyed to the soma. We identified an NGF-induced protein that we termed Pincher (pinocytic chaperone) that mediates endocytosis and trafficking of NGF and its receptor TrkA. In PC12 cells, overexpression of Pincher dramatically stimulated NGF-induced endocytosis of TrkA, unexpectedly at sites of clathrin-independent macropinocytosis within cell surface ruffles. Subsequently, a system of Pincher-containing tubules mediated the delivery of NGF/TrkA-containing vesicles to cytoplasmic accumulations. These vesicles selectively and persistently mediated TrkA-erk5 mitogen-activated protein kinase signaling. A dominant inhibitory mutant form of Pincher inhibited the NGF-induced endocytosis of TrkA, and selectively blocked TrkA-mediated cytoplasmic signaling of erk5, but not erk1/2, kinases. Our results indicate that Pincher mediates pinocytic endocytosis of functionally specialized NGF/TrkA endosomes with persistent signaling potential. PMID:12011113

  7. The persistence of the gravity signal in flax roots

    NASA Astrophysics Data System (ADS)

    Hasenstein, Karl H.

    Although the presentation time of gravitropism has been studied, no data exist as to how long a reorientation stimulus affects the gravitropic response of a root. We tested the duration of gravitropic curvature in roots of Linum usitatissimum after reversing a one hour, 90 degree gravistimulus by increasing time intervals in vertical orientation before clinorotating the roots and acquiring infrared digital images. Clinorotation was performed either parallel or perpendicular to the gravity vector. Under either condition the gravistimulus affected curvature during clinorotation only between two to three minutes. Maximal curvature after one minute of vertical reorientation was 15 degrees within one hour. After three minutes in vertical orientation the observed curvature was not statistically different from vertically growing roots. In both orientations, maximum curvature occurred after 1hr. Perpendicular (horizontal) clinorotation showed decreasing curvature with increasing reorientation time. Parallel (vertical) clinorotation resulted in greater variability to the reorientation time. These data indicate that the gravity stimulus operates essentially memory free and that clinorotation affects the gravity response. Therefore all aspects of clinorotation need to be studied before an assessment of clinostats for the simulation of microgravity is possible and a time limit for memory effects of mechanostimulation can be determined.

  8. Long-distance signals positively regulate the expression of iron uptake genes in tobacco roots.

    PubMed

    Enomoto, Yusuke; Hodoshima, Hirotaka; Shimada, Hiroaki; Shoji, Kazuhiro; Yoshihara, Toshihiro; Goto, Fumiyuki

    2007-12-01

    Long-distance signals generated in shoots are thought to be associated with the regulation of iron uptake from roots; however, the signaling mechanism is still unknown. To elucidate whether the signal regulates iron uptake genes in roots positively or negatively, we analyzed the expressions of two representative iron uptake genes: NtIRT1 and NtFRO1 in tobacco (Nicotiana tabacum L.) roots, after shoots were manipulated in vitro. When iron-deficient leaves were treated with Fe(II)-EDTA, the expressions of both genes were significantly reduced; nevertheless iron concentration in the roots maintained a similar level to that in roots grown under iron-deficient conditions. Next, all leaves from tobacco plants grown under the iron-deficient condition were excised. The expression of two genes were quickly reduced below half within 2 h after the leaf excision and gradually disappeared by the end of a 24-h period. The NtIRT1 expression was compared among the plants whose leaves were cut off in various patterns. The expression increased in proportion to the dry weight of iron-deficient leaves, although no relation was observed between the gene expression and the position of excised leaves. Interestingly, the NtIRT1 expression in hairy roots increased under the iron-deficient condition, suggesting that roots also have the signaling mechanism of iron status as well as shoots. Taken together, these results indicate that the long-distance signal generated in iron-deficient tissues including roots is a major factor in positive regulation of the expression of NtIRT1 and NtFRO1 in roots, and that the strength of the signal depends on the size of plants.

  9. Induced jasmonate signaling leads to contrasting effects on root damage and herbivore performance.

    PubMed

    Lu, Jing; Robert, Christelle Aurélie Maud; Riemann, Michael; Cosme, Marco; Mène-Saffrané, Laurent; Massana, Josep; Stout, Michael Joseph; Lou, Yonggen; Gershenzon, Jonathan; Erb, Matthias

    2015-03-01

    Induced defenses play a key role in plant resistance against leaf feeders. However, very little is known about the signals that are involved in defending plants against root feeders and how they are influenced by abiotic factors. We investigated these aspects for the interaction between rice (Oryza sativa) and two root-feeding insects: the generalist cucumber beetle (Diabrotica balteata) and the more specialized rice water weevil (Lissorhoptrus oryzophilus). Rice plants responded to root attack by increasing the production of jasmonic acid (JA) and abscisic acid, whereas in contrast to in herbivore-attacked leaves, salicylic acid and ethylene levels remained unchanged. The JA response was decoupled from flooding and remained constant over different soil moisture levels. Exogenous application of methyl JA to the roots markedly decreased the performance of both root herbivores, whereas abscisic acid and the ethylene precursor 1-aminocyclopropane-1-carboxylic acid did not have any effect. JA-deficient antisense 13-lipoxygenase (asLOX) and mutant allene oxide cyclase hebiba plants lost more root biomass under attack from both root herbivores. Surprisingly, herbivore weight gain was decreased markedly in asLOX but not hebiba mutant plants, despite the higher root biomass removal. This effect was correlated with a herbivore-induced reduction of sucrose pools in asLOX roots. Taken together, our experiments show that jasmonates are induced signals that protect rice roots from herbivores under varying abiotic conditions and that boosting jasmonate responses can strongly enhance rice resistance against root pests. Furthermore, we show that a rice 13-lipoxygenase regulates root primary metabolites and specifically improves root herbivore growth.

  10. Induced Jasmonate Signaling Leads to Contrasting Effects on Root Damage and Herbivore Performance1

    PubMed Central

    Lu, Jing; Robert, Christelle Aurélie Maud; Riemann, Michael; Cosme, Marco; Mène-Saffrané, Laurent; Massana, Josep; Stout, Michael Joseph; Lou, Yonggen; Gershenzon, Jonathan; Erb, Matthias

    2015-01-01

    Induced defenses play a key role in plant resistance against leaf feeders. However, very little is known about the signals that are involved in defending plants against root feeders and how they are influenced by abiotic factors. We investigated these aspects for the interaction between rice (Oryza sativa) and two root-feeding insects: the generalist cucumber beetle (Diabrotica balteata) and the more specialized rice water weevil (Lissorhoptrus oryzophilus). Rice plants responded to root attack by increasing the production of jasmonic acid (JA) and abscisic acid, whereas in contrast to in herbivore-attacked leaves, salicylic acid and ethylene levels remained unchanged. The JA response was decoupled from flooding and remained constant over different soil moisture levels. Exogenous application of methyl JA to the roots markedly decreased the performance of both root herbivores, whereas abscisic acid and the ethylene precursor 1-aminocyclopropane-1-carboxylic acid did not have any effect. JA-deficient antisense 13-lipoxygenase (asLOX) and mutant allene oxide cyclase hebiba plants lost more root biomass under attack from both root herbivores. Surprisingly, herbivore weight gain was decreased markedly in asLOX but not hebiba mutant plants, despite the higher root biomass removal. This effect was correlated with a herbivore-induced reduction of sucrose pools in asLOX roots. Taken together, our experiments show that jasmonates are induced signals that protect rice roots from herbivores under varying abiotic conditions and that boosting jasmonate responses can strongly enhance rice resistance against root pests. Furthermore, we show that a rice 13-lipoxygenase regulates root primary metabolites and specifically improves root herbivore growth. PMID:25627217

  11. Time-Dependent Nerve Growth Factor Signaling Changes in the Rat Retina During Optic Nerve Crush-Induced Degeneration of Retinal Ganglion Cells.

    PubMed

    Mesentier-Louro, Louise A; De Nicolò, Sara; Rosso, Pamela; De Vitis, Luigi A; Castoldi, Valerio; Leocani, Letizia; Mendez-Otero, Rosalia; Santiago, Marcelo F; Tirassa, Paola; Rama, Paolo; Lambiase, Alessandro

    2017-01-05

    Nerve growth factor (NGF) is suggested to be neuroprotective after nerve injury; however, retinal ganglion cells (RGC) degenerate following optic-nerve crush (ONC), even in the presence of increased levels of endogenous NGF. To further investigate this apparently paradoxical condition, a time-course study was performed to evaluate the effects of unilateral ONC on NGF expression and signaling in the adult retina. Visually evoked potential and immunofluorescence staining were used to assess axonal damage and RGC loss. The levels of NGF, proNGF, p75(NTR), TrkA and GFAP and the activation of several intracellular pathways were analyzed at 1, 3, 7 and 14 days after crush (dac) by ELISA/Western Blot and PathScan intracellular signaling array. The progressive RGC loss and nerve impairment featured an early and sustained activation of apoptotic pathways; and GFAP and p75(NTR) enhancement. In contrast, ONC-induced reduction of TrkA, and increased proNGF were observed only at 7 and 14 dac. We propose that proNGF and p75(NTR) contribute to exacerbate retinal degeneration by further stimulating apoptosis during the second week after injury, and thus hamper the neuroprotective effect of the endogenous NGF. These findings might aid in identifying effective treatment windows for NGF-based strategies to counteract retinal and/or optic-nerve degeneration.

  12. Time-Dependent Nerve Growth Factor Signaling Changes in the Rat Retina During Optic Nerve Crush-Induced Degeneration of Retinal Ganglion Cells

    PubMed Central

    Mesentier-Louro, Louise A.; De Nicolò, Sara; Rosso, Pamela; De Vitis, Luigi A.; Castoldi, Valerio; Leocani, Letizia; Mendez-Otero, Rosalia; Santiago, Marcelo F.; Tirassa, Paola; Rama, Paolo; Lambiase, Alessandro

    2017-01-01

    Nerve growth factor (NGF) is suggested to be neuroprotective after nerve injury; however, retinal ganglion cells (RGC) degenerate following optic-nerve crush (ONC), even in the presence of increased levels of endogenous NGF. To further investigate this apparently paradoxical condition, a time-course study was performed to evaluate the effects of unilateral ONC on NGF expression and signaling in the adult retina. Visually evoked potential and immunofluorescence staining were used to assess axonal damage and RGC loss. The levels of NGF, proNGF, p75NTR, TrkA and GFAP and the activation of several intracellular pathways were analyzed at 1, 3, 7 and 14 days after crush (dac) by ELISA/Western Blot and PathScan intracellular signaling array. The progressive RGC loss and nerve impairment featured an early and sustained activation of apoptotic pathways; and GFAP and p75NTR enhancement. In contrast, ONC-induced reduction of TrkA, and increased proNGF were observed only at 7 and 14 dac. We propose that proNGF and p75NTR contribute to exacerbate retinal degeneration by further stimulating apoptosis during the second week after injury, and thus hamper the neuroprotective effect of the endogenous NGF. These findings might aid in identifying effective treatment windows for NGF-based strategies to counteract retinal and/or optic-nerve degeneration. PMID:28067793

  13. A fungal endophyte helps plants to tolerate root herbivory through changes in gibberellin and jasmonate signaling.

    PubMed

    Cosme, Marco; Lu, Jing; Erb, Matthias; Stout, Michael Joseph; Franken, Philipp; Wurst, Susanne

    2016-08-01

    Plant-microbe mutualisms can improve plant defense, but the impact of root endophytes on below-ground herbivore interactions remains unknown. We investigated the effects of the root endophyte Piriformospora indica on interactions between rice (Oryza sativa) plants and its root herbivore rice water weevil (RWW; Lissorhoptrus oryzophilus), and how plant jasmonic acid (JA) and GA regulate this tripartite interaction. Glasshouse experiments with wild-type rice and coi1-18 and Eui1-OX mutants combined with nutrient, jasmonate and gene expression analyses were used to test: whether RWW adult herbivory above ground influences subsequent damage caused by larval herbivory below ground; whether P. indica protects plants against RWW; and whether GA and JA signaling mediate these interactions. The endophyte induced plant tolerance to root herbivory. RWW adults and larvae acted synergistically via JA signaling to reduce root growth, while endophyte-elicited GA biosynthesis suppressed the herbivore-induced JA in roots and recovered plant growth. Our study shows for the first time the impact of a root endophyte on plant defense against below-ground herbivores, adds to growing evidence that induced tolerance may be an important root defense, and implicates GA as a signal component of inducible plant tolerance against biotic stress.

  14. STZ causes depletion of immune cells in sciatic nerve and dorsal root ganglion in experimental diabetes.

    PubMed

    Hidmark, Asa S; Nawroth, Peter P; Fleming, Thomas

    2017-05-15

    Streptozotocin (STZ) treatment, a common model for inducing diabetes in rodent models, induces thermal hyperalgesia and neuronal toxicity independently of hyperglycemia by oxidizing and activating TRPA1 and TRPV1. Following treatment with STZ, CD45(+) immune cells were found to be depleted in sciatic nerve (SN) and DRG in mice, prior to hyperglycemia. Macrophages were also lost in DRG and NFκB-p65-activation was increased in SN macrophages. Immune cells were significantly reduced in both SN and DRG up to three weeks, post-treatment. Loss of PNS-resident macrophages in response to STZ-mediated toxicity may affect the regenerative capacity of the nerve in response to further injury caused by diabetes.

  15. Wnt-Ror signaling to SIA and SIB neurons directs anterior axon guidance and nerve ring placement in C. elegans

    PubMed Central

    Kennerdell, Jason R.; Fetter, Richard D.; Bargmann, Cornelia I.

    2009-01-01

    Summary Wnt signaling through Frizzled proteins guides posterior cells and axons in C. elegans into different spatial domains. Here we demonstrate an essential role for Wnt signaling through Ror tyrosine kinase homologs in the most prominent anterior neuropil, the nerve ring. A genetic screen uncovered cwn-2, the C. elegans homolog of Wnt5, as a regulator of nerve ring placement. In cwn-2 mutants, all neuronal structures in and around the nerve ring are shifted to an abnormal anterior position. cwn-2 is required at the time of nerve ring formation; it is expressed by cells posterior of the nerve ring, but its precise site of expression is not critical for its function. In nerve ring development, cwn-2 acts primarily through the Wnt receptor CAM-1 (Ror), together with the Frizzled protein MIG-1, with parallel roles for the Frizzled protein CFZ-2. The identification of CAM-1 as a CWN-2 receptor contrasts with CAM-1 action as a non-receptor in other C. elegans Wnt pathways. Cell-specific rescue of cam-1 and cell ablation experiments reveal a crucial role for the SIA and SIB neurons in positioning the nerve ring, linking Wnt signaling to specific cells that organize the anterior nervous system. PMID:19855022

  16. Jak/Stat Signaling Stimulates Zebrafish Optic Nerve Regeneration and Overcomes the Inhibitory Actions of Socs3 and Sfpq

    PubMed Central

    Elsaeidi, Fairouz; Bemben, Michael A.; Zhao, Xiao-Feng

    2014-01-01

    The regenerative failure of mammalian optic axons is partly mediated by Socs3-dependent inhibition of Jak/Stat signaling (Smith et al., 2009, 2011). Whether Jak/Stat signaling is part of the normal regenerative response observed in animals that exhibit an intrinsic capacity for optic nerve regeneration, such as zebrafish, remains unknown. Nor is it known whether the repression of regenerative inhibitors, such as Socs3, contributes to the robust regenerative response of zebrafish to optic nerve damage. Here we report that Jak/Stat signaling stimulates optic nerve regeneration in zebrafish. We found that IL-6 family cytokines, acting via Gp130-coupled receptors, stimulate Jak/Stat3 signaling in retinal ganglion cells after optic nerve injury. Among these cytokines, we found that CNTF, IL-11, and Clcf1/Crlf1a can stimulate optic axon regrowth. Surprisingly, optic nerve injury stimulated the expression of Socs3 and Sfpq (splicing factor, proline/glutamine rich) that attenuate optic nerve regeneration. These proteins were induced in a Jak/Stat-dependent manner, stimulated each other's expression and suppressed the expression of regeneration-associated genes. In vivo, the injury-dependent induction of Socs3 and Sfpq inhibits optic nerve regeneration but does not block it. We identified a robust induction of multiple cytokine genes in zebrafish retinal ganglion cells that may contribute to their ability to overcome these inhibitory factors. These studies not only identified mechanisms underlying optic nerve regeneration in fish but also suggest new molecular targets for enhancing optic nerve regeneration in mammals. PMID:24523552

  17. Mechanisms of nerve growth factor signaling in bone nociceptors and in an animal model of inflammatory bone pain.

    PubMed

    Nencini, Sara; Ringuet, Mitchell; Kim, Dong-Hyun; Chen, Yu-Jen; Greenhill, Claire; Ivanusic, Jason J

    2017-01-01

    Sequestration of nerve growth factor has been used successfully in the management of pain in animal models of bone disease and in human osteoarthritis. However, the mechanisms of nerve growth factor-induced bone pain and its role in modulating inflammatory bone pain remain to be determined. In this study, we show that nerve growth factor receptors (TrkA and p75) and some other nerve growth factor-signaling molecules (TRPV1 and Nav1.8, but not Nav1.9) are expressed in substantial proportions of rat bone nociceptors. We demonstrate that nerve growth factor injected directly into rat tibia rapidly activates and sensitizes bone nociceptors and produces acute behavioral responses with a similar time course. The nerve growth factor-induced changes in the activity and sensitivity of bone nociceptors we report are dependent on signaling through the TrkA receptor, but are not affected by mast cell stabilization. We failed to show evidence for longer term changes in expression of TrkA, TRPV1, Nav1.8 or Nav1.9 in the soma of bone nociceptors in a rat model of inflammatory bone pain. Thus, retrograde transport of NGF/TrkA and increased expression of some of the common nerve growth factor signaling molecules do not appear to be important for the maintenance of inflammatory bone pain. The findings are relevant to understand the basis of nerve growth factor sequestration and other therapies directed at nerve growth factor signaling, in managing pain in bone disease.

  18. Functional Reinnervation of the Canine Bladder after Spinal Root Transection and Genitofemoral Nerve Transfer at One and Three Months after Denervation

    PubMed Central

    RUGGIERI, MICHAEL R.; BRAVERMAN, ALAN S.; D'ANDREA, LINDA; BETZ, RANDALL; BARBE, MARY F.

    2013-01-01

    In the immediate management of patients with spinal cord injury (SCI), patients are typically observed for a period of time to determine whether voluntary control of bladder function returns. Therefore, bladder reinnervation surgeries are not likely to be performed immediately after the injury. We performed genitofemoral to pelvic nerve transfer (GF NT) surgery in canines at 1 and 3 months after bladder denervation (transection of S1 and S2 spinal roots) to determine whether this type of bladder reinnervation surgery has potential clinical feasibility. Nerve cuff electrodes were implanted on the genitofemoral nerves proximal to the pelvic nerve transfer site. Evidence for bladder reinnervation includes (1) increased bladder pressure and urethral fluid flow following electrical stimulation in four out of 20 nerve cuff electrodes implanted on the transferred GF nerves, (2) bilateral pelvic nerve stimulation induced bladder pressure and urethral fluid flow in three of four denervated animals with 1-month delay GF NT, and in five of six denervated animals with 3-month delay GF NT, and (3) abundant L1 and L2 spinal cord cell bodies (the origin of the GF nerve) retrogradely labeled with fluorogold injected into the bladder in all 10 of the GF NT animals, except one animal on one side. This study presents initial proof of concept that GF NT is a potentially viable clinical approach to reinnervation of the lower motor neuron–lesioned urinary bladder. PMID:18373487

  19. MADS-box transcription factor AGL21 regulates lateral root development and responds to multiple external and physiological signals.

    PubMed

    Yu, Lin-Hui; Miao, Zi-Qing; Qi, Guo-Feng; Wu, Jie; Cai, Xiao-Teng; Mao, Jie-Li; Xiang, Cheng-Bin

    2014-11-01

    Plant root system morphology is dramatically influenced by various environmental cues. The adaptation of root system architecture to environmental constraints, which mostly depends on the formation and growth of lateral roots, is an important agronomic trait. Lateral root development is regulated by the external signals coordinating closely with intrinsic signaling pathways. MADS-box transcription factors are known key regulators of the transition to flowering and flower development. However, their functions in root development are still poorly understood. Here we report that AGL21, an AGL17-clade MADS-box gene, plays a crucial role in lateral root development. AGL21 was highly expressed in root, particularly in the root central cylinder and lateral root primordia. AGL21 overexpression plants produced more and longer lateral roots while agl21 mutants showed impaired lateral root development, especially under nitrogen-deficient conditions. AGL21 was induced by many plant hormones and environmental stresses, suggesting a function of this gene in root system plasticity in response to various signals. Furthermore, AGL21 was found positively regulating auxin accumulation in lateral root primordia and lateral roots by enhancing local auxin biosynthesis, thus stimulating lateral root initiation and growth. We propose that AGL21 may be involved in various environmental and physiological signals-mediated lateral root development and growth. © The Author 2014. Published by Oxford University Press on behalf of CSPB and IPPE, SIBS, CAS.

  20. The effects of anticonvulsants on 4-aminopyridine-induced bursting: in vitro studies on rat peripheral nerve and dorsal roots.

    PubMed Central

    Lees, G.

    1996-01-01

    1. Aminopyridines have been used as beneficial symptomatic treatments in a variety of neurological conditions including multiple sclerosis but have been associated with considerable toxicity in the form of abdominal pain, paraesthesias and (rarely) convulsions. 2. Extracellular and intracellular recording was used to characterize action potentials in rat sciatic nerves and dorsal roots and the effects of 4-aminopyridine (4-AP). 3. In sciatic nerve trunks, 1 mM 4-AP produced pronounced after potentials at room temperature secondary to regenerative firing in affected axons (5-10 spikes per stimulus). At physiological temperatures, after potentials (2-3 spikes) were greatly attenuated in peripheral axons. 4. 4-AP evoked more pronounced and prolonged after discharges in isolated dorsal roots at 37 degrees C (3-5.5 mV and 80-100 ms succeeded by a smaller inhibitory/depolarizing voltage shift) which were used to assess the effects of anticonvulsants. 5. Phenytoin, carbamazepine and lamotrigine dose-dependently reduced the area of 4-AP-induced after potentials at 100 and 320 microM but the amplitude of compound action potentials (evoked at 0.5 Hz) was depressed in parallel. 6. The tonic block of sensory action potentials by all three drugs (at 320 microM) was enhanced by high frequency stimulation (5-500 Hz). 7. The lack of selectivity of these frequency-dependent Na+ channel blockers for burst firing compared to low-frequency spikes, is discussed in contrast to their effects on 4-AP-induced seizures and paroxysmal activity in CNS tissue (which is associated with large and sustained depolarizing plateau potentials). 8. In conclusion, these in vitro results confirm the marked sensitivity of sensory axons to 4-AP (the presumptive basis for paraesthesias). Burst firing was not preferentially impaired at relatively high concentrations suggesting that anticonvulsants will not overcome the toxic peripheral actions of 4-AP in neurological patients. PMID:8821551

  1. Sciatic nerve injury induces apoptosis of dorsal root ganglion satellite glial cells and selectively modifies neurosteroidogenesis in sensory neurons.

    PubMed

    Schaeffer, Véronique; Meyer, Laurence; Patte-Mensah, Christine; Eckert, Anne; Mensah-Nyagan, Ayikoe G

    2010-01-15

    Neurosteroids are synthesized either by glial cells, by neurons, or within the context of neuron-glia cross-talk. Various studies suggested neurosteroid involvement in the control of neurodegeneration but there is no evidence showing that the natural protection of nerve cells against apoptosis directly depends on their own capacity to produce neuroprotective neurosteroids. Here, we investigated the interactions between neurosteroidogenesis and apoptosis occurring in sensory structures of rats subjected to neuropathic pain generated by sciatic nerve chronic constriction injury (CCI). Using the terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL), we observed no apoptotic cells in the spinal cord up to 30 days after CCI although pain symptoms such as mechano-allodynia, thermal and mechanical hyperalgesia were evidenced with the Hargreaves's behavioral and von Frey filament tests. In contrast, double-labeling experiments combining TUNEL and immunostaining with antibodies against glutamine synthetase or neuronal nuclei protein revealed apoptosis occurrence in satellite glial cells (SGC) (not in neurons) of CCI rat ipsilateral dorsal root ganglia (DRG) at day 30 after injury. Pulse-chase experiments coupled with high performance liquid chromatography and flow scintillation detection showed that, among numerous biosynthetic pathways converting [(3)H]pregnenolone into various [(3)H]neurosteroids, only [(3)H]estradiol formation was selectively modified and upregulated in DRG of CCI rats. Consistently, immunohistochemical investigations localized aromatase (estradiol-synthesizing enzyme) in DRG neurons but not in SGC. Pharmacological inhibition of aromatase caused apoptosis of CCI rat DRG neurons. Altogether, our results suggest that endogenously produced neurosteroids such as estradiol may be pivotal for the protection of DRG sensory neurons against sciatic nerve CCI-induced apoptosis.

  2. Microsurgical procedures in the peripheral nerves and the dorsal root entry zone for the treatment of spasticity.

    PubMed

    Sindou, M; Keravel, Y

    1988-01-01

    When spasticity becomes severe and harmful, in spite of physical and medical therapy, neurosurgery can give functional improvement. This paper deals with the long term results of Selective Peripheral Neurotomies of the Tibial Nerve and Selective Posterior Rhizotomies in the Dorsal Root Entry Zone, in 123 patients with spastic disorders localized to the limbs. The micro-techniques and intra-operative electro-stimulation for identification of the nervous structures responsible for the spastic components, can give a substantial reduction of the harmful spasticity, without suppressing the useful muscle tone and impairing the residual motor and sensory functions. The results were effective, with a 1 to 13 year follow-up (5 on average), in 89% of 47 Selective Peripheral Neurotomies of the tibial nerve for spastic foot, in 92% of 53 Selective Posterior Rhizotomies for paraplegia and in 87% of 23 Selective Posterior Rhizotomies for hemiplegia. In the most severe situations ("comfort" indications), correction of the abnormal postures and relief of pain facilitated nursing and physiotherapy. Sometimes there was reappearance of some useful voluntary movements. In the less affected patients ("functional" indications), the suppression of the harmful spastic components made the persistant capacities more effective.

  3. Diagnostic accuracy of standardised qualitative sensory test in the detection of lumbar lateral stenosis involving the L5 nerve root.

    PubMed

    Lin, Jiann-Her; Hsieh, Yi-Chen; Chen, Yi-Chen; Wang, Yun; Chen, Chih-Cheng; Chiang, Yung-Hsiao

    2017-09-06

    Misdiagnosis of symptomatic lumbar lateral stenosis (LS) may result in an unfavourable prognosis after surgical treatment. This study investigated the diagnostic accuracy of a standardised qualitative sensory test (SQST) in the detection of symptomatic LS in patients who had degenerative spinal disorders involving the L5 spinal nerve. We prospectively identified 75 patients, of which 60 met the inclusion criteria. Lateral recess stenosis at the L5 level or foraminal stenosis at the L5/S1 level on MRI was identified and graded by a neurosurgeon blinded to any clinical information. The reference criteria for the diagnosis of symptomatic LS were grade III LS on MRI and relevant clinical symptoms. Cutaneous sensory functions of the L5 dermatome on the symptomatic side were evaluated using the SQST. Each item of the SQST showed a satisfactory performance in the diagnosis of LS (sensitivity = 0.455-0.727, specificity = 0.868-1.0). A stepwise selection model identified low-strength von-Frey, high-strength von-Frey, and vibration as the most accurate predictors of symptomatic LS with an area under the receiver operating characteristic curve of 0.9563 (95% confidence interval = 0.9003-1.0). In combination with MRI, the SQST is a promising diagnostic tool for detecting symptomatic LS involving L5 nerve roots.

  4. Regulation of Root Greening by Light and Auxin/Cytokinin Signaling in Arabidopsis[W

    PubMed Central

    Kobayashi, Koichi; Baba, Shinsuke; Obayashi, Takeshi; Sato, Mayuko; Toyooka, Kiminori; Keränen, Mika; Aro, Eva-Mari; Fukaki, Hidehiro; Ohta, Hiroyuki; Sugimoto, Keiko; Masuda, Tatsuru

    2012-01-01

    Tight coordination between plastid differentiation and plant development is best evidenced by the synchronized development of photosynthetic tissues and the biogenesis of chloroplasts. Here, we show that Arabidopsis thaliana roots demonstrate accelerated chlorophyll accumulation and chloroplast development when they are detached from shoots. However, this phenomenon is repressed by auxin treatment. Mutant analyses suggest that auxin transported from the shoot represses root greening via the function of INDOLE-3-ACETIC ACID14, AUXIN RESPONSE FACTOR7 (ARF7), and ARF19. Cytokinin signaling, on the contrary, is required for chlorophyll biosynthesis in roots. The regulation by auxin/cytokinin is dependent on the transcription factor LONG HYPOCOTYL5 (HY5), which is required for the expression of key chlorophyll biosynthesis genes in roots. The expression of yet another root greening transcription factor, GOLDEN2-LIKE2 (GLK2), was found to be regulated in opposing directions by auxin and cytokinin. Furthermore, both the hormone signaling and the GLK transcription factors modified the accumulation of HY5 in roots. Overexpression of GLKs in the hy5 mutant provided evidence that GLKs require HY5 to maximize their activities in root greening. We conclude that the combination of HY5 and GLKs, functioning downstream of light and auxin/cytokinin signaling pathways, is responsible for coordinated expression of the key genes in chloroplast biogenesis. PMID:22415275

  5. Root Bending Is Antagonistically Affected by Hypoxia and ERF-Mediated Transcription via Auxin Signaling.

    PubMed

    Eysholdt-Derzsó, Emese; Sauter, Margret

    2017-09-01

    When plants encounter soil water logging or flooding, roots are the first organs to be confronted with reduced gas diffusion resulting in limited oxygen supply. Since roots do not generate photosynthetic oxygen, they are rapidly faced with oxygen shortage rendering roots particularly prone to damage. While metabolic adaptations to low oxygen conditions, which ensure basic energy supply, have been well characterized, adaptation of root growth and development have received less attention. In this study, we show that hypoxic conditions cause the primary root to grow sidewise in a low oxygen environment, possibly to escape soil patches with reduced oxygen availability. This growth behavior is reversible in that gravitropic growth resumes when seedlings are returned to normoxic conditions. Hypoxic root bending is inhibited by the group VII ethylene response factor (ERFVII) RAP2.12, as rap2.12-1 seedlings show exaggerated primary root bending. Furthermore, overexpression of the ERFVII member HRE2 inhibits root bending, suggesting that primary root growth direction at hypoxic conditions is antagonistically regulated by hypoxia and hypoxia-activated ERFVIIs. Root bending is preceded by the establishment of an auxin gradient across the root tip as quantified with DII-VENUS and is synergistically enhanced by hypoxia and the auxin transport inhibitor naphthylphthalamic acid. The protein abundance of the auxin efflux carrier PIN2 is reduced at hypoxic conditions, a response that is suppressed by RAP2.12 overexpression, suggesting antagonistic control of auxin flux by hypoxia and ERFVII. Taken together, we show that hypoxia triggers an escape response of the primary root that is controlled by ERFVII activity and mediated by auxin signaling in the root tip. © 2017 American Society of Plant Biologists. All Rights Reserved.

  6. Electrical signaling, stomatal conductance, ABA and ethylene content in avocado trees in response to root hypoxia.

    PubMed

    Gil, Pilar M; Gurovich, Luis; Schaffer, Bruce; García, Nicolás; Iturriaga, Rodrigo

    2009-02-01

    Avocado (Persea americana Mill.) trees are among the most sensitive of fruit tree species to root hypoxia as a result of flooded or poorly drained soil. Similar to drought stress, an early physiological response to root hypoxia in avocado is a reduction of stomatal conductance. It has been previously determined in avocado trees that an extracellular electrical signal between the base of stem and leaves is produced and related to reductions in stomatal conductance in response to drought stress. The current study was designed to determine if changes in the extracellular electrical potential between the base of the stem and leaves in avocado trees could also be detected in response to short-term (min) or long-term (days) root hypoxia, and if these signals could be related to stomatal conductance (gs), root and leaf ABA and ACC concentrations, ethylene emission from leaves and leaf abscission. In contrast to previous observations for drought-stressed trees, short-term or long-term root hypoxia did not stimulate an electrical potential difference between the base of the stem and leaves. Short-term hypoxia did not result in a significant decrease in gs compared with plants in the control treatment, and no differences in ABA concentration were found between plants subjected to hypoxia and control plants. Long-term hypoxia in the root zone resulted in a significant decrease in gs, increased leaf ethylene and increased leaf abscission. The results indicate that for avocado trees exposed to root hypoxia, electrical signals do not appear to be the primary root-to-shoot communication mechanism involved in signaling for stomatal closure as a result of hypoxia in the root zone.

  7. Electrical signaling, stomatal conductance, ABA and Ethylene content in avocado trees in response to root hypoxia

    PubMed Central

    Gurovich, Luis; Schaffer, Bruce; García, Nicolás; Iturriaga, Rodrigo

    2009-01-01

    Avocado (Persea americana Mill.) trees are among the most sensitive of fruit tree species to root hypoxia as a result of flooded or poorly drained soil. Similar to drought stress, an early physiological response to root hypoxia in avocado is a reduction of stomatal conductance. It has been previously determined in avocado trees that an extracellular electrical signal between the base of stem and leaves is produced and related to reductions in stomatal conductance in response to drought stress. The current study was designed to determine if changes in the extracellular electrical potential between the base of the stem and leaves in avocado trees could also be detected in response to short-term (min) or long-term (days) root hypoxia, and if these signals could be related to stomatal conductance (gs), root and leaf ABA and ACC concentrations, ethylene emission from leaves and leaf abscission. In contrast to previous observations for drought-stressed trees, short-term or long-term root hypoxia did not stimulate an electrical potential difference between the base of the stem and leaves. Short-term hypoxia did not result in a significant decrease in gs compared with plants in the control treatment, and no differences in ABA concentration were found between plants subjected to hypoxia and control plants. Long-term hypoxia in the root zone resulted in a significant decrease in gs, increased leaf ethylene and increased leaf abscission. The results indicate that for avocado trees exposed to root hypoxia, electrical signals do not appear to be the primary root-to-shoot communication mechanism involved in signaling for stomatal closure as a result of hypoxia in the root zone. PMID:19649181

  8. Antagonism of nerve growth factor-TrkA signaling and the relief of pain.

    PubMed

    Mantyh, Patrick W; Koltzenburg, Martin; Mendell, Lorne M; Tive, Leslie; Shelton, David L

    2011-07-01

    Nerve growth factor (NGF) was originally discovered as a neurotrophic factor essential for the survival of sensory and sympathetic neurons during development. However, in the adult NGF has been found to play an important role in nociceptor sensitization after tissue injury. The authors outline mechanisms by which NGF activation of its cognate receptor, tropomyosin-related kinase A receptor, regulates a host of ion channels, receptors, and signaling molecules to enhance acute and chronic pain. The authors also document that peripherally restricted antagonism of NGF-tropomyosin-related kinase A receptor signaling is effective for controlling human pain while appearing to maintain normal nociceptor function. Understanding whether there are any unexpected adverse events and how humans may change their behavior and use of the injured/degenerating tissue after significant pain relief without sedation will be required to fully appreciate the patient populations that may benefit from these therapies targeting NGF.

  9. Antagonism of Nerve Growth Factor-TrkA Signaling and the Relief of Pain

    PubMed Central

    Mantyh, Patrick W.; Koltzenburg, Martin; Mendell, Lorne M.; Tive, Leslie; Shelton, David L.

    2011-01-01

    Nerve growth factor (NGF) was originally discovered as a neurotrophic factor essential for the survival of sensory and sympathetic neurons during development. However in the adult, NGF has been found to play an important role in nociceptor sensitization following tissue injury. Here we outline mechanisms by which NGF activation of its cognate receptor, tropomyosin-related kinase A receptor, regulates a host of ion channels, receptors, and signaling molecules to enhance acute and chronic pain. Further, we document that peripherally restricted antagonism of NGF-tropomyosin-related kinase A receptor signaling is effective for controlling human pain while appearing to maintain normal nociceptor function. Understanding whether there are any unexpected adverse events as well as how humans may change their behavior and use of the injured/degenerating tissue following significant pain relief without sedation will be required to fully appreciate the patient populations that may benefit from these therapies targeting NGF. PMID:21602663

  10. Calcium and protein phosphorylation in the transduction of gravity signal in corn roots

    NASA Technical Reports Server (NTRS)

    Friedmann, M.; Poovaiah, B. W.

    1991-01-01

    The involvement of calcium and protein phosphorylation in the transduction of gravity signal was studied using corn roots of a light-insensitive variety (Zea mays L., cv. Patriot). The gravitropic response was calcium-dependent. Horizontal placement of roots preloaded with 32P for three minutes resulted in changes in protein phosphorylation of polypeptides of 32 and 35 kD. Calcium depletion resulted in decreased phosphorylation of these phosphoproteins and replenishment of calcium restored the phosphorylation.

  11. Calcium and protein phosphorylation in the transduction of gravity signal in corn roots

    NASA Technical Reports Server (NTRS)

    Friedmann, M.; Poovaiah, B. W.

    1991-01-01

    The involvement of calcium and protein phosphorylation in the transduction of gravity signal was studied using corn roots of a light-insensitive variety (Zea mays L., cv. Patriot). The gravitropic response was calcium-dependent. Horizontal placement of roots preloaded with 32P for three minutes resulted in changes in protein phosphorylation of polypeptides of 32 and 35 kD. Calcium depletion resulted in decreased phosphorylation of these phosphoproteins and replenishment of calcium restored the phosphorylation.

  12. Microtubule Dynamics in Living Root Hairs: Transient Slowing by Lipochitin Oligosaccharide Nodulation SignalsW⃞

    PubMed Central

    Vassileva, Valya N.; Kouchi, Hiroshi; Ridge, Robert W.

    2005-01-01

    The incorporation of a fusion of green fluorescent protein and tubulin-α 6 from Arabidopsis thaliana in root hairs of Lotus japonicus has allowed us to visualize and quantify the dynamic parameters of the cortical microtubules in living root hairs. Analysis of individual microtubule turnover in real time showed that only plus polymer ends contributed to overall microtubule dynamicity, exhibiting dynamic instability as the main type of microtubule behavior in Lotus root hairs. Comparison of the four standard parameters of in vivo dynamic instability—the growth rate, the disassembly rate, and the frequency of transitions from disassembly to growth (rescue) and from growth to disassembly (catastrophe)—revealed that microtubules in young root hairs were more dynamic than those in mature root hairs. Either inoculation with Mesorhizobium loti or purified M. loti lipochitin oligosaccharide signal molecules (Nod factors) significantly affected the growth rate and transition frequencies in emerging and growing root hairs, making microtubules less dynamic at a specific window after symbiotic inoculation. This response of root hair cells to rhizobial Nod factors is discussed in terms of the possible biological significance of microtubule dynamics in the early signaling events leading to the establishment and progression of the globally important Rhizobium/legume symbiosis. PMID:15863517

  13. Root-Shoot Signaling crosstalk involved in the shoot growth promoting action of rhizospheric humic acids

    PubMed Central

    Olaetxea, Maite; Mora, Verónica; García, Andrés Calderin; Santos, Leandro Azevedo; Baigorri, Roberto; Fuentes, Marta; Garnica, María; Berbara, Ricardo Luis Louro; Zamarreño, Angel Maria; Garcia-Mina, Jose M.

    2016-01-01

    ABSTRACT Numerous studies have shown the ability of humic substances to improve plant development. This action is normally reflected in an enhancement of crop yields and quality. However, the mechanisms responsible for this action of humic substances remain rather unknown. Our studies have shown that the shoot promoting action of sedimentary humic acids is dependent of its ability to increase root hydraulic conductivity through signaling pathways related to ABA, which in turn is affected in roots by humic acids in an IAA-NO dependent way. Furthermore, these studies also indicate that the primary action of humic acids in roots might also be physical, resulting from a transient mild stress caused by humic acids associated with a fouling-cleaning cycle of wall cell pores. Finally the role of alternative signal molecules, such as ROS, and corresponding signaling pathways are also discussed and modeled in the context of the above-mentioned framework. PMID:26966789

  14. Root-Shoot Signaling crosstalk involved in the shoot growth promoting action of rhizospheric humic acids.

    PubMed

    Olaetxea, Maite; Mora, Verónica; García, Andrés Calderin; Santos, Leandro Azevedo; Baigorri, Roberto; Fuentes, Marta; Garnica, María; Berbara, Ricardo Luis Louro; Zamarreño, Angel Maria; Garcia-Mina, Jose M

    2016-01-01

    Numerous studies have shown the ability of humic substances to improve plant development. This action is normally reflected in an enhancement of crop yields and quality. However, the mechanisms responsible for this action of humic substances remain rather unknown. Our studies have shown that the shoot promoting action of sedimentary humic acids is dependent of its ability to increase root hydraulic conductivity through signaling pathways related to ABA, which in turn is affected in roots by humic acids in an IAA-NO dependent way. Furthermore, these studies also indicate that the primary action of humic acids in roots might also be physical, resulting from a transient mild stress caused by humic acids associated with a fouling-cleaning cycle of wall cell pores. Finally the role of alternative signal molecules, such as ROS, and corresponding signaling pathways are also discussed and modeled in the context of the above-mentioned framework.

  15. A molecular mechanism of optic nerve regeneration in fish: the retinoid signaling pathway.

    PubMed

    Kato, Satoru; Matsukawa, Toru; Koriyama, Yoshiki; Sugitani, Kayo; Ogai, Kazuhiro

    2013-11-01

    The fish optic nerve regeneration process takes more than 100 days after axotomy and comprises four stages: neurite sprouting (1-4 days), axonal elongation (5-30 days), synaptic refinement (35-80 days) and functional recovery (100-120 days). We screened genes specifically upregulated in each stage from axotomized fish retina. The mRNAs for heat shock protein 70 and insulin-like growth factor-1 rapidly increased in the retinal ganglion cells soon after axotomy and function as cell-survival factors. Purpurin mRNA rapidly and transiently increased in the photoreceptors and purpurin protein diffusely increased in all nuclear layers at 1-4 days after injury. The purpurin gene has an active retinol-binding site and a signal peptide. Purpurin with retinol functions as a sprouting factor for thin neurites. This neurite-sprouting effect was closely mimicked by retinoic acid and blocked by its inhibitor. We propose that purpurin works as a retinol transporter to supply retinoic acid to damaged RGCs which in turn activates target genes. We also searched for genes involved in the second stage of regeneration. The mRNA of retinoid-signaling molecules increased in retinal ganglion cells at 7-14 days after injury and tissue transglutaminase and neuronal nitric oxide synthase mRNAs, RA-target genes, increased in retinal ganglion cells at 10-30 days after injury. They function as factors for the outgrowth of thick, long neurites. Here we present a retinoid-signaling hypothesis to explain molecular events during the early stages of optic nerve regeneration in fish.

  16. Nitric Oxide Signaling and Neural Stem Cell Differentiation in Peripheral Nerve Regeneration

    PubMed Central

    Tao Li, Jessica; Somasundaram, Chandra; Bian, Ka; Xiong, Weijun; Mahmooduddin, Faiz; Nath, Rahul K.; Murad, Ferid

    2010-01-01

    Objective: The objective was to examine whether nitric oxide signaling plays a role in human embryonic stem cell differentiation into neural cells. This article reviews current literature on nitric oxide signaling and neural stem cell differentiation for potential therapeutic application to peripheral nerve regeneration. Methods: Human embryonic H9-stem cells were grown, maintained on mitomycin C–treated mouse embryonic fibroblast feeder layer, cultured on Matrigel to be feeder-free, and used for all the experiments. Fluorescent dual-immunolabeling and confocal image analysis were used to detect the presence of the neural precursor cell markers nestin and nitric oxide synthase-1. Fluorescence-activated cell sorting analysis was used to determine the percentage of expression. Results: We have shown the confocal image of stage 1 human embryonic stem cells coexpressing nestin and nitric oxide synthase-1. Fluorescence-activated cell sorting analysis indicated 24.3% positive labeling of nitric oxide synthase-1. Adding retinoic acid (10−6 M) to the culture medium increased the percent of nitric oxide synthase-1 positive cells to 33.9%. Combining retinoic acid (10−6 M) with 8-brom cyclic guanosine monophosphate (10−5 M), the fluorescence-activated cell sorting analysis demonstrated a further increase of nitric oxide synthase-1 positive cells to 45.4%. Our current results demonstrate a prodifferentiation potency of nitric oxide synthase-1, stimulated by retinoic acid with and without cyclic guanosine monophosphate. Conclusion: We demonstrated for the first time how nitric oxide/cyclic guanosine monophosphate signaling contributes to the development of neural precursors derived from human embryonic stem cells and enhances the differentiation of precursors toward functional neurons for peripheral nerve regeneration. PMID:20563304

  17. Translaminar Microendoscopic Herniotomy for Cranially Migrated Lumbar Disc Herniations Encroaching on the Exiting Nerve Root in the Preforaminal and Foraminal Zones

    PubMed Central

    Tono, Osamu; Senba, Hideyuki; Kitamura, Takahiro; Komiya, Norihiro; Oga, Masayoshi; Shidahara, Satoshi

    2013-01-01

    Study Design Case series. Purpose The aim of this study was to describe translaminar microendoscopic herniotomy (TL-MEH) for cranially migrated lumbar disc herniations encroaching on the exiting nerve root in the preforaminal and foraminal zones and to report preliminary results of the procedure. Overview of Literature Conventional interlaminar approaches for preforaminal and foraminal lumbar disc herniations result in extensive removal of the lamina and facet joint to remove disc fragments safely. More destructive approaches increase the risk of postoperative segmental instability. Methods TL-MEH is a minimally invasive procedure for herniotomy via the translaminar approach using a microendoscopic technique. TL-MEH was performed in seven patients with a cranially migrated lumbar disc herniation encroaching on the exiting nerve root. The disc fragments were located in the preforaminal zone in four patients, and in the preforaminal and foraminal zones in three. Results All patients experienced immediate relief from symptoms after surgery and satisfactory results at the final follow-up. Surgical complications, such as a dural tear, nerve injury, and surgical site infection, were not investigated. Conclusions TL-MEH seemed to be an effective and safe alternative minimally invasive surgical option for patients with a cranially migrated lumbar disc herniation encroaching the exiting nerve root in the preforaminal and foraminal zones. PMID:24066214

  18. Variations in the lumbosacral ligament and associated changes in the lumbosacral region resulting in compression of the fifth dorsal root ganglion and spinal nerve.

    PubMed

    Briggs, C A; Chandraraj, S

    1995-01-01

    Sixty-five lumbosacral regions from adult cadavers were dissected and the position and relations of the lumbosacral ligament noted. The lumbosacral ligament was present in all specimens; in 22 (34%) it extended medially across the ventral ramus of the fifth lumbar nerve, and in six (9%) of these the underlying nerve was compressed and visibly flattened. On two of these specimens the nerve, together with its dorsal root ganglion, was removed, processed, and stained with Masson's trichrome. The compressed nerve showed increased thickness of endoneurial and perineurial connective tissue, and the cells of the dorsal root ganglion were smaller and surrounded by increased connective tissue, particularly at the periphery of the ganglion. Observation of the lumbosacral ligament and surrounding anatomical structures suggests that anatomical variation in this region may be attributed to the health of the lumbosacral articular elements. In those specimens showing compression of the fifth lumbar spinal nerve there was also narrowing of the lumbosacral interspace. In these the disc itself was compressed and showed degenerative changes. The articular processes at the lumbosacral joint were irregular, with thinning and fissuring of the artiuclar cartilage. It is suggested that the processes which lead to the further development of the ligament, by the formation of additional fibrous bands, are mechanical in nature and result from instability at the lumbosacral region itself. Instability subsequently leads to the initiation of a chain of degenerative changes, involving pathology at the lumbosacral disc and zygapophyseal joints.(ABSTRACT TRUNCATED AT 250 WORDS)

  19. Implementation of linear sensory signaling via multiple coordinated mechanisms at central vestibular nerve synapses

    PubMed Central

    McElvain, Lauren E.; Faulstich, Michael; Jeanne, James M.; Moore, Jeffrey D.; du Lac, Sascha

    2015-01-01

    Summary Signal transfer in neural circuits is dynamically modified by the recent history of neuronal activity. Short-term plasticity endows synapses with nonlinear transmission properties, yet synapses in sensory and motor circuits are capable of signaling linearly over a wide range of presynaptic firing rates. How do such synapses achieve rate-invariant transmission despite history-dependent nonlinearities? Here, ultrastructural, biophysical, and computational analyses demonstrate that concerted molecular, anatomical, and physiological refinements are required for central vestibular nerve synapses to linearly transmit rate-coded sensory signals. Vestibular synapses operate in a physiological regime of steady-state depression imposed by tonic firing. Rate-invariant transmission relies on brief presynaptic action potentials that delimit calcium influx, large pools of rapidly mobilized vesicles, multiple low-probability release sites, robust postsynaptic receptor sensitivity, and efficient transmitter clearance. Broadband linear synaptic filtering of head motion signals is thus achieved by coordinately tuned synaptic machinery that maintains physiological operation within inherent cell biological limitations. PMID:25704949

  20. Nerve root distribution of deltoid and biceps brachii muscle in cervical spondylotic myelopathy: a potential risk factor for postoperative shoulder muscle weakness after posterior decompression.

    PubMed

    Yonemura, Hiroshi; Kaneko, Kazuo; Taguchi, Toshihiko; Fujimoto, Hideaki; Toyoda, Kouichiro; Kawai, Shinya

    2004-01-01

    To investigate the nerve root distribution of deltoid and biceps brachii muscle, compound muscle action potentials (CMAPs) were recorded intraoperatively following nerve root stimulation in cervical spondylotic myelopathy. A total of 19 upper limbs in 12 patients aged 55-72 years (mean, 65.5 years) with cervical spondylotic myelopathy were examined. CMAPs were recorded from deltoid and biceps brachii muscle following C5 and C6 root stimulation. Although both C5 and C6 roots were innervated for deltoid and biceps brachii muscle in all subjects, the amplitude ratio of CMAPs (C5/C6) differed individually depending on the symptomatic intervertebral levels of the spinal cord. The C5 root predominantly innervated both deltoid and biceps brachii in patients with symptomatic cord lesions at the C4-C5 intervertebral level compared to patients with symptomatic cord lesions at the C5-C6 intervertebral level. Although no patients sustained postoperative radiculopathy in our study, severe weakness and unfavorable recovery are expected when the C5 root in patients with C4-C5 myelopathy is damaged. From the electrophysiological aspect, C4-C5 cord lesions are likely to be a potential risk factor for postoperative shoulder muscle weakness in patients with compressive cervical myelopathy.

  1. Endodermal ABA Signaling Promotes Lateral Root Quiescence during Salt Stress in Arabidopsis Seedlings[C][W

    PubMed Central

    Duan, Lina; Dietrich, Daniela; Ng, Chong Han; Chan, Penny Mei Yeen; Bhalerao, Rishikesh; Bennett, Malcolm J.; Dinneny, José R.

    2013-01-01

    The endodermal tissue layer is found in the roots of vascular plants and functions as a semipermeable barrier, regulating the transport of solutes from the soil into the vascular stream. As a gateway for solutes, the endodermis may also serve as an important site for sensing and responding to useful or toxic substances in the environment. Here, we show that high salinity, an environmental stress widely impacting agricultural land, regulates growth of the seedling root system through a signaling network operating primarily in the endodermis. We report that salt stress induces an extended quiescent phase in postemergence lateral roots (LRs) whereby the rate of growth is suppressed for several days before recovery begins. Quiescence is correlated with sustained abscisic acid (ABA) response in LRs and is dependent upon genes necessary for ABA biosynthesis, signaling, and transcriptional regulation. We use a tissue-specific strategy to identify the key cell layers where ABA signaling acts to regulate growth. In the endodermis, misexpression of the ABA insensitive1-1 mutant protein, which dominantly inhibits ABA signaling, leads to a substantial recovery in LR growth under salt stress conditions. Gibberellic acid signaling, which antagonizes the ABA pathway, also acts primarily in the endodermis, and we define the crosstalk between these two hormones. Our results identify the endodermis as a gateway with an ABA-dependent guard, which prevents root growth into saline environments. PMID:23341337

  2. Malignant peripheral nerve sheath tumour (MPNST): the clinical implications of cellular signalling pathways.

    PubMed

    Katz, Daniela; Lazar, Alexander; Lev, Dina

    2009-10-19

    Malignant peripheral nerve sheath tumour (MPNST) is a rare malignancy accounting for 3-10% of all soft tissue sarcomas. Most MPNSTs arise in association with peripheral nerves or deep neurofibromas and may originate from neural crest cells, although the specific cell of origin is uncertain. Approximately half of MPNSTs occur in the setting of neurofibromatosis type 1 (NF1), an autosomal dominant disorder with an incidence of approximately one in 3500 persons; the remainder of MPNSTs develop sporadically. In addition to a variety of clinical manifestations, approximately 8-13% of NF1 patients develop MPNSTs, which are the leading cause of NF1-related mortality. Surgical resection is the mainstay of MPNST clinical management. However, because of invasive growth, propensity to metastasise, and limited sensitivity to chemotherapy and radiation, MPNST has a guarded to poor prognosis. Five-year survival rates of only 20-50% indicate an urgent need for improved therapeutic approaches. Recent work in this field has identified several altered intracellular signal transduction cascades and deregulated tyrosine kinase receptors, posing the possibility of personalised, targeted therapeutics. However, expanded knowledge of MPNST molecular pathobiology will be needed to meaningfully apply such approaches for the benefit of afflicted patients.

  3. Selection of entomopathogenic nematodes for enhanced responsiveness to a volatile root signal helps to control a major root pest.

    PubMed

    Hiltpold, Ivan; Baroni, Mariane; Toepfer, Stefan; Kuhlmann, Ulrich; Turlings, Ted C J

    2010-07-15

    The efficacy of natural enemies as biological control agents against insect pests can theoretically be enhanced by artificial selection for high responsiveness to foraging cues. The recent discovery that maize roots damaged by the western corn rootworm (WCR) emit a key attractant for insect-killing nematodes has opened the way to explore whether a selection strategy can improve the control of root pests. The compound in question, (E)-beta-caryophyllene, is only weakly attractive to Heterorhabditis bacteriophora, one of the most infectious nematodes against WCR. To overcome this drawback, we used a six-arm below-ground olfactometer to select for a strain of H. bacteriophora that is more readily attracted to (E)-beta-caryophyllene. After six generations of selection, the selected strain responded considerably better and moved twice as rapidly towards a (E)-beta-caryophyllene source than the original strain. There was a minor trade-off between this enhanced responsiveness and nematode infectiveness. Yet, in subsequent field tests, the selected strain was significantly more effective than the original strain in reducing WCR populations in plots with a maize variety that releases (E)-beta-caryophyllene, but not in plots with a maize variety that does not emit this root signal. These results illustrate the great potential of manipulating natural enemies of herbivores to improve biological pest control.

  4. Selective inhibition of extracellular signal-regulated kinases 1/2 blocks nerve growth factor to brain-derived neurotrophic factor signaling and suppresses the development of and reverses already established pain behavior in rats.

    PubMed

    Matsuoka, Y; Yang, J

    2012-03-29

    Brain-derived neurotrophic factor (BDNF) plays a key role in the development of pathological pain. Although it is known that nerve growth factor (NGF) induces BDNF mRNA through extracellular signal-regulated kinases (ERK), whether ERK1/2 or ERK5, two closely related members of the ERK family, mediate this signal is still unclear because classical MEK inhibitors block both pathways. We studied the involvement of ERK-signaling in NGF induction of BDNF in PC12 cells, cultured dorsal root ganglia neurons, and in rats subjected to neuropathic pain models using ERK1/2- and ERK5-specific tools. Selective activation of ERK1/2 upregulated BDNF mRNA in PC12 cells, whereas selective ERK5 activation did not. AZD6244, a potent selective inhibitor of ERK1/2 activation, blocked NGF induction of BDNF mRNA in vitro suggesting that NGF induction of BDNF is mediated by ERK1/2. siRNA experiments indicated that both ERK1 or ERK2 can signal suggesting that both pathways must be blocked to prevent NGF-induced increase in BDNF mRNA. I.p. injection of AZD6244 prevented the development of pain in rats subjected to the chronic constriction injury and reversed already established pain in the spared nerve injury model. Immunohistochemical studies showed decreased phospho-ERK1/2-immunoreactivity in dorsal root ganglia and BDNF immunoreactivity in ipsilateral spinal dorsal horn in the drug-treated rats. Our results suggest the possible use of AZD6244, already in human clinical trials as an anticancer agent, for the treatment of pathological pain.

  5. Effects of mechanostimulation on gravitropism and signal persistence in flax roots.

    PubMed

    John, Susan P; Hasenstein, Karl H

    2011-09-01

    Gravitropism describes curvature of plants in response to gravity or differential acceleration and clinorotation is commonly used to compensate unilateral effect of gravity. We report on experiments that examine the persistence of the gravity signal and separate mechanostimulation from gravistimulation. Flax roots were reoriented (placed horizontally for 5, 10 or 15 min) and clinorotated at a rate of 0.5 to 5 rpm either vertically (parallel to the gravity vector and root axis) or horizontally (perpendicular to the gravity vector and parallel to the root axis). Image sequences showed that horizontal clinorotation did not affect root growth rate (0.81 ± 0.03 mm h-1) but vertical clinorotation reduced root growth by about 7%. The angular velocity (speed of clinorotation) did not affect growth for either direction. However, maximal curvature for vertical clinorotation decreased with increasing rate of rotation and produced straight roots at 5 rpm. In contrast, horizontal clinorotation increased curvature with increasing angular velocity. The point of maximal curvature was used to determine the longevity (memory) of the gravity signal, which lasted about 120 min. The data indicate that mechanostimulation modifies the magnitude of the graviresponse but does not affect memory persistence.

  6. Tiam1 as a signaling mediator of nerve growth factor-dependent neurite outgrowth.

    PubMed

    Shirazi Fard, Shahrzad; Kele, Julianna; Vilar, Marçal; Paratcha, Gustavo; Ledda, Fernanda

    2010-03-19

    Nerve Growth Factor (NGF)-induced neuronal differentiation requires the activation of members of the Rho family of small GTPases. However, the molecular mechanisms through which NGF regulates cytoskeletal changes and neurite outgrowth are not totally understood. In this work, we identify the Rac1-specific guanine exchange factor (GEF) Tiam1 as a novel mediator of NGF/TrkA-dependent neurite elongation. In particular, we report that knockdown of Tiam1 causes a significant reduction in Rac1 activity and neurite outgrowth induced by NGF. Physical interaction between Tiam1 and active Ras (Ras-GTP), but not tyrosine phosphorylation of Tiam1, plays a central role in Rac1 activation by NGF. In addition, our findings indicate that Ras is required to associate Tiam1 with Rac1 and promote Rac1 activation upon NGF stimulation. Taken together, these findings define a novel molecular mechanism through which Tiam1 mediates TrkA signaling and neurite outgrowth induced by NGF.

  7. Increased TNFR1 expression and signaling in injured peripheral nerves of mice with reduced BACE1 activity.

    PubMed

    Liu, Lijuan; Fissel, John A; Tasnim, Aniqa; Borzan, Jasenka; Gocke, Anne; Calabresi, Peter A; Farah, Mohamed H

    2016-09-01

    Hematogenous macrophages remove myelin debris from injured peripheral nerves to provide a micro-environment conducive to axonal regeneration. Previously, we observed that injured peripheral nerves from Beta-site APP Cleaving Enzyme 1 (BACE1) knockout (KO) mice displayed earlier influx of and enhanced phagocytosis by macrophages when compared to wild-type (WT) mice. These observations suggest that BACE1 might regulate macrophage influx into distal stumps of injured nerves. To determine through which pathway BACE1 influences macrophage influx, we used a mouse inflammation antibody array to assay the expression of inflammation-related proteins in injured nerves of BACE1 KO and WT mice. The most significant change was in expression of tumor necrosis factor receptor 1 (TNFR1) in the distal stump of injured BACE1 KO nerves. Western blotting of protein extracts confirmed increased expression of TNFR1 and its downstream transcriptional factor NFκB in the BACE1 KO distal stumps. Additionally, treatment of WT mice with a BACE1 inhibitor resulted in increased TNFR1 expression and signaling in the distal stump of injured nerves. Exogenous TNFα increased nuclear translocation of p65 NFκB in BACE1 KO tissue and cultured fibroblasts compared with control WT. BACE1 regulates TNFR1 expression at the level of gene expression and not through proteolytic processing. The accelerated macrophage influx in injured nerves of BACE1 KO mice correlates with increased expression and signaling via TNFR1, indicating a link between BACE1 activity and TNFR1 expression/signaling that might contribute to repair of the injured nervous system. Copyright © 2016 Elsevier Inc. All rights reserved.

  8. Nerve Growth Factor Signaling from Membrane Microdomains to the Nucleus: Differential Regulation by Caveolins

    PubMed Central

    Spencer, Ambre; Yu, Lingli; Guili, Vincent; Reynaud, Florie; Ding, Yindi; Ma, Ji; Jullien, Jérôme; Koubi, David; Gauthier, Emmanuel; Cluet, David; Falk, Julien; Castellani, Valérie; Yuan, Chonggang; Rudkin, Brian B.

    2017-01-01

    Membrane microdomains or “lipid rafts” have emerged as essential functional modules of the cell, critical for the regulation of growth factor receptor-mediated responses. Herein we describe the dichotomy between caveolin-1 and caveolin-2, structural and regulatory components of microdomains, in modulating proliferation and differentiation. Caveolin-2 potentiates while caveolin-1 inhibits nerve growth factor (NGF) signaling and subsequent cell differentiation. Caveolin-2 does not appear to impair NGF receptor trafficking but elicits prolonged and stronger activation of MAPK (mitogen-activated protein kinase), Rsk2 (ribosomal protein S6 kinase 2), and CREB (cAMP response element binding protein). In contrast, caveolin-1 does not alter initiation of the NGF signaling pathway activation; rather, it acts, at least in part, by sequestering the cognate receptors, TrkA and p75NTR, at the plasma membrane, together with the phosphorylated form of the downstream effector Rsk2, which ultimately prevents CREB phosphorylation. The non-phosphorylatable caveolin-1 serine 80 mutant (S80V), no longer inhibits TrkA trafficking or subsequent CREB phosphorylation. MC192, a monoclonal antibody towards p75NTR that does not block NGF binding, prevents exit of both NGF receptors (TrkA and p75NTR) from lipid rafts. The results presented herein underline the role of caveolin and receptor signaling complex interplay in the context of neuronal development and tumorigenesis. PMID:28338624

  9. ARL2, ARG1 and PIN3 define a gravity signal transduction pathway in root statocytes.

    PubMed

    Harrison, Benjamin R; Masson, Patrick H

    2008-01-01

    ALTERED RESPONSE TO GRAVITY1 (ARG1) and its paralog ARG1-LIKE2 (ARL2) are J-domain proteins that are required for normal root and hypocotyl gravitropism. In this paper, we show that both ARL2 and ARG1 function in a gravity signal transduction pathway with PIN3, an auxin efflux facilitator that is expressed in the statocytes. In gravi-stimulated roots, PIN3 relocalizes to the lower side of statocytes, a process that is thought to, in part, drive the asymmetrical redistribution of auxin toward the lower flank of the root. We show that ARL2 and ARG1 are required for PIN3 relocalization and asymmetrical distribution of auxin upon gravi-stimulation. ARL2 is expressed specifically in the root statocytes, where it localizes to the plasma membrane. Upon ectopic expression, ARL2 is also found at the cell plate of dividing cells during cytokinesis, an area of intense membrane dynamics. Mutations in ARL2 and ARG1 also result in auxin-related expansion of the root cap columella, consistent with a role for ARL2 and ARG1 in regulating auxin flux through the root tip. Together these data suggest that ARL2 and ARG1 functionally link gravity sensation in the statocytes to auxin redistribution through the root cap.

  10. [Disease resistance signal transfer between roots of different tomato plants through common arbuscular mycorrhiza networks].

    PubMed

    Xie, Li-Jun; Song, Yuan-Yuan; Zeng, Ren-Sen; Wang, Rui-Long; Wei, Xiao-Chen; Ye, Mao; Hu, Lin; Zhang, Hui

    2012-05-01

    Common mycorrhizal networks (CMNs) are the underground conduits of nutrient exchange between plants. However, whether the CMNs can serve as the underground conduits of chemical communication to transfer the disease resistance signals between plants are unknown. By inoculating arbuscular mycorrhizal fungus (AMF) Glomus mosseae to establish CMNs between 'donor' and 'receiver' tomato plants, and by inoculating Alternaria solani, the causal agent of tomato early blight disease, to the 'donor' plants, this paper studied whether the potential disease resistance signals can be transferred between the 'donor' and 'receiver' plants roots. The real time RT-PCR analysis showed that after inoculation with A. solani, the AMF-inoculated 'donor' plants had strong expression of three test defense-related genes in roots, with the transcript levels of the phenylalanine ammonia-lyase (PAL), lipoxygenase (LOX) and chitinase (PR3) being significantly higher than those in the roots of the 'donor' plants only inoculated with A. solani, not inoculated with both A. solani and AMF, and only inoculated with AMF. More importantly, in the presence of CMNs, the expression levels of the three genes in the roots of the 'receiver' plants were significantly higher than those of the 'receiver' plants without CMNs connection, with the connection blocking, and with the connection but the 'donor' plants not A. solani-inoculated. Compared with the control (without CMNs connection), the transcript level of the PAL, LOX and PR3 in the roots of the 'receiver' plants having CMNs connection with the 'donor' plants was 4.2-, 4.5- and 3.5-fold higher, respectively. In addition, the 'donor' plants activated their defensive responses more quickly than the 'receiver' plants (18 and 65 h vs. 100 and 140 h). These findings suggested that the disease resistance signals produced by the pathogen-induced 'donor' tomato plant roots could be transferred to the 'receiver' plant roots through CMNs.

  11. Brassinosteroid signaling directs formative cell divisions and protophloem differentiation in Arabidopsis root meristems.

    PubMed

    Kang, Yeon Hee; Breda, Alice; Hardtke, Christian S

    2017-01-15

    Brassinosteroids (BRs) trigger an intracellular signaling cascade through its receptors BR INSENSITIVE 1 (BRI1), BRI1-LIKE 1 (BRL1) and BRL3. Recent studies suggest that BR-independent inputs related to vascular differentiation, for instance root protophloem development, modulate downstream BR signaling components. Here, we report that protophloem sieve element differentiation is indeed impaired in bri1 brl1 brl3 mutants, although this effect might not be mediated by canonical downstream BR signaling components. We also found that their small meristem size is entirely explained by reduced cell elongation, which is, however, accompanied by supernumerary formative cell divisions in the radial dimension. Thus, reduced cell expansion in conjunction with growth retardation, because of the need to accommodate supernumerary formative divisions, can account for the overall short root phenotype of BR signaling mutants. Tissue-specific re-addition of BRI1 activity partially rescued subsets of these defects through partly cell-autonomous, partly non-cell-autonomous effects. However, protophloem-specific BRI1 expression essentially rescued all major bri1 brl1 brl3 root meristem phenotypes. Our data suggest that BR perception in the protophloem is sufficient to systemically convey BR action in the root meristem context.

  12. Clinical validation study to measure the performance of the Nerve Root Sedimentation Sign for the diagnosis of lumbar spinal stenosis.

    PubMed

    Staub, Lukas P; Barz, Thomas; Melloh, Markus; Lord, Sarah J; Chatfield, Mark; Bossuyt, Patrick M

    2011-05-01

    Lumbar spinal stenosis is a common degenerative disorder of the spine in elderly patients that can be effectively treated with decompression surgery in some patients. Radiological findings in the diagnostic work-up of the patients do not always correlate well with clinical symptoms, and guidance about when to proceed to surgery is inconsistent. The recently described Nerve Root Sedimentation Sign in magnetic resonance scans has been shown to discriminate well between selected patients with and without lumbar spinal stenosis, but the performance of this new test, when used in a broad patient population, is not yet known. We describe the design of a single-centre retrospective chart review to assess the clinical validity of the Sedimentation Sign by evaluating its association with health outcomes in patients with suspected lumbar spinal stenosis. The Sedimentation Sign will be cross-classified with decisions for surgery based on existing tests and patient outcomes in follow-up examinations at 24months. The results will be used to estimate: i) how well the Sedimentation Sign can distinguish between patients that do or do not benefit from surgery, and ii) the concordance between the Sedimentation Sign and existing tests to explore its possible value as a triage test. This study design will provide data to estimate the potential benefits and harms of using the Sedimentation Sign to guide surgical decisions. The observed proportion of discordant test results will help inform the design of future randomised controlled trials of the Sedimentation Sign. Copyright © 2011 Elsevier Inc. All rights reserved.

  13. The efficacy of forward head correction on nerve root function and pain in cervical spondylotic radiculopathy: a randomized trial.

    PubMed

    Diab, Aliaa A; Moustafa, Ibrahim M

    2012-04-01

    To investigate the effect of forward head posture correction on pain and nerve root function in cases of cervical spondylotic radiculopathy. A randomized controlled study with six months follow-up. University research laboratory. Ninety-six patients with unilateral lower cervical spondylotic radiculopathy (C5-C6 and C6-C7) and craniovertebral angle measured less than or equal to 50° were randomly assigned to an exercise or a control group. The control group (n = 48) received ultrasound and infrared radiation, whereas the exercise group (n = 48) received a posture corrective exercise programme in addition to ultrasound and infrared radiation. The peak-to-peak amplitude of dermatomal somatosensory evoked potentials, craniovertebral angle, visual analogue scale were measured for all patients at three intervals (before treatment, after 10 weeks of treatment, and at follow-up of six months). There was a significant difference between groups adjusted to baseline value of outcome at 10 weeks post-treatment for craniovertebral angle, pain, C6 and C7 peak-to-peak amplitude of dermatomal somatosensory evoked potentials P = 0.000, 0.01, 0.000, 0.001 respectively and at follow-up for all previous variables (P = 0.000). Forward head posture correction using a posture corrective exercise programme in addition to ultrasound and infrared radiation decreased pain and craniovertebral angle and increased the peak-to-peak amplitude of dermatomal somatosensory evoked potentials for C6 and C7 in cases of lower cervical spondylotic radiculopathy.

  14. Monocyte Traffic, Dorsal Root Ganglion Histopathology, and Loss of Intraepidermal Nerve Fiber Density in SIV Peripheral Neuropathy

    PubMed Central

    Lakritz, Jessica R.; Bodair, Ayman; Shah, Neal; O'Donnell, Ryan; Polydefkis, Michael J.; Miller, Andrew D.; Burdo, Tricia H.

    2016-01-01

    HIV-associated sensory neuropathy remains the most common neurological complication of HIV infection and is characterized by dorsal root ganglion (DRG) inflammation and intraepidermal nerve fiber density (IENFD) loss. Chronic peripheral immune cell activation and accumulation may cause damage to the DRG, but has not been fully investigated yet. By using an SIV-infected, CD8-lymphocyte–depleted rhesus macaque model, we defined immune cells surrounding DRG neurons and their role in DRG pathology, measured cell traffic from the bone marrow to the DRGs using 5-bromo-2-deoxyuridine (BrdU) pulse, and serially measured IENFD. We found an increase in CD68+ and CD163+ macrophages in DRGs of SIV-infected animals. MAC387+ recently recruited monocytes/macrophages were increased, along with BrdU+ cells, in the DRGs of SIV-infected macaques. We demonstrated that 78.1% of all BrdU+ cells in DRGs were also MAC387+. The number of BrdU+ monocytes correlated with severe DRG histopathology, which included neuronophagia, neuronal loss, and Nageotte nodules. These data demonstrate that newly recruited MAC387+BrdU+ macrophages may play a significant role in DRG pathogenesis. IENFD decreased early (day 21), consistent with the development of sensory neuropathy in SIV-infected macaques. Decreased IENFD was associated with elevated BrdU+ cells in the DRG. These data suggest that increased recruitment of macrophages to DRG is associated with severe DRG histopathology and IENFD loss. PMID:25956030

  15. Multi-scale simulations predict responses to non-invasive nerve root stimulation

    NASA Astrophysics Data System (ADS)

    Laakso, Ilkka; Matsumoto, Hideyuki; Hirata, Akimasa; Terao, Yasuo; Hanajima, Ritsuko; Ugawa, Yoshikazu

    2014-10-01

    Objective. Established biophysical neurone models have achieved limited success in reproducing electrophysiological responses to non-invasive stimulation of the human nervous system. This is related to our insufficient knowledge of the induced electric currents inside the human body. Despite the numerous research and clinical applications of non-invasive stimulation, it is still unclear which internal sites are actually affected by it. Approach. We performed multi-scale computer simulations that, by making use of advances in computing power and numerical algorithms, combine a microscopic model of electrical excitation of neurones with a macroscopic electromagnetic model of the realistic whole-body anatomy. Main results. The simulations yield responses consistent with those experimentally recorded following magnetic and electrical motor root stimulation in human subjects, and reproduce the observed amplitudes and latencies for a wide variety of stimulation parameters. Significance. Our findings demonstrate that modern computational techniques can produce detailed predictions about which and where neurones are activated, leading to improved understanding of the physics and basic mechanisms of non-invasive stimulation and enabling potential new applications that make use of improved targeting of stimulation.

  16. Isolated paramedullary hemangioblastoma originating from the first cervical nerve root: case report.

    PubMed

    Bertalanffy, Helmut; Mennel, Hans-Dieter; Benes, Ludwig; Riegel, Thomas; Aboul-Enein, Hisham

    2003-05-15

    A retrospective case of an isolated paramedullary hemangioblastoma originating from the first cervical root is reported. To describe an uncommon type of spinal hemangioblastoma and its operative treatment. Spinal hemangioblastoma, rare finding accounting for approximately 1.5% to 2.5% of all spinal cord tumors, may have an intramedullary, extramedullary, or extradural location. Cervical hemangioblastomas occur in approximately 45% of the cases and are intramedullary in about 83% of the cases. A 59-year-old man presented with acute subarachnoid hemorrhage in the basal cisterns. Four-vessel angiography showed a highly vascular small tumor at the dorsolateral side of the cervicomedullary junction fed by a branch of the vertebral artery. The lesion was surgically removed. Total removal of the lesion was achieved after identification of both the arterial feeder and the draining vein with the aid of microvascular Doppler sonography. There were no complications, and the patient did well after surgery. Although hemangioblastomas occurring in the cervicomedullary area usually may cause progressive neural compression, occasionally they also can present clinically as acute subarachnoid hemorrhage. This situation requires urgent and adequate treatment as in the reported case.

  17. Characterization of Thoracic Motor and Sensory Neurons and Spinal Nerve Roots in Canine Degenerative Myelopathy, a Potential Disease Model of Amyotrophic Lateral Sclerosis

    PubMed Central

    Morgan, Brandie R.; Coates, Joan R.; Johnson, Gayle C.; Shelton, G. Diane; Katz, Martin L.

    2014-01-01

    Canine Degenerative Myelopathy (DM) is a progressive adult-onset multisystem degenerative disease with many features in common with amyotrophic lateral sclerosis (ALS). As with some forms of ALS, DM is associated with mutations in superoxide dismutase 1 (SOD1). Clinical signs include general proprioceptive ataxia and spastic upper motor neuron paresis in pelvic limbs, which progress to flaccid tetraplegia and dysphagia. The purpose of this study was to characterize DM as a potential disease model for ALS. We previously reported that intercostal muscle atrophy develops in dogs with advanced stage DM. To determine if other components of the thoracic motor unit (MU) also demonstrated morphological changes consistent with dysfunction, histopathologic and morphometric analyses were conducted on thoracic spinal motor neurons (MN) and dorsal root ganglia (DRG), and in motor and sensory nerve root axons from DM-affected Boxers and Pembroke Welsh Corgis (PWCs). No alterations in MNs, or motor root axons were observed in either breed. However, advanced stage PWCs exhibited significant losses of sensory root axons, and numerous DRG sensory neurons displayed evidence of degeneration. These results indicate that intercostal muscle atrophy in DM is not preceded by physical loss of the motor neurons innervating these muscles, or of their axons. Axonal loss in thoracic sensory roots and sensory nerve death suggest sensory involvement may play an important role in DM disease progression. Further analysis of the mechanisms responsible for these morphological findings would aid in the development of therapeutic intervention for DM and some forms of ALS. PMID:24375814

  18. Chronic recording of hand prosthesis control signals via a regenerative peripheral nerve interface in a rhesus macaque

    NASA Astrophysics Data System (ADS)

    Irwin, Z. T.; Schroeder, K. E.; Vu, P. P.; Tat, D. M.; Bullard, A. J.; Woo, S. L.; Sando, I. C.; Urbanchek, M. G.; Cederna, P. S.; Chestek, C. A.

    2016-08-01

    Objective. Loss of even part of the upper limb is a devastating injury. In order to fully restore natural function when lacking sufficient residual musculature, it is necessary to record directly from peripheral nerves. However, current approaches must make trade-offs between signal quality and longevity which limit their clinical potential. To address this issue, we have developed the regenerative peripheral nerve interface (RPNI) and tested its use in non-human primates. Approach. The RPNI consists of a small, autologous partial muscle graft reinnervated by a transected peripheral nerve branch. After reinnervation, the graft acts as a bioamplifier for descending motor commands in the nerve, enabling long-term recording of high signal-to-noise ratio (SNR), functionally-specific electromyographic (EMG) signals. We implanted nine RPNIs on separate branches of the median and radial nerves in two rhesus macaques who were trained to perform cued finger movements. Main results. No adverse events were noted in either monkey, and we recorded normal EMG with high SNR (>8) from the RPNIs for up to 20 months post-implantation. Using RPNI signals recorded during the behavioral task, we were able to classify each monkey’s finger movements as flexion, extension, or rest with >96% accuracy. RPNI signals also enabled functional prosthetic control, allowing the monkeys to perform the same behavioral task equally well with either physical finger movements or RPNI-based movement classifications. Significance. The RPNI signal strength, stability, and longevity demonstrated here represents a promising method for controlling advanced prosthetic limbs and fully restoring natural movement.

  19. Intercostal nerve crossing to restore elbow flexion and sensibility of the hand for a root avulsion type of brachial plexus injury.

    PubMed

    Ogino, T; Naito, T

    1995-01-01

    Ten patients with a root avulsion type of brachial plexus injury were treated with simultaneous intercostal nerve crossing to the musculocutaneous and median nerves, and nine cases were followed for more than 40 months. The average interval from injury to surgery was 2.7 months. The average age at operation was 18.6 years. The elbow flexor was M4 in six patients, M3 in two patients, and M1 in one patient. The wrist flexor was more than M3 in six patients and less than M2 in four patients. The finger flexor was more than M3 in four patients and less than M2 in five patients. Protective sensation in the areas innervated by the musculocutaneous and median nerves was restored in all cases.

  20. Multilayered Organization of Jasmonate Signalling in the Regulation of Root Growth.

    PubMed

    Gasperini, Debora; Chételat, Aurore; Acosta, Ivan F; Goossens, Jonas; Pauwels, Laurens; Goossens, Alain; Dreos, René; Alfonso, Esteban; Farmer, Edward E

    2015-06-01

    Physical damage can strongly affect plant growth, reducing the biomass of developing organs situated at a distance from wounds. These effects, previously studied in leaves, require the activation of jasmonate (JA) signalling. Using a novel assay involving repetitive cotyledon wounding in Arabidopsis seedlings, we uncovered a function of JA in suppressing cell division and elongation in roots. Regulatory JA signalling components were then manipulated to delineate their relative impacts on root growth. The new transcription factor mutant myc2-322B was isolated. In vitro transcription assays and whole-plant approaches revealed that myc2-322B is a dosage-dependent gain-of-function mutant that can amplify JA growth responses. Moreover, myc2-322B displayed extreme hypersensitivity to JA that totally suppressed root elongation. The mutation weakly reduced root growth in undamaged plants but, when the upstream negative regulator NINJA was genetically removed, myc2-322B powerfully repressed root growth through its effects on cell division and cell elongation. Furthermore, in a JA-deficient mutant background, ninja1 myc2-322B still repressed root elongation, indicating that it is possible to generate JA-responses in the absence of JA. We show that NINJA forms a broadly expressed regulatory layer that is required to inhibit JA signalling in the apex of roots grown under basal conditions. By contrast, MYC2, MYC3 and MYC4 displayed cell layer-specific localisations and MYC3 and MYC4 were expressed in mutually exclusive regions. In nature, growing roots are likely subjected to constant mechanical stress during soil penetration that could lead to JA production and subsequent detrimental effects on growth. Our data reveal how distinct negative regulatory layers, including both NINJA-dependent and -independent mechanisms, restrain JA responses to allow normal root growth. Mechanistic insights from this work underline the importance of mapping JA signalling components to specific

  1. Multilayered Organization of Jasmonate Signalling in the Regulation of Root Growth

    PubMed Central

    Gasperini, Debora; Chételat, Aurore; Acosta, Ivan F.; Goossens, Jonas; Pauwels, Laurens; Goossens, Alain; Dreos, René; Alfonso, Esteban; Farmer, Edward E.

    2015-01-01

    Physical damage can strongly affect plant growth, reducing the biomass of developing organs situated at a distance from wounds. These effects, previously studied in leaves, require the activation of jasmonate (JA) signalling. Using a novel assay involving repetitive cotyledon wounding in Arabidopsis seedlings, we uncovered a function of JA in suppressing cell division and elongation in roots. Regulatory JA signalling components were then manipulated to delineate their relative impacts on root growth. The new transcription factor mutant myc2-322B was isolated. In vitro transcription assays and whole-plant approaches revealed that myc2-322B is a dosage-dependent gain-of-function mutant that can amplify JA growth responses. Moreover, myc2-322B displayed extreme hypersensitivity to JA that totally suppressed root elongation. The mutation weakly reduced root growth in undamaged plants but, when the upstream negative regulator NINJA was genetically removed, myc2-322B powerfully repressed root growth through its effects on cell division and cell elongation. Furthermore, in a JA-deficient mutant background, ninja1 myc2-322B still repressed root elongation, indicating that it is possible to generate JA-responses in the absence of JA. We show that NINJA forms a broadly expressed regulatory layer that is required to inhibit JA signalling in the apex of roots grown under basal conditions. By contrast, MYC2, MYC3 and MYC4 displayed cell layer-specific localisations and MYC3 and MYC4 were expressed in mutually exclusive regions. In nature, growing roots are likely subjected to constant mechanical stress during soil penetration that could lead to JA production and subsequent detrimental effects on growth. Our data reveal how distinct negative regulatory layers, including both NINJA-dependent and -independent mechanisms, restrain JA responses to allow normal root growth. Mechanistic insights from this work underline the importance of mapping JA signalling components to specific

  2. Root to leaf electrical signaling in avocado in response to light and soil water content.

    PubMed

    Gil, Pilar M; Gurovich, Luis; Schaffer, Bruce; Alcayaga, Julio; Rey, Sergio; Iturriaga, Rodrigo

    2008-07-07

    Phytomonitoring techniques for irrigation of avocado orchards indicate that plants respond very rapidly to fluctuations in soil water content. Root to leaf abscicic acid transport cannot fully explain the almost immediate response of stomata to either irrigation and/or sudden changes in climatic conditions. Therefore, we studied the existence of a fast conducting signal between roots and leaves, and the possible involvement of such a signal in the regulation of stomatal behavior. Two-year-old avocado trees were subjected to drying and re-watering cycles or changes in incident radiation (light or darkness). The difference in extracellular electrical potential between the leaf petiole and the base of stem (DeltaV(L-S)) was continuously recorded. Stomatal conductance (gs) was also recorded for the same leaves that were used for voltage difference measurements. A sudden change in soil water content induced by root drying and re-watering was accompanied by a slow, significant change in the recorded DeltaV(L-S) signal, which was fully developed at 52 and 32min for root drying and re-watering, respectively. We found an inverse correlation (r=-0.56) between the change of DeltaV(L-S) and the gs difference measured before and after each soil-drying treatment. Plants that were girdled to disrupt the phloem and then irrigated tended to have lower DeltaV(L-S) differences over time than non-girdled irrigated plants, suggesting that the electrical signal was transmitted in the phloem. The existence of a fast signal transmitted from the root to the leaf that can be measured and correlated with stomatal control opens the possibility of developing a new phytomonitoring technique and/or artificially modifying plant responses by imposing agronomic management strategies aimed at rapid stomatal adaptation to changes in soil water content.

  3. Relative effectiveness of electrically- vs mechanically-elicited EMGs in detecting pedicle wall perforation and surgically-induced nerve root damage.

    PubMed

    Kobara, N; Owen, J H; Kostuik, J; Huckell, C; Tooke, S M

    2000-02-01

    Electrical stimulation of a pedicle hole and screw with recording EMGs from the lower extremities has been used as an indicator in detecting perforations of the pedicle. Mechanically-elicited EMGs are reported to be sensitive to mechanical irritation of nerve roots. This study analyzed the sensitivity of the data elicited by two EMG monitoring methods in the presence of a neurologic deficit caused by a malpositioned screw to determine the relative effectiveness of electrically- vs mechanically-elicited EMGs in detecting pedicle wall perforations and nerve root damage in patients undergoing spinal surgery utilizing transpedicular instrumentation. One hundred and four surgeries were monitored using the two EMG methods. Six hundred and fifty-four pedicle holes were prepared and 650 placed pedicle screws were electrically tested. Mechanically-elicited EMGs were monitored from a total of 618 muscles. Electrically-elicited EMGs showed a 62% true-positive rate and a 0.2% false-negative rate in detecting pedicle wall perforations. None of the patients who initially demonstrated abnormal electrically-elicited EMGs demonstrated any post-operative neurologic problems due to an incorrect screw placement. Only one patient who had abnormal mechanically-elicited EMGs during the procedures related to instrumentation developed new L4 radiculopathy immediately post-operatively which was consistent with the level of mechanically-elicited EMGs. Mechanically-elicited EMGs showed a 100% true-positive rate for nerve root irritation and a 3.5% false-negative rate in detecting pedicle wall perforations by malpositioned screw. In conclusion, although mechanically-elicited EMGs were an insensitive technique in detecting a perforation of the pedicle, mechanically-elicited EMGs were more beneficial than electrically-elicited EMGs in detecting the risk of nerve root irritation.

  4. Up-regulation of brain-derived neurotrophic factor is regulated by extracellular signal-regulated protein kinase 5 and by nerve growth factor retrograde signaling in colonic afferent neurons in colitis

    PubMed Central

    Yu, Sharon J; Grider, John R; Gulick, Melisa A; Xia, Chun-mei; Shen, Shanwei; Qiao, Li-Ya

    2012-01-01

    Brain-derived neurotrophic factor (BDNF) plays an essential role in sensory neuronal activation in response to visceral inflammation. Here we report that BDNF up-regulation in the primary afferent neurons in the dorsal root ganglia (DRG) in a rat model of colitis is mediated by the activation of endogenous extracellular signal-regulated protein kinases (ERK) 5 and by nerve growth factor (NGF) retrograde signaling. At 7 days of colitis, the expression level of BDNF is increased in conventional neuronal tracing dye Fast Blue labeled primary afferent neurons project to the distal colon. In these neurons, the phosphorylation (activation) level of ERK5 is also increased. In contrast, the level of phospho-ERK1/2 is not changed in the DRG during colitis. Prevention of the ERK5 activation in vivo with an intrathecal application of the MEK inhibitor PD98059 significantly attenuates the colitis-induced increases in BDNF expression in the DRG. Further studies show that BDNF up-regulation in the DRG is triggered by NGF retrograde signaling which also involves activation of the MEK/ERK pathways. Application of exogenous NGF exclusively to the compartment containing DRG nerve terminals in an ex vivo ganglia-nerve preparation has markedly increased the BDNF expression level in the DRG neuronal cell body that is placed in a different compartment; this BDNF elevation is attenuated by U0126, PD98059 and a specific ERK5 inhibitor BIX02188. These results demonstrate the mechanisms and pathways by which BDNF expression is elevated in primary sensory neurons following visceral inflammation that is mediated by increased activity of ERK5 and is likely to be triggered by the elevated NGF level in the inflamed viscera. PMID:22921460

  5. Signal Strength Is an Important Determinant of Accuracy of Nerve Fiber Layer Thickness Measurement by Optical Coherence Tomography

    PubMed Central

    Wu, Ziqiang; Huang, Jingjing; Dustin, Laurie; Sadda, Srinivas

    2009-01-01

    Purpose To investigate the effect of signal strength on the measurement of the retinal nerve fiber layer (RNFL) using optical coherence tomography (OCT). Methods Eyes with known or suspected glaucoma or non-glaucomatous optic atrophy were scanned twice within the same visit using Stratus OCT's Fast Nerve Fiber Layer Thickness (FNFLT) protocol. Only those eyes with two high quality scans (signal strengths of at least 5 and different from each other, no error messages, and no obvious segmentation errors) were included in the study. The RNFL thickness measurements from the initial and the repeat scans were compared and then correlated with the differences in signal strength. Subgroup analyses were performed similarly among patients with average RNFL thickness less than 90 microns and those with at least 90 microns. Results Scans with higher signal strengths are associated with greater RNFL thickness measurements if the signal strength is less than 7. Scans with signal strength of at least 7 have higher reproducibility. This is true among all patients as well as subgroups divided on the basis of average RNFL thickness. Additionally, we found that the greater the variability between the initial and repeat scans, the greater the variability in the RNFL thickness measurements. Scans with higher signal strengths have less variability, especially when the optic nerve is relatively healthy. Conclusions When measuring the RNFL thickness with the Stratus OCT, it is important to aim for a signal strength of at least 7. Visual field testing may be more reliable in some patients, especially when the optic nerve is significantly compromised. PMID:19295375

  6. Response of cervicogenic headaches and occipital neuralgia to radiofrequency ablation of the C2 dorsal root ganglion and/or third occipital nerve.

    PubMed

    Hamer, John F; Purath, Traci A

    2014-03-01

    This article investigates the degree and duration of pain relief from cervicogenic headaches or occipital neuralgia following treatment with radiofrequency ablation of the C2 dorsal root ganglion and/or third occipital nerves. It also addresses the procedure's complication rate and patient's willingness to repeat the procedure if severe symptoms recur. This is a single-center retrospective observational study of 40 patients with refractory cervicogenic headaches and or occipital neuralgia. Patients were all referred by a headache specialty clinic for evaluation for radiofrequency ablation of the C2 dorsal root ganglion and/or third occipital nerves. After treatment, patients were followed for a minimum of 6 months to a year. Patient demographics and the results of radiofrequency ablation were recorded on the same day, after 3-4 days, and at 6 months to 1 year following treatment. Thirty-five percent of patients reported 100% pain relief and 70% reported 80% or greater pain relief. The mean duration of improvement is 22.35 weeks. Complication rate was 12-13%. 92.5% of patients reported they would undergo the procedure again if severe symptoms returned. Radiofrequency ablation of the C2 dorsal root ganglion and/or third occipital nerve can provide many months of greater than 50% pain relief in the vast majority of recipients with an expected length of symptom improvement of 5-6 months. © 2014 American Headache Society.

  7. Ultrasonographic reference values for peripheral nerves and nerve roots in the normal population of children and adolescents: study protocol for an observational-prospective trial

    PubMed Central

    Décard, Bernhard F; Schädelin, Sabine; Grimm, Alexander; Fischer, Dirk; Hafner, Patricia

    2016-01-01

    Background High-resolution ultrasonography is a new and promising technique to evaluate peripheral and spinal nerves. Its validity as a diagnostic tool in neurological diseases has been demonstrated in adults. Up to now no reference values have been published in children and adolescents although this technique would be ideal in this population as it is fast and non-invasive. Methods/design Our aim is to generate ultrasonographic reference values for several peripheral nerves (median, ulnar, radial, tibial, sural, peroneal and tibial nerve) as well as for the spinal nerves C5 and C6 and the vagus nerve in children and adolescents. In an observational prospective study, we will recruit 205 children and adolescents aged between ≥2 and ≤18 years without neuromuscular symptoms/signs and without a history of neuromuscular disease. After the collection of demographic and anthropometric data (height, weight, body mass index, age, gender and handedness) and a neurologic examination, a high-resolution ultrasonography of peripheral and spinal nerves at several anatomic landmarks will be performed. These data will be used to estimate age-dependent percentile curves and to evaluate inter-rater, intrarater and interequipment reliability of the measurements. Ethics and dissemination This study was approved by the local ethics committee (EKNZ 2015-210). The findings from this study will be disseminated through peer-reviewed publications and conference presentations. Trial registration number NCT02570802, pre-results publication. PMID:27940636

  8. Restoring a maize root signal that attracts insect-killing nematodes to control a major pest

    PubMed Central

    Degenhardt, Jörg; Hiltpold, Ivan; Köllner, Tobias G.; Frey, Monika; Gierl, Alfons; Gershenzon, Jonathan; Hibbard, Bruce E.; Ellersieck, Mark R.; Turlings, Ted C. J.

    2009-01-01

    When attacked by herbivorous insects, plants emit volatile compounds that attract natural enemies of the insects. It has been proposed that these volatile signals can be manipulated to improve crop protection. Here, we demonstrate the full potential of this strategy by restoring the emission of a specific belowground signal emitted by insect-damaged maize roots. The western corn rootworm induces the roots of many maize varieties to emit (E)-β-caryophyllene, which attracts entomopathogenic nematodes that infect and kill the voracious root pest. However, most North American maize varieties have lost the ability to emit (E)-β-caryophyllene and may therefore receive little protection from the nematodes. To restore the signal, a nonemitting maize line was transformed with a (E)-β-caryophyllene synthase gene from oregano, resulting in constitutive emissions of this sesquiterpene. In rootworm-infested field plots in which nematodes were released, the (E)-β-caryophyllene-emitting plants suffered significantly less root damage and had 60% fewer adult beetles emerge than untransformed, nonemitting lines. This demonstration that plant volatile emissions can be manipulated to enhance the effectiveness of biological control agents opens the way for novel and ecologically sound strategies to fight a variety of insect pests. PMID:19666594

  9. Cyclic GMP is involved in auxin signalling during Arabidopsis root growth and development

    PubMed Central

    Nan, Wenbin; Wang, Xiaomin; Bi, Yurong

    2014-01-01

    The second messenger cyclic guanosine 3′,5′-monophosphate (cGMP) plays an important role in plant development and responses to stress. Recent studies indicated that cGMP is a secondary signal generated in response to auxin stimulation. cGMP also mediates auxin-induced adventitious root formation in mung bean and gravitropic bending in soybean. Nonetheless, the mechanism of the participation of cGMP in auxin signalling to affect these growth and developmental processes is largely unknown. In this report we provide evidence that indole-3-acetic acid (IAA) induces cGMP accumulation in Arabidopsis roots through modulation of the guanylate cyclase activity. Application of 8-bromo-cGMP (a cell-permeable cGMP derivative) increases auxin-dependent lateral root formation, root hair development, primary root growth, and gene expression. In contrast, inhibitors of endogenous cGMP synthesis block these processes induced by auxin. Data also showed that 8-bromo-cGMP enhances auxin-induced degradation of Aux/IAA protein modulated by the SCFTIR1 ubiquitin-proteasome pathway. Furthermore, it was found that 8-bromo-cGMP is unable to directly influence the auxin-dependent TIR1-Aux/IAA interaction as evidenced by pull-down and yeast two-hybrid assays. In addition, we provide evidence for cGMP-mediated modulation of auxin signalling through cGMP-dependent protein kinase (PKG). Our results suggest that cGMP acts as a mediator to participate in auxin signalling and may govern this process by PKG activity via its influence on auxin-regulated gene expression and auxin/IAA degradation. PMID:24591051

  10. Cyclic GMP is involved in auxin signalling during Arabidopsis root growth and development.

    PubMed

    Nan, Wenbin; Wang, Xiaomin; Yang, Lei; Hu, Yanfeng; Wei, Yuantao; Liang, Xiaolei; Mao, Lina; Bi, Yurong

    2014-04-01

    The second messenger cyclic guanosine 3',5'-monophosphate (cGMP) plays an important role in plant development and responses to stress. Recent studies indicated that cGMP is a secondary signal generated in response to auxin stimulation. cGMP also mediates auxin-induced adventitious root formation in mung bean and gravitropic bending in soybean. Nonetheless, the mechanism of the participation of cGMP in auxin signalling to affect these growth and developmental processes is largely unknown. In this report we provide evidence that indole-3-acetic acid (IAA) induces cGMP accumulation in Arabidopsis roots through modulation of the guanylate cyclase activity. Application of 8-bromo-cGMP (a cell-permeable cGMP derivative) increases auxin-dependent lateral root formation, root hair development, primary root growth, and gene expression. In contrast, inhibitors of endogenous cGMP synthesis block these processes induced by auxin. Data also showed that 8-bromo-cGMP enhances auxin-induced degradation of Aux/IAA protein modulated by the SCF(TIR1) ubiquitin-proteasome pathway. Furthermore, it was found that 8-bromo-cGMP is unable to directly influence the auxin-dependent TIR1-Aux/IAA interaction as evidenced by pull-down and yeast two-hybrid assays. In addition, we provide evidence for cGMP-mediated modulation of auxin signalling through cGMP-dependent protein kinase (PKG). Our results suggest that cGMP acts as a mediator to participate in auxin signalling and may govern this process by PKG activity via its influence on auxin-regulated gene expression and auxin/IAA degradation.

  11. Selective decrease of small sensory neurons in lumbar dorsal root ganglia labeled with horseradish peroxidase after ND:YAG laser irradiation of the tibial nerve in the rat

    SciTech Connect

    Wesselmann, U.; Lin, S.F.; Rymer, W.Z. )

    1991-02-01

    Recent electrophysiological evidence indicates that Q-switched Nd:YAG laser irradiation might have selective effects on neural impulse transmission in small slow conducting sensory nerve fibers as compared to large diameter afferents. In an attempt to clarify the ultimate fate of sensory neurons after laser application to their peripheral axons, we have used horseradish peroxidase (HRP) as a cell marker to retrogradely label sensory neurons innervating the distal hindlimb in the rat. Pulsed Nd:YAG laser light was applied to the tibial nerve at pulse energies of 70 or 80 mJ/pulse for 5 min in experimental rats. Seven days later HRP was applied to the left (laser-treated) and to the contralateral (untreated) tibial nerve proximal to the site of laser irradiation. In control animals the numbers of HRP-labeled dorsal root ganglion cells were not significantly different between the right and the left side. In contrast, after previous laser irradiation labeling was always less on the laser-treated side (2183 +/- 513 cells, mean +/- SEM) as compared to the untreated side (3937 +/- 225). Analysis of the dimensions of labeled cells suggested that the reduction of labeled cells on the laser-treated side was mainly due to a deficit in small sensory neurons. Since the conduction velocity of nerve fibers is related to the size of their somata, our histological data imply that laser light selectively affects retrograde transport mechanisms for HRP in slow conducting sensory nerve fibers.

  12. Different functional reorganization of motor cortex after transfer of the contralateral C7 to different recipient nerves in young rats with total brachial plexus root avulsion.

    PubMed

    Pan, Feng; Wei, Hai-feng; Chen, Liang; Gu, Yu-dong

    2012-12-07

    Clinically, contralateral C7 transfer is used for nerve reconstruction in brachial plexus injuries. Postoperatively, synchronous motions at the donor limb are noteworthy. This study studied if different recipient nerves influenced transhemispheric functional reorganization of motor cortex after this procedure. 90 young rats with total root avulsion of the brachial plexus were divided into groups 1-3 of contralateral C7 transfer to anterior division of the upper trunk, to both the musculocutaneous and median nerves, and to the median nerve, respectively. After reinnervation of target muscles, number of sites for forelimb representations in bilateral motor cortices was determined by intracortical microstimulation at 1.5, 3, 6, 9, and 12 months postoperatively. At nine months, transhemispheric reorganization of nerves neurotized by contralateral C7 was fulfilled in four of six rats in group 1, one of six in group 2 and none in group 3, respectively; at 12 months, that was fulfilled in five of six in group 1, four of six in groups 2 and 3, respectively. Logistic regression analysis showed that rate of fulfilled transhemispheric reorganization in group 1 was 12.19 times that in group 3 (95% CI 0.006-0.651, p=0.032). At 12 months, number of sites for hindlimb representations which had encroached upon original forelimb representations on the uninjured side was statistically more in group 3 than in group 2 (t=9.5, p<0.0001). It is concluded that contralateral C7 transfer to upper trunk or to both the musculocutaneous and median nerves induces faster transhemispheric functional reorganization of motor cortex than that to median nerve alone in rats.

  13. Leptin signaling in the nucleus tractus solitarii increases sympathetic nerve activity to the kidney.

    PubMed

    Mark, Allyn L; Agassandian, Khristofor; Morgan, Donald A; Liu, Xuebo; Cassell, Martin D; Rahmouni, Kamal

    2009-02-01

    The hypothalamic arcuate nucleus was initially regarded as the principal site of leptin action, but there is increasing evidence for functional leptin receptors in extrahypothalamic sites, including the nucleus tractus solitarii (NTS). We demonstrated previously that arcuate injection of leptin increases sympathetic nerve activity (SNA) to brown adipose tissue and kidney. In this study, we tested the hypothesis that leptin signaling in the NTS affects sympathetic neural outflow. Using a stereotaxic device in anesthetized rats, we microinjected leptin (0.25 to 1.00 microg) or saline into the NTS while recording SNA to kidney and brown adipose tissue. Microinjection of leptin into the commissural and medial subnuclei of the caudal NTS at the level of the area postrema in Sprague-Dawley rats produced a dose-related increase in renal SNA (+112+/-15% with leptin 1 microg; n=7; P<0.001) but did not increase SNA to brown adipose tissue (-15+/-12%; P value not significant). This effect depended on intact functional leptin receptors, because it was not observed in Zucker obese rats that have a missense mutation in the leptin receptor. Rostral NTS injection of leptin failed to increase SNA, indicating that leptin signaling in the NTS is probably confined to the caudal NTS at the level of the area postrema. In summary, this study demonstrates that leptin signaling in the caudal NTS increases SNA to the kidney but not to the brown adipose tissue. The study strengthens the concept of a distributed brain network of leptin action and demonstrates that these distributed brain sites can mediate contrasting sympathetic responses to leptin.

  14. [Exploration Research of Treatment Effect Improvement of Transcutaneous Electrical Nerve Stimulation Using Parameter-changing Chaotic Signal].

    PubMed

    Zheng, Jincun; Zhang, Hui; Qin, Binyi; Wang, Hai; Nie, Guochao; Chen, Tiejun

    2015-10-01

    This article presents a transcutaneous electric stimulator that is based on chaotic signal. Firstly, we in the study used the MATLAB platform in the PC to generate chaotic signal through the chaos equation, and then we transferred the signal out by data acquisition equipment of USB-6251 manufactured by NI Company. In order to obtain high-power signal for transcutaneous electric stimulator, we used the chip of LM3886 to amplify the signal. Finally, we used the power-amplified chaotic signal to stimulate the internal nerve of human through the electrodes fixed on the skin. We obtained different stimulation effects of transcutaneous electric stimulator by changing the parameters of chaotic model. The preliminary test showed that the randomness of chaotic signals improved the applicability of electrical stimulation and the rules of chaos ensured that the stimulation was comfort. The method reported in this paper provides a new way for the design of transcutaneous electric stimulator.

  15. Reactive oxygen species (ROS) as early signals in root hair cells responding to rhizobial nodulation factors

    PubMed Central

    Quinto, Carmen

    2008-01-01

    Reactive oxygen species (ROS) are involved in supporting polar growth in pollen tubes, fucoid cells and root hair cells. However, there is limited evidence showing ROS changes during the earliest stages of the interaction between legume roots and rhizobia. We recently reported using Phaseolus vulgaris as a model system, the occurrence of a transient increase of ROS, within seconds, at the tip of actively growing root hair cells after treatment with Nod factors (NFs).1 This transient response is NFs-specific, and clearly distinct from the ROS changes induced by a fungal elicitor, with which sustained increases in ROS signal, is observed. Since ROS levels are transiently elevated after NFs perception, we propose that this ROS response is specific of the symbiotic interaction. Furthermore, the observed ROS changes correlate spatially and temporarily with the reported transient increases in calcium levels suggesting key roles for calcium and ROS during the early NF perception. PMID:19704506

  16. Reactive oxygen species (ROS) as early signals in root hair cells responding to rhizobial nodulation factors.

    PubMed

    Cárdenas, Luis; Quinto, Carmen

    2008-12-01

    Reactive oxygen species (ROS) are involved in supporting polar growth in pollen tubes, fucoid cells and root hair cells. However, there is limited evidence showing ROS changes during the earliest stages of the interaction between legume roots and rhizobia. We recently reported using Phaseolus vulgaris as a model system, the occurrence of a transient increase of ROS, within seconds, at the tip of actively growing root hair cells after treatment with Nod factors (NFs).1 This transient response is NFs-specific, and clearly distinct from the ROS changes induced by a fungal elicitor, with which sustained increases in ROS signal, is observed. Since ROS levels are transiently elevated after NFs perception, we propose that this ROS response is specific of the symbiotic interaction. Furthermore, the observed ROS changes correlate spatially and temporarily with the reported transient increases in calcium levels suggesting key roles for calcium and ROS during the early NF perception.

  17. Clinical significance of postoperative changes in redundant nerve roots after decompressive laminectomy for lumbar spinal canal stenosis.

    PubMed

    Yokoyama, Kunio; Kawanishi, Masahiro; Yamada, Makoto; Tanaka, Hidekazu; Ito, Yutaka; Hirano, Masashi; Kawabata, Shinji; Kuroiwa, Toshihiko

    2014-12-01

    The postoperative time course of redundant nerve roots (RNRs) in patients with lumbar spinal canal stenosis (LSCS) is currently unknown. The purpose of this study is to investigate the relationship between postoperative morphologic changes in detected RNRs and the clinical outcome of patients with LSCS. A total of 33 symptomatic patients with LSCS who demonstrated RNRs on magnetic resonance imaging (MRI) were treated with decompressive laminectomy alone. On the basis of the MRI scans obtained 7 days after surgery, patients were stratified into two groups: group 1 included patients with resolution of RNRs and group 2 included patients with persistent RNRs. Comparative parameters were examined between the two groups of patients. We found that 24 of the 33 patients showed resolution of RNRs and 9 showed persistent RNRs. Although there was no difference in the Japanese Orthopedic Association score between the two groups before treatment, group 1 showed a greater recovery of Japanese Orthopedic Association score 1 month postoperatively. MRI demonstrated that the cross-sectional area of the preoperative dural sac at the stenotic lesion was smaller in group 2 than in group 1; however, there was no difference in cross-sectional area of the postoperative dural sac between the two groups. Within 12 months, there was no evidence of RNRs in six of the nine cases in group 2. Although most patients with LSCS show postoperative resolution of RNRs detected on MRI, some show persistent RNRs postoperatively. The functional outcome of these patients remains poor even if sufficient expansion of the dural sac is achieved postoperatively. Copyright © 2014 Elsevier Inc. All rights reserved.

  18. The impact of spinal cord nerve roots and denticulate ligaments on cerebrospinal fluid dynamics in the cervical spine.

    PubMed

    Heidari Pahlavian, Soroush; Yiallourou, Theresia; Tubbs, R Shane; Bunck, Alexander C; Loth, Francis; Goodin, Mark; Raisee, Mehrdad; Martin, Bryn A

    2014-01-01

    Cerebrospinal fluid (CSF) dynamics in the spinal subarachnoid space (SSS) have been thought to play an important pathophysiological role in syringomyelia, Chiari I malformation (CM), and a role in intrathecal drug delivery. Yet, the impact that fine anatomical structures, including nerve roots and denticulate ligaments (NRDL), have on SSS CSF dynamics is not clear. In the present study we assessed the impact of NRDL on CSF dynamics in the cervical SSS. The 3D geometry of the cervical SSS was reconstructed based on manual segmentation of MRI images of a healthy volunteer and a patient with CM. Idealized NRDL were designed and added to each of the geometries based on in vivo measurments in the literature and confirmation by a neuroanatomist. CFD simulations were performed for the healthy and patient case with and without NRDL included. Our results showed that the NRDL had an important impact on CSF dynamics in terms of velocity field and flow patterns. However, pressure distribution was not altered greatly although the NRDL cases required a larger pressure gradient to maintain the same flow. Also, the NRDL did not alter CSF dynamics to a great degree in the SSS from the foramen magnum to the C1 level for the healthy subject and CM patient with mild tonsillar herniation (∼ 6 mm). Overall, the NRDL increased fluid mixing phenomena and resulted in a more complex flow field. Comparison of the streamlines of CSF flow revealed that the presence of NRDL lead to the formation of vortical structures and remarkably increased the local mixing of the CSF throughout the SSS.

  19. Redundant nerve roots of the cauda equina in lumbar spinal canal stenosis, an MR study on 500 cases.

    PubMed

    Poureisa, Masoud; Daghighi, Mohammad Hossein; Eftekhari, Payam; Bookani, Kaveh Rezaei; Fouladi, Daniel Fadaei

    2015-10-01

    The purpose of this study was to evaluate magnetic resonance (MR)-detected redundant nerve roots (RNRs) of the cauda equina in patients with lumbar spinal canal stenosis. A total of 500 lumbar MR studies in patients with lumbar spinal canal stenosis were reviewed for the presence and characteristics of RNRs of the cauda equina. The length of the RNRs relative to the height of the upper vertebral body of the level of the stenosis was used as a prognostic indicator. RNRs were detected in 15% of the patients, the majority above the level of the stenosis (85%) and loop shaped (72%). Advanced age (i.e., ≥56 years old, odds ratio=1), a lumbar spinal canal stenosis at L2-4 (odds ratio=2.5), and the presence of an intracanal protuberance with sharp margin in the site of the stenosis (odds ratio=7.2) were independent risk factors for the development of RNRs. A direct, significant correlation was found between the relative length of the RNRs and patients' age (Pearson r=0.36, p=0.001). The mean relative length of the RNRs was significantly higher in patients with RNRs located above the level of the stenosis than those with RNRs located below the site of the block. The degree of stenosis was associated with neither the presence nor the relative length of the RNRs. With an occurrence rate of 15%, RNRs of the cauda equina are not uncommon in cases with lumbar spinal canal stenosis. Advanced age, a canal stenosis at L2-4, and the presence of a sharp intracanal protuberance in the site of the stenosis are the related risk factors. Patients' age and the location of RNRs may be of prognostic value.

  20. The Impact of Spinal Cord Nerve Roots and Denticulate Ligaments on Cerebrospinal Fluid Dynamics in the Cervical Spine

    PubMed Central

    Heidari Pahlavian, Soroush; Yiallourou, Theresia; Tubbs, R. Shane; Bunck, Alexander C.; Loth, Francis; Goodin, Mark; Raisee, Mehrdad; Martin, Bryn A.

    2014-01-01

    Cerebrospinal fluid (CSF) dynamics in the spinal subarachnoid space (SSS) have been thought to play an important pathophysiological role in syringomyelia, Chiari I malformation (CM), and a role in intrathecal drug delivery. Yet, the impact that fine anatomical structures, including nerve roots and denticulate ligaments (NRDL), have on SSS CSF dynamics is not clear. In the present study we assessed the impact of NRDL on CSF dynamics in the cervical SSS. The 3D geometry of the cervical SSS was reconstructed based on manual segmentation of MRI images of a healthy volunteer and a patient with CM. Idealized NRDL were designed and added to each of the geometries based on in vivo measurments in the literature and confirmation by a neuroanatomist. CFD simulations were performed for the healthy and patient case with and without NRDL included. Our results showed that the NRDL had an important impact on CSF dynamics in terms of velocity field and flow patterns. However, pressure distribution was not altered greatly although the NRDL cases required a larger pressure gradient to maintain the same flow. Also, the NRDL did not alter CSF dynamics to a great degree in the SSS from the foramen magnum to the C1 level for the healthy subject and CM patient with mild tonsillar herniation (∼6 mm). Overall, the NRDL increased fluid mixing phenomena and resulted in a more complex flow field. Comparison of the streamlines of CSF flow revealed that the presence of NRDL lead to the formation of vortical structures and remarkably increased the local mixing of the CSF throughout the SSS. PMID:24710111

  1. Selenite-induced hormonal and signalling mechanisms during root growth of Arabidopsis thaliana L.

    PubMed

    Lehotai, Nóra; Kolbert, Zsuzsanna; Peto, Andrea; Feigl, Gábor; Ördög, Attila; Kumar, Devanand; Tari, Irma; Erdei, László

    2012-09-01

    Selenium excess can cause toxicity symptoms, e.g. root growth inhibition in non-hyperaccumulator plants such as Arabidopsis. Selenite-induced hormonal and signalling mechanisms in the course of development are poorly understood; therefore this study set out to investigate the possible hormonal and signalling processes using transgenic and mutant Arabidopsis plants. Significant alterations were observed in the root architecture of the selenite-treated plants, due to the loss of cell viability in the root apex. During mild selenite excess, the plants showed symptoms of the morphogenic response: primary root (PR) shortening and increased initiation of laterals, ensuring better nutrient and water uptake and stress acclimation. As well as lower meristem cell activity, the second reason for the Se-induced growth hindrance is the hormonal imbalance, since the in situ expression of the auxin-responsive DR5::GUS, and consequently the auxin levels, significantly decreased, while that of the cytokinin-inducible ARR5::GUS and the ethylene biosynthetic ACS8::GUS increased. It is assumed that auxin and ethylene might positively regulate selenium tolerance, since reduced levels of them resulted in sensitivity. Moreover, high cytokinin levels caused notable selenite tolerance. During early seedling development, nitric oxide (NO) contents decreased but hydrogen peroxide levels increased reflecting the antagonism between the two signal molecules during Se excess. High levels of NO in gsnor1-3, lead to selenite tolerance, while low NO production in nia1nia2 resulted in selenite sensitivity. Consequently, NO derived from the root nitrate reductase activity is responsible for the large-scale selenite tolerance in Arabidopsis.

  2. Polarity reversal of the optical rotation signals with change in direction of impulse conduction along the lobster nerve.

    PubMed Central

    Watanabe, A

    1993-01-01

    1. The optical rotation signal of nerve associated with excitation was recorded from peripheral nerve taken from a walking leg of a spiny lobster and its properties were analysed. 2. The polarity of the optical rotation signal was reversed when the site of stimulation was changed with reference to the site of optical recording, so that the direction of impulse conduction was reversed, in most of the preparations. 3. Apart from the main response, which is associated with the conducted impulse, a pre-response was found to exist, which manifested itself on anodic stimulation, in a tetrodotoxin-treated nerve, or during the refractory period of the nerve, when the site of stimulation was close to the site of optical recording. The polarity of the pre-response was also reversed when the site of stimulation was changed with reference to the site of optical recording. 4. When the nerve was inclined from the horizontal level, so that the angle of incidence of light to the nerve was changed, the main response changed its amplitude and sometimes its polarity, whereas the pre-response remained practically unchanged. Thus the dependence on the angle of incidence was different between the pre-response and the main response. 5. It is suggested that the dependence of amplitude and polarity of the main response on the angle of incidence of light cannot be explained by the change in molecular axes of the membrane macromolecules, but can only be explained by their conformational change; and therefore the main response can be used as a monitor for the molecular conformation. PMID:8410706

  3. Ultrasonographic reference values for peripheral nerves and nerve roots in the normal population of children and adolescents: study protocol for an observational-prospective trial.

    PubMed

    Rasenack, Maria; Décard, Bernhard F; Schädelin, Sabine; Grimm, Alexander; Fischer, Dirk; Hafner, Patricia

    2016-12-09

    High-resolution ultrasonography is a new and promising technique to evaluate peripheral and spinal nerves. Its validity as a diagnostic tool in neurological diseases has been demonstrated in adults. Up to now no reference values have been published in children and adolescents although this technique would be ideal in this population as it is fast and non-invasive. Our aim is to generate ultrasonographic reference values for several peripheral nerves (median, ulnar, radial, tibial, sural, peroneal and tibial nerve) as well as for the spinal nerves C5 and C6 and the vagus nerve in children and adolescents. In an observational prospective study, we will recruit 205 children and adolescents aged between ≥2 and ≤18 years without neuromuscular symptoms/signs and without a history of neuromuscular disease. After the collection of demographic and anthropometric data (height, weight, body mass index, age, gender and handedness) and a neurologic examination, a high-resolution ultrasonography of peripheral and spinal nerves at several anatomic landmarks will be performed. These data will be used to estimate age-dependent percentile curves and to evaluate inter-rater, intrarater and interequipment reliability of the measurements. This study was approved by the local ethics committee (EKNZ 2015-210). The findings from this study will be disseminated through peer-reviewed publications and conference presentations. NCT02570802, pre-results publication. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

  4. Asymmetric gibberellin signaling regulates vacuolar trafficking of PIN auxin transporters during root gravitropism.

    PubMed

    Löfke, Christian; Zwiewka, Marta; Heilmann, Ingo; Van Montagu, Marc C E; Teichmann, Thomas; Friml, Jirí

    2013-02-26

    Gravitropic bending of plant organs is mediated by an asymmetric signaling of the plant hormone auxin between the upper and lower side of the respective organ. Here, we show that also another plant hormone, gibberellic acid (GA), shows asymmetric action during gravitropic responses. Immunodetection using an antibody against GA and monitoring GA signaling output by downstream degradation of DELLA proteins revealed an asymmetric GA distribution and response with the maximum at the lower side of gravistimulated roots. Genetic or pharmacological manipulation of GA levels or response affects gravity-mediated auxin redistribution and root bending response. The higher GA levels at the lower side of the root correlate with increased amounts of PIN-FORMED2 (PIN2) auxin transporter at the plasma membrane. The observed increase in PIN2 stability is caused by a specific GA effect on trafficking of PIN proteins to lytic vacuoles that presumably occurs downstream of brefeldin A-sensitive endosomes. Our results suggest that asymmetric auxin distribution instructive for gravity-induced differential growth is consolidated by the asymmetric action of GA that stabilizes the PIN-dependent auxin stream along the lower side of gravistimulated roots.

  5. Root signalling and modulation of stomatal closure in flooded citrus seedlings.

    PubMed

    Rodríguez-Gamir, Juan; Ancillo, Gema; González-Mas, M Carmen; Primo-Millo, Eduardo; Iglesias, Domingo J; Forner-Giner, M Angeles

    2011-06-01

    In this work, we studied the sequence of responses induced by flooding in citrus plants, with the aim of identifying the signals that lead to stomatal closure. One-year-old seedlings of Carrizo citrange, grown in sand under greenhouse conditions, were waterlogged for 35 d and compared with normally watered well-drained plants. Significant decreases in stomatal conductance and transpiration were detected between flooded and control seedlings from a week after the beginning of the experiment. However ABA concentration in leaves only started to increase after three weeks of flooding, suggesting that stomata closed in the absence of a rise in foliar ABA. Therefore, stomatal closure in waterlogged seedlings does not appear to be induced by ABA, at least during the early stages of flood-stress. The low levels of ABA detected in roots and xylem sap from flooded seedlings indicated that it is very unlikely that the ABA increase in the leaves of these plants is due to ABA translocation from roots to shoots. We propose that ABA is produced in old leaves and transported to younger leaves. Flooding had no effect on water potential or the relative water content of leaves. Soil flooding reduced root hydraulic conductance in citrus seedlings. This effect was already evident after a week of waterlogging, and at the end of the experiment, flood-stressed seedlings reached values of root hydraulic conductance below 12% of that of control plants. This reduction was related to down-regulation of the expression of PIP aquaporins. In addition, whole plant transpiration was reduced by 56% after 35 d under flooding conditions. Flood-stress also decreased the pH of sap extracted from citrus roots. Evidence is presented suggesting that acidosis induced by anoxic stress in roots causes gating of aquaporins, thereby decreasing hydraulic conductance. Additionally, stomatal closure finely balances-out low pH-mediated losses of root hydraulic conductance therefore maintaining stable leaf

  6. Differential proton secretion in the apical elongation zone caused by gravistimulation is induced by a signal from the root cap.

    PubMed

    Monshausen, G B; Zieschang, H E; Sievers, A

    1996-12-01

    The extracellular proton activity along primary roots of Phleum pratense L. was measured using proton-selective microelectrodes. Removal of the root cap caused a reduction of the proton influx in the transitional region between the meristem and the apical elongation zone of the vertical root and inhibited the development of pH differences between the physically upper and lower flanks of the gravistimulated root. Disruption of the actin filament system of the root with 5 mmol m-3 cytochalasin D did not result in an altered proton flux and pH pattern compared with untreated vertical control roots, but inhibited the gravity-induced development of pH differences between the physically upper and lower root flanks as well as gravitropic curvature. These results provide evidence that pH changes following gravistimulation are induced by a signal transmitted from the root cap and that the actin filament system is involved in the gravity perception/transduction mechanism.

  7. Median nerve stimulation modulates extracellular signals in the primary motor area of a macaque monkey.

    PubMed

    Papazachariadis, Odysseas; Dante, Vittorio; Ferraina, Stefano

    2013-08-29

    Aiming to better define the functional influence of somatosensory stimuli on the primary motor cortex (M1) of primates, we investigated changes in extracellular neural activity induced by repetitive median nerve stimulation (MNS). We described neural adaptation and signal integration in both the multiunit activity (MUA) and the local field potential (LFP). To identify integration of initial M1 activity in the MNS response, we tested the correlation between peak amplitude responses and band energy preceding the peaks. Most of the sites studied in the M1 resulted responsive to MNS. MUA response peak amplitude decreased significantly in time in all sites during repetitive MNS, LFP response peak amplitude instead resulted more variable. Similarly, correlation analysis with the initial activity revealed a significant influence when tested using MUA peak amplitude modulation and a less significant correlation when tested using LFP peak amplitude. Our findings improve current knowledge on mechanisms underlying early M1 changes consequent to afferent somatosensory stimuli. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  8. Effects of Myoga on Memory and Synaptic Plasticity by Regulating Nerve Growth Factor-Mediated Signaling.

    PubMed

    Kim, Hyo Geun; Lim, Soonmin; Hong, Jongki; Kim, Ae-Jung; Oh, Myung Sook

    2016-02-01

    The flower bud of Zingiber mioga Roscoe, known as 'myoga' or Japanese ginger, has a pungent aroma and is commonly consumed as a spice, with pickles, or as a health supplement in Eastern Asia. Here, we evaluated the activity of myoga in the brain, focusing especially on nerve growth factor (NGF), which is believed to mediate synaptic plasticity, supporting learning and memory. In a rat primary hippocampal astrocyte culture system, treatment with myoga extract for 24 h significantly stimulated the production of NGF. In mice administered myoga extract for 14 days, 200 and 400 mg/kg/day treatment resulted in increased NGF levels in the hippocampus. Myoga extract treatment also regulated the phosphorylation of extracellular signal-regulated kinases and cAMP response element-binding protein in the mouse hippocampus, leading to increased synaptic plasticity. In addition, it significantly increased novel object recognition time and spontaneous alternation, indicating improvement in learning and memory. These results suggest that myoga helps regulate NGF and synaptic plasticity, increasing memory ability.

  9. Tiam1 as a Signaling Mediator of Nerve Growth Factor-Dependent Neurite Outgrowth

    PubMed Central

    Vilar, Marçal; Paratcha, Gustavo; Ledda, Fernanda

    2010-01-01

    Nerve Growth Factor (NGF)-induced neuronal differentiation requires the activation of members of the Rho family of small GTPases. However, the molecular mechanisms through which NGF regulates cytoskeletal changes and neurite outgrowth are not totally understood. In this work, we identify the Rac1-specific guanine exchange factor (GEF) Tiam1 as a novel mediator of NGF/TrkA-dependent neurite elongation. In particular, we report that knockdown of Tiam1 causes a significant reduction in Rac1 activity and neurite outgrowth induced by NGF. Physical interaction between Tiam1 and active Ras (Ras-GTP), but not tyrosine phosphorylation of Tiam1, plays a central role in Rac1 activation by NGF. In addition, our findings indicate that Ras is required to associate Tiam1 with Rac1 and promote Rac1 activation upon NGF stimulation. Taken together, these findings define a novel molecular mechanism through which Tiam1 mediates TrkA signaling and neurite outgrowth induced by NGF. PMID:20333299

  10. Nerve signaling regulates basal keratinocyte proliferation in the blastema apical epithelial cap in the axolotl (Ambystoma mexicanum).

    PubMed

    Satoh, Akira; Bryant, Susan V; Gardiner, David M

    2012-06-15

    The ability of adult vertebrates to repair tissue damage is widespread and impressive; however, the ability to regenerate structurally complex organs such as the limb is limited largely to the salamanders. The fact that most of the tissues of the limb can regenerate has led investigators to question and identify the barriers to organ regeneration. From studies in the salamander, it is known that one of the earliest steps required for successful regeneration involves signaling between nerves and the wound epithelium/apical epithelial cap (AEC). In this study we confirm an earlier report that the keratinocytes of the AEC acquire their function coincident with exiting the cell cycle. We have discovered that this unique, coordinated behavior is regulated by nerve signaling and is associated with the presence of gap junctions between the basal keratinocytes of the AEC. Disruption of nerve signaling results in a loss of gap junction protein, the reentry of the cells into the cell cycle, and regenerative failure. Finally, coordinated exit from the cell cycle appears to be a conserved behavior of populations of cells that function as signaling centers during both development and regeneration. Copyright © 2012 Elsevier Inc. All rights reserved.

  11. Upregulation of nuclear factor‑κB and acid sensing ion channel 3 in dorsal root ganglion following application of nucleus pulposus onto the nerve root in rats.

    PubMed

    Wang, Dong; Pan, Hao; Zhu, Hang; Zhu, Li; He, Yong-Jiang; Wang, Jian; Jia, Gao-Yong

    2017-10-01

    The nucleus pulposus (NP) is an avascular, hydrated tissue that permits the intervertebral disc to resist compressive loads to the spine. To determine the mechanisms by which intervertebral disc degeneration is caused by the nucleus pulposus, the expression and regulation of nuclear factor (NF)‑κB and acid sensing ion channel 3 (ASIC3) were examined. For the intervertebral disc degeneration model, NP was harvested from the tail of rats and applied to the L5 dorsal root ganglion (DRG). The mechanical pain withdrawal threshold (PWT) in NP model rats was assessed. Reverse transcription‑quantitative polymerase chain reaction and western blotting were used to examine NF‑κB and ASIC3 expression levels in DRG. Finally, the effect of the NF‑κB inhibitor pyrrolidine dithiocarbamate (PDTC) and the ASIC3 signaling pathway blocker amiloride were examined. Rats exposed to NP exhibited decreased PWT for 12 days, and NF‑κB and ASIC3 was upregulated in DRG induced by NP 14 days after surgery. After administration of amiloride and PDTC to DRG affected by NP, the levels of nitric oxide (NO), tumor necrosis factor‑α (TNF‑α), interleukin‑6 (IL‑6), NF‑κB and ASIC3 were downregulated, and the levels of aquaporin (AQP) 1 and AQP3 were significantly increased for 14 days. In conclusion, these results suggested that NF‑κB and ASIC3 may serve an important role in intervertebral disc degeneration caused by NP.

  12. Translatome analyses capture of opposing tissue-specific brassinosteroid signals orchestrating root meristem differentiation.

    PubMed

    Vragović, Kristina; Sela, Ayala; Friedlander-Shani, Lilach; Fridman, Yulia; Hacham, Yael; Holland, Neta; Bartom, Elizabeth; Mockler, Todd C; Savaldi-Goldstein, Sigal

    2015-01-20

    The mechanisms ensuring balanced growth remain a critical question in developmental biology. In plants, this balance relies on spatiotemporal integration of hormonal signaling pathways, but the understanding of the precise contribution of each hormone is just beginning to take form. Brassinosteroid (BR) hormone is shown here to have opposing effects on root meristem size, depending on its site of action. BR is demonstrated to both delay and promote onset of stem cell daughter differentiation, when acting in the outer tissue of the root meristem, the epidermis, and the innermost tissue, the stele, respectively. To understand the molecular basis of this phenomenon, a comprehensive spatiotemporal translatome mapping of Arabidopsis roots was performed. Analyses of wild type and mutants featuring different distributions of BR revealed autonomous, tissue-specific gene responses to BR, implying its contrasting tissue-dependent impact on growth. BR-induced genes were primarily detected in epidermal cells of the basal meristem zone and were enriched by auxin-related genes. In contrast, repressed BR genes prevailed in the stele of the apical meristem zone. Furthermore, auxin was found to mediate the growth-promoting impact of BR signaling originating in the epidermis, whereas BR signaling in the stele buffered this effect. We propose that context-specific BR activity and responses are oppositely interpreted at the organ level, ensuring coherent growth.

  13. AtrbohD and AtrbohF positively regulate abscisic acid-inhibited primary root growth by affecting Ca2+ signalling and auxin response of roots in Arabidopsis.

    PubMed

    Jiao, Yiheng; Sun, Lirong; Song, Yalin; Wang, Limin; Liu, Liping; Zhang, Liyue; Liu, Bo; Li, Ning; Miao, Chen; Hao, Fushun

    2013-11-01

    Reactive oxygen species (ROS) originating from the NADPH oxidases AtrbohD and AtrbohF play an important role in abscisic acid (ABA)-inhibited primary root growth in Arabidopsis. However, the mechanisms underlying this process remain elusive. In this study, the double mutant atrbohD1/F1 and atrbohD2/F2, in which both AtrbohD and AtrbohF were disrupted, were less sensitive to ABA suppression of root cell elongation than wild-type (WT) plants. Furthermore, the double mutants showed impaired ABA responses in roots, including ROS generation, cytosolic Ca(2+) increases, and activation of plasma membrane Ca(2+)-permeable channels compared with WT. Exogenous H2O2 can activate the Ca(2+) currents in roots of atrbohD1/F1. In addition, exogenous application of the auxin transport inhibitor naphthylphthalamic acid effectively promoted ABA inhibition of root growth of the mutants relative to that of WT. The ABA-induced decreases in auxin sensitivity of the root tips were more pronounced in WT than in atrbohD1/F1. These findings suggest that both AtrbohD and AtrbohF are essential for ABA-promoted ROS production in roots. ROS activate Ca(2+) signalling and reduce auxin sensitivity of roots, thus positively regulating ABA-inhibited primary root growth in Arabidopsis.

  14. Tomato susceptibility to root-knot nematodes requires an intact jasmonic acid signaling pathway.

    PubMed

    Bhattarai, Kishor K; Xie, Qi-Guang; Mantelin, Sophie; Bishnoi, Usha; Girke, Thomas; Navarre, Duroy A; Kaloshian, Isgouhi

    2008-09-01

    Responses of resistant (Mi-1/Mi-1) and susceptible (mi-1/ mi-1) tomato (Solanum lycopersicum) to root-knot nematodes (RKNs; Meloidogyne spp.) infection were monitored using cDNA microarrays, and the roles of salicylic acid (SA) and jasmonic acid (JA) defense signaling were evaluated in these interactions. Array analysis was used to compare transcript profiles in incompatible and compatible interactions of tomato roots 24 h after RKN infestation. The jai1 and def1 tomato mutant, altered in JA signaling, and tomato transgenic line NahG, altered in SA signaling, in the presence or absence of the RKN resistance gene Mi-1, were evaluated. The array analysis identified 1,497 and 750 genes differentially regulated in the incompatible and compatible interactions, respectively. Of the differentially regulated genes, 37% were specific to the incompatible interactions. NahG affected neither Mi-1 resistance nor basal defenses to RKNs. However, jai1 reduced tomato susceptibility to RKNs while not affecting Mi-1 resistance. In contrast, the def1 mutant did not affect RKN susceptibility. These results indicate that JA-dependent signaling does not play a role in Mi-1-mediated defense; however, an intact JA signaling pathway is required for tomato susceptibility to RKNs. In addition, low levels of SA might be sufficient for basal and Mi-1 resistance to RKNs.

  15. Flavonoids and strigolactones in root exudates as signals in symbiotic and pathogenic plant-fungus interactions.

    PubMed

    Steinkellner, Siegrid; Lendzemo, Venasius; Langer, Ingrid; Schweiger, Peter; Khaosaad, Thanasan; Toussaint, Jean-Patrick; Vierheilig, Horst

    2007-07-05

    Secondary plant compounds are important signals in several symbiotic and pathogenic plant-microbe interactions. The present review is limited to two groups of secondary plant compounds, flavonoids and strigolactones, which have been reported in root exudates. Data on flavonoids as signaling compounds are available from several symbiotic and pathogenic plant-microbe interactions, whereas only recently initial data on the role of strigolactones as plant signals in the arbuscular mycorrhizal symbiosis have been reported. Data from other plant-microbe interactions and strigolactones are not available yet. In the present article we are focusing on flavonoids in plant-fungal interactions such as the arbuscular mycorrhizal (AM) association and the signaling between different Fusarium species and plants. Moreover the role of strigolactones in the AM association is discussed and new data on the effect of strigolactones on fungi, apart from arbuscular mycorrhizal fungi (AMF), are provided.

  16. AtNIGT1/HRS1 integrates nitrate and phosphate signals at the Arabidopsis root tip

    PubMed Central

    Medici, Anna; Marshall-Colon, Amy; Ronzier, Elsa; Szponarski, Wojciech; Wang, Rongchen; Gojon, Alain; Crawford, Nigel M; Ruffel, Sandrine; Coruzzi, Gloria M; Krouk, Gabriel

    2015-01-01

    Nitrogen and phosphorus are among the most widely used fertilizers worldwide. Nitrate (NO3−) and phosphate (PO43−) are also signaling molecules whose respective transduction pathways are being intensively studied. However, plants are continuously challenged with combined nutritional deficiencies, yet very little is known about how these signaling pathways are integrated. Here we report the identification of a highly NO3−-inducible NRT1.1-controlled GARP transcription factor, HRS1, document its genome-wide transcriptional targets, and validate its cis-regulatory-elements. We demonstrate that this transcription factor and a close homolog repress primary root growth in response to P deficiency conditions, but only when NO3− is present. This system defines a molecular logic gate integrating P and N signals. We propose that NO3− and P signaling converge via double transcriptional and post-transcriptional control of the same protein, HRS1 PMID:25723764

  17. AtNIGT1/HRS1 integrates nitrate and phosphate signals at the Arabidopsis root tip.

    PubMed

    Medici, Anna; Marshall-Colon, Amy; Ronzier, Elsa; Szponarski, Wojciech; Wang, Rongchen; Gojon, Alain; Crawford, Nigel M; Ruffel, Sandrine; Coruzzi, Gloria M; Krouk, Gabriel

    2015-02-27

    Nitrogen and phosphorus are among the most widely used fertilizers worldwide. Nitrate (NO3(-)) and phosphate (PO4(3-)) are also signalling molecules whose respective transduction pathways are being intensively studied. However, plants are continuously challenged with combined nutritional deficiencies, yet very little is known about how these signalling pathways are integrated. Here we report the identification of a highly NO3(-)-inducible NRT1.1-controlled GARP transcription factor, HRS1, document its genome-wide transcriptional targets, and validate its cis-regulatory elements. We demonstrate that this transcription factor and a close homologue repress the primary root growth in response to P deficiency conditions, but only when NO3(-) is present. This system defines a molecular logic gate integrating P and N signals. We propose that NO3(-) and P signalling converge via double transcriptional and post-transcriptional control of the same protein, HRS1.

  18. Dorsal root ganglia neurons and differentiated adipose-derived stem cells: an in vitro co-culture model to study peripheral nerve regeneration.

    PubMed

    de Luca, Alba C; Faroni, Alessandro; Reid, Adam J

    2015-02-26

    Dorsal root ganglia (DRG) neurons, located in the intervertebral foramina of the spinal column, can be used to create an in vitro system facilitating the study of nerve regeneration and myelination. The glial cells of the peripheral nervous system, Schwann cells (SC), are key facilitators of these processes; it is therefore crucial that the interactions of these cellular components are studied together. Direct contact between DRG neurons and glial cells provides additional stimuli sensed by specific membrane receptors, further improving the neuronal response. SC release growth factors and proteins in the culture medium, which enhance neuron survival and stimulate neurite sprouting and extension. However, SC require long proliferation time to be used for tissue engineering applications and the sacrifice of an healthy nerve for their sourcing. Adipose-derived stem cells (ASC) differentiated into SC phenotype are a valid alternative to SC for the set-up of a co-culture model with DRG neurons to study nerve regeneration. The present work presents a detailed and reproducible step-by-step protocol to harvest both DRG neurons and ASC from adult rats; to differentiate ASC towards a SC phenotype; and combines the two cell types in a direct co-culture system to investigate the interplay between neurons and SC in the peripheral nervous system. This tool has great potential in the optimization of tissue-engineered constructs for peripheral nerve repair.

  19. Neurotrophic and neuroprotective actions of Achyranthes bidentata polypeptides on cultured dorsal root ganglia of rats and on crushed common peroneal nerve of rabbits.

    PubMed

    Cheng, Qiong; Yuan, Ying; Sun, Changnan; Gu, Xiaosong; Cao, Zheng; Ding, Fei

    2014-03-06

    We have isolated Achyranthes bidentata Blume polypeptides (ABPP) from the aqueous extract of A. bidentata Blume, a traditional Chinese medicine with multiple therapeutic applications. In this study, we aimed to investigate neurotrophic effects of ABPP on cultured dorsal root ganglia (DRGs) of rats and neuroprotective effects on crushed common peroneal nerve of rabbits. Immunochemistry and Western blot analysis indicated that ABPP (0.01, 0.1, and 1.0 μg/ml) encouraged neurite outgrowth from cultured DRG explants/neurons in a concentration-dependent manner through activation of ERK1/2. After crush injury to rabbit common peroneal nerve, animals received daily administration of ABPP for 5 weeks. Electrophysiological assessments and histomorphological evaluation showed that 6.0mg/kg ABPP significantly enhanced nerve regeneration and function restoration. Our findings suggest that ABPP could be used as a neurotrophic and neuroprotective agent to treat peripheral nerve crush injury. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  20. A temporal variation in nonneuronal protein synthesis in dorsal root ganglia and nerve and its significance to studies of axonal transport

    SciTech Connect

    Snyder, R.E.; O'Brien, D.W.; Nihei, T.

    1984-03-01

    Protein synthesis and fast axonal transport were studied in vitro using dorsal root ganglia (DRG)-sciatic nerve preparations from the amphibian Xenopus laevis. It was observed that the rate of incorporation of (/sup 3/H)leucine into protein in DRG and isolated segments of nerve began to increase 9 to 11 h after killing the animal, attaining at 13 to 17 h a maximum of 5- to 10-times preincrease (less than 9 h) values. At the same time as an increase in the rate of incorporation began, synthesis commenced in DRG and nerve exposed to cycloheximide (125 micrograms/ml). Whereas cycloheximide reduced fast axonal transport to 1 to 3% of control values in preparations maintained 20 to 24 h in vitro, cycloheximide reduced incorporation in DRG to only 80% of control values. N-terminal labeling studies showed that both the increased incorporation and cycloheximide-insensitive incorporation resulted from protein synthesis. Autoradiographic and incorporation studies indicated that nonneuronal cells situated in the ganglion capsule and perineural sheath of the nerve were responsible for both the increased incorporation and cycloheximide-insensitive synthesis. The findings have implications for the study of axonal transport.

  1. Strigolactones: Chemical Signals for Fungal Symbionts and Parasitic Weeds in Plant Roots

    PubMed Central

    AKIYAMA, KOHKI; HAYASHI, HIDEO

    2006-01-01

    • Aims Arbuscular mycorrhizae are formed between >80 % of land plants and arbuscular mycorrhizal (AM) fungi. This Botanical Briefing highlights the chemical identification of strigolactones as a host-recognition signal for AM fungi, and their role in the establishment of arbuscular mycorrhizae as well as in the seed germination of parasitic weeds. • Scope Hyphal branching has long been described as the first morphological event in host recognition by AM fungi during the pre-infection stages. Host roots release signalling molecules called ‘branching factors’ that induce extensive hyphal branching in AM fungi. Strigolactones exuded from host roots have recently been identified as an inducer of hyphal branching in AM fungi. Strigolactones are a group of sesquiterpenes, previously isolated as seed germination stimulants for the parasitic weeds Striga and Orobanche. Parasitic weeds might find their potential hosts by detecting strigolactones, which are released from plant roots upon phosphate deficiency in communication with AM fungi. In addition to acting as a signalling molecule, strigolactones might stimulate the production of fungal symbiotic signals called ‘Myc factors’ in AM fungi. • Conclusions Isolation and identification of plant symbiotic signals open up new ways for studying the molecular basis of plant–AM-fungus interactions. This discovery provides a clear answer to a long-standing question in parasitic plant biology: what is the natural role for germination stimulants? It could also provide a new strategy for the management and control of beneficial fungal symbionts and of devastating parasitic weeds in agriculture and natural ecosystems. PMID:16574693

  2. Inhibition of the TRPM2 and TRPV1 Channels through Hypericum perforatum in Sciatic Nerve Injury-induced Rats Demonstrates their Key Role in Apoptosis and Mitochondrial Oxidative Stress of Sciatic Nerve and Dorsal Root Ganglion

    PubMed Central

    Uslusoy, Fuat; Nazıroğlu, Mustafa; Çiğ, Bilal

    2017-01-01

    Sciatic nerve injury (SNI) results in neuropathic pain, which is characterized by the excessive Ca2+ entry, reactive oxygen species (ROS) and apoptosis processes although involvement of antioxidant Hypericum perforatum (HP) through TRPM2 and TRPV1 activation has not been clarified on the processes in SNI-induced rat, yet. We investigated the protective property of HP on the processes in the sciatic nerve and dorsal root ganglion neuron (DRGN) of SNI-induced rats. The rats were divided into five groups as control, sham, sham+HP, SNI, and SNI+HP. The HP groups received 30 mg/kg HP for 4 weeks after SNI induction. TRPM2 and TRPV1 channels were activated in the neurons by ADP-ribose or cumene peroxide and capsaicin, respectively. The SNI-induced TRPM2 and TRPV1 currents and intracellular free Ca2+ and ROS concentrations were reduced by HP, N-(p-amylcinnamoyl) anthranilic acid (ACA), and capsazepine (CapZ). SNI-induced increase in apoptosis and mitochondrial depolarization in sciatic nerve and DRGN of SNI group were decreased by HP, ACA, and CapZ treatments. PARP-1, caspase 3 and 9 expressions in the sciatic nerve, DRGN, skin, and musculus piriformis of SNI group were also attenuated by HP treatment. In conclusion, increase of mitochondrial ROS, apoptosis, and Ca2+ entry through inhibition of TRPM2 and TRPV1 in the sciatic nerve and DRGN neurons were decreased by HP treatment. The results may be relevant to the etiology and treatment of SNI by HP. PMID:28620309

  3. Inhibition of the TRPM2 and TRPV1 Channels through Hypericum perforatum in Sciatic Nerve Injury-induced Rats Demonstrates their Key Role in Apoptosis and Mitochondrial Oxidative Stress of Sciatic Nerve and Dorsal Root Ganglion.

    PubMed

    Uslusoy, Fuat; Nazıroğlu, Mustafa; Çiğ, Bilal

    2017-01-01

    Sciatic nerve injury (SNI) results in neuropathic pain, which is characterized by the excessive Ca(2+) entry, reactive oxygen species (ROS) and apoptosis processes although involvement of antioxidant Hypericum perforatum (HP) through TRPM2 and TRPV1 activation has not been clarified on the processes in SNI-induced rat, yet. We investigated the protective property of HP on the processes in the sciatic nerve and dorsal root ganglion neuron (DRGN) of SNI-induced rats. The rats were divided into five groups as control, sham, sham+HP, SNI, and SNI+HP. The HP groups received 30 mg/kg HP for 4 weeks after SNI induction. TRPM2 and TRPV1 channels were activated in the neurons by ADP-ribose or cumene peroxide and capsaicin, respectively. The SNI-induced TRPM2 and TRPV1 currents and intracellular free Ca(2+) and ROS concentrations were reduced by HP, N-(p-amylcinnamoyl) anthranilic acid (ACA), and capsazepine (CapZ). SNI-induced increase in apoptosis and mitochondrial depolarization in sciatic nerve and DRGN of SNI group were decreased by HP, ACA, and CapZ treatments. PARP-1, caspase 3 and 9 expressions in the sciatic nerve, DRGN, skin, and musculus piriformis of SNI group were also attenuated by HP treatment. In conclusion, increase of mitochondrial ROS, apoptosis, and Ca(2+) entry through inhibition of TRPM2 and TRPV1 in the sciatic nerve and DRGN neurons were decreased by HP treatment. The results may be relevant to the etiology and treatment of SNI by HP.

  4. Jasmonate signaling is activated in the very early stages of iron deficiency responses in rice roots.

    PubMed

    Kobayashi, Takanori; Itai, Reiko Nakanishi; Senoura, Takeshi; Oikawa, Takaya; Ishimaru, Yasuhiro; Ueda, Minoru; Nakanishi, Hiromi; Nishizawa, Naoko K

    2016-07-01

    Under low iron availability, plants induce the expression of various genes involved in iron uptake and translocation at the transcriptional level. This iron deficiency response is affected by various plant hormones, but the roles of jasmonates in this response are not well-known. We investigated the involvement of jasmonates in rice iron deficiency responses. High rates of jasmonate-inducible genes were induced during the very early stages of iron deficiency treatment in rice roots. Many jasmonate-inducible genes were also negatively regulated by the ubiquitin ligases OsHRZ1 and OsHRZ2 and positively regulated by the transcription factor IDEF1. Ten out of 35 genes involved in jasmonate biosynthesis and signaling were rapidly induced at 3 h of iron deficiency treatment, and this induction preceded that of known iron deficiency-inducible genes involved in iron uptake and translocation. Twelve genes involved in jasmonate biosynthesis and signaling were also upregulated in HRZ-knockdown roots. Endogenous concentrations of jasmonic acid and jasmonoyl isoleucine tended to be rapidly increased in roots in response to iron deficiency treatment, whereas these concentrations were higher in HRZ-knockdown roots under iron-sufficient conditions. Analysis of the jasmonate-deficient cpm2 mutant revealed that jasmonates repress the expression of many iron deficiency-inducible genes involved in iron uptake and translocation under iron sufficiency, but this repression is partly canceled under an early stage of iron deficiency. These results indicate that jasmonate signaling is activated during the very early stages of iron deficiency, which is partly regulated by IDEF1 and OsHRZs.

  5. Smad4-Shh-Nfic signaling cascade-mediated epithelial-mesenchymal interaction is crucial in regulating tooth root development.

    PubMed

    Huang, Xiaofeng; Xu, Xun; Bringas, Pablo; Hung, Yee Ping; Chai, Yang

    2010-05-01

    Transforming growth factor beta (TGF-beta)/bone morphogenetic protein (BMP) signaling is crucial for regulating epithelial-mesenchymal interaction during organogenesis, and the canonical Smad pathway-mediated TGF-beta/BMP signaling plays important roles during development and disease. During tooth development, dental epithelial cells, known as Hertwig's epithelial root sheath (HERS), participate in root formation following crown development. However, the functional significance of HERS in regulating root development remains unknown. In this study we investigated the signaling mechanism of Smad4, the common Smad for TGF-beta/BMP signaling, in HERS in regulating root development. Tissue-specific inactivation of Smad4 in HERS results in abnormal enamel and dentin formation in K14-Cre;Smad4(fl/fl) mice. HERS enlarges but cannot elongate to guide root development without Smad4. At the molecular level, Smad4-mediated TGF-beta/BMP signaling is required for Shh expression in HERS and Nfic (nuclear factor Ic) expression in the cranial neural crest (CNC)-derived dental mesenchyme. Nfic is crucial for root development, and loss of Nfic results in a CNC-derived dentin defect similar to the one of K14-Cre;Smad4(fl/fl) mice. Significantly, we show that ectopic Shh induces Nfic expression in dental mesenchyme and partially rescues root development in K14-Cre;Smad4(fl/fl) mice. Taken together, our study has revealed an important signaling mechanism in which TGF-beta/BMP signaling relies on a Smad-dependent mechanism in regulating Nfic expression via Shh signaling to control root development. The interaction between HERS and the CNC-derived dental mesenchyme may guide the size, shape, and number of tooth roots.

  6. The kinetics of root gravitropism in PIN mutants suggest redundancy in the signal transduction pathway

    NASA Astrophysics Data System (ADS)

    Wolverton, Chris

    plays a role in efflux to the columella. Pin4 mutants showed no deficiencies in gravitropism, in fact responding at a greater rate than wild-type roots over the first hour (22 deg h-1 ). PIN7 has been localized to the vascular tissue of the elongation zone and to the central columella. Like pin4 mutants, pin7 mutants did not show a significantly reduced gravitropic response relative to wild-type roots. Interestingly, roots of pin3pin7 double mutants showed curvature and growth rates similar to pin7 single mutants and wild-type roots, suggesting a genetic interaction between PIN3 and PIN7 in this pathway. These results suggest a significant degree of redundancy in the regulation of directional auxin transport and perhaps in the gravity signaling pathway in roots in general.

  7. Characterization of thoracic motor and sensory neurons and spinal nerve roots in canine degenerative myelopathy, a potential disease model of amyotrophic lateral sclerosis.

    PubMed

    Morgan, Brandie R; Coates, Joan R; Johnson, Gayle C; Shelton, G Diane; Katz, Martin L

    2014-04-01

    Canine degenerative myelopathy (DM) is a progressive, adult-onset, multisystem degenerative disease with many features in common with amyotrophic lateral sclerosis (ALS). As with some forms of ALS, DM is associated with mutations in superoxide dismutase 1 (SOD1). Clinical signs include general proprioceptive ataxia and spastic upper motor neuron paresis in pelvic limbs, which progress to flaccid tetraplegia and dysphagia. The purpose of this study was to characterize DM as a potential disease model for ALS. We previously reported that intercostal muscle atrophy develops in dogs with advanced-stage DM. To determine whether other components of the thoracic motor unit (MU) also demonstrated morphological changes consistent with dysfunction, histopathologic and morphometric analyses were conducted on thoracic spinal motor neurons (MNs) and dorsal root ganglia (DRG) and in motor and sensory nerve root axons from DM-affected boxers and Pembroke Welsh corgis (PWCs). No alterations in MNs or motor root axons were observed in either breed. However, advanced-stage PWCs exhibited significant losses of sensory root axons, and numerous DRG sensory neurons displayed evidence of degeneration. These results indicate that intercostal muscle atrophy in DM is not preceded by physical loss of the motor neurons innervating these muscles, nor of their axons. Axonal loss in thoracic sensory roots and sensory neuron death suggest that sensory involvement may play an important role in DM disease progression. Further analysis of the mechanisms responsible for these morphological findings would aid in the development of therapeutic intervention for DM and some forms of ALS.

  8. The effect of intraluminal contact mediated guidance signals on axonal mismatch during peripheral nerve repair.

    PubMed

    Daly, William T; Yao, Li; Abu-rub, Mohammad T; O'Connell, Claire; Zeugolis, Dimitrios I; Windebank, Anthony J; Pandit, Abhay S

    2012-10-01

    The current microsurgical gold standard for repairing long gap nerve injuries is the autograft. Autograft provides a protective environment for repair and a natural internal architecture, which is essential for regeneration. Current clinically approved hollow nerve guidance conduits allow provision of this protective environment; however they fail to provide an essential internal architecture to the regenerating nerve. In the present study both structured and unstructured intraluminal collagen fibres are investigated to assess their ability to enhance conduit mediated nerve repair. This study presents a direct comparison of both structured and unstructured fibres in vivo. The addition of intraluminal guidance structures was shown to significantly decrease axonal dispersion within the conduit and reduced axonal mismatch of distal nerve targets (p < 0.05). The intraluminal fibres were shown to be successfully incorporated into the host regenerative process, acting as a platform for Schwann cell migration and axonal regeneration. Ultimately the fibres were able to provide a platform for nerve regeneration in a long term regeneration study (16 weeks) and facilitated increased guidance of regenerating axons towards their distal nerve targets. Copyright © 2012 Elsevier Ltd. All rights reserved.

  9. The Impact of Low-Dose Insulin on Peripheral Nerve Insulin Receptor Signaling in Streptozotocin-Induced Diabetic Rats

    PubMed Central

    Sugimoto, Kazuhiro; Baba, Masayuki; Suzuki, Susumu; Yagihashi, Soroku

    2013-01-01

    Background The precise mechanisms of the neuroprotective effects of insulin in streptozotocin (STZ)-induced diabetic animals remain unknown, but altered peripheral nerve insulin receptor signaling due to insulin deficiency might be one cause. Methodology and Principal Findings Diabetes was induced in 10-week-old, male Wistar rats by injecting them with STZ (45 mg/kg). They were assigned to one group that received half of an insulin implant (∼1 U/day; I-group, n = 11) or another that remained untreated (U-group, n = 10) for 6 weeks. The controls were age- and sex-matched, non-diabetic Wistar rats (C-group, n = 12). Low-dose insulin did not change haemoglobin A1c, which increased by 136% in the U-group compared with the C-group. Thermal hypoalgesia and mechanical hyperalgesia developed in the U-group, but not in the I-group. Sensory and motor nerve conduction velocities decreased in the U-group, whereas sensory nerve conduction velocity increased by 7% (p = 0.0351) in the I-group compared with the U-group. Western blots showed unaltered total insulin receptor (IR), but a 31% decrease and 3.1- and 4.0-fold increases in phosphorylated IR, p44, and p42 MAPK protein levels, respectively, in sciatic nerves from the U-group compared with the C-group. Phosphorylated p44/42 MAPK protein decreased to control levels in the I-group (p<0.0001). Conclusions and Significance Low-dose insulin deactivated p44/42 MAPK and ameliorated peripheral sensory nerve dysfunction in rats with STZ-induced diabetes. These findings support the notion that insulin deficiency per se introduces impaired insulin receptor signaling in type 1 diabetic neuropathy. PMID:24023699

  10. Nerve injury induces a Gem-GTPase-dependent downregulation of P/Q-type Ca2+ channels contributing to neurite plasticity in dorsal root ganglion neurons.

    PubMed

    Scamps, Frédérique; Sangari, Sina; Bowerman, Melissa; Rousset, Mathieu; Bellis, Michel; Cens, Thierry; Charnet, Pierre

    2015-02-01

    Small RGK GTPases, Rad, Gem, Rem1, and Rem2, are potent inhibitors of high-voltage-activated (HVA) Ca(2+) channels expressed in heterologous expression systems. However, the role of this regulation has never been clearly demonstrated in the nervous system. Using transcriptional analysis, we show that peripheral nerve injury specifically upregulates Gem in mice dorsal root ganglia. Following nerve injury, protein expression was increased in ganglia and peripheral nerve, mostly under its phosphorylated form. This was confirmed in situ and in vitro in dorsal root ganglia sensory neurons. Knockdown of endogenous Gem, using specific small-interfering RNA (siRNA), increased the HVA Ca(2+) current only in the large-somatic-sized neurons. Combining pharmacological analysis of the HVA Ca(2+) currents together with Gem siRNA-transfection of larger sensory neurons, we demonstrate that only the P/Q-type Ca(2+) channels were enhanced. In vitro analysis of Gem affinity to various CaVβx-CaV2.x complexes and immunocytochemical studies of Gem and CaVβ expression in sensory neurons suggest that the specific inhibition of the P/Q channels relies on both the regionalized upregulation of Gem and the higher sensitivity of the endogenous CaV2.1-CaVβ4 pair in a subset of sensory neurons including the proprioceptors. Finally, pharmacological inhibition of P/Q-type Ca(2+) current reduces neurite branching of regenerating axotomized neurons. Taken together, the present results indicate that a Gem-dependent P/Q-type Ca(2+) current inhibition may contribute to general homeostatic mechanisms following a peripheral nerve injury.

  11. SCFTIR1/AFB-auxin signalling regulates PIN vacuolar trafficking and auxin fluxes during root gravitropism

    PubMed Central

    Baster, Paweł; Robert, Stéphanie; Kleine-Vehn, Jürgen; Vanneste, Steffen; Kania, Urszula; Grunewald, Wim; De Rybel, Bert; Beeckman, Tom; Friml, Jiří

    2013-01-01

    The distribution of the phytohormone auxin regulates many aspects of plant development including growth response to gravity. Gravitropic root curvature involves coordinated and asymmetric cell elongation between the lower and upper side of the root, mediated by differential cellular auxin levels. The asymmetry in the auxin distribution is established and maintained by a spatio-temporal regulation of the PIN-FORMED (PIN) auxin transporter activity. We provide novel insights into the complex regulation of PIN abundance and activity during root gravitropism. We show that PIN2 turnover is differentially regulated on the upper and lower side of gravistimulated roots by distinct but partially overlapping auxin feedback mechanisms. In addition to regulating transcription and clathrin-mediated internalization, auxin also controls PIN abundance at the plasma membrane by promoting their vacuolar targeting and degradation. This effect of elevated auxin levels requires the activity of SKP-Cullin-F-boxTIR1/AFB (SCFTIR1/AFB)-dependent pathway. Importantly, also suboptimal auxin levels mediate PIN degradation utilizing the same signalling pathway. These feedback mechanisms are functionally important during gravitropic response and ensure fine-tuning of auxin fluxes for maintaining as well as terminating asymmetric growth. PMID:23211744

  12. Rhizobium Lipo-chitooligosaccharide Signaling Triggers Accumulation of Cytokinins in Medicago truncatula Roots.

    PubMed

    van Zeijl, Arjan; Op den Camp, Rik H M; Deinum, Eva E; Charnikhova, Tatsiana; Franssen, Henk; Op den Camp, Huub J M; Bouwmeester, Harro; Kohlen, Wouter; Bisseling, Ton; Geurts, René

    2015-08-01

    Legume rhizobium symbiosis is initiated upon perception of bacterial secreted lipo-chitooligosaccharides (LCOs). Perception of these signals by the plant initiates a signaling cascade that leads to nodule formation. Several studies have implicated a function for cytokinin in this process. However, whether cytokinin accumulation and subsequent signaling are an integral part of rhizobium LCO signaling remains elusive. Here, we show that cytokinin signaling is required for the majority of transcriptional changes induced by rhizobium LCOs. In addition, we demonstrate that several cytokinins accumulate in the root susceptible zone 3 h after rhizobium LCO application, including the biologically most active cytokinins, trans-zeatin and isopentenyl adenine. These responses are dependent on calcium- and calmodulin-dependent protein kinase (CCaMK), a key protein in rhizobial LCO-induced signaling. Analysis of the ethylene-insensitive Mtein2/Mtsickle mutant showed that LCO-induced cytokinin accumulation is negatively regulated by ethylene. Together with transcriptional induction of ethylene biosynthesis genes, it suggests a feedback loop negatively regulating LCO signaling and subsequent cytokinin accumulation. We argue that cytokinin accumulation is a key step in the pathway leading to nodule organogenesis and that this is tightly controlled by feedback loops.

  13. The contribution of SERF1 to root-to-shoot signaling during salinity stress in rice.

    PubMed

    Schmidt, Romy; Caldana, Camila; Mueller-Roeber, Bernd; Schippers, Jos H M

    2014-01-01

    Stress perception and communication play important roles in the adaptation of plants to changing environmental conditions. Plant roots are the first organs to detect changes in the soil water potential induced by salt stress. In the presence of salinity stress, root-to-shoot communication occurs to adjust the growth of the whole plant. So far, the phytohormone abscisic acid (ABA), hydraulic signals and reactive oxygen species (ROS) have been proposed to mediate this communication under salt stress. Recently, we identified the rice transcription factor SALT-RESPONSIVE ERF1 (SERF1), which regulates a ROS-dependent transcriptional cascade in roots required for salinity tolerance. Upon salt stress, SERF1 knockout mutant plants show an increased leaf temperature as compared with wild type. As this occurs within the first 20 min of salt stress, we here evaluated the involvement of SERF1 in the perception of salt stress in the shoot. By metabolic profiling and expression analysis we show that the action of SERF1 in signal communication to the shoot is independent from ABA, but does affect the accumulation of ROS-related metabolites and transcripts under short-term salt stress.

  14. Response to pulsed and continuous radiofrequency lesioning of the dorsal root ganglion and segmental nerves in patients with chronic lumbar radicular pain.

    PubMed

    Simopoulos, Thomas T; Kraemer, Jan; Nagda, Jyotsna V; Aner, Musa; Bajwa, Zahid H

    2008-01-01

    We aimed to prospectively evaluate the response and safety of pulsed and continuous radiofrequecy lesioning of the dorsal root ganglion/segmental nerves in patients with chronic lumbosacral radicular pain. Seventy-six patients with chronic lumbosacral radicular pain refractory to conventional therapy met the inclusion criteria and were randomly assigned to one of 2 types of treatment, pulsed radiofrequency lesioning of the dorsal root ganglion/segmental nerve or pulsed radiofrequency followed immediately by continuous radiofrequency. Patients were carefully evaluated for neurologic deficits and side effects. The response was evaluated at 2 months and was then tracked monthly. A Kaplan-Meier analysis was used to illustrate the probability of success over time and a Box-Whisker analysis was applied to determine the mean duration of a successful analgesic effect. Two months after undergoing radiofrequency treatment, 70% of the patients treated with pulsed radiofrequency and 82% treated with pulsed and continuous radiofrequency had a successful reduction in pain intensity. The average duration of successful analgesic response was 3.18 months (+/- 2.81) in the group treated with pulsed radiofrequency and 4.39 months (+/-3.50) in those patients treated with pulsed and continuous radiofrequency lesioning. A Kaplan-Meier analysis illustrated that in both treatment groups the chance of success approached 50% in each group at 3 months. The vast majority of patients had lost any beneficial effects by 8 months. There was no statistical difference between the 2 treatment groups. No side effects or neurological deficits were found in either group. Pulsed mode radiofrequency of the dorsal root ganglion of segmental nerves appears to be a safe treatment for chronic lumbosacral radicular pain. A significant number of patients can derive at least a short-term benefit. The addition of heat via continuous radiofrequency does not offer a significant advantage. A randomized controlled

  15. Characteristic anatomical conformation of the vertebral artery causing vascular compression against the root exit zone of the facial nerve in patients with hemifacial spasm.

    PubMed

    Park, Jung-Soo; Koh, Eun-Jeong; Choi, Ha-Young; Lee, Jong-Myong

    2015-03-01

    Hemifacial spasm (HFS) is caused by tortuous offending vessels near the facial nerve root exit zone. However, the definitive mechanism of offending vessel formation remains unclear. We hypothesized that vascular angulation and tortuosity, probably caused by uneven vertebral artery blood flow, result in vascular compression of the facial nerve root exit zone. The authors observed two anatomical characteristics of the vertebrobasilar arterial system in 120 subjects in the surgical group and 188 controls. The presence of the dominant vertebral artery (DVA) and laterality of the vertebrobasilar junction (VBJ) were observed. We also analyzed the morphological characteristics of the surgical group showing the presence of DVA. The morphological characteristics were classified into three types: type I had the VBJ and DVA on the same side, type II had the VBJ within 2 mm of the midline, and type III had the VBJ opposite the DVA. The DVA was more prevalent in the surgical group than in the control group (71 % versus 54 %, P < 0.05). The surgical group patients with HFS on the left were more likely to have a DVA on the left (P < 0.05) and with HFS on the right were more likely to have a DVA on the right (P < 0.01) compared with controls. The direction of the VBJ was more common on the same side as the DVA, which corresponds with the laterality of the HFS. In the surgical group with the DVA and HFS on the same side, type I was predominant, but in the surgical group with a contralateral DVA and HFS, type III was predominant. The presence of a DVA and shifting of the VBJ on the same side plays a role in the angulation and tortuosity of vessels in the perivertebrobasilar junction, resulting in neurovascular compression of the facial nerve root exit zone and thereby causing HFS.

  16. A Novel Collaborative Protocol for Successful Management of Penile Pain Mediated by Radiculitis of Sacral Spinal Nerve Roots From Tarlov Cysts.

    PubMed

    Goldstein, Irwin; Komisaruk, Barry R; Rubin, Rachel S; Goldstein, Sue W; Elliott, Stacy; Kissee, Jennifer; Kim, Choll W

    2017-09-01

    Since 14 years of age, the patient had experienced extreme penile pain within seconds of initial sexual arousal through masturbation. Penile pain was so severe that he rarely proceeded to orgasm or ejaculation. After 7 years of undergoing multiple unsuccessful treatments, he was concerned for his long-term mental health and for his future ability to have relationships. To describe a novel collaboration among specialists in sexual medicine, neurophysiology, and spine surgery that led to successful management. Collaborating health care providers conferred with the referring physician, patient, and parents and included a review of all medical records. Elimination of postpubertal intense penile pain during sexual arousal. The patient presented to our sexual medicine facility at 21 years of age. The sexual medicine physician identifying the sexual health complaint noted a pelvic magnetic resonance imaging report of an incidental sacral Tarlov cyst. A subsequent sacral magnetic resonance image showed four sacral Tarlov cysts, with the largest measuring 18 mm. Neuro-genital testing result were abnormal. The neurophysiologist hypothesized the patient's pain at erection was produced by Tarlov cyst-induced neuropathic irritation of sensory fibers that course within the pelvic nerve. The spine surgeon directed a diagnostic injection of bupivacaine to the sacral nerve roots and subsequently morphine to the conus medullaris of the spinal cord. The bupivacaine produced general penile numbness; the morphine selectively decreased penile pain symptoms during sexual arousal without blocking penile skin sensation. The collaboration among specialties led to the conclusion that the Tarlov cysts were pathophysiologically mediating the penile pain symptoms during arousal. Long-term follow-up after surgical repair showed complete symptom elimination at 18 months after treatment. This case provides evidence that (i) Tarlov cysts can cause sacral spinal nerve root radiculitis through

  17. Action potential broadening and frequency-dependent facilitation of calcium signals in pituitary nerve terminals.

    PubMed

    Jackson, M B; Konnerth, A; Augustine, G J

    1991-01-15

    Hormone release from nerve terminals in the neurohypophysis is a sensitive function of action potential frequency. We have investigated the cellular mechanisms responsible for this frequency-dependent facilitation by combining patch clamp and fluorimetric Ca2+ measurements in single neurosecretory terminals in thin slices of the rat posterior pituitary. In these terminals both action potential-induced changes in the intracellular Ca2+ concentration ([Ca2+]i) and action potential duration were enhanced by high-frequency stimuli, all with a frequency dependence similar to that of hormone release. Furthermore, brief voltage clamp pulses inactivated a K+ current with a very similar frequency dependence. These results support a model for frequency-dependent facilitation in which the inactivation of a K+ current broadens action potentials, leading to an enhancement of [Ca2+]i signals. Further experiments tested for a causal relationship between action potential broadening and facilitation of [Ca2+]i changes. First, increasing the duration of depolarization, either by broadening action potentials with the K(+)-channel blocker tetraethylammonium or by applying longer depolarizing voltage clamp steps, increased [Ca2+]i changes. Second, eliminating frequency-dependent changes in duration, by voltage clamping the terminal with constant duration pulses, substantially reduced the frequency-dependent enhancement of [Ca2+]i changes. These results indicate that action potential broadening contributes to frequency-dependent facilitation of [Ca2+]i changes. However, the small residual frequency dependence of [Ca2+]i changes seen with constant duration stimulation suggests that a second process, distinct from action potential broadening, also contributes to facilitation. These two frequency-dependent mechanisms may also contribute to activity-dependent plasticity in synaptic terminals.

  18. The soybean root-specific protein kinase GmWNK1 regulates stress-responsive ABA signaling on the root system architecture.

    PubMed

    Wang, Yingxiang; Suo, Haicui; Zheng, Yan; Liu, Kaidong; Zhuang, Chuxiong; Kahle, Kristopher T; Ma, Hong; Yan, Xiaolong

    2010-10-01

    In humans, members of the WNK protein kinase family are osmosensitive regulators of cell volume homeostasis and epithelial ion transport, and mutation of these proteins causes a rare inherited form of hypertension due to increased renal NaCl re-absorption. A related class of kinases was recently discovered in plants, but their functions are largely unknown. We have identified a root-specific WNK kinase homolog, GmWNK1, in soybean (Glycine max). GmWNK1 expression was detected in the root, specifically in root cells associated with lateral root formation, and was down-regulated by abscisic acid (ABA), as well as by mannitol, sucrose, polyethylene glycol and NaCl. In vitro and in vivo experiments showed that GmWNK1 interacts with another soybean protein, GmCYP707A1, which is a key ABA 8'-hydroxylase that functions in ABA catabolism. Furthermore, 35S-GmWNK1 transgenic soybean plants had reduced lateral root number and length compared with wild-type, suggesting a role of GmWNK1 in the regulation of root system architecture. We propose that GmWNK1 functions to fine-tune ABA-dependent ABA homeostasis, thereby mediating the regulation of the root system architecture by ABA and osmotic signals. The study has revealed a new function of a plant WNK1 gene from the important staple crop soybean, and has identified a new component of a regulatory pathway that is involved not only in ABA signaling, but also in the repression of lateral root formation by an ABA-dependent mechanism distinct from known ABA signaling pathways. © 2010 The Authors. Journal compilation © 2010 Blackwell Publishing Ltd.

  19. Strigolactones spatially influence lateral root development through the cytokinin signaling network.

    PubMed

    Jiang, Lingxiang; Matthys, Cedrick; Marquez-Garcia, Belen; De Cuyper, Carolien; Smet, Lien; De Keyser, Annick; Boyer, François-Didier; Beeckman, Tom; Depuydt, Stephen; Goormachtig, Sofie

    2016-01-01

    Strigolactones are important rhizosphere signals that act as phytohormones and have multiple functions, including modulation of lateral root (LR) development. Here, we show that treatment with the strigolactone analog GR24 did not affect LR initiation, but negatively influenced LR priming and emergence, the latter especially near the root-shoot junction. The cytokinin module ARABIDOPSIS HISTIDINE KINASE3 (AHK3)/ARABIDOPSIS RESPONSE REGULATOR1 (ARR1)/ARR12 was found to interact with the GR24-dependent reduction in LR development, because mutants in this pathway rendered LR development insensitive to GR24. Additionally, pharmacological analyses, mutant analyses, and gene expression analyses indicated that the affected polar auxin transport stream in mutants of the AHK3/ARR1/ARR12 module could be the underlying cause. Altogether, the data reveal that the GR24 effect on LR development depends on the hormonal landscape that results from the intimate connection with auxins and cytokinins, two main players in LR development.

  20. Effect of nerve injury on the number of dorsal root ganglion neurons and autotomy behavior in adult Bax-deficient mice

    PubMed Central

    Lyu, Chuang; Lyu, Gong-Wei; Martinez, Aurora; Shi, Tie-Jun Sten

    2017-01-01

    Background The proapoptotic molecule BAX, plays an important role in mitochondrial apoptotic pathway. Dorsal root ganglion (DRG) neurons depend on neurotrophic factors for survival at early developmental stages. Withdrawal of neurotrophic factors will induce apoptosis in DRG neurons, but this type of cell death can be delayed or prevented in neonatal Bax knockout (KO) mice. In adult animals, evidence also shows that DRG neurons are less dependent upon neurotrophic factors for survival. However, little is known about the effect of Bax deletion on the survival of normal and denervated DRG neurons in adult mice. Methods A unilateral sciatic nerve transection was performed in adult Bax KO mice and wild-type (WT) littermates. Stereological method was employed to quantify the number of lumbar-5 DRG neurons 1 month post-surgery. Nerve injury-induced autotomy behavior was also examined on days 1, 3, and 7 post-surgery. Results There were significantly more neurons in contralateral DRGs of KO mice as compared with WT mice. The number of neurons was reduced in ipsilateral DRGs in both KO and WT mice. No changes in size distributions of DRG neuron profiles were detected before or after nerve injury. Injury-induced autotomy behavior developed much earlier and was more serious in KO mice. Conclusion Although postnatal death or loss of DRG neurons is partially prevented by Bax deletion, this effect cannot interfere with long-term nerve injury-induced neuronal loss. The exaggerated self-amputation behavior observed in the mutant mice indicates that Bax deficiency may enhance the development of spontaneous pain following nerve injury. PMID:28919807

  1. Bilateral changes of IL-10 protein in lumbar and cervical dorsal root ganglia following proximal and distal chronic constriction injury of peripheral nerve.

    PubMed

    Jancalek, R; Svizenska, I; Klusakova, I; Dubovy, P

    2011-08-26

    Interleukin-10 prevents transition of a physiological inflammatory reaction to a pathological state that may result in neuropathic pain. We studied bilateral changes of IL-10 protein levels in L4-L5 and C7-C8 dorsal root ganglia (DRG) after a chronic constriction injury (CCI) of either L4-L5 spinal nerves (pCCI) or the sciatic nerve (dCCI). Rats undergoing pCCI or dCCI were left to survive for 1, 3, 7 or 14 d, sham-operated rats for 3 or 14 d. After the survival time, C7-C8 and L4-L5 DRG were removed bilaterally from naïve, operated, and sham-operated rats and IL-10 protein was detected by immunohistochemical staining and measured using ELISA analysis. Unilateral pCCI and dCCI induced a transient bilateral elevation in IL-10 protein level not only in the homonymous lumbar DRG but also in the heteronymous cervical DRG nonassociated with the spinal segments of constricted nerve. Sham operations also induced bilateral elevation of IL-10 protein in both homonymous and heteronymous DRG. Our experiments revealed that the more proximal is a nerve injury the more rapid is the initial increase and slower the subsequent decrease of IL-10 protein level in DRG. Changes of IL-10 protein in DRG nonassociated with damaged nerve could be related to a general neuroinflammatory reaction of the nervous system to injury and thereby promote potential of the DRG neurons for regenerating their axons following a conditioning lesion. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  2. Ethylene's role in phosphate starvation signaling: more than just a root growth regulator.

    PubMed

    Nagarajan, Vinay K; Smith, Aaron P

    2012-02-01

    Phosphate (Pi) is a common limiter of plant growth due to its low availability in most soils. Plants have evolved elaborate mechanisms for sensing Pi deficiency and for initiating adaptive responses to low Pi conditions. Pi signaling pathways are modulated by both local and long-distance, or systemic, sensing mechanisms. Local sensing of low Pi initiates major root developmental changes aimed at enhancing Pi acquisition, whereas systemic sensing governs pathways that modulate expression of numerous genes encoding factors involved in Pi transport and distribution. The gaseous phytohormone ethylene has been shown to play an integral role in regulating local, root developmental responses to Pi deficiency. Comparatively, a role for ethylene in systemic Pi signaling has been more circumstantial. However, recent studies have revealed that ethylene acts to modulate a number of systemically controlled Pi starvation responses. Herein we highlight the findings from these studies and offer a model for how ethylene biosynthesis and responsiveness are integrated into both local and systemic Pi signaling pathways.

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

    PubMed Central

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

    2015-01-01

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

  4. Catechol, a major component of smoke, influences primary root growth and root hair elongation through reactive oxygen species-mediated redox signaling.

    PubMed

    Wang, Ming; Schoettner, Matthias; Xu, Shuqing; Paetz, Christian; Wilde, Julia; Baldwin, Ian T; Groten, Karin

    2017-03-01

    Nicotiana attenuata germinates from long-lived seedbanks in native soils after fires. Although smoke signals have been known to break seed dormancy, whether they also affect seedling establishment and root development remains unclear. In order to test this, seedlings were treated with smoke solutions. Seedlings responded in a dose-dependent manner with significantly increased primary root lengths, due mainly to longitudinal cell elongation, increased numbers of lateral roots and impaired root hair development. Bioassay-driven fractionations and NMR were used to identify catechol as the main active compound for the smoke-induced root phenotype. The transcriptome analysis revealed that mainly genes related to auxin biosynthesis and redox homeostasis were altered after catechol treatment. However, histochemical analyses of reactive oxygen species (ROS) and the inability of auxin applications to rescue the phenotype clearly indicated that highly localized changes in the root's redox-status, rather than in levels of auxin, are the primary effector. Moreover, H2 O2 application rescued the phenotype in a dose-dependent manner. Chemical cues in smoke not only initiate seed germination, but also influence seedling root growth; understanding how these cues work provides new insights into the molecular mechanisms by which plants adapt to post-fire environments.

  5. Root-to-shoot signalling when soil moisture is heterogeneous: increasing the proportion of root biomass in drying soil inhibits leaf growth and increases leaf abscisic acid concentration.

    PubMed

    Martin-Vertedor, Ana Isabel; Dodd, Ian C

    2011-07-01

    To determine whether root-to-shoot signalling of soil moisture heterogeneity depended on root distribution, wild-type (WT) and abscisic acid (ABA)-deficient (Az34) barley (Hordeum vulgare) plants were grown in split pots into which different numbers of seminal roots were inserted. After establishment, all plants received the same irrigation volumes, with one pot watered (w) and the other allowed to dry the soil (d), imposing three treatments (1 d: 3 w, 2 d: 2 w, 3 d: 1 w) that differed in the number of seminal roots exposed to drying soil. Root distribution did not affect leaf water relations and had no sustained effect on plant evapotranspiration (ET). In both genotypes, leaf elongation was less and leaf ABA concentrations were higher in plants with more roots in drying soil, with leaf ABA concentrations and water potentials 30% and 0.2 MPa higher, respectively, in WT plants. Whole-pot soil drying increased xylem ABA concentrations, but maximum values obtained when leaf growth had virtually ceased (100 nm in Az34, 330 nm in WT) had minimal effects (<40% leaf growth inhibition) when xylem supplied to detached shoots. Although ABA may not regulate leaf growth in vivo, genetic variation in foliar ABA concentration in the field may indicate different root distributions between upper (drier) and lower (wetter) soil layers.

  6. Plant Hormone Homeostasis, Signaling, and Function during Adventitious Root Formation in Cuttings

    PubMed Central

    Druege, Uwe; Franken, Philipp; Hajirezaei, Mohammad R.

    2016-01-01

    Adventitious root (AR) formation in cuttings is a multiphase developmental process, resulting from wounding at the cutting site and isolation from the resource and signal network of the whole plant. Though, promotive effects of auxins are widely used for clonal plant propagation, the regulation and function of plant hormones and their intricate signaling networks during AR formation in cuttings are poorly understood. In this focused review, we discuss our recent publications on the involvement of polar auxin transport (PAT) and transcriptional regulation of auxin and ethylene action during AR formation in petunia cuttings in a broad context. Integrating new findings on cuttings of other plant species and general models on plant hormone networks, a model on the regulation and function of auxin, ethylene, and jasmonate in AR formation of cuttings is presented. PAT and cutting off from the basipetal auxin drain are considered as initial principles generating early accumulation of IAA in the rooting zone. This is expected to trigger a self-regulatory process of auxin canalization and maximization to responding target cells, there inducing the program of AR formation. Regulation of auxin homeostasis via auxin influx and efflux carriers, GH3 proteins and peroxidases, of flavonoid metabolism, and of auxin signaling via AUX/IAA proteins, TOPLESS, ARFs, and SAUR-like proteins are postulated as key processes determining the different phases of AR formation. NO and H2O2 mediate auxin signaling via the cGMP and MAPK cascades. Transcription factors of the GRAS-, AP2/ERF-, and WOX-families link auxin signaling to cell fate specification. Cyclin-mediated governing of the cell cycle, modifications of sugar metabolism and microtubule and cell wall remodeling are considered as important implementation processes of auxin function. Induced by the initial wounding and other abiotic stress factors, up-regulation of ethylene biosynthesis, and signaling via ERFs and early accumulation of

  7. Plant Hormone Homeostasis, Signaling, and Function during Adventitious Root Formation in Cuttings.

    PubMed

    Druege, Uwe; Franken, Philipp; Hajirezaei, Mohammad R

    2016-01-01

    Adventitious root (AR) formation in cuttings is a multiphase developmental process, resulting from wounding at the cutting site and isolation from the resource and signal network of the whole plant. Though, promotive effects of auxins are widely used for clonal plant propagation, the regulation and function of plant hormones and their intricate signaling networks during AR formation in cuttings are poorly understood. In this focused review, we discuss our recent publications on the involvement of polar auxin transport (PAT) and transcriptional regulation of auxin and ethylene action during AR formation in petunia cuttings in a broad context. Integrating new findings on cuttings of other plant species and general models on plant hormone networks, a model on the regulation and function of auxin, ethylene, and jasmonate in AR formation of cuttings is presented. PAT and cutting off from the basipetal auxin drain are considered as initial principles generating early accumulation of IAA in the rooting zone. This is expected to trigger a self-regulatory process of auxin canalization and maximization to responding target cells, there inducing the program of AR formation. Regulation of auxin homeostasis via auxin influx and efflux carriers, GH3 proteins and peroxidases, of flavonoid metabolism, and of auxin signaling via AUX/IAA proteins, TOPLESS, ARFs, and SAUR-like proteins are postulated as key processes determining the different phases of AR formation. NO and H2O2 mediate auxin signaling via the cGMP and MAPK cascades. Transcription factors of the GRAS-, AP2/ERF-, and WOX-families link auxin signaling to cell fate specification. Cyclin-mediated governing of the cell cycle, modifications of sugar metabolism and microtubule and cell wall remodeling are considered as important implementation processes of auxin function. Induced by the initial wounding and other abiotic stress factors, up-regulation of ethylene biosynthesis, and signaling via ERFs and early accumulation of

  8. Cycloartane Glycosides from the Roots of Cimicifuga foetida with Wnt Signaling Pathway Inhibitory Activity.

    PubMed

    Zhu, Di-Fan; Zhu, Guo-Lei; Kong, Ling-Mei; Bao, Ni-Man; Zhou, Lin; Nian, Yin; Qiu, Ming-Hua

    2015-04-01

    Four new 9,19-cycloartane triterpenoids, cimilactone E (1), cimilactone F (2), 2'-O-(E)-butenoyl-23-epi-26-deoxyactein (3), and 2',12β-O-diacetylcimiracemonol-3-O-β-d-xylopyranoside (4), together with four known constituents (5-8) were isolated from the roots of Cimicifuga foetida. The new structures were elucidated by extensive spectroscopic analysis. In addition, compounds 7 and 8 showed significant Wnt signaling pathway inhibitory activity, with IC50 values of 3.33 and 13.34 μM, respectively, using the luciferase reporter gene assay.

  9. Verification of nerve decompression using mechanomyography.

    PubMed

    Wessell, Nolan; Khalil, Jad; Zavatsky, Joseph; Ghacham, Wael; Bartol, Stephen

    2016-06-01

    Assessment of nerve root decompression in surgery is largely based on visualization and tactile feedback. Often times, visualization can be limited, such as in minimally invasive surgery, and tactile feedback is a subjective assessment that makes the evaluation of successful nerve decompression difficult. Electromyography (EMG) has been proposed as an assessment tool, but EMG responses are often difficult to quantify. Alternatively, mechanomyography (MMG) provides a quantifiable response with high signal-to-noise ratio compared with EMG. MMG provides a sensitive tool to accurately quantify mechanical responses to motor action potentials generated by electrical stimulus, allowing more reliable assessment of nerve decompression. The aim of this study was to assess the ability of MMG to quantitatively demonstrate successful nerve root decompression. Prospective cohort, Therapeutic Level III, Urban Level I Trauma Center. A total of 46 patients (72 affected nerve roots) undergoing decompression procedures for lower extremity radiculopathy caused by nerve root compression were enrolled in the study. The study population included 15 patients with herniated nucleus pulposus (HNP) and 31 with lateral recess stenosis (LRS). Visual analog scale (VAS) score. A total of 72 nerves roots in 46 patients undergoing lumbar decompression procedures, for lower extremity radicular symptoms, were tested using MMG. Nerves were stimulated upstream from the compression site, and the lowest threshold current needed to generate a muscle response was determined. Signal response sizes were recorded before and after decompression. VAS scores were collected pre- and postoperatively. Of the patients, 90% (65/72) had elevated stimulation thresholds (>1 milliamp [mA]) before decompression. After decompression, 98% of patients (64/65) with elevated current thresholds exhibited a drop in threshold of ≥1 mA (p<.001). A postdecompression increase in response amplitude was recorded in all patients

  10. New insights into the signaling pathways controlling defense gene expression in rice roots during the arbuscular mycorrhizal symbiosis.

    PubMed

    Campos-Soriano, Lidia; Segundo, Blanca San

    2011-04-01

    Mycorrhizal fungi form a mutualistic relationship with the roots of most plant species. This association provides the arbuscular mycorrhizal (AM) fungus with sugars while the fungus improves the uptake of water and mineral nutrients in the host plant. Moreover, the induction of defence gene expression in mycorrhizal roots has been described. While salicylic acid (SA)-regulated Pathogenesis-Related (PR) proteins accumulate in rice roots colonized by the AM fungus G. intraradices, the SA content is not significantly altered in the mycorrhizal roots. Sugars, in addition to being a source of carbon for the fungus, might act as signals for the control of defence gene expression. We hypothesize that increased demands for sugars by the fungus might be responsible for the activation of the host defence responses which will then contribute to the stabilization of root colonization by the AM fungus. An excessive root colonization might change a mutualistic association into a parasitic association.

  11. A CLE-WOX signalling module regulates root meristem maintenance and vascular tissue development in rice.

    PubMed

    Chu, Huangwei; Liang, Wanqi; Li, Juan; Hong, Fan; Wu, Yunfei; Wang, Likai; Wang, Juan; Wu, Ping; Liu, Chunming; Zhang, Qifa; Xu, Jian; Zhang, Dabing

    2013-12-01

    CLAVATA3 (CLV3)/ENDOSPERM SURROUNDING REGION (ESR)-related (CLE) proteins belong to a small peptide family conserved in plants. Recent studies in Arabidopsis and rice have revealed a key role for CLEs in mediating cell-cell communication and stem cell maintenance during plant development, but how CLE signalling controls root development in the rice remains largely unknown. Here it is shown that exogenous application of a synthetic dodeca-amino acid peptide corresponding to the CLE motif of the rice FON2-LIKE CLE PROTEIN2 (FCP2p) protein or overexpression of FCP2 terminates root apical meristem (RAM) activity and impairs late metaxylem formation. FCP2p treatment suppresses the expression of the rice QUIESCENT-CENTER-SPECIFIC HOMEOBOX (QHB) gene, a putative orthologue of Arabidopsis WUSCHEL (WUS)-RELATED HOMEOBOX 5 (WOX5) gene, in both quiescent centre and late metaxylem cells; whereas inducible overexpression of QHB reduces the sensitivity of rice to FCP2p treatment. These results together suggest that in rice RAM maintenance and late metaxylem development are probably controlled by the mutual regulation between FCP2 and QHB. Moreover, a cross-species peptide treatment experiment in Arabidopsis implies that FCP2 has both evolutionarily conserved and species-specific roles in root development.

  12. Strigolactones, host recognition signals for root parasitic plants and arbuscular mycorrhizal fungi, from Fabaceae plants.

    PubMed

    Yoneyama, Kaori; Xie, Xiaonan; Sekimoto, Hitoshi; Takeuchi, Yasutomo; Ogasawara, Shin; Akiyama, Kohki; Hayashi, Hideo; Yoneyama, Koichi

    2008-07-01

    Both root parasitic plants and arbuscular mycorrhizal (AM) fungi take advantage of strigolactones, released from plant roots as signal molecules in the initial communication with host plants, in order to commence parasitism and mutualism, respectively. In this study, strigolactones in root exudates from 12 Fabaceae plants, including hydroponically grown white lupin (Lupinus albus), a nonhost of AM fungi, were characterized by comparing retention times of germination stimulants on reverse-phase high-performance liquid chromatography (HPLC) with those of standards and by using tandem mass spectrometry (LC/MS/MS). All the plant species examined were found to exude known strigolactones, such as orobanchol, orobanchyl acetate, and 5-deoxystrigol, suggesting that these strigolactones are widely distributed in the Fabaceae. It should be noted that even the nonmycotrophic L. albus exuded orobanchol, orobanchyl acetate, 5-deoxystrigol, and novel germination stimulants. By contrast to the mycotrophic Fabaceae plant Trifolium pratense, in which phosphorus deficiency promoted strigolactone exudation, neither phosphorus nor nitrogen deficiency increased exudation of these strigolactones in L. albus. Therefore, the regulation of strigolactone production and/or exudation seems to be closely related to the nutrient acquisition strategy of the plants.

  13. Receptor kinase complex transmits RALF peptide signal to inhibit root growth in Arabidopsis

    PubMed Central

    Du, Changqing; Li, Xiushan; Chen, Jia; Chen, Weijun; Li, Bin; Li, Chiyu; Wang, Long; Li, Jianglin; Zhao, Xiaoying; Lin, Jianzhong; Liu, Xuanming; Luan, Sheng; Yu, Feng

    2016-01-01

    A number of hormones work together to control plant cell growth. Rapid Alkalinization Factor 1 (RALF1), a plant-derived small regulatory peptide, inhibits cell elongation through suppression of rhizosphere acidification in plants. Although a receptor-like kinase, FERONIA (FER), has been shown to act as a receptor for RALF1, the signaling mechanism remains unknown. In this study, we identified a receptor-like cytoplasmic kinase (RPM1-induced protein kinase, RIPK), a plasma membrane-associated member of the RLCK-VII subfamily, that is recruited to the receptor complex through interacting with FER in response to RALF1. RALF1 triggers the phosphorylation of both FER and RIPK in a mutually dependent manner. Genetic analysis of the fer-4 and ripk mutants reveals RIPK, as well as FER, to be required for RALF1 response in roots. The RALF1–FER–RIPK interactions may thus represent a mechanism for peptide signaling in plants. PMID:27930296

  14. New insights into the signal transmission from taste cells to gustatory nerve fibers.

    PubMed

    Yoshida, Ryusuke; Ninomiya, Yuzo

    2010-01-01

    Taste receptor cells detect chemical compounds in the oral cavity and transfer their messages to gustatory afferent nerve fibers. Considering the coding of taste information, the sensitivity of taste cells and the connection between taste cells and gustatory fibers may be critical in this process. Broadly tuned taste cells and random connections between taste cells and fibers would produce gustatory fibers that have broad sensitivity to multiple taste qualities. Narrowly tuned taste cells and selective connections would yield gustatory nerve fibers that respond to specific taste quality. This review summarizes results showing molecular and morphological aspects of taste bud cells, physiological responses of taste cells, possible connections between taste cells and gustatory fibers, and transmitter release from taste cells, and discusses how taste qualities are encoded among taste bud cells and how taste information is transmitted from taste cells to gustatory nerve fibers. Copyright 2010 Elsevier Inc. All rights reserved.

  15. GENETIC MODIFICATION OF GIBBERELLIC ACID SIGNALING TO PROMOTE CARBON SEQUESTRATION IN TREE ROOTS AND STEMS

    SciTech Connect

    Busov, Victor

    2013-03-05

    Semidwarfism has been used extensively in row crops and horticulture to promote yield, reduce lodging, and improve harvest index, and it might have similar benefits for trees for short-rotation forestry or energy plantations, reclamation, phytoremediation, or other applications. We studied the effects of the dominant semidwarfism transgenes GA Insensitive (GAI) and Repressor of GAI-Like, which affect gibberellin (GA) action, and the GA catabolic gene, GA 2-oxidase, in nursery beds and in 2-year-old high-density stands of hybrid poplar (Populus tremula - Populus alba). Twenty-nine traits were analyzed, including measures of growth, morphology, and physiology. Endogenous GA levels were modified in most transgenic events; GA(20) and GA(8), in particular, had strong inverse associations with tree height. Nearly all measured traits varied significantly among genotypes, and several traits interacted with planting density, including aboveground biomass, root-shoot ratio, root fraction, branch angle, and crown depth. Semidwarfism promoted biomass allocation to roots over shoots and substantially increased rooting efficiency with most genes tested. The increased root proportion and increased leaf chlorophyll levels were associated with changes in leaf carbon isotope discrimination, indicating altered water use efficiency. Semidwarf trees had dramatically reduced growth when in direct competition with wild-type trees, supporting the hypothesis that semidwarfism genes could be effective tools to mitigate the spread of exotic, hybrid, and transgenic plants in wild and feral populations. We modified gibberellin (GA) metabolism and signaling in transgenic poplars using dominant transgenes and studied their effects for 3 years under field conditions. The transgenes that we employed either reduced the bioactive GAs, or attenuated their signaling. The majority of transgenic trees had significant and in many cases dramatic changes in height, crown architecture, foliage morphology

  16. The Role of 5-HT3 Receptors in Signaling from Taste Buds to Nerves.

    PubMed

    Larson, Eric D; Vandenbeuch, Aurelie; Voigt, Anja; Meyerhof, Wolfgang; Kinnamon, Sue C; Finger, Thomas E

    2015-12-02

    Activation of taste buds triggers the release of several neurotransmitters, including ATP and serotonin (5-hydroxytryptamine; 5-HT). Type III taste cells release 5-HT directly in response to acidic (sour) stimuli and indirectly in response to bitter and sweet tasting stimuli. Although ATP is necessary for activation of nerve fibers for all taste stimuli, the role of 5-HT is unclear. We investigated whether gustatory afferents express functional 5-HT3 receptors and, if so, whether these receptors play a role in transmission of taste information from taste buds to nerves. In mice expressing GFP under the control of the 5-HT(3A) promoter, a subset of cells in the geniculate ganglion and nerve fibers in taste buds are GFP-positive. RT-PCR and in situ hybridization confirmed the presence of 5-HT(3A) mRNA in the geniculate ganglion. Functional studies show that only those geniculate ganglion cells expressing 5-HT3A-driven GFP respond to 10 μM 5-HT and this response is blocked by 1 μM ondansetron, a 5-HT3 antagonist, and mimicked by application of 10 μM m-chlorophenylbiguanide, a 5-HT3 agonist. Pharmacological blockade of 5-HT3 receptors in vivo or genetic deletion of the 5-HT3 receptors reduces taste nerve responses to acids and other taste stimuli compared with controls, but only when urethane was used as the anesthetic. We find that anesthetic levels of pentobarbital reduce taste nerve responses apparently by blocking the 5-HT3 receptors. Our results suggest that 5-HT released from type III cells activates gustatory nerve fibers via 5-HT3 receptors, accounting for a significant proportion of the neural taste response.

  17. Auxin and the integration of environmental signals into plant root development.

    PubMed

    Kazan, Kemal

    2013-12-01

    Auxin is a versatile plant hormone with important roles in many essential physiological processes. In recent years, significant progress has been made towards understanding the roles of this hormone in plant growth and development. Recent evidence also points to a less well-known but equally important role for auxin as a mediator of environmental adaptation in plants. This review briefly discusses recent findings on how plants utilize auxin signalling and transport to modify their root system architecture when responding to diverse biotic and abiotic rhizosphere signals, including macro- and micro-nutrient starvation, cold and water stress, soil acidity, pathogenic and beneficial microbes, nematodes and neighbouring plants. Stress-responsive transcription factors and microRNAs that modulate auxin- and environment-mediated root development are also briefly highlighted. The auxin pathway constitutes an essential component of the plant's biotic and abiotic stress tolerance mechanisms. Further understanding of the specific roles that auxin plays in environmental adaptation can ultimately lead to the development of crops better adapted to stressful environments.

  18. Auxin and the integration of environmental signals into plant root development

    PubMed Central

    Kazan, Kemal

    2013-01-01

    Background Auxin is a versatile plant hormone with important roles in many essential physiological processes. In recent years, significant progress has been made towards understanding the roles of this hormone in plant growth and development. Recent evidence also points to a less well-known but equally important role for auxin as a mediator of environmental adaptation in plants. Scope This review briefly discusses recent findings on how plants utilize auxin signalling and transport to modify their root system architecture when responding to diverse biotic and abiotic rhizosphere signals, including macro- and micro-nutrient starvation, cold and water stress, soil acidity, pathogenic and beneficial microbes, nematodes and neighbouring plants. Stress-responsive transcription factors and microRNAs that modulate auxin- and environment-mediated root development are also briefly highlighted. Conclusions The auxin pathway constitutes an essential component of the plant's biotic and abiotic stress tolerance mechanisms. Further understanding of the specific roles that auxin plays in environmental adaptation can ultimately lead to the development of crops better adapted to stressful environments. PMID:24136877

  19. Nerve Growth Factor Receptor TrkA, a New Receptor in Insulin Signaling Pathway in PC12 Cells*

    PubMed Central

    Geetha, Thangiah; Rege, Shraddha D.; Mathews, Salome E.; Meakin, Susan O.; White, Morris F.; Babu, Jeganathan Ramesh

    2013-01-01

    TrkA is a cell surface transmembrane receptor tyrosine kinase for nerve growth factor (NGF). TrkA has an NPXY motif and kinase regulatory loop similar to insulin receptor (INSR) suggesting that NGF→TrkA signaling might overlap with insulin→INSR signaling. During insulin or NGF stimulation TrkA, insulin receptor substrate-1 (IRS-1), INSR (and presumably other proteins) forms a complex in PC12 cells. In PC12 cells, tyrosine phosphorylation of INSR and IRS-1 is dependent upon the functional TrkA kinase domain. Moreover, expression of TrkA kinase-inactive mutant blocked the activation of Akt and Erk5 in response to insulin or NGF. Based on these data, we propose that TrkA participates in insulin signaling pathway in PC12 cells. PMID:23749991

  20. Nerve growth factor receptor TrkA, a new receptor in insulin signaling pathway in PC12 cells.

    PubMed

    Geetha, Thangiah; Rege, Shraddha D; Mathews, Salome E; Meakin, Susan O; White, Morris F; Babu, Jeganathan Ramesh

    2013-08-16

    TrkA is a cell surface transmembrane receptor tyrosine kinase for nerve growth factor (NGF). TrkA has an NPXY motif and kinase regulatory loop similar to insulin receptor (INSR) suggesting that NGF→TrkA signaling might overlap with insulin→INSR signaling. During insulin or NGF stimulation TrkA, insulin receptor substrate-1 (IRS-1), INSR (and presumably other proteins) forms a complex in PC12 cells. In PC12 cells, tyrosine phosphorylation of INSR and IRS-1 is dependent upon the functional TrkA kinase domain. Moreover, expression of TrkA kinase-inactive mutant blocked the activation of Akt and Erk5 in response to insulin or NGF. Based on these data, we propose that TrkA participates in insulin signaling pathway in PC12 cells.

  1. The promoting effects of alginate oligosaccharides on root development in Oryza sativa L. mediated by auxin signaling.

    PubMed

    Zhang, Yunhong; Yin, Heng; Zhao, Xiaoming; Wang, Wenxia; Du, Yuguang; He, Ailing; Sun, Kegang

    2014-11-26

    Alginate oligosaccharides (AOS), which are marine oligosaccharides, are involved in regulating plant root growth, but the promotion mechanism for AOS remains unclear. Here, AOS (10-80 mg/L) induced the expression of auxin-related gene (OsYUCCA1, OsYUCCA5, OsIAA11 and OsPIN1) in rice (Oryza sativa L.) tissues to accelerate auxin biosynthesis and transport, and reduced indole-3-acetic acid (IAA) oxidase activity in rice roots. These changes resulted in the increase of 37.8% in IAA concentration in rice roots, thereby inducing the expression of root development-related genes, promoting root growth in a dose-dependent manner, which were inhibited by auxin transport inhibitor 2,3,5-triiodo benzoic acid (TIBA) and calcium-chelating agent ethylene glycol bis (2-aminoethyl) tetraacetic acid (EGTA). AOS also induced calcium signaling generation in rice roots. Those results indicated that auxin mediated AOS regulation of root development, and calcium signaling may act mainly in the upstream of auxin in the regulation of AOS on rice root development.

  2. N,N-dimethyl hexadecylamine and related amines regulate root morphogenesis via jasmonic acid signaling in Arabidopsis thaliana.

    PubMed

    Raya-González, Javier; Velázquez-Becerra, Crisanto; Barrera-Ortiz, Salvador; López-Bucio, José; Valencia-Cantero, Eduardo

    2017-05-01

    Plant growth-promoting rhizobacteria are natural inhabitants of roots, colonize diverse monocot and dicot species, and affect several functional traits such as root architecture, adaptation to adverse environments, and protect plants from pathogens. N,N-dimethyl-hexadecylamine (C16-DMA) is a rhizobacterial amino lipid that modulates the postembryonic development of several plants, likely as part of volatile blends. In this work, we evaluated the bioactivity of C16-DMA and other related N,N-dimethyl-amines with varied length and found that inhibition of primary root growth was related to the length of the acyl chain. C16-DMA inhibited primary root growth affecting cell division and elongation, while promoting lateral root formation and root hair growth and density in Arabidopsis thaliana (Arabidopsis) wild-type (WT) seedlings. Interestingly, C16-DMA induced the expression of the jasmonic acid (JA)-responsive gene marker pLOX2:uidA, while JA-related mutants jar1, coi1-1, and myc2 affected on JA biosynthesis and perception, respectively, are compromised in C16-DMA responses. Comparison of auxin-regulated gene expression, root architectural changes in WT, and auxin-related mutants aux1-7, tir1/afb2/afb3, and arf7-1/arf19-1 to C16-DMA shows that the C16-DMA effects occur independently of auxin signaling. Together, these results reveal a novel class of aminolipids modulating root organogenesis via crosstalk with the JA signaling pathway.

  3. Salt stress reduces root meristem size by nitric oxide-mediated modulation of auxin accumulation and signaling in Arabidopsis.

    PubMed

    Liu, Wen; Li, Rong-Jun; Han, Tong-Tong; Cai, Wei; Fu, Zheng-Wei; Lu, Ying-Tang

    2015-05-01

    The development of the plant root system is highly plastic, which allows the plant to adapt to various environmental stresses. Salt stress inhibits root elongation by reducing the size of the root meristem. However, the mechanism underlying this process remains unclear. In this study, we explored whether and how auxin and nitric oxide (NO) are involved in salt-mediated inhibition of root meristem growth in Arabidopsis (Arabidopsis thaliana) using physiological, pharmacological, and genetic approaches. We found that salt stress significantly reduced root meristem size by down-regulating the expression of PINFORMED (PIN) genes, thereby reducing auxin levels. In addition, salt stress promoted AUXIN RESISTANT3 (AXR3)/INDOLE-3-ACETIC ACID17 (IAA17) stabilization, which repressed auxin signaling during this process. Furthermore, salt stress stimulated NO accumulation, whereas blocking NO production with the inhibitor N(ω)-nitro-l-arginine-methylester compromised the salt-mediated reduction of root meristem size, PIN down-regulation, and stabilization of AXR3/IAA17, indicating that NO is involved in salt-mediated inhibition of root meristem growth. Taken together, these findings suggest that salt stress inhibits root meristem growth by repressing PIN expression (thereby reducing auxin levels) and stabilizing IAA17 (thereby repressing auxin signaling) via increasing NO levels. © 2015 American Society of Plant Biologists. All Rights Reserved.

  4. Serotonin modulates Arabidopsis root growth via changes in reactive oxygen species and jasmonic acid-ethylene signaling.

    PubMed

    Pelagio-Flores, Ramón; Ruiz-Herrera, León Francisco; López-Bucio, José

    2016-09-01

    Serotonin (5-hydroxytryptamine) is a bioactive indoleamine with neurotransmitter function in vertebrates, which represents an emerging signaling molecule in plants, playing key roles in the development and defense. In this study, the role of reactive oxygen species (ROS) and jasmonic acid (JA)-ethylene (Et) signaling in root developmental alterations induced by serotonin was investigated. An Arabidopsis thaliana mutant defective at the RADICAL-INDUCED CELL DEATH1 (RCD1) locus was resistant to paraquat-induced ROS accumulation in primary roots and showed decreased inhibition or root growth in response to serotonin. A suite of JA- and Et-related mutants including coronatine insensitive1, jasmonic acid resistant1 (jar1), etr1, ein2 and ein3 showed tolerance to serotonin in the inhibition of primary root growth and ROS redistribution within the root tip when compared with wild-type (WT) seedlings. Competence assays between serotonin and AgNO3 , a well-known blocker of Et action, showed that primary root growth in medium supplemented with serotonin was normalized by AgNO3 , whereas roots of eto3, an Et overproducer mutant, were oversensitive to serotonin. Comparison of ROS levels in WT, etr1, jar1 and rcd1 primary root tips using the ROS-specific probe 2',7'-dichlorofluorescein diacetate and confocal imaging showed that serotonin inhibition of primary root growth likely occurs independently of its conversion into melatonin. Our results provide compelling evidence that serotonin affects ROS distribution in roots, involving RCD1 and components of the JA-Et signaling pathways. © 2016 Scandinavian Plant Physiology Society.

  5. Pressure changes under the ischial tuberosities during gluteal neuromuscular stimulation in spinal cord injury: a comparison of sacral nerve root stimulation with surface functional electrical stimulation.

    PubMed

    Liu, Liang Qin; Ferguson-Pell, Martin

    2015-04-01

    To compare the magnitude of interface pressure changes during gluteal maximus contraction by stimulating sacral nerve roots with surface electrical stimulations in patients with spinal cord injuries (SCIs). Pilot interventional study. Spinal injury research laboratory. Adults (N=18) with suprasacral complete SCI. Sacral nerve root stimulation (SNRS) via a functional magnetic stimulator (FMS) or a sacral anterior root stimulator (SARS) implant; and surface functional electrical stimulation (FES). Interface pressure under the ischial tuberosity (IT) defined as peak pressure, gradient at peak pressure, and average pressure. With optimal FMS, a 29% average reduction of IT peak pressure was achieved during FMS (mean ± SD: 160.1±24.3mmHg at rest vs 114.7±18.0mmHg during FMS, t5=6.3, P=.002). A 30% average reduction of peak pressure during stimulation via an SARS implant (143.2±31.7mmHg at rest vs 98.5±21.5mmHg during SARS, t5=4.4, P=.007) and a 22% average decrease of IT peak pressure during FES stimulation (153.7±34.8mmHg at rest vs 120.5±26.1mmHg during FES, t5=5.3, P=.003) were obtained. In 4 participants who completed both the FMS and FES studies, the percentage of peak pressure reduction with FMS was slightly greater than with FES (mean difference, 7.8%; 95% confidence interval, 1.6%-14.0; P=.04). SNRS or surface FES can induce sufficient gluteus maximus contraction and significantly reduce ischial pressure. SNRS via an SARS implant may be more convenient and efficient for frequently activating the gluteus maximus. Copyright © 2015 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

  6. Uranium perturbs signaling and iron uptake response in Arabidopsis thaliana roots.

    PubMed

    Doustaly, Fany; Combes, Florence; Fiévet, Julie B; Berthet, Serge; Hugouvieux, Véronique; Bastien, Olivier; Aranjuelo, Iker; Leonhardt, Nathalie; Rivasseau, Corinne; Carrière, Marie; Vavasseur, Alain; Renou, Jean-Pierre; Vandenbrouck, Yves; Bourguignon, Jacques

    2014-04-01

    Uranium is a natural element which is mainly redistributed in the environment due to human activity, including accidents and spillages. Plants may be useful in cleaning up after incidents, although little is yet known about the relationship between metal speciation and plant response. Here, J-Chess modeling was used to predict U speciation and exposure conditions affecting U bioavailability for plants. The model was confirmed by exposing Arabidopsis thaliana plants to U under hydroponic conditions. The early root response was characterized using complete Arabidopsis transcriptome microarrays (CATMA). Expression of 111 genes was modified at the three timepoints studied. The associated biological processes were further examined by real-time quantitative RT-PCR. Annotation revealed that oxidative stress, cell wall and hormone biosynthesis, and signaling pathways (including phosphate signaling) were affected by U exposure. The main actors in iron uptake and signaling (IRT1, FRO2, AHA2, AHA7 and FIT1) were strongly down-regulated upon exposure to uranyl. A network calculated using IRT1, FRO2 and FIT1 as bait revealed a set of genes whose expression levels change under U stress. Hypotheses are presented to explain how U perturbs the iron uptake and signaling response. These results give preliminary insights into the pathways affected by uranyl uptake, which will be of interest for engineering plants to help clean areas contaminated with U.

  7. The CLE40 and CRN/CLV2 signaling pathways antagonistically control root meristem growth in Arabidopsis.

    PubMed

    Pallakies, Helge; Simon, Rüdiger

    2014-11-01

    Differentiation processes in the primary root meristem are controlled by several signaling pathways that are regulated by phytohormones or by secreted peptides. Long-term maintenance of an active root meristem requires that the generation of new stem cells and the loss of these from the meristem due to differentiation are precisely coordinated. Via phenotypic and large-scale transcriptome analyses of mutants, we show that the signaling peptide CLE40 and the receptor proteins CLV2 and CRN act in two genetically separable pathways that antagonistically regulate cell differentiation in the proximal root meristem. CLE40 inhibits cell differentiation throughout the primary root meristem by controlling genes with roles in abscisic acid, auxin, and cytokinin signaling. CRN and CLV2 jointly control target genes that promote cell differentiation specifically in the transition zone of the proximal root meristem. While CRN and CLV2 are not acting in the CLE40 signaling pathway under normal growth conditions, both proteins are required when the levels of CLE40 or related CLE peptides increase. We show here that two antagonistically acting pathways controlling root meristem differentiation can be activated by the same peptide in a dosage-dependent manner. © The Author 2014. Published by the Molecular Plant Shanghai Editorial Office in association with Oxford University Press on behalf of CSPB and IPPE, SIBS, CAS.

  8. Activation of the insulin-signaling pathway in sciatic nerve and hippocampus of type 1 diabetic rats

    PubMed Central

    King, MR.; Anderson, NJ.; Liu, C.; Law, E.; Cundiff, M.; Mixcoatl-Zecuatl, TM.; Jolivalt, CG

    2015-01-01

    Peripheral neuropathy is a major complication associated with diabetes and central neuropathy characterized by Alzheimer’s disease-like features in the brain is associated with increased dementia risk for patients with diabetes. Although glucose uptake into the cells of the nervous system is insulin-independent, contribution of impaired insulin support is clearly recognized to play a role, however not yet fully understood, in the development of neuropathy. In this study, we assessed the direct role of insulin on the PNS and CNS of insulin-dependent type 1 diabetic rats. Fresh sciatic nerve and hippocampus from control and diabetic rats were incubated with varied ex vivo concentrations of insulin and phosphorylation levels of insulin receptor and GSK3β were assessed by Western blot analysis. Both sciatic nerve and hippocampus from type 1 diabetic rats were highly responsive to exogenous insulin with a significantly increased phosphorylation of insulin receptor and GSK3 compared to tissues from control rats. Further, sustained in vivo insulin delivery, not sufficient to restore normal blood glucose, normalized the activation of both insulin receptor and GSK3 in both PNS and CNS tissues. These results suggest that the insulin-signaling pathway is responsive to exogenous insulin in the nervous system of insulin-deficient type 1 diabetic rats and that constant insulin delivery restore normal nerve function and may protect peripheral and central nervous system from damage. PMID:26149351

  9. Variation in optical coherence tomography signal quality as an indicator of retinal nerve fibre layer segmentation error.

    PubMed

    Folio, Lindsey S; Wollstein, Gadi; Ishikawa, Hiroshi; Bilonick, Richard A; Ling, Yun; Kagemann, Larry; Noecker, Robert J; Fujimoto, James G; Schuman, Joel S

    2012-04-01

    Commercial optical coherence tomography (OCT) systems use global signal quality indices to quantify scan quality. Signal quality can vary throughout a scan, contributing to local retinal nerve fibre layer segmentation errors (SegE). The purpose of this study was to develop an automated method, using local scan quality, to predict SegE. Good-quality (global signal strength (SS) ≥ 6; manufacturer specification) peripapillary circular OCT scans (fast retinal nerve fibre layer scan protocol; Stratus OCT; Carl Zeiss Meditec, Dublin, California, USA) were obtained from 6 healthy, 19 glaucoma-suspect and 43 glaucoma subjects. Scans were grouped based on SegE. Quality index (QI) values were computed for each A-scan using software of our own design. Logistic mixed-effects regression modelling was applied to evaluate SS, global mean and SD of QI, and the probability of SegE. The difference between local mean QI in SegE regions and No-SegE regions was -5.06 (95% CI -6.38 to 3.734) (p<0.001). Using global mean QI, QI SD and their interaction term resulted in the model of best fit (Akaike information criterion=191.8) for predicting SegE. Global mean QI ≥ 20 or SS ≥ 8 shows little chance for SegE. Once mean QI<20 or SS<8, the probability of SegE increases as QI SD increases. When combined with a signal quality parameter, the variation of signal quality between A-scans provides significant information about the quality of an OCT scan and can be used as a predictor of segmentation error.

  10. Does the presence of the nerve root sedimentation sign on MRI correlate with the operative level in patients undergoing posterior lumbar decompression for lumbar stenosis?

    PubMed

    Fazal, Akil; Yoo, Andrew; Bendo, John A

    2013-08-01

    Recent research describes the use of a nerve root sedimentation sign to diagnose lumbar spinal stenosis (LSS). The lack of sedimentation of the nerve roots (positive sedimentation sign) to the dorsal part of the dural sac is the characteristic feature of this new radiological parameter. To demonstrate how the nerve root sedimentation sign compares with other more traditional radiological parameters in patients who have been operated for LSS. A retrospective chart and image review. Preoperative magnetic resonance images (MRIs) were reviewed from 71 consecutive operative patients who presented with LSS and received spinal decompression surgery from 2006 to 2010. Preoperative T2-weighted MRIs were reviewed for each patient. One hundred thirty-four vertebral levels from L1 to L5 were measured for: sedimentation sign, cross-sectional area (CSA) and anterior/posterior (A/P) diameter of the dural sac, thickness of the ligamentum flavum, and Fujiwara grade of facet hypertrophy. Radiological measurements were made using Surgimap 1.1.2.169 software (Nemaris, Inc., New York, NY, USA). Statistical analyses were performed using the SPSS 17.0 statistical software (SPSS Inc., Chicago, IL, USA). Significance was demonstrated using unpaired t tests and chi-squared tests. Study funding was departmental. There were no study-specific conflicts of interest-associated biases. A positive sedimentation sign was determined in 120 operated levels (89.5%), whereas 14 levels (10.5%) had no sign (negative sedimentation sign). The mean CSA and A/P diameter were 140.62 mm(2) (standard deviation [SD]=53) and 11.76 mm (SD=3), respectively, for the no-sign group; the mean CSA and A/P diameter were 81.87 mm(2) (SD=35) and 8.76 mm (SD=2.2), respectively, for the sedimentation sign group (p<.001). We found that 60% of levels with Fujiwara Grade A facet hypertrophy did not have a sedimentation sign, whereas 86.3% of levels with Grade B, 93.2% of levels with Grade C, and 100.0% of levels with Grade D

  11. Novel features of radiation-induced bystander signaling in Arabidopsis thaliana demonstrated using root micro-grafting

    PubMed Central

    Wang, Ting; Li, Fanghua; Xu, Wei; Bian, Po; Wu, Yuejin; Wu, Lijun

    2012-01-01

    Radiation-induced bystander effects (RIBE) have been well demonstrated in whole organisms, as well as in single-cell culture models in vitro and multi-cellular tissues models in vitro, however, the underlying mechanisms remain unclear, including the temporal and spatial course of bystander signaling. The RIBE in vivo has been shown to exist in the model plant Arabidopsis thaliana (A. thaliana). Importantly, the unique plant grafting provides a delicate approach for studying the temporal and spatial course of bystander signaling in the context of whole plants. In our previous study, the time course of bystander signaling in plants has been well demonstrated using the root micro-grafting technique. In this study, we further investigated the temporal cooperation pattern of multiple bystander signals, the directionality of bystander signaling, and the effect of bystander tissues on the bystander signaling. The results showed that the bystander response could also be induced efficiently when the asynchronously generated bystander signals reached the bystander tissues in the same period, but not when they entered into the bystander tissues in an inversed sequence. The absence of bystander response in root-inversed grafting indicated that the bystander signaling along roots might be of directionality. The bystander signaling was shown to be independent of the bystander tissues. PMID:23072991

  12. Nerve injury-induced changes in Homer/glutamate receptor signaling contribute to the development and maintenance of neuropathic pain.

    PubMed

    Obara, Ilona; Goulding, Scott P; Hu, Jia-Hua; Klugmann, Matthias; Worley, Paul F; Szumlinski, Karen K

    2013-10-01

    While group 1 metabotropic glutamate receptors (mGluRs) and ionotropic N-methyl-d-aspartate (NMDA) receptors regulate nociception, the precise molecular mechanism(s) contributing to glutamate signaling in chronic pain remain unclear. Here we not only confirmed the key involvement of Homer proteins in neuropathic pain, but also distinguished between the functional roles for different Homer family members and isoforms. Chronic constriction injury (CCI) of the sciatic nerve induced long-lasting, time-dependent increases in the postsynaptic density expression of the constitutively expressed (CC) isoforms Homer1b/c and/or Homer2a/b in the spinal dorsal horn and supraspinal structures involved in nociception (prefrontal cortex, thalamus), that co-occurred with increases in their associated mGluRs, NR2 subunits of the NMDA receptor, and the activation of downstream kinases. Virus-mediated overexpression of Homer1c and Homer2b after spinal (intrathecal) virus injection exacerbated CCI-induced mechanical and cold hypersensitivity, however, Homer1 and Homer2 gene knockout (KO) mice displayed no changes in their neuropathic phenotype. In contrast, overexpression of the immediate early gene (IEG) Homer1a isoform reduced, while KO of Homer1a gene potentiated neuropathic pain hypersensitivity. Thus, nerve injury-induced increases in CC-Homers expression promote pain in pathological states, but IEG-Homer induction protects against both the development and maintenance of neuropathy. Additionally, exacerbated pain hypersensitivity in transgenic mice with reduced Homer binding to mGluR5 supports also an inhibitory role for Homer interactions with mGluR5 in mediating neuropathy. Such data indicate that nerve injury-induced changes in glutamate receptor/Homer signaling contribute in dynamic but distinct ways to neuropathic pain processing, which has relevance for the etiology of chronic pain symptoms and its treatment.

  13. Studies on conversion of motor function in intercostal nerves crossing for complete brachial plexus injuries of root avulsion type.

    PubMed

    Takahashi, M

    1983-11-01

    The progress of the functional conversion in cases where the 3rd and 4th intercostal nerves were crossed to the musculocutaneous nerve to regain elbow flexion after a total avulsion type of brachial plexus injury was followed up by means of the electromyogram, goniogram and spirogram in 25 patients. The joint position sense was further studied. It was found that in the early stage of reinnervation, spontaneous activity which synchronized with respiration was found in the biceps brachii muscles, but this involuntary element disappeared gradually and followed this the volitional control and endurance improved and became quite satisfactory within several years. It was observed that skin sensation played an important role in judging joint position.

  14. Cytosolic Ca(2+) Signals Enhance the Vacuolar Ion Conductivity of Bulging Arabidopsis Root Hair Cells.

    PubMed

    Wang, Yi; Dindas, Julian; Rienmüller, Florian; Krebs, Melanie; Waadt, Rainer; Schumacher, Karin; Wu, Wei-Hua; Hedrich, Rainer; Roelfsema, M Rob G

    2015-11-02

    Plant cell expansion depends on the uptake of solutes across the plasma membrane and their storage within the vacuole. In contrast to the well-studied plasma membrane, little is known about the regulation of ion transport at the vacuolar membrane. We therefore established an experimental approach to study vacuolar ion transport in intact Arabidopsis root cells, with multi-barreled microelectrodes. The subcellular position of electrodes was detected by imaging current-injected fluorescent dyes. Comparison of measurements with electrodes in the cytosol and vacuole revealed an average vacuolar membrane potential of -31 mV. Voltage clamp recordings of single vacuoles resolved the activity of voltage-independent and slowly deactivating channels. In bulging root hairs that express the Ca(2+) sensor R-GECO1, rapid elevation of the cytosolic Ca(2+) concentration was observed, after impalement with microelectrodes, or injection of the Ca(2+) chelator BAPTA. Elevation of the cytosolic Ca(2+) level stimulated the activity of voltage-independent channels in the vacuolar membrane. Likewise, the vacuolar ion conductance was enhanced during a sudden increase of the cytosolic Ca(2+) level in cells injected with fluorescent Ca(2+) indicator FURA-2. These data thus show that cytosolic Ca(2+) signals can rapidly activate vacuolar ion channels, which may prevent rupture of the vacuolar membrane, when facing mechanical forces.

  15. Chemical signals from plants previously infected with root knot nematodes affect behavior of infective juvenile root knot nematodes

    USDA-ARS?s Scientific Manuscript database

    Nematodes are a worldwide problem in agriculture, with losses estimated to $100 billion per year in the US. Damage caused by root-knot nematodes (Meloidogyne spp.) (RKN) disrupts the flow of water and nutrients to the plant and increases the plant’s vulnerability to other pathogens. While studies ...

  16. Validity of the vertical tube-shift method in determining the relationship between the mandibular third molar roots and the inferior alveolar nerve canal.

    PubMed

    Arora, Anjana; Patil, Bharati A; Sodhi, Amandeep

    2015-04-01

    To assess the validity of the vertical tube-shift method using intraoral periapical radiography (IOPAR) for determining the relationship between the mandibular third molar roots and the inferior alveolar nerve (IAN) canal in comparison with cone-beam computed tomography (CBCT). Fifty impacted mandibular third molars were analyzed using the IOPAR vertical tube-shift method and CBCT. The relationship of the IAN canal to the impacted mandibular third molar was recorded as buccal, lingual or in line with the apex and was compared with CBCT findings. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of the vertical tube-shift method in depicting the relationship (buccal/lingual/in line with the apex) of the IAN canal to the third molar root apex was calculated. The sensitivity and specificity PPV and NPV of the IOPAR vertical tube-shift technique was found to be highest for a lingual relationship (100%) followed by buccal (94.4%, 92.3%, 97.1%, and 85.7%) and in line with the apex relationship (88.9%, 95.0%, 80.0%, and 97.4%) of the IAN canal with the third molar root apex, respectively. A statistically significant association was observed between the IOPAR vertical tube-shift method and the CBCT with a P-value <0.01. The vertical tube-shift method can be used as an effective diagnostic tool in assessing the relationship of the IAN canal to the third molar root apex with high sensitivity, specificity, PPV, and NPV.

  17. Nerve Growth Factor Regulates Transient Receptor Potential Vanilloid 2 via Extracellular Signal-Regulated Kinase Signaling To Enhance Neurite Outgrowth in Developing Neurons

    PubMed Central

    Cohen, Matthew R.; Johnson, William M.; Pilat, Jennifer M.; Kiselar, Janna; DeFrancesco-Lisowitz, Alicia; Zigmond, Richard E.

    2015-01-01

    Neurite outgrowth is key to the formation of functional circuits during neuronal development. Neurotrophins, including nerve growth factor (NGF), increase neurite outgrowth in part by altering the function and expression of Ca2+-permeable cation channels. Here we report that transient receptor potential vanilloid 2 (TRPV2) is an intracellular Ca2+-permeable TRPV channel upregulated by NGF via the mitogen-activated protein kinase (MAPK) signaling pathway to augment neurite outgrowth. TRPV2 colocalized with Rab7, a late endosome protein, in addition to TrkA and activated extracellular signal-regulated kinase (ERK) in neurites, indicating that the channel is closely associated with signaling endosomes. In line with these results, we showed that TRPV2 acts as an ERK substrate and identified the motifs necessary for phosphorylation of TRPV2 by ERK. Furthermore, neurite length, TRPV2 expression, and TRPV2-mediated Ca2+ signals were reduced by mutagenesis of these key ERK phosphorylation sites. Based on these findings, we identified a previously uncharacterized mechanism by which ERK controls TRPV2-mediated Ca2+ signals in developing neurons and further establish TRPV2 as a critical intracellular ion channel in neuronal function. PMID:26416880

  18. Analysis of the spinal nerve roots in relation to the adjacent vertebral bodies with respect to a posterolateral vertebral body replacement procedure

    PubMed Central

    Awwad, Waleed; Bourget-Murray, Jonathan; Zeiadin, Nadil; Mejia, Juan P; Steffen, Thomas; Algarni, Abdulrahman D; Alsaleh, Khalid; Ouellet, Jean; Weber, Michael; Jarzem, Peter F

    2017-01-01

    Objective: This study aims to improve the understanding of the anatomic variations along the thoracic and lumbar spine encountered during an all-posterior vertebrectomy, and reconstruction procedure. This information will help improve our understanding of human spine anatomy and will allow better planning for a vertebral body replacement (VBR) through either a transpedicular or costotransversectomy approach. Summary of Background Data: The major challenge to a total posterior approach vertebrectomy and VBR in the thoracolumbar spine lies in the preservation of important neural structures. Methods: This was a retrospective analysis. Hundred normal magnetic resonance imaging (MRI) spinal studies (T1–L5) on sagittal T2-weighted MRI images were studied to quantify: (1) mid-sagittal vertebral body (VB) dimensions (anterior, midline, and posterior VB height), (2) midline VB and associated intervertebral discs height, (3) mean distance between adjacent spinal nerve roots (DNN) and mean distance between the inferior endplate of the superior vertebrae to its respective spinal nerve root (DNE), and (4) posterior approach expansion ratio (PAER). Results: (1) The mean anterior VB height gradually increased craniocaudally from T1 to L5. The mean midline and posterior VB height showed a similar pattern up to L2. Mean posterior VB height was larger than the mean anterior VB height from T1 to L2, consistent with anterior wedging, and then measured less than the mean anterior VB height, indicating posterior wedging. (2) Midline VB and intervertebral disc height gradually increased from T1 to L4. (3) DNN and DNE were similar, whereby they gradually increased from T1 to L3. (5) Mean PAER varied between 1.69 (T12) and 2.27 (L5) depending on anatomic level. Conclusions: The dimensions of the thoracic and lumbar vertebrae and discs vary greatly. Thus, any attempt at carrying out a VBR from a posterior approach should take into account the specifications at each spinal level. PMID

  19. Spinal nerve ligation decreases γ-aminobutyric acidB receptors on specific populations of immunohistochemically identified neurons in L5 dorsal root ganglion of the rat.

    PubMed

    Engle, Mitchell P; Merrill, Michelle A; Marquez De Prado, Blanca; Hammond, Donna L

    2012-06-01

    This study examined the distribution of γ-aminobutyric acid (GABA)(B) receptors on immunohistochemically identified neurons, and levels of GABA(B(1)) and GABA(B(2)) mRNA, in the L4 and L5 dorsal root ganglia (DRG) of the rat in the absence of injury and 2 weeks after L5 spinal nerve ligation. In uninjured DRG, GABA(B(1)) immunoreactivity colocalized exclusively with the neuronal marker (NeuN) and did not colocalize with the satellite cell marker S-100. The GABA(B(1)) subunit colocalized to >97% of DRG neurons immunoreactive (IR) for neurofilament 200 (N52) or calcitonin gene-related peptide (CGRP), or labeled by isolectin B4 (IB4). Immunoreactivity for GABA(B(2)) was not detectable. L5 spinal nerve ligation did not alter the number of GABA(B(1)) -IR neurons or its colocalization pattern in the L4 DRG. However, ligation reduced the number of GABA(B(1)) -IR neurons in the L5 DRG by ≈38% compared with sham-operated and naïve rats. Specifically, ligation decreased the number of CGRP-IR neurons in the L5 DRG by 75%, but did not decrease the percent colocalization of GABA(B(1)) in those that remained. In the few IB4-positive neurons that remained in the L5 DRG, colocalization of GABA(B(1)) -IR decreased to 75%. Ligation also decreased levels of GABA(B(1)) and GABA(B(2)) mRNA in the L5, but not the L4 DRG compared with sham-operated or naïve rats. These findings indicate that the GABA(B) receptor is positioned to presynaptically modulate afferent transmission by myelinated, unmyelinated, and peptidergic afferents in the dorsal horn. Loss of GABA(B) receptors on primary afferent neurons may contribute to the development of mechanical allodynia after L5 spinal nerve ligation.

  20. The neuronal architecture of the anteroventral cochlear nucleus of the cat in the region of the cochlear nerve root: Golgi and Nissl methods.

    PubMed

    Tolbert, L P; Morest, D K

    1982-01-01

    This report characterizes the cells and fibers in one part of the cochlear nucleus, the posterior division of the anteroventral cochlear nucleus. This includes the region where the cochlear nerve root enters the brain and begins to form endings. Nissl stains reveal the somata of globular cells with dispersed Nissl substance and those of multipolar cells with coarse, clumped Nissl bodies. Both parts of the posterior division contain cells with each Nissl pattern, but in different relative numbers and locations. Golgi impregnations demonstrate two types of neurons: bushy cells, with short bush-like dendrites, and stellate and elongate cells, with long tapered dendrites. Several varieties of bushy cells, differing in the morphology of the cell body and in the size and extent of the dendritic field, can be distinguished. Comparison of the distributions of these cell types, as well as cellular morphology, suggest that the globular cells recognized in Nissl stains correspond to bushy neurons, while the multipolar cells correspond to stellate and elongate neurons. Golgi impregnations reveal large end-bulbs and smaller boutons from cochlear nerve fibers, as well as boutons from other, unidentified sources, ending in this region. The particular arrangements of the dendritic fields of the different cell types and the axonal endings associated with them indicate that these neurons must have different physiological properties, since they define different domains with respect to the cochlear and non-cochlear inputs.

  1. Dual regulation of the Arabidopsis high-affinity root iron uptake system by local and long-distance signals.

    PubMed

    Vert, Grégory A; Briat, Jean-François; Curie, Catherine

    2003-06-01

    Regulation of the root high-affinity iron uptake system by whole-plant signals was investigated at the molecular level in Arabidopsis, through monitoring FRO2 and IRT1 gene expression. These two genes encode the root ferric-chelate reductase and the high-affinity iron transporter, respectively, involved in the iron deficiency-induced uptake system. Recovery from iron-deficient conditions and modulation of apoplastic iron pools indicate that iron itself plays a major role in the regulation of root iron deficiency responses at the mRNA and protein levels. Split-root experiments show that the expression of IRT1 and FRO2 is controlled both by a local induction from the root iron pool and through a systemic pathway involving a shoot-borne signal, both signals being integrated to tightly control production of the root iron uptake proteins. We also show that IRT1 and FRO2 are expressed during the day and down-regulated at night and that this additional control is overruled by iron starvation, indicating that the nutritional status prevails on the diurnal regulation. Our work suggests, for the first time to our knowledge, that like in grasses, the root iron acquisition in strategy I plants may also be under diurnal regulation. On the basis of the new molecular insights provided in this study and given the strict coregulation of IRT1 and FRO2 observed, we present a model of local and long-distance regulation of the root iron uptake system in Arabidopsis.

  2. Cdc42 Promotes Schwann Cell Proliferation and Migration Through Wnt/β-Catenin and p38 MAPK Signaling Pathway After Sciatic Nerve Injury.

    PubMed

    Han, Bin; Zhao, Jun-Ying; Wang, Wu-Tao; Li, Zheng-Wei; He, Ai-Ping; Song, Xiao-Yang

    2017-01-17

    Schwann cells (SCs) are unique glial cells in the peripheral nerve and may secrete multiple neurotrophic factors, adhesion molecules, extracellular matrix molecules to form the microenvironment of peripheral nerve regeneration, guiding and supporting nerve proliferation and migration. Cdc42 plays an important regulatory role in dynamic changes of the cytoskeleton. However, there is a little study referred to regulation and mechanism of Cdc42 on glial cells after peripheral nerve injury. The present study investigated the role of Cdc42 in the proliferation and migration of SCs after sciatic nerve injury. Cdc42 expression was tested, showing that the mRNA and protein expression levels of Cdc42 were significantly up-regulated after sciatic nerve injury. Then, we isolated and purified SCs from injuried sciatic nerve at day 7. The purified SCs were transfected with Cdc42 siRNA and pcDNA3.1-Cdc42, and the cell proliferation, cell cycle and migration were assessed. The results implied that Cdc42 siRNA remarkably inhibited Schwann cell proliferation and migration, and resulted in S phase arrest. While pcDNA3.1-Cdc42 showed a contrary effect. Besides, we also observed that Cdc42 siRNA down-regulated the protein expression of β-catenin, Cyclin D1, c-myc and p-p38, which were up-regulated by pcDNA3.1-Cdc42. Meanwhile, the inhibitor of Wnt/β-catenin and p38 MAPK signaling pathway IWP-2 and SB203580 significantly inhibited the effect of pcDNA3.1-Cdc42 on cell proliferation and migration. Overall, our data indicate that Cdc42 regulates Schwann cell proliferation and migration through Wnt/β-catenin and p38 MAPK signaling pathway after sciatic nerve injury, which provides further insights into the therapy of the sciatic nerve injury.

  3. Using Nerve Signals From Muscle Afferent Electrodes to Control FES-Based Ankle Motion in a Rabbit

    DTIC Science & Technology

    2007-11-02

    nerves in the left hind limb. A neural network was used for extraction of joint angles from the recorded ENGs. For stimulation purposes, percutaneous ...Natural sensors, neural prosthesis, implanted electrodes, functional electrical stimulation , closed-loop control, artificial neural networks, nerve ...branches of the sciatic nerve in the left hind limb. To minimize cutaneous inputs, the sural nerve was transected distal to its origin in the tibial nerve

  4. Two populations of cold-sensitive neurons in rat dorsal root ganglia and their modulation by nerve growth factor.

    PubMed

    Babes, Alexandru; Zorzon, Daniel; Reid, Gordon

    2004-11-01

    Cold sensing in mammals is not completely understood, although significant progress has been made recently with the cloning of two cold-activated ion channels, TRPM8 and TRPA1. We have used rat DRG neurons in primary culture and calcium fluorimetry to identify distinct populations of cold-sensitive neurons, which may underlie different functions. Menthol sensitivity clearly separated two classes of cold-responding neurons. One group was menthol-sensitive (MS), was activated at warmer temperatures and responded faster and with a larger increase in intracellular calcium concentration during cooling; the fraction of MS neurons in culture and their cold sensitivity were both increased in the presence of nerve growth factor. Neurons in the menthol-insensitive (MI) group required stronger cooling for activation than MS cells and neither their proportion nor their cold sensitivity were significantly altered by nerve growth factor. The two groups of cold-sensitive neurons also had different pharmacology. A larger fraction of MS cells were capsaicin-sensitive and coexpression of menthol and capsaicin sensitivity was observed in the absence of NGF. MI neurons were not stimulated by the super-cooling agent icilin or by the irritant mustard oil. Taken together these findings support a picture in which TRPM8 is the major player in detecting gentle cooling, while TRPA1 does not seem to be involved in cold sensing by MI neurons, at least in the temperature range between 32 and 12 degrees C.

  5. Increased expression of HCN2 channel protein in L4 dorsal root ganglion neurons following axotomy of L5- and inflammation of L4-spinal nerves in rats.

    PubMed

    Smith, T; Al Otaibi, M; Sathish, J; Djouhri, L

    2015-06-04

    A hallmark of peripheral neuropathic pain (PNP) is chronic spontaneous pain and/or hypersensitivity to normally painful stimuli (hyperalgesia) or normally nonpainful stimuli (allodynia).This pain results partly from abnormal hyperexcitability of dorsal root ganglion (DRG) neurons. We have previously shown, using a modified version of the lumbar 5 (L5)-spinal nerve ligation model of PNP (mSNA model involving L5-spinal nerve axotomy plus loose ligation of the lumbar 4 (L4)-spinal nerve with neuroinflammation-inducing chromic-gut), that L4 DRG neurons exhibit increased spontaneous activity, the key characteristic of neuronal hyperexcitability. The underlying ionic and molecular mechanisms of the hyperexcitability of L4 DRG neurons are incompletely understood, but could result from changes in expression and/or function of ion channels including hyperpolarization-activated cyclic nucleotide-gated (HCN) channels, which are active near the neuron's resting membrane potential, and which produce an excitatory inward current that depolarizes the membrane potential toward the threshold of action potential generation. Therefore, in the present study we used the mSNA model to investigate whether: (a) expression of HCN1-HCN3 channels is altered in L4 DRG neurons which, in the mSNA model, are essential for transmission of the evoked pain, and which contribute to chronic spontaneous pain, and (b) local (intraplantar) blockade of these HCN channels, with a specific blocker, ZD7288, attenuates chronic spontaneous pain and/or evoked pain in mSNA rats. We found 7days after mSNA: (1) a significant increase in HCN2-immunoreactivity in small (<30μm) DRG neurons (predominantly IB4-negative neurons), and in the proportion of small neurons expressing HCN2 (putative nociceptors); (2) no significant change in HCN1- or HCN3-immunoreactivity in all cell types; and (3) attenuation, with ZD7288 (100μM intraplantar), of chronic spontaneous pain behavior (spontaneous foot lifting) and mechanical

  6. Geometric analysis of Arabidopsis root apex reveals a new aspect of the ethylene signal transduction pathway in development

    NASA Technical Reports Server (NTRS)

    Cervantes, Emilio; Tocino, Angel

    2005-01-01

    Structurally, ethylene is the simplest phytohormone and regulates multiple aspects of plant growth and development. Its effects are mediated by a signal transduction cascade involving receptors, MAP kinases and transcription factors. Many morphological effects of ethylene in plant development, including root size, have been previously described. In this article a combined geometric and algebraic approach has been used to analyse the shape and the curvature in the root apex of Arabidopsis seedlings. The process requires the fitting of Bezier curves that reproduce the root apex shape, and the calculation of the corresponding curvatures. The application of the method has allowed us to identify significant differences in the root curvatures of ethylene insensitive mutants (ein2-1 and etr1-1) with respect to the wild-type Columbia.

  7. Geometric analysis of Arabidopsis root apex reveals a new aspect of the ethylene signal transduction pathway in development.

    PubMed

    Cervantes, Emilio; Tocino, Angel

    2005-09-01

    Structurally, ethylene is the simplest phytohormone and regulates multiple aspects of plant growth and development. Its effects are mediated by a signal transduction cascade involving receptors, MAP kinases and transcription factors. Many morphological effects of ethylene in plant development, including root size, have been previously described. In this article a combined geometric and algebraic approach has been used to analyse the shape and the curvature in the root apex of Arabidopsis seedlings. The process requires the fitting of Bézier curves that reproduce the root apex shape, and the calculation of the corresponding curvatures. The application of the method has allowed us to identify significant differences in the root curvatures of ethylene insensitive mutants (ein2-1 and etr1-1) with respect to the wild-type Columbia.

  8. Geometric analysis of Arabidopsis root apex reveals a new aspect of the ethylene signal transduction pathway in development

    NASA Technical Reports Server (NTRS)

    Cervantes, Emilio; Tocino, Angel

    2005-01-01

    Structurally, ethylene is the simplest phytohormone and regulates multiple aspects of plant growth and development. Its effects are mediated by a signal transduction cascade involving receptors, MAP kinases and transcription factors. Many morphological effects of ethylene in plant development, including root size, have been previously described. In this article a combined geometric and algebraic approach has been used to analyse the shape and the curvature in the root apex of Arabidopsis seedlings. The process requires the fitting of Bezier curves that reproduce the root apex shape, and the calculation of the corresponding curvatures. The application of the method has allowed us to identify significant differences in the root curvatures of ethylene insensitive mutants (ein2-1 and etr1-1) with respect to the wild-type Columbia.

  9. Root gravitropism: an experimental tool to investigate basic cellular and molecular processes underlying mechanosensing and signal transmission in plants

    NASA Technical Reports Server (NTRS)

    Boonsirichai, K.; Guan, C.; Chen, R.; Masson, P. H.

    2002-01-01

    The ability of plant organs to use gravity as a guide for growth, named gravitropism, has been recognized for over two centuries. This growth response to the environment contributes significantly to the upward growth of shoots and the downward growth of roots commonly observed throughout the plant kingdom. Root gravitropism has received a great deal of attention because there is a physical separation between the primary site for gravity sensing, located in the root cap, and the site of differential growth response, located in the elongation zones (EZs). Hence, this system allows identification and characterization of different phases of gravitropism, including gravity perception, signal transduction, signal transmission, and curvature response. Recent studies support some aspects of an old model for gravity sensing, which postulates that root-cap columellar amyloplasts constitute the susceptors for gravity perception. Such studies have also allowed the identification of several molecules that appear to function as second messengers in gravity signal transduction and of potential signal transducers. Auxin has been implicated as a probable component of the signal that carries the gravitropic information between the gravity-sensing cap and the gravity-responding EZs. This has allowed the identification and characterization of important molecular processes underlying auxin transport and response in plants. New molecular models can be elaborated to explain how the gravity signal transduction pathway might regulate the polarity of auxin transport in roots. Further studies are required to test these models, as well as to study the molecular mechanisms underlying a poorly characterized phase of gravitropism that is independent of an auxin gradient.

  10. Root gravitropism: an experimental tool to investigate basic cellular and molecular processes underlying mechanosensing and signal transmission in plants

    NASA Technical Reports Server (NTRS)

    Boonsirichai, K.; Guan, C.; Chen, R.; Masson, P. H.

    2002-01-01

    The ability of plant organs to use gravity as a guide for growth, named gravitropism, has been recognized for over two centuries. This growth response to the environment contributes significantly to the upward growth of shoots and the downward growth of roots commonly observed throughout the plant kingdom. Root gravitropism has received a great deal of attention because there is a physical separation between the primary site for gravity sensing, located in the root cap, and the site of differential growth response, located in the elongation zones (EZs). Hence, this system allows identification and characterization of different phases of gravitropism, including gravity perception, signal transduction, signal transmission, and curvature response. Recent studies support some aspects of an old model for gravity sensing, which postulates that root-cap columellar amyloplasts constitute the susceptors for gravity perception. Such studies have also allowed the identification of several molecules that appear to function as second messengers in gravity signal transduction and of potential signal transducers. Auxin has been implicated as a probable component of the signal that carries the gravitropic information between the gravity-sensing cap and the gravity-responding EZs. This has allowed the identification and characterization of important molecular processes underlying auxin transport and response in plants. New molecular models can be elaborated to explain how the gravity signal transduction pathway might regulate the polarity of auxin transport in roots. Further studies are required to test these models, as well as to study the molecular mechanisms underlying a poorly characterized phase of gravitropism that is independent of an auxin gradient.

  11. Ageing-induced changes in the redox status of peripheral motor nerves imply an effect on redox signalling rather than oxidative damage.

    PubMed

    McDonagh, Brian; Scullion, Siobhan M; Vasilaki, Aphrodite; Pollock, Natalie; McArdle, Anne; Jackson, Malcolm J

    2016-05-01

    Ageing is associated with loss of skeletal muscle fibres, atrophy of the remaining fibres and weakness. These changes in muscle are accompanied by disruption of motor neurons and neuromuscular junctions although the direct relationship between the nerve and muscle degeneration is not understood. Oxidative changes have been implicated in the mechanisms leading to age-related loss of muscle mass and in degeneration of the central nervous system, but little is known about age-related changes in oxidation in specific peripheral nerves that supply muscles that are affected by ageing. We have therefore examined the sciatic nerve of old mice at an age when loss of tibialis anterior muscle mass and function is apparent. Sciatic nerve from old mice did not show a gross increase in oxidative damage, but electron paramagnetic resonance (EPR) studies indicated an increase in the activity of superoxide and/or peroxynitrite in the nerves of old mice at rest that was further exacerbated by electrical stimulation of the nerve to activate muscle contractions. Proteomic analyses indicated that specific redox-sensitive proteins are increased in content in the nerves of old mice that may reflect an adaptation to regulate the increased superoxide/peroxynitrite and maintain redox homoeostasis. Analysis of redox active cysteines showed some increase in reversible oxidation in specific proteins in nerves of old mice, but this was not universally seen across all redox-active cysteines. Detailed analysis of the redox-active cysteine in one protein in the nerve of old mice that is key to redox signalling (Peroxiredoxin 6, Cys 47) showed a minor increase in reversible oxidation that would be compatible with a change in its redox signalling function. In conclusion, the data presented indicate that sciatic nerve from old mice does not show a gross increase in oxidative damage similar to that seen in the TA and other muscles that it innervates. Our results indicate an adaptation to increased

  12. Ageing-induced changes in the redox status of peripheral motor nerves imply an effect on redox signalling rather than oxidative damage

    PubMed Central

    McDonagh, Brian; Scullion, Siobhan M.; Vasilaki, Aphrodite; Pollock, Natalie; McArdle, Anne; Jackson, Malcolm J.

    2016-01-01

    Ageing is associated with loss of skeletal muscle fibres, atrophy of the remaining fibres and weakness. These changes in muscle are accompanied by disruption of motor neurons and neuromuscular junctions although the direct relationship between the nerve and muscle degeneration is not understood. Oxidative changes have been implicated in the mechanisms leading to age-related loss of muscle mass and in degeneration of the central nervous system, but little is known about age-related changes in oxidation in specific peripheral nerves that supply muscles that are affected by ageing. We have therefore examined the sciatic nerve of old mice at an age when loss of tibialis anterior muscle mass and function is apparent. Sciatic nerve from old mice did not show a gross increase in oxidative damage, but electron paramagnetic resonance (EPR) studies indicated an increase in the activity of superoxide and/or peroxynitrite in the nerves of old mice at rest that was further exacerbated by electrical stimulation of the nerve to activate muscle contractions. Proteomic analyses indicated that specific redox-sensitive proteins are increased in content in the nerves of old mice that may reflect an adaptation to regulate the increased superoxide/peroxynitrite and maintain redox homoeostasis. Analysis of redox active cysteines showed some increase in reversible oxidation in specific proteins in nerves of old mice, but this was not universally seen across all redox-active cysteines. Detailed analysis of the redox-active cysteine in one protein in the nerve of old mice that is key to redox signalling (Peroxiredoxin 6, Cys 47) showed a minor increase in reversible oxidation that would be compatible with a change in its redox signalling function. In conclusion, the data presented indicate that sciatic nerve from old mice does not show a gross increase in oxidative damage similar to that seen in the TA and other muscles that it innervates. Our results indicate an adaptation to increased

  13. Perception of root-derived peptides by shoot LRR-RKs mediates systemic N-demand signaling.

    PubMed

    Tabata, Ryo; Sumida, Kumiko; Yoshii, Tomoaki; Ohyama, Kentaro; Shinohara, Hidefumi; Matsubayashi, Yoshikatsu

    2014-10-17

    Nitrogen (N) is a critical nutrient for plants but is often distributed unevenly in the soil. Plants therefore have evolved a systemic mechanism by which N starvation on one side of the root system leads to a compensatory and increased nitrate uptake on the other side. Here, we study the molecular systems that support perception of N and the long-distance signaling needed to alter root development. Rootlets starved of N secrete small peptides that are translocated to the shoot and received by two leucine-rich repeat receptor kinases (LRR-RKs). Arabidopsis plants deficient in this pathway show growth retardation accompanied with N-deficiency symptoms. Thus, signaling from the root to the shoot helps the plant adapt to fluctuations in local N availability. Copyright © 2014, American Association for the Advancement of Science.

  14. Root water potential integrates discrete soil physical properties to influence ABA signalling during partial rootzone drying.

    PubMed

    Dodd, Ian C; Egea, Gregorio; Watts, Chris W; Whalley, W Richard

    2010-08-01

    To investigate the influence of different growing substrates (two mineral, two organic) on root xylem ABA concentration ([ABA](root)) and the contribution of the drying root system to total sap flow during partial rootzone drying (PRD), sunflower (Helianthus annuus L.) shoots were grafted onto the root systems of two plants grown in separate pots. Sap flow through each hypocotyl was measured below the graft union when one pot ('wet') was watered and other ('dry') was not. Each substrate gave unique relationships between dry pot matric potential (Psi(soil)), volumetric water content ((v)) or penetrometer resistance (Q) and either the fraction of photoperiod sap flow from roots in drying soil or [ABA](root). However, decreased relative sap flow, and increased [ABA](root), from roots in drying soil varied with root water potential (Psi(root)) more similarly across a range of substrates. The gradient between Psi(soil) and Psi(root) was greater in substrates with high sand or peat proportions, which may have contributed to a more sensitive response of [ABA](root) to Psi(soil) in these substrates. Whole plant transpiration was most closely correlated with the mean Psi(soil) of both pots, and then with detached leaf xylem ABA concentration. Although Psi(root) best predicted decreased relative sap flow, and increased [ABA](root), from roots in drying soil across a range of substrates, the inaccessibility of this variable in field studies requires a better understanding of how measurable soil variables (Psi(soil), (v), Q) affect Psi(root).

  15. Soybean nodule-enhanced CLE peptides in roots act as signals in GmNARK-mediated nodulation suppression.

    PubMed

    Lim, Chae Woo; Lee, Young Woo; Hwang, Cheol Ho

    2011-09-01

    The number of nodules formed in the roots of leguminous plants is systemically controlled by autoregulation of nodulation (AON). This study characterized two of the CLAVATA3/endosperm-surrounding region (CLE) genes involved in AON signal transduction. The GmRIC1 and GmRIC2 genes initiated expression solely in the roots at approximately 3 days after inoculation (DAI) with Nod factor-producing rhizobia, corresponding to the time point of AON, and the expression was up-regulated by cytokinins. Levels of GmRIC1 and GmRIC2 gene expression were much higher in the supernodulation mutant, SS2-2, than in wild-type (WT) soybeans during nodule development, even after initiation of nitrogen fixation. At 3 DAI, GmRIC2 was induced in the cells of the pericycle and the outer cortex, which undergo cell division to form nodule primordia and spreads from the central region to the whole nodule as it develops. Overexpression of GmRIC1 and GmRIC2 strongly suppressed the nodulation of WT roots as well as transgenic hairy roots in a GmNARK-dependent manner. This systemic suppression of nodulation was caused by the secretion of two CLE proteins into the extracellular space. Double grafting between WT and SS2-2 soybeans showed that signal Q is larger in SS2-2 than in WT roots during nodulation. The results of this study suggest that GmRIC1 and GmRIC2 are good candidates for root-derived signal Q in AON signal transduction.

  16. Root-targeted biotechnology to mediate hormonal signalling and improve crop stress tolerance.

    PubMed

    Ghanem, Michel Edmond; Hichri, Imène; Smigocki, Ann C; Albacete, Alfonso; Fauconnier, Marie-Laure; Diatloff, Eugene; Martinez-Andujar, Cristina; Lutts, Stanley; Dodd, Ian C; Pérez-Alfocea, Francisco

    2011-05-01

    Since plant root systems capture both water and nutrients essential for the formation of crop yield, there has been renewed biotechnological focus on root system improvement. Although water and nutrient uptake can be facilitated by membrane proteins known as aquaporins and nutrient transporters, respectively, there is a little evidence that root-localised overexpression of these proteins improves plant growth or stress tolerance. Recent work suggests that the major classes of phytohormones are involved not only in regulating aquaporin and nutrient transporter expression and activity, but also in sculpting root system architecture. Root-specific expression of plant and bacterial phytohormone-related genes, using either root-specific or root-inducible promoters or grafting non-transformed plants onto constitutive hormone producing rootstocks, has examined the role of root hormone production in mediating crop stress tolerance. Root-specific traits such as root system architecture, sensing of edaphic stress and root-to-shoot communication can be exploited to improve resource (water and nutrients) capture and plant development under resource-limited conditions. Thus, root system engineering provides new opportunities to maintain sustainable crop production under changing environmental conditions.

  17. A diagnosis challenge-L4 nerve root compression as the initial presentation of chronic inflammatory demyelinating polyneuropathy.

    PubMed

    Cojocaru, Inimioara Mihaela; Alexianu, Marilena; Bastian, Alexandra; Sapira, Violeta; Herţea, Cristina; Cojocaru, M

    2012-01-01

    The authors present the case of a 65-year-old woman who was admitted for paraparesis and paresthesias in the inferior limbs. The neurological examination revealed the difficulty in extension of the right foot and of the right toe, accompanied by paresthesias located in the anterolateral area of the right leg, dorsum and plantar area of the foot, the reduction of the right knee jerk, and of the ankle tendon jerk both sides. The vertebro-spinal MRI showed lumbar canal stenosis with L4 intraforaminal compression on the right, and L2-L3 on the left. CSF examination revealed mild increase in protein concentration. The morphological picture of the sural nerve biopsy was compatible with a chronic inflammatory neuropathy and severe muscular lesions of neurogenic origin were observed on right gastrocnemius muscle biopsy. The diagnosis of chronic inflammatory demyelinating polyneuropathy (CIDP) was established. Solu-medrol (0.5 g/d)-5 days, then medrol (prednisolone) was done, followed by improving of the symptomatology. For the relapse of the disease intravenous immunoglobulins (IVIG)-0.4 g/kg/d-5 days was the elective treatment. Six months later she presented a new relapse. IVIG were administered with the remission of the sensitive symptoms. A chronic treatment with medrol was recommended. The diagnosis of L4 disc herniation was obvious in the studied case, but the electroneurographic examination brought extra data for the associated diagnosis of CIDP whose onset was asymmetrical and initially paucisymptomatic. Neither the electroneurographic examination nor the CSF examination were total relevant for CIDP, imposing the sural nerve biopsy. The diagnosis of CIDP involves a team-work composed of neurologist, electroneurophysiologist and neuropathologist.

  18. 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

  19. Involvement of PACAP/ADNP signaling in the resistance to cell death in malignant peripheral nerve sheath tumor (MPNST) cells.

    PubMed

    Castorina, Alessandro; Giunta, Salvatore; Scuderi, Soraya; D'Agata, Velia

    2012-11-01

    Malignant peripheral nerve sheath tumors (MPNSTs) are sarcomas able to grow under conditions of metabolic stress caused by insufficient nutrients or oxygen. Both pituitary adenylate cyclase-activating polypeptide (PACAP) and activity-dependent neuroprotective protein (ADNP) have glioprotective potential. However, whether PACAP/ADNP signaling is involved in the resistance to cell death in MPNST cells remains to be clarified. Here, we investigated the involvement of this signaling system in the survival response of MPNST cells against hydrogen peroxide (H(2)O(2))-evoked death both in the presence of normal serum (NS) and in serum-starved (SS) cells. Results showed that ADNP levels increased time-dependently (6-48 h) in SS cells. Treatment with PACAP38 (10(-9) to 10(-5) M) dose-dependently increased ADNP levels in NS but not in SS cells. PAC(1)/VPAC receptor antagonists completely suppressed PACAP-stimulated ADNP increase and partially reduced ADNP expression in SS cells. NS-cultured cells exposed to H(2)O(2) showed significantly reduced cell viability (~50 %), increased p53 and caspase-3, and DNA fragmentation, without affecting ADNP expression. Serum starvation significantly reduced H(2)O(2)-induced detrimental effects in MPNST cells, which were not further ameliorated by PACAP38. Altogether, these finding provide evidence for the involvement of an endogenous PACAP-mediated ADNP signaling system that increases MPNST cell resistance to H(2)O(2)-induced death upon serum starvation.

  20. Sulphate as a xylem-borne chemical signal precedes the expression of ABA biosynthetic genes in maize roots.

    PubMed

    Ernst, Laura; Goodger, Jason Q D; Alvarez, Sophie; Marsh, Ellen L; Berla, Bert; Lockhart, Eric; Jung, Jiyul; Li, Pinghua; Bohnert, Hans J; Schachtman, Daniel P

    2010-07-01

    Recent reports suggest that early sensing of soil water stress by plant roots and the concomitant reduction in stomatal conductance may not be mediated by root-sourced abscisic acid (ABA), but that other xylem-borne chemicals may be the primary stress signal(s). To gain more insight into the role of root-sourced ABA, the timing and location of the expression of genes for key enzymes involved in ABA biosynthesis in Zea mays roots was measured and a comprehensive analysis of root xylem sap constituents from the early to the later stages of water stress was conducted. Xylem sap and roots were sampled from plants at an early stage of water stress when only a reduction in leaf conductance was measured, as well as at later stages when leaf xylem pressure potential decreased. It was found that the majority of ABA biosynthetic genes examined were only significantly expressed in the elongation region of roots at a later stage of water stress. Apart from ABA, sulphate was the only xylem-borne chemical that consistently showed significantly higher concentrations from the early to the later stages of stress. Moreover, there was an interactive effect of ABA and sulphate in decreasing maize transpiration rate and Vicia faba stomatal aperture, as compared to ABA alone. The expression of a sulphate transporter gene was also analysed and it was found that it had increased in the elongation region of roots from the early to the later stages of water stress. Our results support the suggestion that in the early stage of water stress, increased levels of ABA in xylem sap may not be due to root biosynthesis, ABA glucose ester catabolism or pH-mediated redistribution, but may be due to shoot biosynthesis and translocation to the roots. The analysis of xylem sap mineral content and bioassays indicate that the anti-transpirant effect of the ABA reaching the stomata at the early stages of water stress may be enhanced by the increased concentrations of sulphate in the xylem which is also

  1. The role of flavonoids in root-rhizosphere signalling: opportunities and challenges for improving plant-microbe interactions.

    PubMed

    Hassan, Samira; Mathesius, Ulrike

    2012-05-01

    The flavonoid pathway produces a diverse array of plant compounds with functions in UV protection, as antioxidants, pigments, auxin transport regulators, defence compounds against pathogens and during signalling in symbiosis. This review highlights some of the known function of flavonoids in the rhizosphere, in particular for the interaction of roots with microorganisms. Depending on their structure, flavonoids have been shown to stimulate or inhibit rhizobial nod gene expression, cause chemoattraction of rhizobia towards the root, inhibit root pathogens, stimulate mycorrhizal spore germination and hyphal branching, mediate allelopathic interactions between plants, affect quorum sensing, and chelate soil nutrients. Therefore, the manipulation of the flavonoid pathway to synthesize specifically certain products has been suggested as an avenue to improve root-rhizosphere interactions. Possible strategies to alter flavonoid exudation to the rhizosphere are discussed. Possible challenges in that endeavour include limited knowledge of the mechanisms that regulate flavonoid transport and exudation, unforeseen effects of altering parts of the flavonoid synthesis pathway on fluxes elsewhere in the pathway, spatial heterogeneity of flavonoid exudation along the root, as well as alteration of flavonoid products by microorganisms in the soil. In addition, the overlapping functions of many flavonoids as stimulators of functions in one organism and inhibitors of another suggests caution in attempts to manipulate flavonoid rhizosphere signals.

  2. Nerve Repulsion by the Lens and Cornea during Cornea Innervation is Dependent on Robo-Slit Signaling and Diminishes with Neuron Age

    PubMed Central

    Schwend, Tyler; Lwigale, Peter Y.; Conrad, Gary W.

    2012-01-01

    The cornea, the most densely innervated tissue on the surface of the body, becomes innervated in a series of highly coordinated developmental events. During cornea development, chick trigeminal nerve growth cones reach the cornea margin at embryonic day (E)5, where they are initially repelled for days from E5-8, instead encircling the corneal periphery in a nerve ring prior to entering on E9. The molecular events coordinating growth cone guidance during cornea development are poorly understood. Here we evaluated a potential role for the Robo-Slit nerve guidance family. We found that Slit 1, 2 and 3 expression in the cornea and lens persisted during all stages of cornea innervation examined. Robo1 expression was developmentally regulated in trigeminal cell bodies, expressed robustly during nerve ring formation (E5-8), then later declining concurrent with projection of growth cones into the cornea. In this study we provide in vivo and in vitro evidence that Robo-Slit signaling guides trigeminal nerves during cornea innervation. Transient, localized inhibition of Robo-Slit signaling, by means of beads loaded with inhibitory Robo-Fc protein implanted into the developing eyefield in vivo, led to disorganized nerve ring formation and premature cornea innervation. Additionally, when trigeminal explants (source of neurons) were oriented adjacent to lens vesicles or corneas (source of repellant molecules) in organotypic tissue culture both lens and cornea tissues strongly repelled E7 trigeminal neurites, except in the presence of inhibitory Robo-Fc protein. In contrast, E10 trigeminal neurites were not as strongly repelled by cornea, and presence of Robo-Slit inhibitory protein had no effect. In full, these findings suggest that nerve repulsion from the lens and cornea during nerve ring formation is mediated by Robo-Slit signaling. Later, a shift in nerve guidance behavior occurs, in part due to molecular changes in trigeminal neurons, including Robo1 downregulation, thus

  3. Nerve repulsion by the lens and cornea during cornea innervation is dependent on Robo-Slit signaling and diminishes with neuron age.

    PubMed

    Schwend, Tyler; Lwigale, Peter