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Sample records for rat spinal nerve

  1. Retrograde tracing of fluorescent gold after autogenous nerve transplantation on spinal cord injured in rats

    DEFF Research Database (Denmark)

    Lin, X; Liu, W; Ding, Ming;

    2016-01-01

    Objective To investigate the changes of the fluorescent gold retrograde tracing autogenous nerve transplantation on spinal cord injured in rats. Methods The animals were divided into two groups, with modified Allen impact method to establish model of spinal cord injury. After 4 weeks......, the transplantation group using autologous sural nerve graft to repair spinal cord injury period and non-transplantation group was only exposed incision without treatment. In the 4, 6 and 8 weeks after operation, the retrograde tracing of FG Fluoro-Gold was performed to discover the recovery of the axial plasma.......01). Conclusion After spinal cord injury, autologous nerve graft was repaired and survived well and promote the recovery of spinal cord injury segment shaft pulp transportation function....

  2. Vascularized peripheral nerve trunk autografted in the spinal cord: a new experimental model in adult rats

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    Objective: To investigate the effect of vascularized peripheral nerve trunk autografted in spinal cord. Methods: With modern microsurgical technique,vascularized peripheral median and ulnar nerve trunk autografted in the upper thoracic region of the spinal cord were established in 20 female adult rats. The origin and the termination of axons in the graft were studied by retrograde neuronal labeling with horseradish peroxidase (HRP).Cord, nerve grafts and some normal median and ulnar nerves in the right upper limb were removed and sectioned for Bielschowsky's silver stain and haematoxylin and eosin (H&E) stain. Light and electron microscopic examination and electrophysiological examination were applied.Results: The grafts were innervated by many new fibers. Studies with HRP indicated that new axons in graft were originated from intrinsic central nervous system (CNS) neurons with their cell bodies from brain stem to sacral segments of spinal cord. Other axons arose from dorsal root ganglia at the level of graft and at least 19 distal segments to them. Together with electron microscopy, electrophysiological examination, silver and H&E stain, the results demonstrated that vascularized peripheral nerve trunk grafted in spinal cord attracted many neurons to grow into the nerve grafts.Conclusions: The findings implicate that CNS is able to regenerate much better in vascularized nerve autografted in spinal cord.

  3. Constituent ratio of motor fibers from the C5-C7 spinal nerves in the radial nerve is greater in pup rats than in adult rats.

    Science.gov (United States)

    Nie, Mingbo; Chen, Liang; Gu, Yudong

    2012-06-01

    Clinically, injuries of C5-C7 of the brachial plexus cause falling of the wrist and fingers in infants but not in adults unless 4 consecutive spinal nerves are injured. The purpose of this study was to compare the constituent difference of spinal nerves in the radial nerve between pup and adult rats.A group of 16 pup rats and a group of 16 adult rats were each divided into 2 groups of 8 (P1 and A1 groups, C5-C6 were divided; P2 and A2 groups, C5-C7 were divided]). A nerve conduction study and histological examination were performed to evaluate radial nerve innervation to the extensor digitorum communis muscle after dividing the spinal nerves. Retrograde tracing with 5% cholera toxin B for anterior horn motoneurons of the spinal cord innervating the radial nerve was performed in 8 pup rats and 8 adult rats. Results showed that the division of C5-C7 caused more significant damage to radial nerve innervation to the extensor digitorum communis in pups than in adults, although the division of C5-C6 did not. In pups, the percentages (median with interquartile) of anterior horn motoneurons of the spinal cord innervating the radial nerve were 36.4 (28.3-38.5) in C5-C6, 28.1 (24.5-32.5) in C7, and 37.5 (36.5-39.3) in C8-T1. In adults, they were 24.2 (23.6-27.8) in C5-C6, 21.8 (19.5-26.3) in C7, and 50.7 (48.7-55.5) C8-T1.This study implies that C7 innervation in the radial nerve in humans may be more critical to the function of this nerve in infants than in adults.

  4. Effects of nerve growth factor on neuronal nitric oxide production after spinal cord injury in rats

    Institute of Scientific and Technical Information of China (English)

    汤长华; 曹晓建; 王道新

    2002-01-01

    To explore the protective effects of nerve growth factor (NGF) on injured spinal cord. Methods: The spinal cord injury (SCI) model of Wistar rats was established by a 10 g×2.5 cm impact force on the T8 spinal cord. NGF (60 μg/20 μl) was given to the rats of the treatment group immediately and at 2, 4, 8, 12, 24 hours after SCI. The level of neuronal constitutive nitric oxide synthase (ncNOS) and the expression of ncNOS mRNA in the spinal cord were detected by the immunohistochemistry assay and in situ hybridization method. Results: Abnormal expression of ncNOS was detected in the spinal ventral horn motorneuron in injured rats. The levels of ncNOS protein in the NGF group were significantly lower than those in the normal saline group (P<0.05 ). The ncNOS mRNA expression was found in the spinal ventral horn motorneuron in injured rats and the expression in the NGF group was significantly decreased compared with that in the normal saline group (P<0.01). Conclusions: NGF can protect the injured tissue of the spinal cord by prohibiting abnormal expression of nitric oxide synthase and the neurotoxicity of nitric oxide.

  5. Implantation of juvenile human chondrocytes demonstrates no adverse effect on spinal nerve tissue in rats.

    Science.gov (United States)

    Külling, Fabrice A; Liu, Jane J; Liebenberg, Ellen; Lotz, Jeffrey C

    2016-09-01

    Degenerative disc disease (DDD) is a common disabling condition for millions of individuals. Injection of xenogenic juvenile chondrocytes (XJC) into the disc space has been shown to have a therapeutic potential for disc repair. In the current study, XJC were injected extra-discally on neural structures in an in vivo rat hemilaminectomy model to compare the histological and behavioral effects on XJC and fibrin glue carrier. Twenty-four rats were assigned to four groups: cells plus carrier, carrier alone, sham hemi-laminectomy, and a positive control (nerve root ligation). A right-sided hemilaminectomy was performed and the study material was placed on and around the exposed L4 nerve root and the spinal cord. Pre- and postoperatively mechanical allodynia was tested on the ipsilateral hind paw using the von Frey up-down method. The lumbar spines were harvested after 6 and 12 weeks for nerve histology and TNF-α quantification. After a brief period of hyperalgesia, the von Frey data indicate there are no adverse effects of placing XJC on spinal nerve roots in rats. However ligation of nerve root showed significant allodynia compared to the other groups. These behavioral data were supported by histological analyses. While these results need to be confirmed over a larger period of time, they suggest that XJC transplantation into the disc space shows no adverse effect on nerve tissue.

  6. Contribution of spinal glia activation to mechanical hyperalgesia induced by spared nerve injury in rats

    Institute of Scientific and Technical Information of China (English)

    FENG Si-zhe; WEI Xue-zhong; ZHANG Xiang

    2004-01-01

    Objective: To investigate the role of spinal glial cells activation in neuropathic pain in a recently developed spared nerve injury (SNI) animal model by Decosterd and Woolf. Methods: A lesion was made to two of the three terminal branches of the sciatic nerve of rats (tibial and common peroneal nerves) leaving the sural nerve intact. Continuous intrathecai administration of propentofyliine, a glial modulating agent, 1 d before and 5 d after operation, was performed to disrupt spinal cord glia function. The vehicle was intrathecally administrated as control. The paw withdrawal threshold to mechanical stimulation (paw withdrawal mechaical threshold PWMT), body mass and motor function were determined pre- and post-surgery. Results: It produced a prolonged mechanical allodynia in the medial and lateral part of the ipsilateral hind paw in SNL models. The treatment with propentofylline significantly prevented the development of mechanical allodynia located in either medial or lateral plantar surface. Rats in two groups showed normal motor function and body weight increase. Conclusion:SNI model can be applied as a useful method with little variance in searching the mechanism of neuropathic pain. These study suggest that spinal glia activation may contribute to mechanical allodynia induced by SNI.

  7. EFFECTS OF NERVE GROWTH FACTOR ON ENDOTHELIN AFTER SPINAL CORD INJURY IN RATS

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    Objective To investigate the protective mechanisms of nerve growth factor (NGF) on spinal cord injury.Methods The spinal cord injury (SCI) of Wistar rats was performed by a 10g×2.5cm impact on the posterior T12 spinal cord.The experimental animals received NGF liquid by subarachnoid space tube.The radioimmunological techniques were applied to examine the level of endothelin.Results The level of endothelin was significantly increased after the injury as compared with that in control group(P<0.01).The level of endothelin in NGF group as obviously lowered as compared with that in normal saline group 4 h after injury (P<0.01).Conclusion NGF can protect spinal cord against injury in vivo.One of the mechanisms is that NGF could inhibit endothelin-induced vicious circle.

  8. Effect of nerve growth factor on neuronal apoptosis after spinal cord injury in rats

    Institute of Scientific and Technical Information of China (English)

    曹晓建; 汤长华; 罗永湘

    2002-01-01

    To explore the molecular mechanism of the protective effect of nerve growth factor (NGF) on injured spinal cord. Methods: The posterior T8 (the 8th thoracic segment) spinal cords of 60 Wistar rats were injured by impacts caused by objects (weighing 10 g) falling from a height of 2.5 cm with Allens way. Solution with nerve growth factors (NGF) was given to 30 rats (the NGF group) through a microtubule inserted into the subarachnoid cavity immediately, and at 2, 4, 8, 12 and 24 hours after spinal cord injury (SCI) respectively. Normal saline (NS) with same volume was given to the other 30 rats (the NS group) with the same method. And 5 normal rats were taken as the normal controls. The expression of bcl-2 and bax proteins in spinal cord was detected with immunohistochemistry. The apoptotic neurons in spinal cord were measured with terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end-labeling of DNA fragments (TUNEL) staining. Results: The positive expression of bcl-2 protein was strong in the normal controls, but decreased in the NS group, and increased significantly in the NGF group as compared with that of the NS group (P<0.01). The positive expression of bax protein was also strong in the normal controls, but increased in the NS group, and decreased significantly in the NGF group as compared with that of the NS group (P<0.01). Apoptotic neurons were found in the NS group, and they decreased significantly in the NGF group as compared with that of the NS group (P<0.01). Conclusions: NGF can protect the injured nerve tissues through stimulating the expression of bcl-2 protein, inhibiting the expression of bax protein and inhibiting the neuronal apoptosis after SCI.

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

    Directory of Open Access Journals (Sweden)

    Joost L M Jongen

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

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

    Science.gov (United States)

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

    2014-01-01

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

  11. Effects of Nerve Growth Factor on Bcl-2 Protein after Spinal Cord Injury in Rats

    Institute of Scientific and Technical Information of China (English)

    汤长华; 曹晓建; 王道新

    2002-01-01

    Objective To explore the protective mechanisms of nerve growth factor( NGF) ou spinal cord injury(SCI) and provide theoretical basis for its clinical application. MethodsThe SCI of Wistar rats was done by Allens weight dropping way by a 10 g × 2.5 cm impact on theposterior of spinal cord T8 NGF ( 3 g/L, 20d) or normal saline was injected to treatment group ratsthrough catheter into subarachnoid space at 0,2,4,8,12 and 24 h after SCI. The expression of bcl-2 protein levels in rat spinal cord was detected by immunohistoclemistry. Results The strong expres-sion sequence of bcl-2 protein was found in spinal cord of normal rat group. The levels of bcl-2 pro-tein after SCI in NGF treatment group increased more significantly than those in normal saline treatmentgroup (P<0. 01). Conclusion NGF could protect injured spinal cord by stimulating bcl-2 pro-tein expression and suppressing apoptosis after SCI.

  12. Neonatal sciatic nerve transection induces TUNEL labeling of neurons in the rat spinal cord and DRG.

    Science.gov (United States)

    Oliveira, A L; Risling, M; Deckner, M; Lindholm, T; Langone, F; Cullheim, S

    1997-09-08

    Transection of a peripheral nerve in neonatal rats induces an extensive death of axotomized neurons. We demonstrate here that spinal motoneurons and sensory dorsal root ganglia neurons become TUNEL-labeled after sciatic nerve transection in neonatal rats, thus indicating that apoptotic mechanisms are involved in the death process. Interestingly, there is also a profound increase of TUNEL-labeled interneurons in the deep dorsal horn. This location suggests that an intact afferent input and/or contact with target cells is essential for interneuronal survival. Death of motoneurons and sensory neurons could be a result of the injury per se and/or the deprivation of neurotrophic substances, secondary to the loss of contact with target cells.

  13. Tail nerve electrical stimulation induces body weight-supported stepping in rats with spinal cord injury.

    Science.gov (United States)

    Zhang, Shu-Xin; Huang, Fengfa; Gates, Mary; White, Jason; Holmberg, Eric G

    2010-03-30

    Walking or stepping has been considered the result from the activation of the central pattern generator (CPG). In most patients with spinal cord injury (SCI) the CPG is undamaged. To date, there are no noninvasive approaches for activating the CPG. Recently we developed a noninvasive technique, tail nerve electrical stimulation (TANES), which can induce positive hind limb movement of SCI rats. The purpose of this study is to introduce the novel technique and examine the effect of TANES on CPG activation. A 25 mm contusion injury was produced at spinal cord T10 of female, adult Long-Evans rats by using the NYU impactor device. Rats received TANES ( approximately 40 mA at 4 kHz) 7 weeks after injury. During TANES all injured rats demonstrated active body weight-supported stepping of hind limbs with left-right alternation and occasional front-hind coordination, resulting in significant, temporary increase in BBB scores (pelectrical stimulation. Therefore the TANES may have considerable potential for achieving improvement of functional recovery in animal models and a similar method may be suggested for human study. Copyright (c) 2010 Elsevier B.V. All rights reserved.

  14. [Effect of embryonic anlage allografts of the rat spinal cord on growth of regenerating fibers of the recipient nerve].

    Science.gov (United States)

    Petrova, E S; Isaeva, E N

    2014-01-01

    A comparative study of the effect of tissue and suspension allografts of an embryonic spinal cord on regeneration of nerve fibers of impaired (by application of a ligature) sciatic nerve in rats was conducted. It was demonstrated that unlike tissue grafts that reach a large volume 21 and 60 days after transplantation, suspension grafts do not inhibit the growth of axons of the recipient to the periphery. It was established that introduction of a suspension of dissociated cells of the spinal cord embryonic anlages (but not fragments of these anlages) into the impaired sciatic nerve in rats results in an increase in the amount of myelinated regenerating nerve fibers of the recipient 60 days after the operation.

  15. Contralateral Metabolic Activation Related to Plastic Changes in the Spinal Cord after Peripheral Nerve Injury in Rats

    Directory of Open Access Journals (Sweden)

    Ran Won

    2015-01-01

    Full Text Available We have previously reported the crossed-withdrawal reflex in which the rats with nerve injury developed behavioral pain responses of the injured paw to stimuli applied to the contralateral uninjured paw. This reflex indicates that contralateral plastic changes may occur in the spinal cord after unilateral nerve injury. The present study was performed to elucidate the mechanisms and morphological correlates underlying the crossed-withdrawal reflex by using quantitative 14C-2-deoxyglucose (2-DG autoradiography which can examine metabolic activities and spatial patterns simultaneously. Under pentobarbital anesthesia, rats were subjected to unilateral nerve injury. Mechanical allodynia was tested for two weeks after nerve injury. After nerve injury, neuropathic pain behaviors developed progressively. The crossed-withdrawal reflex was observed at two weeks postoperatively. Contralateral enhancement of 2-DG uptake in the ventral horn of the spinal cord to electrical stimulation of the uninjured paw was observed. These results suggest that the facilitation of information processing from the uninjured side to the injured side may contribute to the crossed-withdrawal reflex by plastic changes in the spinal cord of nerve-injured rats.

  16. Tramadol and Propentofylline Coadministration Exerted Synergistic Effects on Rat Spinal Nerve Ligation-Induced Neuropathic Pain

    Science.gov (United States)

    Wang, Huan; Wang, Wei; Zhang, Hui; Liu, Rui; Xu, Li-Xian; Mei, Xiao-Peng

    2013-01-01

    Neuropathic pain is an intractable clinical problem. Drug treatments such as tramadol have been reported to effectively decrease neuropathic pain by inhibiting the activity of nociceptive neurons. It has also been reported that modulating glial activation could also prevent or reverse neuropathic pain via the administration of a glial modulator or inhibitor, such as propentofylline. Thus far, there has been no clinical strategy incorporating both neuronal and glial participation for treating neuropathic pain. Therefore, the present research study was designed to assess whether coadministration of tramadol and propentofylline, as neuronal and glial activation inhibitors, respectively, would exert a synergistic effect on the reduction of rat spinal nerve ligation (SNL)-induced neuropathic pain. Rats underwent SNL surgery to induce neuropathic pain. Pain behavioral tests were conducted to ascertain the effect of drugs on SNL-induced mechanical allodynia with von-Frey hairs. Proinflammatory factor interleukin-1β (IL-1β) expression was also detected by Real-time RT-PCR. Intrathecal tramadol and propentofylline administered alone relieved SNL-induced mechanical allodynia in a dose-dependent manner. Tramadol and propentofylline coadministration exerted a more potent effect in a synergistic and dose dependent manner than the intrathecal administration of either drug alone. Real-time RT-PCR demonstrated IL-1β up-expression in the ipsilateral spinal dorsal horn after the lesion, which was significantly decreased by tramadol and propentofylline coadministration. Inhibiting proinflammatory factor IL-1β contributed to the synergistic effects of tramadol and propentofylline coadministration on rat peripheral nerve injury-induced neuropathic pain. Thus, our study provided a rationale for utilizing a novel strategy for treating neuropathic pain by blocking the proinflammatory factor related pathways in the central nervous system. PMID:24009718

  17. Effects of nerve growth factor on N-methyI-D-asparate receptor 1 after spinal cord injury in rats

    Institute of Scientific and Technical Information of China (English)

    曹晓建; 汤长华; 罗永湘

    2002-01-01

    To explore the effects of the nerve growth factor ( NGF ) on N-methyI-D-asparate receptor 1(NMDAR 1 ) after spinal cord injury. Methods: Spinal cord injury of Wistar rats was performed with Allen's method by a 10 g x 2.5 cm impact on the posterior T8 spinal cord. NGF was given to the rats of the treatment group via subarachnoid space tube at once,2, 4, 8, 12 and 24 hours after spinal cord injury,respectively. The expression of NMDAR1 mRNA in spinal cord was detected by in situ hybridization. Results: Rare expression sequence of NMDAR1 mRNA was found in rat spinal cord of the normal group. A strong expression sequence of NMDAR1 mRNA was found in rat spinal cord of the normal saline group. The expression of NMDAR1 mRNA in the NGF group was significantly decreased as compared with that in the normal saline group ( P = 0.01 ). Conclusions: NGF can relieve damage of injured spinal cord by prohibiting the expression of NMDAR1 mRNA.

  18. Baicalin ameliorates neuropathic pain by suppressing HDAC1 expression in the spinal cord of spinal nerve ligation rats

    Directory of Open Access Journals (Sweden)

    Chen-Hwan Cherng

    2014-08-01

    Conclusion: The present findings suggest that baicalin can ameliorate neuropathic pain by suppressing HDAC1 expression and preventing histone-H3 acetylation in the spinal cord dorsal horn of SNL rats.

  19. Tail Nerve Electrical Stimulation and Electro-Acupuncture Can Protect Spinal Motor Neurons and Alleviate Muscle Atrophy after Spinal Cord Transection in Rats

    Directory of Open Access Journals (Sweden)

    Yu-Ting Zhang

    2017-01-01

    Full Text Available Spinal cord injury (SCI often results in death of spinal neurons and atrophy of muscles which they govern. Thus, following SCI, reorganizing the lumbar spinal sensorimotor pathways is crucial to alleviate muscle atrophy. Tail nerve electrical stimulation (TANES has been shown to activate the central pattern generator (CPG and improve the locomotion recovery of spinal contused rats. Electroacupuncture (EA is a traditional Chinese medical practice which has been proven to have a neural protective effect. Here, we examined the effects of TANES and EA on lumbar motor neurons and hindlimb muscle in spinal transected rats, respectively. From the third day postsurgery, rats in the TANES group were treated 5 times a week and those in the EA group were treated once every other day. Four weeks later, both TANES and EA showed a significant impact in promoting survival of lumbar motor neurons and expression of choline acetyltransferase (ChAT and ameliorating atrophy of hindlimb muscle after SCI. Meanwhile, the expression of neurotrophin-3 (NT-3 in the same spinal cord segment was significantly increased. These findings suggest that TANES and EA can augment the expression of NT-3 in the lumbar spinal cord that appears to protect the motor neurons as well as alleviate muscle atrophy.

  20. Tail Nerve Electrical Stimulation and Electro-Acupuncture Can Protect Spinal Motor Neurons and Alleviate Muscle Atrophy after Spinal Cord Transection in Rats.

    Science.gov (United States)

    Zhang, Yu-Ting; Jin, Hui; Wang, Jun-Hua; Wen, Lan-Yu; Yang, Yang; Ruan, Jing-Wen; Zhang, Shu-Xin; Ling, Eng-Ang; Ding, Ying; Zeng, Yuan-Shan

    2017-01-01

    Spinal cord injury (SCI) often results in death of spinal neurons and atrophy of muscles which they govern. Thus, following SCI, reorganizing the lumbar spinal sensorimotor pathways is crucial to alleviate muscle atrophy. Tail nerve electrical stimulation (TANES) has been shown to activate the central pattern generator (CPG) and improve the locomotion recovery of spinal contused rats. Electroacupuncture (EA) is a traditional Chinese medical practice which has been proven to have a neural protective effect. Here, we examined the effects of TANES and EA on lumbar motor neurons and hindlimb muscle in spinal transected rats, respectively. From the third day postsurgery, rats in the TANES group were treated 5 times a week and those in the EA group were treated once every other day. Four weeks later, both TANES and EA showed a significant impact in promoting survival of lumbar motor neurons and expression of choline acetyltransferase (ChAT) and ameliorating atrophy of hindlimb muscle after SCI. Meanwhile, the expression of neurotrophin-3 (NT-3) in the same spinal cord segment was significantly increased. These findings suggest that TANES and EA can augment the expression of NT-3 in the lumbar spinal cord that appears to protect the motor neurons as well as alleviate muscle atrophy.

  1. Tail Nerve Electrical Stimulation and Electro-Acupuncture Can Protect Spinal Motor Neurons and Alleviate Muscle Atrophy after Spinal Cord Transection in Rats

    Science.gov (United States)

    Zhang, Yu-Ting; Jin, Hui; Wang, Jun-Hua; Wen, Lan-Yu; Yang, Yang; Ruan, Jing-Wen; Zhang, Shu-Xin; Ling, Eng-Ang

    2017-01-01

    Spinal cord injury (SCI) often results in death of spinal neurons and atrophy of muscles which they govern. Thus, following SCI, reorganizing the lumbar spinal sensorimotor pathways is crucial to alleviate muscle atrophy. Tail nerve electrical stimulation (TANES) has been shown to activate the central pattern generator (CPG) and improve the locomotion recovery of spinal contused rats. Electroacupuncture (EA) is a traditional Chinese medical practice which has been proven to have a neural protective effect. Here, we examined the effects of TANES and EA on lumbar motor neurons and hindlimb muscle in spinal transected rats, respectively. From the third day postsurgery, rats in the TANES group were treated 5 times a week and those in the EA group were treated once every other day. Four weeks later, both TANES and EA showed a significant impact in promoting survival of lumbar motor neurons and expression of choline acetyltransferase (ChAT) and ameliorating atrophy of hindlimb muscle after SCI. Meanwhile, the expression of neurotrophin-3 (NT-3) in the same spinal cord segment was significantly increased. These findings suggest that TANES and EA can augment the expression of NT-3 in the lumbar spinal cord that appears to protect the motor neurons as well as alleviate muscle atrophy. PMID:28744378

  2. Survival and migration of Schwann cells after the vascularized peripheral nerve grafted into spinal cord in rats

    Institute of Scientific and Technical Information of China (English)

    GUO Qing-shan; WANG Ai-min; WANG Xiao-jun; SUN Hong-zhen; DU Quan-yin

    2005-01-01

    Objective:To study the survival and ability of inducing axonal regeneration of the Schwann cells after the peripheral nerve being grafted into spinal cord. Methods:A total of 30 adult female Wistar rats were randomly divided into the VN (vascularized peripheral nerve) and PN (peripheral nerve) groups. A 5-mm spinal cord defect of the left posterior column was made at the T1-3 vertebral level. The defect was grafted with the vascularized or isolated peripheral nerve respectively. The survival and proliferation of the Schwann cells were assessed by histological and morphometric analysis 8 weeks after the operation. Results:In the VN group, the peripheral nerve grew into the cord with lots of Schwann cells survived and proliferated, and had more NF and S-100 positive fibers than in the PN group. Conclusion:The vascularized peripheral nerve enhances the survival and proliferation of the Schwann cells and prompts the regeneration of injured axon of the central nerve system to certain degree.

  3. Protective effect of sodium valproate on motor neurons in the spinal cord following sciatic nerve injury in rats

    Institute of Scientific and Technical Information of China (English)

    Fei Wu; Danmou Xing; Zhengren Peng; Wusheng Kan

    2006-01-01

    BACKGROUND: Sodium valproate (VPA) is used to be an effective anti-epileptic drug. VPA possesses the characteristics of penetrating rapidly through the blood-brain barrier (BBB) and increasing levels of Bcl-2 and growth cone-associated protein (GAP) 43 in spinal cord.OBJECTIVE: To observe the effect of VPA on Bcl-2 expression and motor neuronal apoptosis in spinal cord of rats following sciatic nerve transection.DESIGN: Randomized controlled experiment.SETTING: Department of Hand Surgery and Microsurgery, Wuhan Puai Hospital.MATERIALS: A total of 30 male healthy SD rats of olean grade and with the body mass of 180-220 g were provided by Experimental Animal Center of Medical College of Wuhan University. Sodium Valproate Tablets were purchases from Hengrui Pharmaceutical Factory, Jiangsu.METHODS: The experiment was performed in the Central Laboratory of Wuhan Puai Hospital and Medical College of Wuhan University from February to May 2006. Totally 30 rats were randomly divided into two groups:treatment group (n =15) and model group (n =15). Longitudinal incision along backside of right hind limbs of rats was made to expose sciatic nerves, which were sharply transected 1 cm distal to the inferior margin of piriform muscle after nerve liberation under operation microscope to establish sciatic nerve injury rat models.Sodium Valproate Tablets were pulverized and diluted into 50 g/L suspension with saline. On the day of operation, the rats in the treatment group received 6 Ml/kg VPA suspension by gastric perfusion, once a day,whereas model group received 10 Ml/kg saline by gastric perfusion, once a day. L4-6 spinal cords were obtained at days 1, 4, 7, 14 and 28 after operation, respectively. Terminal deoxyribonucleotidyl transferase (TdT)-mediated Dutp-biotin nick end labeling (TUNEL) technique and immunohistochemical method (SP method) were used to detect absorbance (A) of neurons with positive Bcl-2 expression. Apoptotic rate of cells (number of apoptotic cells

  4. Spinal SIRPα1-SHP2 interaction regulates spinal nerve ligation-induced neuropathic pain via PSD-95-dependent NR2B activation in rats.

    Science.gov (United States)

    Peng, Hsien-Yu; Chen, Gin-Den; Lai, Cheng-Yuang; Hsieh, Ming-Chun; Lin, Tzer-Bin

    2012-05-01

    The fact that neuropathic pain mechanisms are not well understood is a major impediment in the development of effective clinical treatments. We examined whether the interaction between signal regulatory protein alpha 1 (SIRPα1) and Src homology-2 domain-containing protein tyrosine phosphatase 2 (SHP2), and the downstream spinal SHP2/postsynaptic density 95 (PSD-95)/N-methyl-d-aspartate receptor NR2B subunit signaling cascade play a role in neuropathic pain. Following spinal nerve ligation (L5), we assessed tactile allodynia using the von Frey filament test and analyzed dorsal horn samples (L4-5) by Western blotting, reverse transcription polymerase chain reaction, coimmunoprecipitation, and immunofluorescence. Nerve ligation induced allodynia, SIRPα1, SHP2, phosphorylated SHP2 (pSHP2), and phosphorylated NR2B (pNR2B) expression, and SHP2-PSD-95, pSHP2-PSD-95, PSD-95-NR2B, and PSD-95-pNR2B coimmunoprecipitation in the ipsilateral dorsal horn. In allodynic rats, injury-induced SHP2 immunoreactivity was localized in the ipsilateral dorsal horn neurons and coincident with PSD-95 and NR2B immunoreactivity. SIRPα1 silencing using small interfering RNA (siRNA; 1, 3, or 5μg/rat for 7days) prevented injury-induced allodynia and the associated changes in protein expression, phosphorylation, and coimmunoprecipitation. Intrathecal administration of NSC-87877 (an SHP2 antagonist; 1, 10, or 100μM/rat) and SIRPα1-neutralizing antibodies (1, 10, or 30μg/rat) suppressed spinal nerve ligation-induced allodynia, spinal SHP2 and NR2B phosphorylation, and SHP2/phosphorylated SHP2-PSD-95 and PSD-95-NR2B/phosphorylated NR2B coprecipitation. SHP2 siRNA led to similar effects as the NSC-87877 and SIRPα1 antibody treatments, except it prevented the allodynia-associated spinal SHP2 expression. In conclusion, our results suggest that a spinal SIRPα1-SHP2 interaction exists that subsequently triggers SHP2/PSD-95/NR2B signaling, thereby playing a role in neuropathic pain development

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

    Science.gov (United States)

    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.

  6. Nerve growth factor delivery by ultrasound-mediated nanobubble destruction as a treatment for acute spinal cord injury in rats

    Science.gov (United States)

    Song, Zhaojun; Wang, Zhigang; Shen, Jieliang; Xu, Shengxi; Hu, Zhenming

    2017-01-01

    Background Spinal cord injuries (SCIs) can cause severe disability or death. Treatment options include surgical intervention, drug therapy, and stem cell transplantation. However, the efficacy of these methods for functional recovery remains unsatisfactory. Purpose This study was conducted to explore the effect of ultrasound (US)-mediated destruction of poly(lactic-co-glycolic acid) (PLGA) nanobubbles (NBs) expressing nerve growth factor (NGF) (NGF/PLGA NBs) on nerve regeneration in rats following SCI. Materials and methods Adult male Sprague Dawley rats were randomly divided into four treatment groups after Allen hit models of SCI were established. The groups were normal saline (NS) group, NGF and NBs group, NGF and US group, and NGF/PLGA NBs and US group. Histological changes after SCI were observed by hematoxylin and eosin staining. Neuron viability was determined by Nissl staining. Terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling staining was used to examine cell apoptosis. NGF gene and protein expressions were detected by quantitative reverse transcription polymerase chain reaction and Western blotting. Green fluorescent protein expression in the spinal cord was examined using an inverted fluorescence microscope. The recovery of neural function was determined using the Basso, Beattie, and Bresnahan test. Results NGF therapy using US-mediated NGF/PLGA NBs destruction significantly increased NGF expression, attenuated histological injury, decreased neuron loss, inhibited neuronal apoptosis in injured spinal cords, and increased BBB scores in rats with SCI. Conclusion US-mediated NGF/PLGA NBs destruction effectively transfects the NGF gene into target tissues and has a significant effect on the injured spinal cord. The combination of US irradiation and gene therapy through NGF/PLGA NBs holds great promise for the future of nanomedicine and the development of noninvasive treatment options for SCI and other diseases.

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

    NARCIS (Netherlands)

    J.L.M. Jongen (Joost); H. Smits (Helwin); T. Pederzani (Tiziana); M. Bechakra (Malik); S.M. Hossaini (Mehdi); S.K.E. Koekkoek (Bas); F.J.P.M. Huygen; C.I. de Zeeuw (Chris); J.C. Holstege (Jan C.); E.A.J. Joosten (Elbert A.J.)

    2014-01-01

    textabstractNerve injury may cause neuropathic pain, which involves hyperexcitability of spinal dorsal horn neurons. The mechanisms of action of spinal cord stimulation (SCS), an established treatment for intractable neuropathic pain, are only partially understood. We used Autofluorescent Flavoprote

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

    NARCIS (Netherlands)

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

    2014-01-01

    Nerve injury may cause neuropathic pain, which involves hyperexcitability of spinal dorsal horn neurons. The mechanisms of action of spinal cord stimulation (SCS), an established treatment for intractable neuropathic pain, are only partially understood. We used Autofluorescent Flavoprotein Imaging (

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

    NARCIS (Netherlands)

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

    2014-01-01

    Nerve injury may cause neuropathic pain, which involves hyperexcitability of spinal dorsal horn neurons. The mechanisms of action of spinal cord stimulation (SCS), an established treatment for intractable neuropathic pain, are only partially understood. We used Autofluorescent Flavoprotein Imaging

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

    NARCIS (Netherlands)

    J.L.M. Jongen (Joost); H. Smits (Helwin); T. Pederzani (Tiziana); M. Bechakra (Malik); S.M. Hossaini (Mehdi); S.K.E. Koekkoek (Bas); F.J.P.M. Huygen; C.I. de Zeeuw (Chris); J.C. Holstege (Jan C.); E.A.J. Joosten (Elbert A.J.)

    2014-01-01

    textabstractNerve injury may cause neuropathic pain, which involves hyperexcitability of spinal dorsal horn neurons. The mechanisms of action of spinal cord stimulation (SCS), an established treatment for intractable neuropathic pain, are only partially understood. We used Autofluorescent

  11. Electrical stimulation at distinct peripheral sites in spinal nerve injured rats leads to different afferent activation profiles.

    Science.gov (United States)

    Yang, Fei; Chung, Chih-Yang; Wacnik, Paul W; Carteret, Alene F; McKelvy, Alvin D; Meyer, Richard A; Raja, Srinivasa N; Guan, Yun

    2011-11-07

    The neurophysiological basis by which neuromodulatory techniques lead to relief of neuropathic pain remains unclear. We investigated whether electrical stimulation at different peripheral sites induces unique profiles of A-fiber afferent activation in nerve-injured rats. At 4-6weeks after subjecting rats to L5 spinal nerve injury (SNL) or sham operation, we recorded the orthodromic compound action potential (AP) at the ipsilateral L4 dorsal root in response to (1) transcutaneous electrical nerve stimulation (TENS, a patch electrode placed on the dorsum of the foot), (2) subcutaneous electrical stimulation (SQS, electrode inserted subcutaneously along the dorsum of the foot), (3) peroneal nerve stimulation (PNS, electrode placed longitudinally abutting the nerve), and (4) sciatic nerve stimulation (SNS). The area under the Aα/β compound AP was measured as a function of the bipolar, constant-current stimulus intensity (0.02-6.0 mA, 0.2 ms). In both nerve-injured and sham-operated groups, the stimulus-response (S-R) functions of the Aα/β compound APs differed substantially with the stimulation site; SNS having the lowest threshold and largest compound AP waveform, followed by PNS, SQS, and TENS. The S-R function to PNS was shifted to the right in the SNL group, compared to that in the sham-operated group. The Aα/β-threshold to PNS was higher in the SNL group than in the sham-operated group. The S-R functions and Aα/β-thresholds to TENS and SQS were comparable between the two groups. Electrical stimulation of different peripheral targets induced distinctive profiles of A-fiber afferent activation, suggesting that the neuronal substrates for the various forms of peripheral neuromodulatory therapies may differ. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  12. Neuronal nitric oxide synthase mRNA upregulation in rat sensory neurons after spinal nerve ligation: lack of a role in allodynia development.

    Science.gov (United States)

    Luo, Z D; Chaplan, S R; Scott, B P; Cizkova, D; Calcutt, N A; Yaksh, T L

    1999-11-01

    Pharmacological evidence suggests a functional role for spinal nitric oxide (NO) in the modulation of thermal and/or inflammatory hyperalgesia. To assess the role of NO in nerve injury-induced tactile allodynia, we examined neuronal NO synthase (nNOS) expression in the spinal cord and dorsal root ganglia (DRG) of rats with tactile allodynia because of either tight ligation of the left fifth and sixth lumbar spinal nerves or streptozotocin-induced diabetic neuropathy. RNase protection assays indicated that nNOS mRNA (1) was upregulated in DRG, but not spinal cord, neurons on the injury side beginning 1 d after nerve ligation, (2) peaked (approximately 10-fold increase) at 2 d, and (3) remained elevated for at least 13 weeks. A corresponding increase in DRG nNOS protein was also observed and localized principally to small and occasionally medium-size sensory neurons. In rats with diabetic neuropathy, there was no significant change in DRG nNOS mRNA. However, similar increases in DRG nNOS mRNA were observed in rats that did not develop allodynia after nerve ligation and in rats fully recovered from allodynia 3 months after the nerve ligation. Systemic treatment with a specific pharmacological inhibitor of nNOS failed to prevent or reverse allodynia in nerve-injured rats. Thus, regulation of nNOS may contribute to the development of neuronal plasticity after specific types of peripheral nerve injury. However, upregulation of nNOS is not responsible for the development and/or maintenance of allodynia after nerve injury.

  13. High-frequency transcutaneous electrical nerve stimulation alleviates spasticity after spinal contusion by inhibiting activated microglia in rats.

    Science.gov (United States)

    Hahm, Suk-Chan; Yoon, Young Wook; Kim, Junesun

    2015-05-01

    Transcutaneous electrical nerve stimulation (TENS) can be used as a physical therapy for spasticity, but the effects of TENS on spasticity and its underlying mechanisms remain unclear. The purpose of this study was to test the effects of TENS on spasticity and the role of activated microglia as underlying mechanisms of TENS treatment for spasticity in rats with a 50-mm contusive spinal cord injury (SCI). A spinal contusion was made at the T12 spinal segment in adult male Sprague-Dawley rats using the NYU impactor. Behavioral tests for motor function were conducted before and after SCI and before and after TENS application. To assess spasticity, the modified Ashworth scale (MAS) was used before and after SCI, high-frequency (HF)/low-frequency (LF) TENS application at 3 different intensities (motor threshold [MT], 50% and 90% MT) or minocycline administration. Immunohistochemistry for microglia was performed at the lumbar spinal segments. Motor recovery reached a plateau approximately 28 days after SCI. Spasticity was well developed and was sustained above the MAS grade of 3, beginning at 28 days after SCI. HF-TENS at 90% MT significantly alleviated spasticity. Motor function did not show any significant changes with LF- or HF-TENS treatment. HF-TENS significantly reduced the proportion of activated microglia observed after SCI. Minocycline, the microglia inhibitor, also significantly alleviated spasticity with the reduction of activated microglia expression. These results suggest that HF-TENS at 90% MT alleviates spasticity in rats with SCI by inhibiting activated microglia. © The Author(s) 2014.

  14. Early application of tail nerve electrical stimulation-induced walking training promotes locomotor recovery in rats with spinal cord injury.

    Science.gov (United States)

    Zhang, S-X; Huang, F; Gates, M; Shen, X; Holmberg, E G

    2016-11-01

    This is a randomized controlled prospective trial with two parallel groups. The objective of this study was to determine whether early application of tail nerve electrical stimulation (TANES)-induced walking training can improve the locomotor function. This study was conducted in SCS Research Center in Colorado, USA. A contusion injury to spinal cord T10 was produced using the New York University impactor device with a 25 -mm height setting in female, adult Long-Evans rats. Injured rats were randomly divided into two groups (n=12 per group). One group was subjected to TANES-induced walking training 2 weeks post injury, and the other group, as control, received no TANES-induced walking training. Restorations of behavior and conduction were assessed using the Basso, Beattie and Bresnahan open-field rating scale, horizontal ladder rung walking test and electrophysiological test (Hoffmann reflex). Early application of TANES-induced walking training significantly improved the recovery of locomotor function and benefited the restoration of Hoffmann reflex. TANES-induced walking training is a useful method to promote locomotor recovery in rats with spinal cord injury.

  15. Selective control by posterior spinal nerve roots of micturition and erection in rats

    Institute of Scientific and Technical Information of China (English)

    Wenting Wang; Mouwang Zhou; Genying Zhu; Tao Li; Nan Liu

    2012-01-01

    The posterior rootlets in L6 and S1 spinal cord of adult male Sprague-Dawley rats underwent electrostimulation. The bladder pressure, urethral perfusion pressure and intracavernous pressure were recorded. When some posterior rootlets of L6 and S1 were electrostimulated, the intracavernous pressure peaked rapidly, but the bladder pressure and the urethral perfusion pressure curve did not show great change. When other rootlets were stimulated, the bladder pressure changed greatly, but the urethral perfusion pressure and the intracavernous pressure did not show great change. When different rootlets were stimulated, the urethral perfusion pressure changed maximally, but there were no great changes in bladder pressure or intracavernous pressure. Furthermore, stimulation of some rootlets produced simultaneous changes in two or three different pressure measures mentioned above. The results demonstrate that regulation by L6 and S1 posterior rootlets of the rat bladder detrusor, external urethral sphincter and penis cavernous body are significantly distinct. Different rootlets can be distinguished by electrostimulation.

  16. Expression of NF-кB in Schwann cells and its effect on motor neuron apoptosis in spinal cord following sciatic nerves injury in rats

    Institute of Scientific and Technical Information of China (English)

    WANG Yong-tang; LU Xiu-min; YU Ying; YANG Yan-hong; GAO Jie

    2007-01-01

    Objective:To explore the expression of nuclear factor-kappa B (NF-кB) in Schwann cells (SCs) and its effect on motor neuron apoptosis in spinal cord following sciatic nerves injury in adult rats. Methods:Thirty-six adult Sprague-Dawley (SD) rats were divided randomly into normal control group (n=6),and sciatic nerves crushing group (n=30),and the later was further equally randomized into 5 nerves were examined by immunohistochemistry staining,and the apoptosis of motor neurons in spinalcord of lumbar 4 to lumbar 6(L4-L6)was investigated by terminal deoxynucleotidyl transferase mediated dUTP-biotin nick end labeling (TUNEL) assay.Both were quantitated by image analysis.Results:In the normal control group (P<0.05,P<0.01).At 1 d after sciatic nerves crushing,the expression of served in the time-course on motor neuron apoptosis after sciatic nerves injury.Correlation analyses refollowing sciatic nerves injury(r=0.976 0,P<0.01).Conclusion:After injury of sciatic nerves,the presence and up-regulation of NF-κB in SCs may be involved in motor neuron apoptosis in L4-L6 spinal cord.

  17. Blockade of spinal nerves inhibits expression of neural growth factor in the myocardium at an early stage of acute myocardial infarction in rats.

    Science.gov (United States)

    Yue, W; Guo, Z

    2012-09-01

    Neural growth factor (NGF) is required for healing and sprouting of cardiac sympathetic and sensory nerves and plays important roles in cardiac protection, sustaining cardiac function and regeneration in ischaemic heart disease. The overexpression or lack of the NGF could be harmful to the heart. In this study, we examined the role of spinal nerves in the modulation of expression of the NGF in the myocardium at risk of ischaemia soon after acute myocardial infarction in rats. Coronary artery occlusion (CAO) was carried out in anaesthetized rats with and without preconditioning of blockade of the spinal nerves. The expression of the NGF protein and mRNA in the myocardium at risk of ischaemia was examined using immunohistochemical assay, enzyme-linked immunosorbent assay, and real-time quantitative reverse transcription polymerase chain reaction assay. In the left ventricle, immunoreactive cells and fibre-like structures were mainly located in the myocardium and in the epicardium. The NGF protein expression was increased by two-fold in the myocardium at risk of ischaemia during the 60 min of CAO, while the NGF mRNA was up-regulated three-fold, at 360 min after acute myocardial infarction. The blockade of the spinal nerves completely abolished the up-regulation of the NGF in the myocardium (Pmyocardial infarction, an effect which can be inhibited by the blockade of these nerves.

  18. Upregulated TLR3 Promotes Neuropathic Pain by Regulating Autophagy in Rat With L5 Spinal Nerve Ligation Model.

    Science.gov (United States)

    Chen, Weijia; Lu, Zhijun

    2016-12-21

    Microglia, rapidly activated following peripheral nerve injury (PNI), accumulate within the spinal cord and adopt inflammation that contributes to development and maintenance of neuropathic pain. Microglia express functional Toll-like receptors (TLRs), which play pivotal roles in regulating inflammatory processes. However, little is known about the role of TLR3 in regulating neuropathic pain after PNI. Here TLR3 expression and autophagy activation was assayed in dorsal root ganglions and in microglia following PNI by using realtime PCR, western blot and immunohistochemistry. The role of TLR3/autophagy signaling in regulating tactile allodynia was evaluated by assaying paw mechanical withdrawal threshold and cold allodynia after intrathecal administration of Poly (I:C) and 3-methyladenine (3-MA). We found that L5 spinal nerve ligation (SNL) induces the expression of TLR3 in dorsal root ganglions and in primary rat microglia at the mRNA and protein level. Meanwhile, L5 SNL results in an increased activation of autophagy, which contributes to microglial activation and subsequent inflammatory response. Intrathecal administration of Poly (I:C), a TLR3 agonist, significantly increases the activation of microglial autophagy, whereas TLR3 knockdown markedly inhibits L5 SNL-induced microglial autophagy. Poly (I:C) treatment promotes the expression of proinflammatory mediators, whereas 3-MA (a specific inhibitor of autophagy) suppresses Poly (I:C)-induced secretion of proinflammatory cytokines. Autophagy inhibition further inhibits TLR3-mediated mechanical and cold hypersensitivity following SNL. These results suggest that inhibition of TLR3/autophagy signaling contributes to alleviate neurophathic pain triggered by SNL.

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

    Directory of Open Access Journals (Sweden)

    Sheng-Hua Wu

    2015-01-01

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

  20. Changes in brain-derived neurotrophic factor expression after transplanting microencapsulated sciatic nerve cells of rabbits into injured spinal cord of rats

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    BACKGROUND: Changes of brain-derived neurotrophic factor (BDNF) expression reflect function of nerve cells; meanwhile, they play a significant role in researching interventions on plerosis of nerve injury.OBJECTIVE: To observe and compare the effects on changes of BDNF expression in rats with spinal cord injury between microencapsulated sciatic nerve cells of rabbits and only transplanting sciatic nerve cells of rabbits.DESIGN: Randomized controlled animal study.SETTING: Medical School of Jiujiang College.MATERIALS: The experiment was carried out in the Medical Science Researching Center, Jiujiang College from May 2004 to May 2006. A total of 90 healthy adult SD rats, weighing 250 - 300 g, of either gender; and 10 rabbits, weighing 2.0 - 2.5 kg, of either gender, were provided by Jiangxi Experimental Animal Center.METHODS: Sciatic nerve tissue of rabbits was separated to make cell suspension. After centrifugation,suspension was mixed with 15 g/L alginate saline solution and ejaculated to 20 mmol/L barium chloride saline solution by double-cavity ejaculator. The obtained cell microcapsules were suspended in saline. Rats were randomly divided into microencapsulated group, only suspension group, and only injured group with 30 animals in each group. After anesthesia, T10 spinous process and vertebra lamina of rats in the former two groups were exposed. Spinal cord tissue in 2-mm length was removed from rats by spinal cord right hemi-section. The gelatin sponges with the size of 2 mm × 2 mm × 2 mm were grafted as filing cage,and absorbed 10 μμ L microencapsulated sciatic nerve cells of rabbit in the microencapsulated group and 10 μ L sciatic nerve cells of rabbits in the only suspension group; respectively. No graft was placed in the only injured group.MAIN OUTCOME MEASURES: On the 1st, 3rd, 7th, 14th and 28th days after operation,immunohistochemistry (SABC technique) was used to detect distribution and amount of positive-reactive neurons in BDNF of spinal cord

  1. Tail nerve electrical stimulation combined with scar ablation and neural transplantation promotes locomotor recovery in rats with chronically contused spinal cord.

    Science.gov (United States)

    Zhang, Shu-xin; Huang, Fengfa; Gates, Mary; Holmberg, Eric G

    2012-05-25

    To date, few treatment strategies applying cellular transplantation to the chronically injured spinal cord have yielded significant functional improvement in animal experiments. Here we report that significant improvement of locomotor function was achieved in rats with chronic spinal cord injury (SCI) by the application of combination treatments with tail nerve electrical stimulation (TANES), which can activate the central pattern generator, inducing active weight-supported stepping. Contusion injury (25 mm) to spinal cord T10 was produced by using the NYU impactor device in female, adult Long-Evans rats. Rats in 2 of 4 groups with SCI received basic treatments (scar ablation followed by transplantation of lamina propria of olfactory mucosa and cultured olfactory ensheathing cells into the lesion cavity) 6 weeks after SCI. Rats both with and without basic treatments were subjected to TANES one week after secondary surgery or 7 weeks after SCI. Sixteen weeks after secondary surgery or 22 weeks after SCI rats in two groups receiving TANES significantly improved their functional recovery compared with those without TANES, when evaluated with BBB open field rating scale (pinjury level, which is critical for functional recovery. Additionally, TANES may promote axonal regeneration, including those from supraspinal level. Since TANES demonstrated considerable potential for achieving improvement of functional recovery in rat model, it would suggest a new strategy for chronic SCI. Copyright © 2012 Elsevier B.V. All rights reserved.

  2. Ameliorating Role of Caffeic Acid Phenethyl Ester (CAPE Against Methotrexate-Induced Oxidative Stress in the Sciatic Nerve, Spinal Cord and Brain Stem Tissues of Rats

    Directory of Open Access Journals (Sweden)

    Ertuğrul Uzar

    2010-03-01

    Full Text Available OBJECTIVE: Methotrexate (MTX-associated neurotoxicity is an important clinical problem in cancer patients, but the mechanisms of MTX-induced neurotoxicity are not yet known exactly. The aims of this study were (1 to investigate the possible role of malondialdehyde (MDA, superoxide dismutase (SOD enzyme, glutathione peroxidase (GSH-Px and catalase (CAT in the pathogenesis of MTX-induced neurotoxicity and (2 to determine whether there is a putative protective effect of caffeic acid phenethyl ester (CAPE on MTX-induced neurotoxicity in the spinal cord, brainstem and sciatic nerve of rats. METHODS: A total of 19 adult Wistar male rats were divided into three experimental groups. Group I, control group; Group II, MTX-treated group; and Group III, MTX + CAPE-treated group. MTX was administered to the MTX and MTX + CAPE groups intraperitoneally (IP with a single dose of 20 mg/kg on the second day of the experiment. CAPE was administered to the MTX + CAPE group IP with a dose of 10 μmol/kg for 7 days. RESULTS: In the sciatic nerve and spinal cord tissue, CAT and GSH-Px activities were increased in the MTX group in comparison with the control group. CAPE treatment with MTX significantly decreased CAT and GSH-Px activities in the neuronal tissues of rats in comparison with the MTX group. In the spinal cord and brainstem tissues, SOD activity in the MTX group was decreased in comparison with the control group, but in the sciatic nerve, there was no significant difference. In the spinal cord and brainstem of rats, SOD activity was increased in the CAPE + MTX group when compared with the MTX group. The level of MDA was higher in the MTX group than in the control group. CAPE administration with MTX injection caused a significant decrease in MDA level when compared with the MTX group. CONCLUSION: These results reveal that MTX increases oxidative stress in the sciatic nerve, spinal cord and brainstem of rats and that CAPE has a preventive effect on the

  3. Ankle joint mobilization reduces axonotmesis-induced neuropathic pain and glial activation in the spinal cord and enhances nerve regeneration in rats.

    Science.gov (United States)

    Martins, Daniel F; Mazzardo-Martins, Leidiane; Gadotti, Vinícius M; Nascimento, Francisney P; Lima, Denise A N; Speckhann, Breno; Favretto, Gisela A; Bobinski, Franciane; Cargnin-Ferreira, Eduardo; Bressan, Elisângela; Dutra, Rafael C; Calixto, João B; Santos, Adair R S

    2011-11-01

    An important issue in physical rehabilitation is how to protect from or to reduce the effects of peripheral nerve injury. In the present study, we examined whether ankle joint mobilization (AJM) would reduce neuropathic pain and enhance motor functional recovery after nerve injury. In the axonotmesis model, AJM during 15 sessions every other day was conducted in rats. Mechanical and thermal hyperalgesia and motor performance deficit were measured for 5 weeks. After 5 weeks, we performed morphological analysis and quantified the immunoreactivity for CD11b/c and glial fibrillary acidic protein (GFAP), markers of glial activation, in the lumbar spinal cord. Mechanical and thermal hyperalgesia and motor performance deficit were found in the Crush+Anesthesia (Anes) group (P<0.001), which was significantly decreased after AJM (P<0.001). In the morphological analysis, the Crush+Anes group presented reduced myelin sheath thickness (P<0.05), but the AJM group presented enhanced myelin sheath thickness (P<0.05). Peripheral nerve injury increased the immunoreactivity for CD11b/c and GFAP in the spinal cord (P<0.05), and AJM markedly reduced CD11b/c and GFAP immunoreactivity (P<0.01). These results show that AJM in rats produces an antihyperalgesic effect and peripheral nerve regeneration through the inhibition of glial activation in the dorsal horn of the spinal cord. These findings suggest new approaches for physical rehabilitation to protect from or reduce the effects of nerve injury. Copyright © 2011 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.

  4. Spinal cord response to laser treatment of injured peripheral nerve

    Energy Technology Data Exchange (ETDEWEB)

    Rochkind, S.; Vogler, I.; Barr-Nea, L. (Ichilov Hospital, Tel-Aviv Medical Center (Israel))

    1990-01-01

    The authors describe the changes occurring in the spinal cord of rats subjected to crush injury of the sciatic nerve followed by low-power laser irradiation of the injured nerve. Such laser treatment of the crushed peripheral nerve has been found to mitigate the degenerative changes in the corresponding neurons of the spinal cord and induce proliferation of neuroglia both in astrocytes and oligodendrocytes. This suggests a higher metabolism in neurons and a better ability for myelin production under the influence of laser treatment.

  5. Time course of immediate early gene protein expression in the spinal cord following conditioning stimulation of the sciatic nerve in rats.

    Science.gov (United States)

    Bojovic, Ognjen; Panja, Debabrata; Bittins, Margarethe; Bramham, Clive R; Tjølsen, Arne

    2015-01-01

    Long-term potentiation induced by conditioning electrical stimulation of afferent fibers is a widely studied form of synaptic plasticity in the brain and the spinal cord. In the spinal cord dorsal horn, long-term potentiation is induced by a series of high-frequency trains applied to primary afferent fibers. Conditioning stimulation (CS) of sciatic nerve primary afferent fibers also induces expression of immediate early gene proteins in the lumbar spinal cord. However, the time course of immediate early gene expression and the rostral-caudal distribution of expression in the spinal cord have not been systematically studied. Here, we examined the effects of sciatic nerve conditioning stimulation (10 stimulus trains, 0.5 ms stimuli, 7.2 mA, 100 Hz, train duration 2 s, 8 s intervals between trains) on cellular expression of immediate early genes, Arc, c-Fos and Zif268, in anesthetized rats. Immunohistochemical analysis was performed on sagittal sections obtained from Th13- L5 segments of the spinal cord at 1, 2, 3, 6 and 12 h post-CS. Strikingly, all immediate early genes exhibited a monophasic increase in expression with peak increases detected in dorsal horn neurons at 2 hours post-CS. Regional analysis showed peak increases at the location between the L3 and L4 spinal segments. Both Arc, c-Fos and Zif268 remained significantly elevated at 2 hours, followed by a sharp decrease in immediate early gene expression between 2 and 3 hours post-CS. Colocalization analysis performed at 2 hours post-CS showed that all c-Fos and Zif268 neurons were positive for Arc, while 30% and 43% of Arc positive neurons were positive for c-Fos and Zif268, respectively. The present study identifies the spinal cord level and time course of immediate early gene (IEGP) expression of relevance for analysis of IEGPs function in neuronal plasticity and nociception.

  6. Intranasal nerve growth factor bypasses the blood-brain barrier and affects spinal cord neurons in spinal cord injur y

    Institute of Scientific and Technical Information of China (English)

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

    2014-01-01

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

  7. Sciatic nerve ligation causes impairment of mitochondria associated with changes in distribution, respiration, and cardiolipin composition in related spinal cord neurons in rats.

    Science.gov (United States)

    Keilhoff, Gerburg; Becker, Axel; Kropf, Siegfried; Schild, Lorenz

    2016-10-01

    Sciatic nerve irritation is often associated with disturbed Ca(2+) homeostasis in related neurons of the spinal cord. Since mitochondria substantially contribute to Ca(2+) homeostasis and little information is available, we studied the effects of loose sciatic nerve ligation, a chronic constriction injury (CCI), on neuronal mitochondria of the L3-L6 regions. Three groups of rats (untreated, sham operated, and ligated) were explored. For the characterization of mitochondria, specimens of the L3-L6 spinal cord regions were evaluated with respect to intracellular localization using pyruvate dehydrogenase immunohistochemistry and Mitotracker Red, and the ATP producing machinery by LC-MS/MS technique for the analysis of cardiolipin and high-resolution respirometry for the measurement of oxygen consumption. Therefore, the phospholipid cardiolipin supports electron transfer within the respiratory chain as part of mitochondrial respiration and is of high impact on the physical properties of the mitochondrial membrane system. Histological analysis of spinal cord motor neurons revealed clustering of mitochondria in ipsilateral samples from ligated animals 14 days after the insult. This phenomenon was similarly evident in the respective contralateral side. The intensity of MT-Red staining was enhanced exclusively at the ipsilateral side, indicating increased mitochondrial activity. CCI of the sciatic nerve caused massive changes in the composition of cardiolipin reflecting mitochondrial impairment in the early phase followed by regeneration processes as late response. Sciatic nerve CCI caused decrease in the capacity of mitochondrial ATP production that recovered within 14 days after treatment. In conclusion, we provide evidence that clustering of mitochondria, already verified for the spinal cord sensory neurons after CCI, also occurs in the respective motor neurons. Further we have demonstrated transient impairment of the capacity of mitochondrial ATP production in tissue

  8. Modified cytoplasmic Ca2+ sequestration contributes to spinal cord injury-induced augmentation of nerve-evoked contractions in the rat tail artery.

    Science.gov (United States)

    Al Dera, Hussain; Callaghan, Brid P; Brock, James A

    2014-01-01

    In rat tail artery (RTA), spinal cord injury (SCI) increases nerve-evoked contractions and the contribution of L-type Ca2+ channels to these responses. In RTAs from unoperated rats, these channels play a minor role in contractions and Bay K8644 (L-type channel agonist) mimics the effects of SCI. Here we investigated the mechanisms underlying the facilitatory actions of SCI and Bay K8644 on nerve-evoked contractions of RTAs and the hypothesis that Ca2+ entering via L-type Ca2+ channels is rapidly sequestered by the sarcoplasmic reticulum (SR) limiting its role in contraction. In situ electrochemical detection of noradrenaline was used to assess if Bay K8644 increased noradrenaline release. Perforated patch recordings were used to assess if SCI changed the Ca2+ current recorded in RTA myocytes. Wire myography was used to assess if SCI modified the effects of Bay K8644 and of interrupting SR Ca2+ uptake on nerve-evoked contractions. Bay K8644 did not change noradrenaline-induced oxidation currents. Neither the size nor gating of Ca2+ currents differed between myocytes from sham-operated (control) and SCI rats. Bay K8644 increased nerve-evoked contractions in RTAs from both control and SCI rats, but the magnitude of this effect was reduced by SCI. By contrast, depleting SR Ca2+ stores with ryanodine or cyclopiazonic acid selectively increased nerve-evoked contractions in control RTAs. Cyclopiazonic acid also selectively increased the blockade of these responses by nifedipine (L-type channel blocker) in control RTAs, whereas ryanodine increased the blockade produced by nifedipine in both groups of RTAs. These findings suggest that Ca2+ entering via L-type channels is normally rapidly sequestered limiting its access to the contractile mechanism. Furthermore, the findings suggest SCI reduces the role of this mechanism.

  9. Modified cytoplasmic Ca2+ sequestration contributes to spinal cord injury-induced augmentation of nerve-evoked contractions in the rat tail artery.

    Directory of Open Access Journals (Sweden)

    Hussain Al Dera

    Full Text Available In rat tail artery (RTA, spinal cord injury (SCI increases nerve-evoked contractions and the contribution of L-type Ca2+ channels to these responses. In RTAs from unoperated rats, these channels play a minor role in contractions and Bay K8644 (L-type channel agonist mimics the effects of SCI. Here we investigated the mechanisms underlying the facilitatory actions of SCI and Bay K8644 on nerve-evoked contractions of RTAs and the hypothesis that Ca2+ entering via L-type Ca2+ channels is rapidly sequestered by the sarcoplasmic reticulum (SR limiting its role in contraction. In situ electrochemical detection of noradrenaline was used to assess if Bay K8644 increased noradrenaline release. Perforated patch recordings were used to assess if SCI changed the Ca2+ current recorded in RTA myocytes. Wire myography was used to assess if SCI modified the effects of Bay K8644 and of interrupting SR Ca2+ uptake on nerve-evoked contractions. Bay K8644 did not change noradrenaline-induced oxidation currents. Neither the size nor gating of Ca2+ currents differed between myocytes from sham-operated (control and SCI rats. Bay K8644 increased nerve-evoked contractions in RTAs from both control and SCI rats, but the magnitude of this effect was reduced by SCI. By contrast, depleting SR Ca2+ stores with ryanodine or cyclopiazonic acid selectively increased nerve-evoked contractions in control RTAs. Cyclopiazonic acid also selectively increased the blockade of these responses by nifedipine (L-type channel blocker in control RTAs, whereas ryanodine increased the blockade produced by nifedipine in both groups of RTAs. These findings suggest that Ca2+ entering via L-type channels is normally rapidly sequestered limiting its access to the contractile mechanism. Furthermore, the findings suggest SCI reduces the role of this mechanism.

  10. Effects of transplantation of microencapsulated rabbit sciatic nerve on nuclear factor-kappa B expression after spinal cord injury in rats

    Institute of Scientific and Technical Information of China (English)

    Xiaolian Wang; Jianmin Ma; Hui Chen; Deming Liu

    2009-01-01

    BACKGROUND: It has been reported that nuclear factor-kappa B (NF- k B), activated after spinal cord injury in rats, plays a key role in inflammatory responses in the central nervous system.OBJECTIVE: To investigate the effects of transplantation of microencapsulated rabbit sciatic nerve on NF- k B expression and motor function after spinal cord injury in rats, and to compare the results with the transplantation of rabbit sciatic nerve alone.DESIGN, TIME AND SETTING: This completely randomized, controlled study was performed at the Department of Neurobiology, Medical College of Nanchang University between December 2007 and July 2008.MATERIALS: A rabbit anti-NF- k B P65 monoclonal antibody was made by the Santa Cruz Company, USA and a streptavidin peroxidase immunohistochemical kit was provided by the Sequoia Company, China.METHODS: Eight rabbits were used to prepare a sciatic nerve cell suspension that was divided into two parts: one stored for transplantation, and the other mixed with a 1.5% sodium alginate solution. One hundred and twenty adult Sprague Dawley rats weighing 220-250 g were randomly divided into four groups: the microencapsulated cell group (n = 36), the non-encapsulated cell group (n = 36), the saline group (n = 36) and the sham operation group (n = 12). The first three groups underwent a right hemisection injury of the spinal cord at the T level, into which was transplanted a gelatin sponge soaked with 10 μ L of a microencapsulated nerve tissue/cell suspension (microencapsulated cell group), a tissue/cell suspension (non-encapsulated cell group) or physiological saline (saline group). In the sham operation group the vertebrae were exposed, but the spinal cord was not injured, and no implantation was given.MAIN OUTCOME MEASURES: Pathological changes were detected using hematoxylin-eosin staining; NF- K B expression was quantified using immunohistochemical staining; motor function was assessed using the Basso, Beattie and Bresnahan (BBB) scale

  11. Analysis of motor fibers in the communicating branch between the cervical nerves and the spinal accessory nerve to innervate trapezius in the rat.

    Science.gov (United States)

    Yan, Jun; Hitomi, Jiro

    2006-11-01

    The communicating branch between the ventral rami of cervical nerves and the spinal accessory nerve (SAN) has been reported to also send motor fibers to supply the trapezius. However, the motor fiber type of the communicating branch and its peripheral distribution are still unclear. To determine the fiber elements within the branch and its peripheral distribution of the motor fibers in the trapezius, the anterograde tracing method was used in this study. The results show that a few a motor end plates from the communicating branch were observed on the extrafusal fibers, while in the muscle spindle the motor elements from the communicating branch were distributed to the polar portions of the intrafusal fibers. These results indicated that the motor fibers passing through the communicating branch to supply the trapezius are mainly y motor fibers, with some a motor fibers. Moreover, the a and y motor fibers from the communicating branch were observed in the clavotrapezius, acromiotrapezius and the rostral part of spinotrapezius. These findings also correlate with the clinical observation indicating that even when the spinal accessory nerve is injured, the trapezius is still capable of slight movement.

  12. Variation in rat sciatic nerve anatomy: implications for a rat model of neuropathic pain.

    Science.gov (United States)

    Asato, F; Butler, M; Blomberg, H; Gordh, T

    2000-03-01

    We discovered a variation of rat sciatic nerve anatomy as an incidental finding during the anatomical exploration of the nerve lesion site in a rat neuropathic pain model. To confirm the composition and distribution of rat sciatic nerve, macroscopic anatomical investigation was performed in both left and right sides in 24 adult Sprague-Dawley rats. In all rats, the L4 and L5 spinal nerves were fused tightly to form the sciatic nerve. However, the L6 spinal nerve did not fuse with this nerve completely as a part of the sciatic nerve, but rather sent a thin branch to it in 13 rats (54%), whereas in the remaining 11 rats (46%), L6 ran separately along with the sciatic nerve. Also, the L3 spinal nerve sent a thin branch to the L4 spinal nerve or sciatic nerve in 6 rats (25%). We conclude that the components of sciatic nerve in Sprague-Dawley rats vary from L3 to L6; however, the major components are L4 and L5 macroscopically. This finding is in contrast to the standard textbooks of rat anatomy which describe the sciatic nerve as having major contributions from L4, L5, and L6.

  13. Precise orientation of brachialis muscle branch in the spinal nerve roots in rats%大鼠肱肌肌支的脊髓神经根定位

    Institute of Scientific and Technical Information of China (English)

    周文俊; 张成钢; 胡韶楠; 朱艺; 徐建光

    2008-01-01

    Objective To compare the efficacy of retrograde tracing and electrophysiologic localization in precise orientation of brachialis muscle branch in the spinal nerve roots in a rat model, and discuss the feasibility of electrophysiological orientation of brachialis muscle branch of the musculocutaneous nerve in human. Methods Adult Sprague Dawley rats were used. Retrograde tracing of brachialis muscle branch or brachialis muscle in various combinations of nerve root transection-preservation was done. Compound muscle action potentials of brachialis muscle were recorded while various roots of the brachial plexus were stimulated. Results Brachialis muscle in rat received dual innervation from the musculocutaneous nerve and radial nerve. The former was mainly from C5 and C6 spinal nerve roots and the latter from C7 spinal nerve root. The results of retrograde tracing agreed with the results of electrophysiologic testing. Conclusion Both retrograde tracing and electrophysiologic testing could be used in precise localization of spinal nerve root origin of forelimb muscles. Electrophysiological studies could be employed in precise orientation of brachialis and its motor branches in human.%目的 比较逆行示踪法及肌电图检测法在定位肱肌肌支及肱肌脊髓神经根起源中的价值,并探讨将肌电图检测法运用于定位人类肌皮神经肱肌肌支脊髓神经根起源的可能性.方法 在大鼠臂丛神经根切断-保留模型中运用神经元逆行示踪法定位肱肌肌支及肱肌的脊髓神经根起源;通过分析刺激大鼠各臂丛神经根时肱肌记录到的CMAP指标定位肱肌肌支及肱肌的脊髓神经根起源.结果 大鼠桡神经肱肌肌支的运动纤维主要来源于C7神经根,大鼠肌皮神经肱肌肌支的运动纤维主要来源于C5、6神经根;在定位大鼠肱肌的脊髓神经根起源时,肌电图法与逆行示踪法的检测结果基本一致.结论 通过分析逆行示踪和肌电图检测的结果,

  14. The Morphofunctional Effect of the Transplantation of Bone Marrow Stromal Cells and Predegenerated Peripheral Nerve in Chronic Paraplegic Rat Model via Spinal Cord Transection

    Science.gov (United States)

    Buzoianu-Anguiano, Vinnitsa; Orozco-Suárez, Sandra; García-Vences, Elisa; Caballero-Chacón, Sara; Guizar-Sahagún, Gabriel; Chavez-Sanchez, Luis; Grijalva, Israel

    2015-01-01

    Functional recovery following spinal cord injury (SCI) is limited by poor axonal and cellular regeneration as well as the failure to replace damaged myelin. Employed separately, both the transplantation of the predegenerated peripheral nerve (PPN) and the transplantation of bone marrow stromal cells (BMSCs) have been shown to promote the regrowth and remyelination of the damaged central axons in SCI models of hemisection, transection, and contusion injury. With the aim to test the effects of the combined transplantation of PPN and BMSC on regrowth, remyelination, and locomotor function in an adult rat model of spinal cord (SC) transection, 39 Fischer 344 rats underwent SC transection at T9 level. Four weeks later they were randomly assigned to traumatic spinal cord injury (TSCI) without treatment, TSCI + Fibrin Glue (FG), TSCI + FG + PPN, and TSCI + FG + PPN + BMSCs. Eight weeks after, transplantation was carried out on immunofluorescence and electron microscope studies. The results showed greater axonal regrowth and remyelination in experimental groups TSCI + FG + PPN and TSCI + FG + PPN + BMSCs analyzed with GAP-43, neuritin, and myelin basic protein. It is concluded that the combined treatment of PPN and BMSCs is a favorable strategy for axonal regrowth and remyelination in a chronic SC transection model. PMID:26634157

  15. [Spinal accessory nerve and lymphatic neck dissection].

    Science.gov (United States)

    Pinsolle, V; Michelet, V; Majoufre, C; Caix, P; Siberchicot, F; Pinsolle, J

    1997-09-01

    Radical neck dissection was the golden standard of treatment for cervical nodes in head and neck tumors. From the seventies, the preservation of the spinal accessory nerve has become increasingly popular in order to improve the functional result of the neck dissections. The aim of this study was to assess the degree of functional disability associated with each type of neck dissection and the value of anatomical references for dissection of the spinal accessory nerve. One hundred twenty seven patients were evaluated 1 month and 1 year after radical, functional or supraomohyoid neck dissection with a questionnaire and a physical examination. Anatomical measurements of the spinal accessory nerve were performed in 20 patients. We found considerable or severe shoulder dysfunction in 7%, 34% and 51% respectively of patients in whom supraomohyoid, functional and radical neck dissections were performed. Furthermore 49% of patients having undergone a radical neck dissection had little or no symptoms. Sacrifice of the spinal accessory nerve in radical neck dissection may lead to shoulder dysfunction. A functional disability may also be associated, although in a less extent, with any neck dissection in which the spinal accessory nerve is dissected and placed in traction. There is a large variation in the degree of functional disability and pain in patients with similar neck dissections. The course of the spinal accessory nerve in the neck makes it particularly vulnerable to injury during the dissection near the sternocleidomastoid muscle and in the posterior cervical triangle.

  16. The Neuroprotective Effect of Alcoholic Extract of Cannabis Sativa on Neuronal Density of Spinal Cord Alpha Motoneurons after Sciatic Nerve Injury in Rats

    Directory of Open Access Journals (Sweden)

    M Tehranipour

    2011-07-01

    Full Text Available Introduction: Injuries of the peripheral nerve system affect the neurons cell body leading to axon injury. Cannabis sativa plant has anti oxidant and anti apoptotic effects. Therefore the aim of present study was to study the neuroprotective effect of alcoholic extract of cannabis sativa leaves on neuronal density of alpha motoneurons in spinal cord after sciatic nerve injury in rats. Methods: In this experimental research, animals were divided into four groups; A: control, B: compression, C: compression+ treatment with 25 mg/kg alcoholic extract, D: compression + treatment with 50 mg/kg extract (n=8. At first, sciatic nerve compression in B, C and D groups was achieved for 60 seconds using locker pincers. Alcoholic extract was injected intra peritoneally in the first and second weeks after compression. Then 28 days after compression, under profusion method, the lumbar spinal cord was sampled and the numerical density in each group was compared with the compression group. The data was analyzed with the use of Minitab 14 software and ANOVA statistical test. Results: Neuronal density showed a meaningful difference in the compression and control groups(P<0.001. Neuronal density in treatment groups(25, 50 mg/kg also had a meaningful increase(P<0.001 as compared to the compression group. Conclusion: Alcoholic extract of cannabis sativa leaves has a neuroprotective effect on spinal cord alpha motoneurons after injury. This could be due to growth and regeneration factors present in the alcoholic extract of cannabis sativa leaves that induce regeneration process in injured neurons or prevent degeneration.

  17. Transcutaneous electrical nerve stimulation attenuates CFA-induced hyperalgesia and inhibits spinal ERK1/2-COX-2 pathway activation in rats.

    Science.gov (United States)

    Fang, Jun-Fan; Liang, Yi; Du, Jun-Ying; Fang, Jian-Qiao

    2013-06-15

    Transcutaneous electrical nerve stimulation (TENS) is a non-pharmacologic treatment for pain relief. In previous animal studies, TENS effectively alleviated Complete Freund's Adjuvant (CFA)- or carrageenan-induced inflammatory pain. Although TENS is known to produce analgesia via opioid activation in the brain and at the spinal level, few reports have investigated the signal transduction pathways mediated by TENS. Prior studies have verified the importance of the activation of extracellular signal-regulated kinase (ERK) signal transduction pathway in the spinal cord dorsal horn (SCDH) in acute and persistent inflammatory pains. Here, by using CFA rat model, we tested the efficacy of TENS on inhibiting the expressions of p-ERK1/2 and of its downstream cyclooxygenase-2 (COX-2) and the level of prostaglandin E2 (PGE2) at spinal level. Rats were randomly divided into control, model and TENS groups, and injected subcutaneously with 100 μl CFA or saline in the plantar surface of right hind paw. Rats in the TENS group were treated with TENS (constant aquare wave, 2 Hz and 100 Hz alternating frequencies, intensities ranging from 1 to 2 mA, lasting for 30 min each time) at 5 h and 24 h after injection. Paw withdrawal thresholds (PWTs) were measured with dynamic plantar aesthesiometer at 3d before modeling and 5 h, 6 h, and 25 h after CFA injection. The ipsilateral sides of the lumbar spinal cord dosral horns were harvested for detecting the expressions of p-ERK1/2 and COX-2 by western blot analysis and qPCR, and PGE2 by ELISA. CFA-induced periphery inflammation decreased PWTs and increased paw volume of rats. TENS treatment significantly alleviated mechanical hyperalgesia caused by CFA. However, no anti-inflammatory effect of TENS was observed. Expression of p-ERK1/2 protein and COX-2 mRNA was significantly up-regualted at 5 h and 6 h after CFA injection, while COX-2 and PGE2 protein level only increased at 6 h after modeling. Furthermore, the high expression of p-ERK1

  18. Peripheral nerve grafts support regeneration after spinal cord injury.

    Science.gov (United States)

    Côté, Marie-Pascale; Amin, Arthi A; Tom, Veronica J; Houle, John D

    2011-04-01

    Traumatic insults to the spinal cord induce both immediate mechanical damage and subsequent tissue degeneration leading to a substantial physiological, biochemical, and functional reorganization of the spinal cord. Various spinal cord injury (SCI) models have shown the adaptive potential of the spinal cord and its limitations in the case of total or partial absence of supraspinal influence. Meaningful recovery of function after SCI will most likely result from a combination of therapeutic strategies, including neural tissue transplants, exogenous neurotrophic factors, elimination of inhibitory molecules, functional sensorimotor training, and/or electrical stimulation of paralyzed muscles or spinal circuits. Peripheral nerve grafts provide a growth-permissive substratum and local neurotrophic factors to enhance the regenerative effort of axotomized neurons when grafted into the site of injury. Regenerating axons can be directed via the peripheral nerve graft toward an appropriate target, but they fail to extend beyond the distal graft-host interface because of the deposition of growth inhibitors at the site of SCI. One method to facilitate the emergence of axons from a graft into the spinal cord is to digest the chondroitin sulfate proteoglycans that are associated with a glial scar. Importantly, regenerating axons that do exit the graft are capable of forming functional synaptic contacts. These results have been demonstrated in acute injury models in rats and cats and after a chronic injury in rats and have important implications for our continuing efforts to promote structural and functional repair after SCI.

  19. Bortezomib Treatment Produces Nocifensive Behavior and Changes in the Expression of TRPV1, CGRP, and Substance P in the Rat DRG, Spinal Cord, and Sciatic Nerve

    Directory of Open Access Journals (Sweden)

    M. Quartu

    2014-01-01

    Full Text Available To investigate neurochemical changes associated with bortezomib-induced painful peripheral neuropathy (PN, we examined the effects of a single-dose intravenous administration of bortezomib and a well-established “chronic” schedule in a rat model of bortezomib-induced PN. The TRPV1 channel and sensory neuropeptides CGRP and substance P (SP were studied in L4-L5 dorsal root ganglia (DRGs, spinal cord, and sciatic nerve. Behavioral measures, performed at the end of the chronic bortezomib treatment, confirmed a reduction of mechanical nociceptive threshold, whereas no difference occurred in thermal withdrawal latency. Western blot analysis showed a relative increase of TRPV1 in DRG and spinal cord after both acute and chronic bortezomib administration. Reverse transcriptase-polymerase chain reaction revealed a decrease of TRPV1 and CGRP mRNA relative levels after chronic treatment. Immunohistochemistry showed that in the DRGs, TRPV1-, CGRP-, and SP-immunoreactive neurons were mostly small- and medium-sized and the proportion of TRPV1- and CGRP-labeled neurons increased after treatment. A bortezomib-induced increase in density of TRPV1- and CGRP-immunoreactive innervation in the dorsal horn was also observed. Our findings show that bortezomib-treatment selectively affects subsets of DRG neurons likely involved in the processing of nociceptive stimuli and that neurochemical changes may contribute to development and persistence of pain in bortezomib-induced PN.

  20. Expression of nerve growth factor in spinal dorsal horn following crushed spinal cord injury

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    AIM: The aim of this study was to explore the expression of nerve growth factor(NGF) in spinal dorsal horn following crushed spinal cord injury. METHODS: The adult Srague-Dawley rat model of crushed spinal cord injury was established by the method in our laboratory, and intact spinal cord was used as control. The rats were sacrificed respectively after 24 hours, 7 days, and 21 days of operation, and the L3 spinal segments were removed out and fixed in 4% polyformaldehyde. The segments were sectioned into sections of 20 μm in thickness. The sections were stained with anti-NGF antibody by ABC method of immunohistochemistry technique. The immunoreactive intensity of NGF and the number of positive neurons as well as glial cells in dorsal horn were observed and counted under light microscope. RESULTS: The number of positive cells and immunoreactive intensity of NGF increased gradually in the dorsal horn at 24 hours, 7 days and 21 days following crushed spinal cord injury compared with control group (P<0.01). CONCLUSION: These results indicated that NGF plays an important role in the postoperative reaction during the early period of the crushed spinal cord injury.

  1. Trigeminally induced cardiovascular reflex responses in spinalized rats.

    Science.gov (United States)

    Ideguchi, S; Hotta, H; Suzuki, A; Umino, M

    2000-03-15

    The effects on cardiovascular functions of noxious stimulation to the orofacial areas innervated by trigeminal afferent nerves were analyzed in urethane-anesthetized, spinal cord-intact rats and in rats acutely spinalized at the second cervical level. In the spinal cord-intact rats, pinching of the upper lip produced increases in both heart rate (HR) and mean arterial pressure (MAP). Both responses were considered to be due to activation of sympathetic efferent nerves to the cardiovascular organs. Both responses were attenuated but did not disappear after spinalization at the C2 level. In spinalized rats, sympathetic preganglionic neurons emerging from the thoracolumbar spinal cord could not receive any neural influences from the brain. The HR response in the spinal rats was abolished after either bilateral vagotomy or intravenous injection of a peripherally acting muscarinic cholinergic receptor antagonist, methylatropine. This suggests that the increase in HR was elicited via vagal cholinergic efferent fibers, probably by decreasing tonic activity of vagus nerves to the heart. In spinal rats, neither vagotomy nor cholinergic blockade affected the increase in MAP, but i.v. injection of the vasopressin V1 receptor antagonist, OPC-21268, abolished the response of MAP. This suggests that the response of MAP was due to peripheral vasoconstriction elicited by vasopressin secreted from the posterior pituitary lobe. The present study demonstrated that, in rats acutely spinalized at the C2 level, noxious stimulation of orofacial areas innervated by the trigeminal nerve could produce reflex increases both in HR, by decreasing cholinergic vagal nerve activity to the heart, and blood pressure, by secreting vasopressin from the pituitary gland, even though sympathetic efferent innervation to the cardiovascular organs could not be directly affected by trigeminal afferent nerve excitation.

  2. The change of neurotrophin 3 in spinal motor neurons following sciatic nerve lesion in rats%周围神经损伤对脊髓运动神经元NT-3表达的影响

    Institute of Scientific and Technical Information of China (English)

    石向群; 范明; 陆兵勋; 杨金升; 赵友岐; 汪泳

    2001-01-01

    Objective:To study the change of neurotroph in 3(NT-3) in the spinal motor neuron and the association between it and the degree of degeneration and death in spinal motor neuron following sciatic nervele sion in the rats.Methods:The sciatic nerve lesion wa s induced with cutting and removing part of the sciatic nerve in the adult and 3 days of age rats.The rats were allowed to survive for 3,7,14,21,28 days.The ext ent of spinal motor neuron death and degeneration was examined,the level of NT- 3 in spinal motor neuron were measured with image analysis.Results :The level of NT-3 in spinal motor neuron in suckling and adultr at groap was significant reduced following sciatic nerve lesion,and it was lowest in the second week after sciatic nerve lesion.The level of NT-3 in spinal mot or neuron in the 28th day following sciatic nerve lesion did not increase to it of the control.The change of spin al motor neuron death and degeneration was similar to the change of the level of NT-3.The level of NT-3 in spinal motor neuron in suckling rat was highter than it in adult rat. Conclusion:The level of NT-3 in spinal motor neurons would take change following sciatic nerve lesion,and the de ath and degeneration of spinal motor neuron may be induced by the peripheral ner ve lesion,The level of NT-3 in spinal motor neuron was negative with the extent of spinal motor neuron death and degeneration.%目的:探讨周围神经损伤后脊髓运动神经元神经营养因子-3(NT-3)水平变化规律及与神经元病理变化的相关性。方法:切断大鼠坐骨神经复制周围神经损伤模型,免疫组织化学染色NT-3阳性脊髓运 动神经元、图像分析计算其吸光度以反映NT-3的水平。结果:成鼠或乳鼠坐骨神经损伤后运动神经元NT-3水平均很快下降,至伤后第2周降至最低 水平,随后逐渐恢复,至4周仍未恢复到对照组水平;神经元病理改变过程与此相似。但乳 鼠NT-3基

  3. The effect of botulinum neurotoxin A on sciatic nerve injury-induced neuroimmunological changes in rat dorsal root ganglia and spinal cord.

    Science.gov (United States)

    Mika, J; Rojewska, E; Makuch, W; Korostynski, M; Luvisetto, S; Marinelli, S; Pavone, F; Przewlocka, B

    2011-02-23

    Botulinum neurotoxin serotype A (BoNT/A) acts by cleaving synaptosome-associated-protein-25 (SNAP-25) in nerve terminals to inhibit neuronal release and shows long-lasting antinociceptive action in neuropathic pain. However, its precise mechanism of action remains unclear. Our study aimed to characterize BoNT/A-induced neuroimmunological changes after chronic constriction injury (CCI) of the sciatic nerve. In the ipsilateral lumbar spinal cords of CCI-exposed rats, the mRNA of microglial marker (complement component 1q, C1q), astroglial marker (glial fibrillary acidic protein, GFAP), and prodynorphin were upregulated, as measured by reverse transcription-polymerase chain reaction (RT-PCR). No changes appeared in mRNA for proenkephalin, pronociceptin, or neuronal and inducible nitric oxide synthase (NOS1 and NOS2, respectively). In the dorsal root ganglia (DRG), an ipsilateral upregulation of prodynorphin, pronociceptin, C1q, GFAP, NOS1 and NOS2 mRNA and a downregulation of proenkephalin mRNA were observed. A single intraplantar BoNT/A (75 pg/paw) injection induced long-lasting antinociception in this model. BoNT/A diminished the injury-induced ipsilateral spinal upregulation of C1q mRNA. In the ipsilateral DRG a significant decrease of C1q-positive cell activation and of the upregulation of prodynorphin, pronociceptin and NOS1 mRNA was also observed following BoNT/A admistration. BoNT/A also diminished the injury-induced upregulation of SNAP-25 expression in both structures. We provide evidence that BoNT/A impedes injury-activated neuronal function in structures distant from the injection site, which is demonstrated by its influence on NOS1, prodynorphin and pronociceptin mRNA levels in the DRG. Moreover, the silence of microglia/macrophages after BoNT/A administration could be secondary to the inhibition of neuronal activity, but this decrease in neuroimmune interactions could be the key to the long-lasting BoNT/A effect on neuropathic pain.

  4. Spinal accessory nerve function following neck dissection.

    Science.gov (United States)

    Zibordi, F; Baiocco, F; Bascelli, C; Bini, A; Canepa, A

    1988-01-01

    Spinal accessory nerve (SAN) function was evaluated by electromyography (EMG) and muscle testing in 36 patients who underwent neck dissection with SAN preservation. The results emphasized that SAN function was relatively good after conservative neck surgery. Muscle testing findings showed better function than did EMG findings. After surgery the trapezius muscle functioned more efficiently than the sternocleidomastoid (SCM) muscle probably because of the more traumatic surgical handling of both the SCM muscle and its SAN branch. In order to obtain the functional advantages of SAN preservation, the authors suggest that the conservative procedure in radical neck dissection be used whenever warranted by oncologic diagnosis.

  5. Transcutaneous electrical nerve stimulation attenuates CFA-induced hyperalgesia and inhibits spinal ERK1/2-COX-2 pathway activation in rats

    OpenAIRE

    Fang, Jun-Fan; Liang, Yi; Du, Jun-Ying; Fang, Jian-Qiao

    2013-01-01

    Background Transcutaneous electrical nerve stimulation (TENS) is a non-pharmacologic treatment for pain relief. In previous animal studies, TENS effectively alleviated Complete Freund’s Adjuvant (CFA)- or carrageenan-induced inflammatory pain. Although TENS is known to produce analgesia via opioid activation in the brain and at the spinal level, few reports have investigated the signal transduction pathways mediated by TENS. Prior studies have verified the importance of the activation of extr...

  6. Spinal myoclonus following a peripheral nerve injury: a case report

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    Erkol Gokhan

    2008-08-01

    Full Text Available Abstract Spinal myoclonus is a rare disorder characterized by myoclonic movements in muscles that originate from several segments of the spinal cord and usually associated with laminectomy, spinal cord injury, post-operative, lumbosacral radiculopathy, spinal extradural block, myelopathy due to demyelination, cervical spondylosis and many other diseases. On rare occasions, it can originate from the peripheral nerve lesions and be mistaken for peripheral myoclonus. Careful history taking and electrophysiological evaluation is important in differential diagnosis. The aim of this report is to evaluate the clinical and electrophysiological characteristics and treatment results of a case with spinal myoclonus following a peripheral nerve injury without any structural lesion.

  7. Phrenic nerve blocage with spinal anesthesia for laparoscopic Nissen fundoplication

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    Murat Dursun

    2015-06-01

    Full Text Available In this case, we describe a patient having laparoscopic Nissen fundoplication (LNF under spinal anesthesia with phrenic nerve blockade. It’s emphasized that in this type of operations, spinal anesthesia may be an alternative method rather the general anesthesia and the resulting shoulder pain in laparoscopic surgery performed under spinal anesthesia can be prevented by phrenic nerve blockade. J Clin Exp Invest 2015; 6 (2: 186-188

  8. The effect of intrathecal gabapentin on mechanical and thermal hyperalgesia in neuropathic rats induced by spinal nerve ligation.

    OpenAIRE

    Cho, Hyun Sung; Kim, Myung Hee; Choi, Duck Hwan; LEE, JUNG IL; Gwak, Mi Sook; Hahm, Tae Soo

    2002-01-01

    Gabapentin decreases the level of glutamate and elevates that of alpha-amino-butyric acid in the central nervous system. Gabapentin was shown to have antinociceptive effects in several facilitated pain models. Intrathecal gabapentin was also known to be effective in reducing mechanical allodynia in animals with neuropathic pain. In this study, we investigated to see whether intrathecal gabapentin produces antihyperalgesic effects on thermal and mechanical hyperalgesia in neuropathic rats and ...

  9. Immunofluorescence laser confocal expression and localization study of rat nerve growth guidance cues Netrin-1 and Slit2 after spinal cord injury

    Institute of Scientific and Technical Information of China (English)

    LU Yao-jun; XU Nan-wei; YANG Wen-qiang

    2008-01-01

    To observe the expression and distribution of adult rat axon guidance cues Netrin-1 and Slit2 at different time points after spinal cord injury and to investigate the guidance mechanism of regenerated axons.Methods:Twenty adult Sprague Dawley(SD)rats were divided randomly into five groups with 4 in each.Four groups of them were used to make Allen's spinal cord punch models and we took materials randomly from one of them on the 2nd,4th,7th and 14th day respectively after operation.The left one group was taken as the control group.Immunofluorescence laser confocal scan was used to examine the co-expression and localization of Netrin-1 and Slit2 proteins in the injured site of the spinal cord.Results:Within two weeks after SCI,the expression of Netrin-1 and Slit2 proteins increased temporarily and there was co-expression of them on the neuron plasma membrane.Conclusions:Synchronous high expression and co-expression of axon attractant Netrin-1 and repellent Slit2 are found in the adult rat injured spinal cord in the damaged local and vicinity parts,and probably,they act as the key regulators of axon guidance regeneration.

  10. Spinal accessory nerve schwannomas masquerading as a fourth ventricular lesion

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    Shyam Sundar Krishnan

    2015-01-01

    Full Text Available Schwannomas are benign lesions that arise from the nerve sheath of cranial nerves. The most common schwannomas arise from the 8 th cranial nerve (the vestibulo-cochlear nerve followed by trigeminal and facial nerves and then from glossopharyngeal, vagus, and spinal accessory nerves. Schwannomas involving the oculomotor, trochlear, abducens and hypoglossal nerves are very rare. We report a very unusual spinal accessory nerve schwannoma which occupied the fourth ventricle and extended inferiorly to the upper cervical canal. The radiological features have been detailed. The diagnostic dilemma was due to its midline posterior location mimicking a fourth ventricular lesion like medulloblastoma and ependymoma. Total excision is the ideal treatment for these tumors. A brief review of literature with tabulations of the variants has been listed.

  11. The influence of NSAIDs on apoptosis of spinal cord nerve cells in rats induced by chronic compressive nerve root injury%非甾体抗炎药对大鼠神经根慢性压迫性损伤诱导的脊髓神经细胞凋亡的影响

    Institute of Scientific and Technical Information of China (English)

    高文; 郭宁

    2012-01-01

    目的 检测大鼠神经根慢性损伤后脊髓神经细胞的凋亡率,同时探讨不同类型非甾体抗炎药(NSAIDs)对此的影响,试图解释腰椎管狭窄症的一些不典型症状.方法 将48只SD大鼠随机分为对照组、结扎组、吲哚美辛组和美洛昔康组各12只.在结扎组、吲哚美辛组和美洛昔康组,造成神经根慢性压迫性损伤模型,后2组术后分别喂服吲哚美辛、美洛昔康,饲养4周处死,提取标本.结果 在结扎组,凋亡指数与神经损伤评分之间存在正相关(r=0.858,P0.05),与结扎组比较均有非常显著差异(P0.05).免疫组化法显示结扎组Bax蛋白表达与各组比较均有非常显著差异(P0.05).结论 神经根慢性压迫性损伤可以引起相应脊髓节段前角运动神经元的凋亡,与损伤程度正相关;非选择性环氧化酶(COX)抑制剂吲哚美辛和选择性COX-2抑制剂美洛昔康均可抑制脊髓神经细胞的凋亡;但未明显改善大鼠的神经损伤症状.%Objective To explore the apoptosis of nerve cells in spinal cord of rats induced by chronic nerve root injury, and to study the influence by different types of JNSAlDs, and to try to explain some atypical symptoms in patients with lumbar spinal stenosis syndrome. Methods Forty eight SD rats were allocated into four groups: control group, ligation group, indometacin group and meloxicam group, each group with 12 rats. The model of chronic compressive injury of spinal nerve had been established in rats. Rats in indometacin group and meloxicam group were fed with indometacin and meloxicam respectively after surgery. Rats were killed after 4 weeks for examination. Results There was positive correlation between apoptotic index and nerve injury scores ( r - 0. 0858 , P 0. 05 ), but there was significant difference between these two groups with ligation group ( P 0.05 ). The results of immunohistochemical method demonstrated that a little expression of bcl - 2 and Bax proteins was presented

  12. Contribution of myelunated fibers from spinal L4, L5 and L6 nerves to the sciatic nerve and its main branches in the adult rat Contribución de fibras mielínicas provenientes de los nervios espinales lumbares L4, L5 y L6 al nervio ciático de rata adulta y sus ramas principales

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    Juan D. Robles

    2000-04-01

    Full Text Available The rat sciatic nerve is composed by the L4, L5 and L6 lumbar spinal nerves. However, the contribution in myelinated fibers originating from these nerves along this nervous trunk has not yet been defined. In the present study, the L4, L5 and L4-L5 spinal nerves were selectively transected. After one week the sciatic, tibial, sural and peroneal nerves were dissected. These samples were fixed and processed for optical microscopy, and both degenerated and normal myelinated fibers were counted in toluidine blue-stained semi-thin sections. L4 contributed with myelinated fibers mainly to the peroneal nerve, and L5 to the sciatic, tibial and sural nerves. In general, the contribution of L6 was smaller and variable along the nervous trunk in comparison to the other two spinal branches. Our results give key information for further studies looking to correlate the contribution of spinal nerves making part of the sciatic nerve and its main branches with hind limb function. El nervio ciático de la rata está formado por los nervios espinales (ne lumbares L4, L5 y L6. Sin embargo, aún no se ha definido el aporte en fibras mielínicas de estos nervios espinales a lo largo del tronco nervioso. En este estudio se transectaron selectivamente los NE L4, L5 y L4-L5. Luego de una semana se disecaron los nervios ciático, tibial, sural y peroneal. Estas muestras se fijaron y procesaron para microscopía óptica y a partir de cortes coloreados con azul de toluidina se contaron las fibras mielínicas degeneradas y normales. L4 contribuyó con fibras mielínicas principalmente al nervio peroneal y L5 a los nervios ciático, tibial y sural. En general, el aporte de L6 fue menor y variable a lo largo del tronco nervioso comparado con las otras dos ramas espinales. Nuestros resultados brindan información valiosa para posteriores estudios que busquen correlacionar la contribución de los nervios espinales que componen el ciático y sus ramas principales con la funci

  13. Structural and Functional Substitution of Deleted Primary Sensory Neurons by New Growth from Intrinsic Spinal Cord Nerve Cells: An Alternative Concept in Reconstruction of Spinal Cord Circuits

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    Nicholas D. James

    2017-07-01

    Full Text Available In a recent clinical report, return of the tendon stretch reflex was demonstrated after spinal cord surgery in a case of total traumatic brachial plexus avulsion injury. Peripheral nerve grafts had been implanted into the spinal cord to reconnect to the peripheral nerves for motor and sensory function. The dorsal root ganglia (DRG containing the primary sensory nerve cells had been surgically removed in order for secondary or spinal cord sensory neurons to extend into the periphery and replace the deleted DRG neurons. The present experimental study uses a rat injury model first to corroborate the clinical finding of a re-established spinal reflex arch, and second, to elucidate some of the potential mechanisms underlying these findings by means of morphological, immunohistochemical, and electrophysiological assessments. Our findings indicate that, after spinal cord surgery, the central nervous system sensory system could replace the traumatically detached original peripheral sensory connections through new neurite growth from dendrites.

  14. EZH2 regulates spinal neuroinflammation in rats with neuropathic pain.

    Science.gov (United States)

    Yadav, Ruchi; Weng, Han-Rong

    2017-02-28

    Alteration in gene expression along the pain signaling pathway is a key mechanism contributing to the genesis of neuropathic pain. Accumulating studies have shown that epigenetic regulation plays a crucial role in nociceptive process in the spinal dorsal horn. In this present study, we investigated the role of enhancer of zeste homolog-2 (EZH2), a subunit of the polycomb repressive complex 2, in the spinal dorsal horn in the genesis of neuropathic pain in rats induced by partial sciatic nerve ligation. EZH2 is a histone methyltransferase, which catalyzes the methylation of histone H3 on K27 (H3K27), resulting in gene silencing. We found that levels of EZH2 and tri-methylated H3K27 (H3K27TM) in the spinal dorsal horn were increased in rats with neuropathic pain on day 3 and day 10 post nerve injuries. EZH2 was predominantly expressed in neurons in the spinal dorsal horn under normal conditions. The number of neurons with EZH2 expression was increased after nerve injury. More strikingly, nerve injury drastically increased the number of microglia with EZH2 expression by more than sevenfold. Intrathecal injection of the EZH2 inhibitor attenuated the development and maintenance of mechanical and thermal hyperalgesia in rats with nerve injury. Such analgesic effects were concurrently associated with the reduced levels of EZH2, H3K27TM, Iba1, GFAP, TNF-α, IL-1β, and MCP-1 in the spinal dorsal horn in rats with nerve injury. Our results highly suggest that targeting the EZH2 signaling pathway could be an effective approach for the management of neuropathic pain.

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

    Science.gov (United States)

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

    2017-02-27

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

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

    Directory of Open Access Journals (Sweden)

    Carolin Ruven

    2017-02-01

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

  17. 脊神经前根吻合重建脊髓损伤大鼠的股四头肌功能*★%Reconstruction of quadriceps femoris by anatomizing the ventral roots of spinal nerves in rats with spinal cord injury

    Institute of Scientific and Technical Information of China (English)

    李伟; 钟贵彬

    2013-01-01

      BACKGROUND: Reconstruction of motor function of limbs in spinal cord injury is significant for patients with paraplegia. OBJECTIVE: To recover the innervations and muscle contraction function of quadriceps femoris in spinal cord injured rats by constructing the neural pathway using the ventral roots of spinal nerves above injured segment of spinal cord and lumbar nerve that dominates the quadriceps femoris. METHODS: L 1 ventral root was anatomized to L 3 ventral root from Sprague-Dawley rats. After 6 months, axonal regeneration was found from L 1 ventral root to L 3 ventral root through the grafting nerve, which may reconstruct muscle contraction function. After nerve suture for 6 months, spinal cord injury was made in L 2 segment for neuroelectrophysiology examination to observe innervation of quadriceps femoris. RESULTS AND CONCLUSION: After semi-dissection of L 2 segment, wave from quadriceps femoris was recorded in electromyogram meter when stimulating the grafting nerve. After injured the segment of L 2 , we also record wave from quadriceps femoris when stimulating L 1 ventral root. Results showed that anastomosis of the L 1 ventral roots of spinal nerves above injured segment of spinal cord and the ventral root below the injured spinal cord segment can reconstruct the reflex path of innervation of quadriceps femoris, and the reflex center of quadriceps femoris in the spinal cord moves up to L 1 segment.%  背景:如何重建脊髓损伤肢体运动功能对截瘫患者具有重要的意义。目的:探索利用脊髓损伤平面以上健存的脊神经前根与支配股四头肌的腰神经建立神经通路,恢复脊髓损伤后股四头肌的神经支配和肌收缩功能。方法:对清洁级SD大鼠L1神经根的前根与L3神经根的前根进行显微吻合。经一段时间(6个月)的轴突再生后,期望建立新的肌肉收缩功能。神经缝合后6个月,在破坏L2脊髓节段前后,分别进行神经电生理检测,

  18. Dynamic alterations of the levels of tumor necrosis factor-α, interleukin-6, and interleukin-1β in rat primary motor cortex during transhemispheric functional reorganization after contralateral seventh cervical spinal nerve root transfer following brachial plexus avulsion injuries.

    Science.gov (United States)

    Yang, Ming-Jie; Li, Shuang; Yang, Chen-Song; Wang, Xu-Jia; Chang, Shi-Min; Sun, Gui-Xin

    2017-03-22

    The transfer of a contralateral healthy seventh cervical spinal nerve root (cC7) to the recipient nerve in the injured side is considered a reliable and effective procedure for restoration of the physiological functions of an injured hand after brachial plexus root avulsion injury (BPAI). Growing evidence shows that the transhemispheric cortical reorganization is induced after cC7 nerve transfer surgery. However, little is known about the underlying molecular mechanism. Proinflammatory cytokines reportedly play an important role in the neural plasticity. We hypothesize that proinflammatory cytokines are involved in the transhemispheric functional reorganization after cC7 transfer. In the present study, we investigated the level of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interleukin-1β (IL-1β) in the rat primary motor cortex after cC7 transfer following BPAI by enzyme-linked immunosorbent assay. The results showed that, in the sham group, no statistical significance was observed between the level of TNF-α, IL-6, and IL-1β at each time point after the operation compared with that at day 0, respectively. However, in the unrepaired and repaired groups, the level of TNF-α, IL-6, and IL-1β changed dynamically. The study is the first to provide evidence for the involvement of proinflammatory cytokines in transhemispheric functional reorganization after cC7 transfer following BPAI, which are useful for understanding the underlying mechanism.

  19. Effect of Touch-stimulus on the Expression of C-fos and TrkA in Spinal Cord Following Chronic Constriction Injury of the Sciatic Nerve in Rats

    Institute of Scientific and Technical Information of China (English)

    2005-01-01

    To study the mechanism of the innoxious touch-stimulus on the modulation of hyperalgesia and the expression of the C-fos and the nerve growth factor (NGF) receptor-TrkA in the spinal dorsal horn neurons following the chronic constriction injury (CCI) of the sciatic nerve in rats, 60female Sprague-Dawley rats were randomly divided into sham-operation group and CCI group, with each group being further divided into 3 subgroups on the 7th, 14 th and 28th day after operation (n=10). The mechanical and the thermal withdrawal threshold were assessed following the touch stiumulation after the CCI, immunohistochemical methods were employed to observe the expression of the C-fos and TrkA in spinal dorsal horn. Our results showed that the hyperalgesia appeared on the 4th day and reached the maximal level on the 14th day after operation. The expression of the C-fos also increased significantly and reached its maximal level on the 14th day after the touch-stimulus.Meanwhile, the TrkA expression was elevated significantly in both groups, as compared with basic data, and the difference was statistically significant (P<0.05). It is concluded that the level of the C-fos expression changed with the paw withdrawal threshold variation and increased markedly following the innoxious touch-stimulus. The expression of the TrkA receptors also increased gradually following the development of the neuropathic pain. The results suggest that C-fos may play a crucial role in the development of the hyperalgesia in the earlier-time of the neuropathic pain, but TrkA receptors may be involved in the long-lasting adaptive changes of the central pathway in neuropathic pain.

  20. Spinal histamine in attenuation of mechanical hypersensitivity in the spinal nerve ligation-induced model of experimental neuropathy.

    Science.gov (United States)

    Wei, Hong; Viisanen, Hanna; You, Hao-Jun; Pertovaara, Antti

    2016-02-05

    Here we studied whether and through which mechanisms spinal administration of histamine dihydrochloride (histamine) attenuates pain behavior in neuropathic animals. Experiments were performed in rats with spinal nerve ligation-induced neuropathy and a chronic intrathecal catheter for spinal drug delivery. Mechanical hypersensitivity was assessed with monofilaments while radiant heat was used for assessing nociception. Ongoing neuropathic pain and its attenuation by histamine was assessed using conditioned place-preference test. Following spinal administration, histamine at doses 0.1-10µg produced a dose-related mechanical antihypersensitivity effect. With prolonged treatment (twice daily 10µg for five days), the antihypersensitivity effect of spinal histamine was reduced. In place-preference test, neuropathic animals preferred the chamber paired with histamine (10µg). Histamine (10µg) failed to influence heat nociception in neuropathic animals or mechanically induced pain behavior in a group of healthy control rats. Histamine-induced mechanical antihypersensitivity effect was prevented by spinal pretreatment with zolantidine (histamine H2 receptor antagonist), prazosine (α1-adrenoceptor antagonist) and bicuculline (γ-aminobutyric acid subtype A, GABA(A), receptor antagonist), but not by pyrilamine (histamine H1 receptor antagonist), atipamezole (α2-adrenoceptor antagonist), or raclopride (dopamine D2 receptor antagonist). A-960656, a histamine H3 receptor antagonist alone that presumably increased endogenous histamine levels reduced hypersensitivity. Additionally, histamine prevented central (presumably postsynaptically-induced) facilitation of hypersensitivity induced by N-methyl-d-aspartate. The results indicate that spinal histamine at the dose range of 0.1-10µg selectively attenuates mechanical hypersensitivity and ongoing pain in neuropathy. The spinal histamine-induced antihypersensitivity effect involves histamine H2 and GABA(A) receptors and

  1. The articulo-cardiac sympathetic reflex in spinalized, anesthetized rats.

    Science.gov (United States)

    Nakayama, Tomohiro; Suzuki, Atsuko; Ito, Ryuzo

    2006-04-01

    Somatic afferent regulation of heart rate by noxious knee joint stimulation has been proven in anesthetized cats to be a reflex response whose reflex center is in the brain and whose efferent arc is a cardiac sympathetic nerve. In the present study we examined whether articular stimulation could influence heart rate by this efferent sympathetic pathway in spinalized rats. In central nervous system (CNS)-intact rats, noxious articular movement of either the knee or elbow joint resulted in an increase in cardiac sympathetic nerve activity and heart rate. However, although in acutely spinalized rats a noxious movement of the elbow joint resulted in a significant increase in cardiac sympathetic nerve activity and heart rate, a noxious movement of the knee joint had no such effect and resulted in only a marginal increase in heart rate. Because this marginal increase was abolished by adrenalectomy suggests that it was due to the release of adrenal catecholamines. In conclusion, the spinal cord appears to be capable of mediating, by way of cardiac sympathetic nerves, the propriospinally induced reflex increase in heart rate that follows noxious stimulation of the elbow joint, but not the knee joint.

  2. Edaravone combined with Schwann cell transplantation may repair spinal cord injury in rats

    Directory of Open Access Journals (Sweden)

    Shu-quan Zhang

    2015-01-01

    Full Text Available Edaravone has been shown to delay neuronal apoptosis, thereby improving nerve function and the microenvironment after spinal cord injury. Edaravone can provide a favorable environment for the treatment of spinal cord injury using Schwann cell transplantation. This study used rat models of complete spinal cord transection at T 9. Six hours later, Schwann cells were transplanted in the head and tail ends of the injury site. Simultaneously, edaravone was injected through the caudal vein. Eight weeks later, the PKH-26-labeled Schwann cells had survived and migrated to the center of the spinal cord injury region in rats after combined treatment with edaravone and Schwann cells. Moreover, the number of PKH-26-labeled Schwann cells in the rat spinal cord was more than that in rats undergoing Schwann cell transplantation alone or rats without any treatment. Horseradish peroxidase retrograde tracing revealed that the number of horseradish peroxidase-positive nerve fibers was greater in rats treated with edaravone combined withSchwann cells than in rats with Schwann cell transplantation alone. The results demonstrated that lower extremity motor function and neurophysiological function were better in rats treated with edaravone and Schwann cells than in rats with Schwann cell transplantation only. These data confirmed that Schwann cell transplantation combined with edaravone injection promoted the regeneration of nerve fibers of rats with spinal cord injury and improved neurological function.

  3. Skin nerve regeneration and burn wound healing following spinal nerve root incision

    Institute of Scientific and Technical Information of China (English)

    Yibing Wang; Pengfei Guo; Yongqiang Feng; Yongqian Cao; Shourong Zhu; Rui Zhang

    2011-01-01

    Burn wounds were produced on two sides on the backs of Wistar rats, in addition to denervation on one side. The skin neural regeneration at the injury site and burn wound healing were evaluated following spinal nerve root incision. No nerve regeneration was observed in the burn wound region post-denervation, and the degree of epithelization was significantly less than the control group. With increasing time, expression of type Ⅰ collagen, which plays a supporting role, and collagen Ⅲ, which exhibits elastic properties, were significantly increased in the two groups, but the expression was less in the denervation group compared with the control group, and the wound healing was faster in the control group. The ratio of type Ⅰ collagen to type Ⅲ collagen was significantly lower in the denervation group compared with the control group. The ratio gradually decreased with prolonged time in the denervation group, but remained unchanged in the control group. However, the elasticity of the tissues in the denervation group was better than the control group. During burn wound healing, innervations can promote wound healing, but denervation can improve the quality of wound remodeling.

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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 (Pthermal 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

  6. Hydraulic spinal cord and cauda equina nerve injuries

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    @@Hydraulic spinal cord and cauda equina nerve injuries are very uncommon. Since 19 96, we have received and treated 4 patients with hydraulic spinal cord and cauda equina injuries. This report gives a detail description. Four patients with hydraulic spinal cord and cauda equina nerve injuries, male: 3, female: 1, aging 13-56 years have been treated in our hospital since 1996. E xtradural blocking injury was in 1 patient, extradural anaesthesia injury in 1 p atient and intraspinal canal myelography injury in 2 patients; the segments of i ntraspinal canal were L2-3 and L3-4. One patient was accompanied b y femoral fracture, 2 patients by intraspinal tumor and 1 patient had operat ion because of prolapse of lumbar intervertebral disc.

  7. The contractile properties of the medial gastrocnemius motor units innervated by L4 and L5 spinal nerves in the rat.

    Science.gov (United States)

    Celichowski, Jan; Taborowska, Malwina

    2011-01-01

    When a muscle innervation originates from more than one spinal cord segment, the injury of one of the respective ventral roots evokes an overload, and alters the activity and properties of the remaining motor units. However, it is not well documented if the three types of motor units are equally represented within the innervating ventral roots. Single motor units in the rat medial gastrocnemius muscle were studied and their contractile properties as well as distribution of different types of motor units belonging to subpopulations innervated by axons in L4 and L5 ventral roots were analyzed. The composition of the three physiological types of motor units in the two subpopulations was similar. Force parameters were similar for motor units belonging to the two subpopulations. However, the twitch time parameters were slightly longer in L4 in comparison to L5 motor units although the difference was significant only for fast resistant to fatigue motor units. The force-frequency relationships in the two subpopulations of motor units were not different. Concluding, the two subpopulations of motor units in the studied muscle differ in the number of motor units, but contain similar proportions of the three physiological types of these units and their contractile properties are similar. Therefore, the injury of one ventral root evokes various degrees of muscle denervation, but is non-selective in relation to the three types of motor units.

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

    Science.gov (United States)

    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.

  9. Identification of CNS neural circuitry involved in the innervation of C7 spinal nerve: a viral transsynaptic tracing study

    Directory of Open Access Journals (Sweden)

    WEI Hai-feng

    2012-02-01

    Full Text Available 【Abstract】 Objective: Contralateral C7 spinal nerve transfer is a useful operation for the treatment of brachial plexus root avulsion. The recovery of the independent function at the ipsilateral side, however, depends on neural circuitry reorganization in the central nervous system (CNS. This study tried to locate the CNS neuronal elements involved in the innervation of C7 spinal nerve. Method: Pseudorabies virus (PRV, TK/gG-, 2 祃, which expressed green fluorescent protein (GFP, was injected into the left C7 spinal nerve in 20 adult Sprague Dawley rats. After rats survived for 6 h, 12 h, 24 h and 36 h, the C1-C7 segments of the spinal cord and brain were processed using a polyclonal immunohistochemical antibody against PRV. Results: PRV-labeled neurons were found mainly in gray matter of the C1-C7 segments of the spinal cord and at the following structures of the brain: lateral vestibular nucleus, lateral paragigantocellular nucleus, A5 cells, red nucleus, primary and secondary motor cortexes, primary and secondary somatosensory cortexes. Although located bilaterally, the PRV-labeled neurons existed predominantly in the ipsilateral side of the spinal cord and the contralateral side of the brain at 6-12 h after injection (p.i.. The number of PRV-labeled neurons in the CNS was increasing with rat抯 survival time and the distribution of these neurons turned bilateral with no obvious dominance to either side at 24 h and 36 h (p.i.. Conclusion: By use of transsynaptic tracing technique with PRV, the anatomically connected set of neurons, which modulates the activity of C7 spinal nerve, is located successfully in the CNS. Key words: Brachial plexus; Innervation; Spinal nerves; Central nervous system

  10. Somatostatinergic nerves in the cervical spinal cord of the monkey.

    Science.gov (United States)

    Burnweit, C; Forssmann, W G

    1979-08-03

    Somatostatinergic nerves in the spinal cord of the monkey were investigated utilizing immunohistochemistry with various antibodies against synthetic somatostatin. In contrast to earlier investigations, it is shown that somatostatinergic nerve endings occur in most of the areas of the grey matter of the spinal cord. The somatostatinergic axons are, however, characteristically distributed in three main regions: (1) Densely-packed endings are seen in lamina II of the substantia gelatinosa, forming a crescent-shaped pattern in the columna dorsalis. Somatostatin immunoreactivity is also seen in lamina I and in the Lissauer tract. (2) A fine network of fibers is observed around the central canal; the endings are concentrated on special cell bodies. Some single perikarya are also stained in this region. (3) A loose network of single fibers is found ending on perikarya of the columna lateralis or ventralis. The perikarya of the nerve axons, with the exception of those terminating in the columna dorsalis, have as yet not been identified. In order to better understand the somatostatinergic system of the spinal cord, these newly-detected somatostatinergic nerves must be studied and their exact pathways analyzed.

  11. Time Course of Immediate Early Gene Protein Expression in the Spinal Cord following Conditioning Stimulation of the Sciatic Nerve in Rats

    NARCIS (Netherlands)

    Bojovic, Ognjen; Panja, Deb; Bittins, Margarethe; Bramham, Clive R.; Tjolsen, Arne

    2015-01-01

    Long-term potentiation induced by conditioning electrical stimulation of afferent fibers is a widely studied form of synaptic plasticity in the brain and the spinal cord. In the spinal cord dorsal horn, long-term potentiation is induced by a series of high-frequency trains applied to primary

  12. Time Course of Immediate Early Gene Protein Expression in the Spinal Cord following Conditioning Stimulation of the Sciatic Nerve in Rats

    NARCIS (Netherlands)

    Bojovic, Ognjen; Panja, Deb; Bittins, Margarethe; Bramham, Clive R.; Tjolsen, Arne

    2015-01-01

    Long-term potentiation induced by conditioning electrical stimulation of afferent fibers is a widely studied form of synaptic plasticity in the brain and the spinal cord. In the spinal cord dorsal horn, long-term potentiation is induced by a series of high-frequency trains applied to primary afferen

  13. Electrical stimulation accelerates nerve regeneration and functional recovery in delayed peripheral nerve injury in rats.

    Science.gov (United States)

    Huang, Jinghui; Zhang, Yongguang; Lu, Lei; Hu, Xueyu; Luo, Zhuojing

    2013-12-01

    The present study aims to investigate the potential of brief electrical stimulation (ES; 3 V, 20 Hz, 20 min) in improving functional recovery in delayed nerve injury repair (DNIR). The sciatic nerve of Sprague Dawley rats was transected, and the repair of nerve injury was delayed for different time durations (2, 4, 12 and 24 weeks). Brief depolarizing ES was applied to the proximal nerve stump when the transected nerve stumps were bridged with a hollow nerve conduit (5 mm in length) after delayed periods. We found that the diameter and number of regenerated axons, the thickness of myelin sheath, as well as the number of Fluoro-Gold retrograde-labeled motoneurons and sensory neurons were significantly increased by ES, suggesting that brief ES to proximal nerve stumps is capable of promoting nerve regeneration in DNIR with different delayed durations, with the longest duration of 24 weeks. In addition, the amplitude of compound muscle action potential (gastrocnemius muscle) and nerve conduction velocity were also enhanced, and gastrocnemius muscle atrophy was partially reversed by brief ES, indicating that brief ES to proximal nerve stump was able to improve functional recovery in DNIR. Furthermore, brief ES was capable of increasing brain-derived neurotrophic factor (BDNF) expression in the spinal cord in DNIR, suggesting that BDNF-mediated neurotrophin signaling might be one of the contributing factors to the beneficial effect of brief ES on DNIR. In conclusion, the present findings indicate the potential of using brief ES as a useful method to improve functional recovery for delayed repair of peripheral nerve lesions. © 2013 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

  14. Effect of FK506 on Expression of Hepatocyte Growth Factor in Murine Spinal Cord Following Peripheral Nerve Injury

    Institute of Scientific and Technical Information of China (English)

    Feng PAN; Anmin CHEN; Fengjing GUO; Chenliang ZHU; Fenghua TAO

    2008-01-01

    This study is to investigate the effect of FK506 on expression of hepatocyte growth factor (HGF) in rats' spinal cord following peripheral nerve injury and to elucidate the mechanisms for neuroprotective property of FKS06. Fifty male rats were randomly divided into normal group, injury group and treatment group. Models of peripheral nerve injury were established by bilateral transection of sciatic nerve 0.5 cm distal to piriform muscle. Then the treatment group received subcutaneons injection of FK506 (1 mg/kg) at the back of neck, while the injury group was given 0.9% saline. The L4-6 spinal cords were harvested at various time points after the surgery. Western blotting and immunofluorescent staining were used to detect the level and position of HGF in spinal cord. Lm munofluorescent staining showed that HGF-positive neurons were located in anterior horn, interme- diate zone and posterior horn of gray matter in normal spinal cord. Western blotting revealed that there was no significant difference in the expressions of HGF between the injury group and the normal group, while the expression of HGF was significantly higher in the treatment group than in the injury group 7 and 14 days after surgery. It is suggested that peripheral nerve injury does not result in up-regulation of the expression of HGF in spinal cord, while FK506 may induce high expression of endogenous HGF after injury thereby protecting neurons and promoting axonal outgrowth.

  15. Using NGF heparin-poloxamer thermosensitive hydrogels to enhance the nerve regeneration for spinal cord injury.

    Science.gov (United States)

    Zhao, Ying-Zheng; Jiang, Xi; Xiao, Jian; Lin, Qian; Yu, Wen-Ze; Tian, Fu-Rong; Mao, Kai-Li; Yang, Wei; Wong, Ho Lun; Lu, Cui-Tao

    2016-01-01

    Nerve growth factor (NGF) has potential in spinal cord injury (SCI) therapy, but limited by the poor physicochemical stability and low ability to cross the blood spinal cord barrier. Novel heparin-poloxamer (HP) thermo-sensitive hydrogel was constructed to enhance the NGF regeneration on SCI. NGF-HP thermo-sensitive hydrogel was prepared and related characteristics including gelation temperature, rheological behavior and micromorphology were measured. Local NGF delivery to the injured spinal cord was achieved by in situ injection in the injured space. The cellular uptake of NGF-HP hydrogel was evaluated with PC12 cells in vitro. Pathologic characteristics and neuron regeneration effects on the SCI rats were studied to evaluate the enhanced therapy of NGF-HP hydrogel. Endoplasmic reticulum (ER) stress-induced apoptosis was analyzed to explore the related mechanism in SCI regeneration. NGF-HP hydrogel showed good morphology and stable bioactivity of NGF in vitro. NGF-HP hydrogel combined treatment significantly enhanced the efficiency of NGF cellular uptake (Pregeneration. Spinal cord injury (SCI) is a devastating condition that can lead to sudden loss of sensory and autonomic function. Current treatment includes decompression surgery, injury stabilization, secondary complications prevention and rehabilitation. However, neurological recovery is limited. Nerve growth factor (NGF) has potential in SCI therapy, but limited by the poor physicochemical stability and low ability to cross the blood spinal cord barrier. Hydrogels have good affinity and compatibility to biological tissue. In this study, we developed a novel heparin-poloxamer (HP) thermo-sensitive hydrogel to enhance the spinal cord regeneration of NGF. From SCI rat experiment, HP hydrogel combined with orthotopic injection technique showed best neuroprotective effects among experimental groups. This novel combined technique will provide an effective strategy for SCI regeneration. Copyright © 2015 Acta

  16. Spinal Cord Stimulation Modulates Gene Expression in the Spinal Cord of an Animal Model of Peripheral Nerve Injury.

    Science.gov (United States)

    Tilley, Dana M; Cedeño, David L; Kelley, Courtney A; Benyamin, Ramsin; Vallejo, Ricardo

    Previously, we found that application of pulsed radiofrequency to a peripheral nerve injury induces changes in key genes regulating nociception concurrent with alleviation of paw sensitivity in an animal model. In the current study, we evaluated such genes after applying spinal cord stimulation (SCS) therapy. Male Sprague-Dawley rats (n = 6 per group) were randomized into test and control groups. The spared nerve injury model was used to simulate a neuropathic pain state. A 4-contact microelectrode was implanted at the L1 vertebral level and SCS was applied continuously for 72 hours. Mechanical hyperalgesia was tested. Spinal cord tissues were collected and analyzed using real-time polymerase chain reaction to quantify levels of IL1β, GABAbr1, subP, Na/K ATPase, cFos, 5HT3ra, TNFα, Gal, VIP, NpY, IL6, GFAP, ITGAM, and BDNF. Paw withdrawal thresholds significantly decreased in spared nerve injury animals and stimulation attenuated sensitivity within 24 hours (P = 0.049), remaining significant through 72 hours (P = 0.003). Nerve injury caused up-regulation of TNFα, GFAP, ITGAM, and cFOS as well as down-regulation of Na/K ATPase. Spinal cord stimulation therapy modulated the expression of 5HT3ra, cFOS, and GABAbr1. Strong inverse relationships in gene expression relative to the amount of applied current were observed for GABAbr1 (R = -0.65) and Na/K ATPase (R = -0.58), and a positive linear correlations between 5HT3r (R = 0.80) and VIP (R = 0.50) were observed. Continuously applied SCS modulates expression of key genes involved in the regulation of neuronal membrane potential.

  17. Reduced Renshaw Recurrent Inhibition after Neonatal Sciatic Nerve Crush in Rats

    Directory of Open Access Journals (Sweden)

    Liang Shu

    2014-01-01

    Full Text Available Renshaw recurrent inhibition (RI plays an important gated role in spinal motion circuit. Peripheral nerve injury is a common disease in clinic. Our current research was designed to investigate the change of the recurrent inhibitory function in the spinal cord after the peripheral nerve crush injury in neonatal rat. Sciatic nerve crush was performed on 5-day-old rat puppies and the recurrent inhibition between lateral gastrocnemius-soleus (LG-S and medial gastrocnemius (MG motor pools was assessed by conditioning monosynaptic reflexes (MSR elicited from the sectioned dorsal roots and recorded either from the LG-S and MG nerves by antidromic stimulation of the synergist muscle nerve. Our results demonstrated that the MSR recorded from both LG-S or MG nerves had larger amplitude and longer latency after neonatal sciatic nerve crush. The RI in both LG-S and MG motoneuron pools was significantly reduced to virtual loss (15–20% of the normal RI size even after a long recovery period upto 30 weeks after nerve crush. Further, the degree of the RI reduction after tibial nerve crush was much less than that after sciatic nerve crush indicatig that the neuron-muscle disconnection time is vital to the recovery of the spinal neuronal circuit function during reinnervation. In addition, sciatic nerve crush injury did not cause any spinal motor neuron loss but severally damaged peripheral muscle structure and function. In conclusion, our results suggest that peripheral nerve injury during neonatal early development period would cause a more sever spinal cord inhibitory circuit damage, particularly to the Renshaw recurrent inhibition pathway, which might be the target of neuroregeneration therapy.

  18. The distribution of rat bladder nerves within the spinal cord: WGA-HRP retrograde tracing study%支配大鼠膀胱的神经在脊髓内的分布-WGA-HRP逆行示踪研究

    Institute of Scientific and Technical Information of China (English)

    胡力丰; 张志成; 孙天胜

    2012-01-01

    Objective To locate bladder afferent and efferent elements within the spinal cord in rats by retrograde tracing. Methods WGA - HRP was injected into the bladder wall of normal male Sprague - Dawley rats ( 250 ~ 300 g ). 48 hours after the injection, the rats were killed, frozen sections were made from the spinal cord and dorsal root ganglian ( DRG ) and color developed with colorimetric tetramethyl benzidine ( TMB ) and H2O2. Results HRP positive neurons located in LI - S3 DRG, mainly in L6 - SI DRG. HRP - positive neurons were also found in the lateral horn of L6 - SI ( more in L6 ). Conclusion According to the experimental results, the lower nerve center - sacral parasympathetic nucleus ( SPN ) for the innervation of the detrusor of bladder was located and determined.%目的 行膀胱逆行示踪,明确支配大鼠膀胱的传入及传出神经在脊髓的位置.方法 正常成年SD雄性大鼠(250~300 g),大鼠膀胱壁内注射麦芽凝集素-辣根过氧化物酶(WGA-HRP),注射后大鼠继续存活48 h.分别取材脊髓和背根神经节,冰冻切片,用四甲基联苯胺(TMB)和H2O2呈色.结果 脊髓L1~S3节段背根神经节内(DRG)均出现染成阳性的神经细胞,以L6-S1节段 DRG中阳线细胞为著;脊髓L6部至S1侧角(以L6多见)出现HRP阳性神经细胞.结论 根据本次实验结果,明确了支配膀胱逼尿肌的低位中枢-骶副交感神经核(SPN)的位置,明确了膀胱传入神经的主要部分.

  19. Identification of CNS neural circuitry involved in the innervation of C7 spinal nerve: a viral transsynaptic tracing study

    Institute of Scientific and Technical Information of China (English)

    WEI Hai-feng; CHEN Liang; GU Yu-dong

    2011-01-01

    Objective: Contralateral C7 spinal nerve transfer is a useful operation for the treatment of brachial plexus root avulsion. The recovery of the independent function at the ipsilateral side, however, depends on neural circuitry reorganization in the central nervous system (CNS).This study tried to locate the CNS neuronal elements involved in the innervation ofC7 spinal nerve.Method: Pseudorabies virus (PRV, TK/gG-,2 μl), which expressed green fluorescent protein (GFP), was injected into the left C7 spinal nerve in 20 adult Sprague Dawley rats.After rats survived for 6 h, 12 h, 24 h and 36 h, the C1-C7segments of the spinal cord and brain were processed using a polyclonal immunohistochemical antibody against PRV.Results: PRV-labeled neurons were found mainly in gray matter of the C1-C7 segments of the spinal cord and at the following structures of the brain: lateral vestibular nucleus, lateral paragigantocellular nucleus, A5 cells, red nucleus, primary and secondary motor cortexes, primary and secondary somatosensory cortexes. Although located bilaterally, the PRV-labeled neurons existed predominantly in the ipsilateral side of the spinal cord and the contralateral side of the brain at 6-12 h after injection (p.i.). The number of PRV-labeled neurons in the CNS was increasing with rat's survival time and the distribution of these neurons turned bilateral with no obvious dominance to either side at 24 h and 36 h (p.i.).Conclusion: By use of transsynaptic tracing technique with PRV, the anatomically connected set of neurons,which modulates the activity of C7 spinal nerve, is located successfully in the CNS.

  20. [APPLICATION OF THREE DIMENSIONAL PRINTING ON MANUFACTURING BIONIC SCAFFOLDS OF SPINAL CORD IN RATS].

    Science.gov (United States)

    Chen, Yisheng; Wang, Jingjing; Chen, Xuyi; Chen, Chong; Tu, Yue; Zhang, Sai; Li, Xiaohong

    2015-03-01

    To fabricate the bionic scaffolds of rat spinal cord by combining three dimensional (3D) printer and 3D software, so as to lay the foundation of theory and technology for the manufacture of scaffolds by using biomaterials. Three female Sprague Dawley rats were scanned by 7.0T MRI to obtain the shape and position data of the cross section and gray matter of T8 to T10 spinal cord. Combined with data of position and shape of nerve conduction beam, the relevant data were obtained via Getdata software. Then the 3D graphics were made and converted to stereolithography (STL) format by using SolidWorks software. Photosensitive resin was used as the materials of spinal cord scaffolds. The bionic scaffolds were fabricated by 3D printer. MRI showed that the section shape of T8 to T10 segments of the spinal cord were approximately oval with a relatively long sagittal diameter of (2.20 ± 0.52) mm and short transverse diameter of (2.05 ± 0.24) mm, and the data of nerve conduction bundle were featured in the STL format. The spinal cord bionic scaffolds of the target segments made by 3D printer were similar to the spinal cord of rat in the morphology and size, and the position of pores simulated normal nerve conduction of rat spinal cord. Spinal cord scaffolds produced by 3D printer which have similar shape and size of normal rat spinal cord are more bionic, and the procedure is simple. This technology combined with biomaterials is also promising in spinal cord repairing after spinal cord injury.

  1. Combination of edaravone and neural stem cell transplantation repairs injured spinal cord in rats.

    Science.gov (United States)

    Song, Y Y; Peng, C G; Ye, X B

    2015-12-29

    This study sought to observe the effect of the combination of edaravone and neural stem cell (NSC) transplantation on the repair of complete spinal cord transection in rats. Eighty adult female Sprague-Dawley (SD) rats were used to establish the injury model of complete spinal cord transection at T9. Animals were divided randomly into four groups (N = 20 each): control, edaravone, transplantation, and edaravone + transplantation. The recovery of spinal function was evaluated with the Basso, Beattie, Bresnahan (BBB) rating scale on days 1, 3, and 7 each week after the surgery. After 8 weeks, the BBB scores of the control, edaravone, transplantation, and combination groups were 4.21 ± 0.11, 8.46 ± 0.1, 8.54 ± 0.13, and 11.21 ± 0.14, respectively. At 8 weeks after surgery, the spinal cord was collected; the survival and transportation of transplanted cells were observed with PKH-26 labeling, and the regeneration and distribution of spinal nerve fibers with fluorescent-gold (FG) retrograde tracing. Five rats died due to the injury. PKH-26-labeled NSCs had migrated into the spinal cord. A few intact nerve fibers and pyramidal neurons passed the injured area in the transplantation and combination groups. The numbers of PKH-26-labeled cells and FG-labeled nerve fibers were in the order: combination group > edaravone group and transplantation group > control group (P injured areas; edaravone with NSC transplantation can improve the effectiveness of spinal cord injury repair in rats.

  2. Nerve transfer for treatment of brachial plexus injury:comparison study between the transfer of partial median and ulnar nerves and that of phrenic and spinal accessary nerves

    Institute of Scientific and Technical Information of China (English)

    侯之启; 徐中和

    2002-01-01

    Objective:To compare the effect of using partial median and ulnar nerves for treatment of C5-6 orC5-7 avulsion of the brachial plexus with that of using phrenic and spinal accessary nerves.Methods:The patients were divided into 2groups randomly according to different surgical procedures.Twelve cases were involved in the first group.The phrenic nerve was transferred to the musculocutaneous nerve or through a sural nerve graft,and the spinal accessary nerve was to the suprascapular nerve.Eleven cases were classified into the second group.A part of the fascicles of median nerve was transferred to be coapted with the motor fascicle of musculocutaneous nerve and a part of fascicles of ulnar nerve was transferred to the axillary nerve.The cases were followed up from 1to 3years and the clinical outcome was compared between the two groups.

  3. Mechanical characterization of the injured spinal cord after lateral spinal hemisection injury in the rat.

    Science.gov (United States)

    Saxena, Tarun; Gilbert, Jeremy; Stelzner, Dennis; Hasenwinkel, Julie

    2012-06-10

    The glial scar formed at the site of traumatic spinal cord injury (SCI) has been classically hypothesized to be a potent physical and biochemical barrier to nerve regeneration. One longstanding hypothesis is that the scar acts as a physical barrier due to its increased stiffness in comparison to uninjured spinal cord tissue. However, the information regarding the mechanical properties of the glial scar in the current literature is mostly anecdotal and not well quantified. We monitored the mechanical relaxation behavior of injured rat spinal cord tissue at the site of mid-thoracic spinal hemisection 2 weeks and 8 weeks post-injury using a microindentation test method. Elastic moduli were calculated and a modified standard linear model (mSLM) was fit to the data to estimate the relaxation time constant and viscosity. The SLM was modified to account for a spectrum of relaxation times, a phenomenon common to biological tissues, by incorporating a stretched exponential term. Injured tissue exhibited significantly lower stiffness and elastic modulus in comparison to uninjured control tissue, and the results from the model parameters indicated that the relaxation time constant and viscosity of injured tissue were significantly higher than controls. This study presents direct micromechanical measurements of injured spinal cord tissue post-injury. The results of this study show that the injured spinal tissue displays complex viscoelastic behavior, likely indicating changes in tissue permeability and diffusivity.

  4. 低频电针对脊神经结扎大鼠痛敏化的干预作用%Effect of Electroacupuncture with Low Frequency on Pain Sensitization of Rats Suffered from Spinal Nerve Ligation

    Institute of Scientific and Technical Information of China (English)

    蒋永亮; 尹小虎; 沈亚芳; 赵晓芸; 何晓芬; 方剑乔

    2014-01-01

    Objective To investigate the effect of electroacupuncture with low frequency on pain sensitization of neuropathic pain rats, and the possible mechanism of regulating peripheral pain sensitization. Methods Rat neuropathic pain model was established with the right L5 spinal nerve ligation. Zusanli (ST36) and Kunlun (BL60) were selected for electroacupuncture intervention. Mechanical allodynia, and the levels of stransient receptor potential vanilloid type 1 (TRPV1) and substance P (SP) in ipsilateral L5 and L4 dorsal root ganglion (DRG) were tested. A further validation experiment with TRPV1 agonist 6'-IRTX was carried out. Results Rats suffered from L5 spinal nerve liga-tion showed obvious pain sensitization. The levels of TRPV1 in ipsilateral L4 DRG and SP in ipsilateral L5 DRG were significantly elevated. Electroacupuncture with low frequency significantly relieved pain sensitization, and suppressed TRPV1 and SP increase. 6'-IRTX intraperito-neally administered significantly counteracted the anti-pain sensitization action of electroacupuncture with low frequency. Conclusion Elec-troacupuncture with low frequency is effective on neuropathic pain by intervening pain sensitization, which may be related to the regulation of DRG TRPV1 and SP.%目的:观察低频电针对脊神经结扎神经病理痛大鼠模型痛敏化的干预作用,探讨其可能的外周痛敏化调节机制。方法建立大鼠L5脊神经结扎模型,电针足三里和昆仑穴,观察大鼠痛觉超敏反应,运用Western blotting法检测L4、L5背根神经节(DRG)辣椒素受体(TRPV1)与P物质(SP)水平,采用TRPV1激动剂6'-IRTX进行验证。结果脊神经结扎大鼠出现明显的痛敏化反应,术侧L4 DRG TRPV1和L5 DRG SP水平升高(P<0.05);低频电针能减轻模型大鼠的痛敏反应,抑制TRPV1、SP水平上升(P<0.05)。6'-IRTX腹腔注射能拮抗低频电针的抗痛敏化作用。结论低频电针可减轻痛敏化,发挥对

  5. Experimental study on regeneration of ascending tract after spinal cord injury with predegenerated peripheral nerve graft and NGF infusion

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    Objective:To explore the effects of predegenerated peripheral nerve graft (PPNG) combined with nerve growth factor (NGF) infusion on ascending sensory tract regeneration after spinal cord injury.Methods: Fifty female SD rats were randomly divided into 5 groups. Group A was treated with PPNG and NGF infusion, group B with PPNG, group C with NGF infusion, group D and group E were blank and normal control, respectively. Horseradish peroxidase-labled (HRP) tracing method was employed to evaluate the regeneration of injured nerves after 8 weeks. The extent of regeneration in and beyond the nerve graft was determined by counting the number of HRP-labeled fibers intersecting imaginary lines perpendicular to the axis of the graft and cord. For the sake of convenience, according to the relation of the PNG and spinal cord, 6 model zones were divided, including caudal of spinal cord, caudal transition zone, caudal zone in graft, rostral zone in graft, rostral transition zone and rostral of spinal cord. Results: On the transverse section of caudal zone in graft, rostral zone in graft, rostral transition zone, the fibers in group A were significantly higher than that in group B and C (P<0.05). Conclusion: PPNG combined with NGF may significantly promote the regeneration of ascending long tract after spinal cord injury. The regenerative fibers can penetrate the 2 graft-host interface scars.

  6. Repair of spinal cord injury by neural stem cells modified with BDNF gene in rats

    Institute of Scientific and Technical Information of China (English)

    Wei LI; Wen-Qin CAI; Cheng-Ren LI

    2006-01-01

    Objective To explore repair of spinal cord injury by neural stem cells (NSCs) modified with brain derived neurotrophic factor (BDNF) gene (BDNF-NSCs) in rats. Methods Neural stem cells modified with BDNF gene were transplanted into the complete transection site of spinal cord at the lumbar 4 (L4) level in rats. Motor function of rats'hind limbs was observed and HE and X-gal immunocytochemical staining, in situ hybridization, and retrograde HRP tracing were also performed. Results BDNF-NSCs survived and integrated well with host spinal cord. In the transplant group, some X-gal positive, NF-200 positive, GFAP positive, BDNF positive, and BDNF mRNA positive cells, and many NF-200 positive nerve fibers were observed in the injury site. Retrograde HRP tracing through sciatic nerve showed some HRP positive cells and nerve fibers near the rostral side of the injury one month after transplant and with time, they increased in number. Examinations on rats' motor function and behavior demonstrated that motor function of rats' hind limbs improved better in the transplant group than the injury group. Conclusion BDNF-NSCs can survive, differentiate,and partially integrate with host spinal cord, and they significantly ameliorate rats ' motor function of hind limbs, indicating their promising role in repairing spinal cord injury.

  7. Immediate electrical stimulation enhances regeneration and reinnervation and modulates spinal plastic changes after sciatic nerve injury and repair.

    Science.gov (United States)

    Vivó, Meritxell; Puigdemasa, Antoni; Casals, Laura; Asensio, Elena; Udina, Esther; Navarro, Xavier

    2008-05-01

    We have studied whether electrical stimulation immediately after nerve injury may enhance axonal regeneration and modulate plastic changes at the spinal cord level underlying the appearance of hyperreflexia. Two groups of adult rats were subjected to sciatic nerve section followed by suture repair. One group (ES) received electrical stimulation (3 V, 0.1 ms at 20 Hz) for 1 h after injury. A second group served as control (C). Nerve conduction, H reflex, motor evoked potentials, and algesimetry tests were performed at 1, 3, 5, 7 and 9 weeks after surgery, to assess muscle reinnervation and changes in excitability of spinal cord circuitry. The electrophysiological results showed higher levels of reinnervation, and histological results a significantly higher number of regenerated myelinated fibers in the distal tibial nerve in group ES in comparison with group C. The monosynaptic H reflex was facilitated in the injured limb, to a higher degree in group C than in group ES. The amplitudes of motor evoked potentials were similar in both groups, although the MEP/M ratio was increased in group C compared to group ES, indicating mild central motor hyperexcitability. Immunohistochemical labeling of sensory afferents in the spinal cord dorsal horn showed prevention of the reduction in expression of substance P at one month postlesion in group ES. In conclusion, brief electrical stimulation applied after sciatic nerve injury promotes axonal regeneration over a long distance and reduces facilitation of spinal motor responses.

  8. Isolated spinal accessory neuropathy and intracisternal schwannomas of the spinal accessory nerve

    Directory of Open Access Journals (Sweden)

    Abdullah M. Al-Ajmi

    2015-03-01

    Full Text Available We report a 40-year-old female patient presenting with isolated left spinal accessory neuropathy that developed insidiously over 6 years. She complained of ill-defined deep neck and shoulder pain. On examination, prominent sternocleidomastoid and trapezoid muscle weakness and atrophy, shoulder instability, and lateral scapular winging were observed. MRI identified a small mass of the cisternal portion of the spinal accessory nerve. Its appearance was typical of schwannoma. Surgical treatment was not offered because of the small tumor size, lack of mass effect and the questionable functional recovery in the presence of muscular atrophy.

  9. Spinal Cord Studies in the African Giant Rat (Cricetomys gambianus ...

    African Journals Online (AJOL)

    olayemitoyin

    Keywords: African giant rat; spinal cord; spinal tract; nuclei; spinal segment; morphometry. ©Physiological Society .... cervical segment appeared as a vertical slit (Figure 3a), the second to the sixth ... Intermediomedial column. Lsg. Laminae of ...

  10. Effect of hyperbaric oxygen on MMP9/2 expression and motor function in rats with spinal cord injury.

    Science.gov (United States)

    Hou, Ying-Nuo; Ding, Wen-Yuan; Shen, Yong; Yang, Da-Long; Wang, Lin-Feng; Zhang, Peng

    2015-01-01

    To study the effect of hyperbaric oxygen intervention on the microenvironment of nerve regeneration after spinal cord injury modeling and to explore the possible mechanism of nerve regeneration and functional recovery in rats with spinal cord injury. In 98 adult female SD rats, 90 successful models were obtained, which were divided into sham group, spinal cord injury group and hyperbaric oxygen group using randomized block method, 30/group. Spinal cord injury rat model was established in accordance with the modified Allen method. Motor function was assessed at the time points of before modeling, one day, three days, one week, two weeks, three weeks and four weeks after modeling respectively by BBB rating, inclined plane test and improved Tarlov score. At 3 days after modeling, apoptosis of neuronal cells in spinal cord injury region in experimental group was detected by TUNEL method; gene and protein expression of MMP9/2 in spinal cord injury and surrounding tissues was detected by RT-PCR and Western blot assay. At 4 weeks after modeling, histopathological morphological changes in spinal cord injury were observed by HE staining; fluorogold retrograde tracing was used to observe the regeneration and distribution of spinal cord nerve fibers and axon regeneration was observed by TEM. The three motor function scores in hyperbaric oxygen group at each time point after two weeks of treatment were significantly increased compared with spinal cord injury group (P hyperbaric oxygen group were significantly lower than those in spinal cord injury group (P hyperbaric oxygen group was significantly lower (P hyperbaric oxygen group and spinal cord injury group in order; the differences among the groups were statistically significant (P hyperbaric oxygen group; unmyelinated and myelinated nerve fibers in hyperbaric oxygen group were more than those in spinal cord injury group. Hyperbaric oxygen therapy played a protective effect on spinal cord injury through reducing apoptosis of

  11. Evidence of sympathetic fibers in the male rat pelvic nerve by gross anatomy, retrograde labeling and high resolution autoradiographic study.

    Science.gov (United States)

    Giuliano, F; Facchinetti, P; Bernabé, J; Benoit, G; Calas, A; Rampin, O

    1997-12-01

    Several arguments exist in various animal species and man for the presence of a sympathetic component in the pelvic nerve, classically regarded as parasympathetic. We tested this hypothesis in the male rat. Nerve bundles issued from the sacral region of the paravertebral sympathetic chain and reaching the S1 spinal nerve were identified. Neurons in the sacral parasympathetic nucleus of the L6-S1 spinal cord and in the L2-S1 paravertebral sympathetic chain were retrogradely labeled from the pelvic nerve. Radioautography evidenced labeling of unmyelinated fibers in the pelvic nerve following in vitro incubation with 3H-noradrenaline. A population of sympathetic fibers issued from the lumbosacral sympathetic chain exists in the pelvic nerve of the male rat. This qualitative study provides a morphological basis to uncover the role of the sympathetic outflow present in the pelvic nerve.

  12. Glutamine synthetase induced spinal seizures in rats.

    Science.gov (United States)

    Shin, Dong Won; Yoon, Young Sul; Matsumoto, Masato; Huang, Wencheng; Ceraulo, Phil; Young, Wise

    2003-02-01

    Glutamine synthetase (GS) is a key enzyme in the regulation of glutamate neurotransmission in the central nervous system. It is responsible for converting glutamate to glutamine, consuming one ATP and NH3 in the process. Glutamate is neurotoxic when it accumulates in extracellular fluids. We investigated the effects of GS in both a spinal cord injury (SCI) model and normal rats. 0.1-ml of low (2- micro M) and high (55- micro M) concentrations of GS were applied, intrathecally, to the spinal cord of rats under pentobarbital anesthesia. Immediately after an intrathecal injection into the L1-L3 space, the rats developed convulsive movements. These movements initially consisted of myoclonic twitches of the paravertebral muscles close to the injection site, repeated tonic and clonic contractions and extensions of the hind limbs (hind limb seizures) that spread to the fore limbs, and finally rotational axial movements of the body. An EMG of the paravertebral muscles, fore and hind limbs, showed the extent of the muscle activities. GS (2- micro M) caused spinal seizures in the rats after the SCI, and GS (6- micro M) produced seizures in the uninjured anesthetized rats. Denatured GS (70 degrees C, 1 hour) also produced spinal seizures, although higher concentrations were required. We suggest that GS may be directly blocking the release of GABA, or the receptors, in the spinal cord.

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

    Science.gov (United States)

    Boehm, Karl E; Kondrashov, Peter

    2016-01-01

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

  14. O ultrassom terapêutico na medula espinhal acelera a regeneração do nervo ciático de ratos Therapeutic ultrasound on the spinal cord accelerates regeneration of the sciatic nerve in rats

    Directory of Open Access Journals (Sweden)

    Fernanda Guadallini Jatte

    2011-01-01

    Full Text Available OBJETIVO: Estudar os efeitos da irradiação ultrassônica de baixa intensidade aplicada sobre a medula espinhal na regeneração do nervo ciático de ratos após lesão por esmagamento controlado, avaliando os resultados pelo índice funcional do ciático (SFI, medido nas imagens vídeo-filmadas das plantas das patas. MÉTODOS: Dezoito ratos foram submetidos a esmagamento controlado (do nervo ciático direito e divididos em dois grupos de acordo com o tratamento: Grupo 1 (n=9, irradiação simulada; Grupo 2 (n=9, irradiação efetiva. Irradiação ultrassônica de baixa intensidade foi iniciada no 7º dia pós-operatório e aplicada diariamente por 6 semanas. Imagens das plantas das patas dos animais foram vídeo-filmadas em uma esteira transparente sob velocidade controlada a intervalos semanais até a 6ª semana de irradiação e o correspondente SFI medido com um programa de computador específico. RESULTADOS: O SFI durante a 1ª e a 6ª semana de tratamento foi de -59,12 e -12,55 no Grupo 1, e -53,31 e -1,32 no Grupo 2, indicando uma melhora de 79% e 97%, respectivamente, mas as diferenças entre os grupos somente foram significantes (pOBJECTIVE: To study the effects of low intensity ultrasound irradiation applied on the spinal cord on the regeneration of the rat's sciatic nerve after a controlled crush injury, evaluating the functional results of the sciatic functional index as measured on the video recorded images of the foot sole. METHODS: Eighteen rats were submitted to a controlled crush injury of the right sciatic nerve and divided into two groups according to the treatment: Group 1 (n=9, simulated irradiation; Group 2 (n=9, effective irradiation. Low-intensity ultrasound irradiation was started on the 7th postoperative day and applied daily for 6 weeks. Images of the animals´ foot sole were video recorded on a see-through treadmill type walking belt machine at weekly intervals until the 6th week of irradiation and the corresponding

  15. Spinal cord bypass surgery with intercostal and spinal accessory nerves: an anatomical feasibility study in human cadavers.

    Science.gov (United States)

    Haque, Raqeeb M; Malone, Hani R; Bauknight, Martin W; Kellner, Michael A; Ogden, Alfred T; Martin, John H; Tanji, Kurenai; Winfree, Christopher J

    2012-02-01

    Despite extensive study, no meaningful progress has been made in encouraging healing and recovery across the site of spinal cord injury (SCI) in humans. Spinal cord bypass surgery is an unconventional strategy in which intact peripheral nerves rostral to the level of injury are transferred into the spinal cord below the injury. This report details the feasibility of using spinal accessory nerves to bypass cervical SCI and intercostal nerves to bypass thoracolumbar SCI in human cadavers. Twenty-three human cadavers underwent cervical and/or lumbar laminectomy and dural opening to expose the cervical cord and/or conus medullaris. Spinal accessory nerves were harvested from the Erb point to the origin of the nerve's first major branch into the trapezius. Intercostal nerves from the T6-12 levels were dissected from the lateral border of paraspinal muscles to the posterior axillary line. The distal ends of dissected nerves were then transferred medially and sequentially inserted 4 mm deep into the ipsilateral cervical cord (spinal accessory nerve) or conus medullaris (intercostals). The length of each transferred nerve was measured, and representative distal and proximal cross-sections were preserved for axonal counting. Spinal accessory nerves were consistently of sufficient length to be transferred to caudal cervical spinal cord levels (C4-8). Similarly, intercostal nerves (from T-7 to T-12) were of sufficient length to be transferred in a tension-free manner to the conus medullaris. Spinal accessory data revealed an average harvested nerve length of 15.85 cm with the average length needed to reach C4-8 of 4.7, 5.9, 6.5, 7.1, and 7.8 cm. The average length of available intercostal nerve from each thoracic level compared with the average length required to reach the conus medullaris in a tension-free manner was determined to be as follows (available, required in cm): T-7 (18.0, 14.5), T-8 (18.7, 11.7), T-9 (18.8, 9.0), T-10 (19.6, 7.0), T-11 (18.8, 4.6), and T-12 (15

  16. New methods of treatment of severely injured sciatic nerve and spinal cord. An experimental study.

    Science.gov (United States)

    Rochkind, S; Barr-Nea, L; Bartal, A; Nissan, M; Lubart, R; Razon, N

    1988-01-01

    It has been demonstrated that low-energy laser irradiation (LELI) applied simultaneously to the injured sciatic nerve and the corresponding segment of the spinal cord, accelerates the process of regeneration of the injured peripheral nerve. A beneficial influence of LELI was also observed when it was applied to the spinal cord following transection and implantation of a segment of an autologous sciatic nerve, but further studies are necessary to evaluate if real regeneration or only earlier distal cord automatism occurred. Both methods are proposed for treatment of peripheral nerve lesions (PNS) and spinal cord injuries.

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

    Science.gov (United States)

    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.

  18. Comparative analysis between thoracic spinal cord and sacral neuromodulation in a rat spinal cord injury model: a preliminary report of a rat spinal cord stimulation model.

    Science.gov (United States)

    Hyun, Seung-Jae; Lee, Chang-Hyun; Kwon, Ji Woong; Yoon, Cheol-Yong; Lim, Jae-Young; Kim, Ki-Jeong; Jahng, Tae-Ahn; Kim, Hyun-Jib

    2013-03-01

    The purpose of this study is to compare a neuroprotective effect of thoracic cord neuromodulation to that of sacral nerve neuromodulation in rat thoracic spinal cord injury (SCI) model. Twenty female Sprague Dawley rats were randomly divided into 4 groups: the normal control group (n=5), SCI with sham stimulation group (SCI, n=5), SCI with electrical stimulation at thoracic spinal cord (SCI + TES, n=5), and SCI with electrical stimulation at sacral nerve (SCI + SES, n=5). Spinal cord was injured by an impactor which dropped from 25mm height. Electrical stimulation was performed by the following protocol: pulse duration, 0.1ms; frequency, 20 Hz; stimulation time, 30 minutes; and stimulation duration at thoracic epidural space and S2 or 3 neural foramina for 4 weeks. Locomotor function, urodynamic study, muscle weights, and fiber cross sectional area (CSA) were investigated. All rats of the SCI + TES group expired within 3 days after the injury. The locomotor function of all survived rats improved over time but there was no significant difference between the SCI and the SCI + SES group. All rats experienced urinary retention after the injury and recovered self-voiding after 3-9 days. Voiding contraction interval was 25.5±7.5 minutes in the SCI group, 16.5±5.3 minutes in the SCI+SES group, and 12.5±4.2 minutes in the control group. The recovery of voiding contraction interval was significant in the SCI + SES group comparing to the SCI group (pspinal cord stimulation model. However, sacral neuromodulation have a therapeutic potential to improve neurogenic bladder and muscle atrophy.

  19. Restoration of shoulder abduction by transfer of the spinal accessory nerve to suprascapular nerve through dorsal approach: a clinical study

    Institute of Scientific and Technical Information of China (English)

    GUAN Shi-bing; HOU Chun-lin; CHEN De-song; GU Yu-dong

    2006-01-01

    Background In recent years, transfer of the spinal accessory nerve to suprascapular nerve has become a routine procedure for restoration of shoulder abduction. However, the operation via the traditional supraclavicular anterior approach often leads to partial denervation of the trapezius muscle. The purpose of the study was to introduce transfer of the spinal accessory nerve through dorsal approach, using distal branch of the spinal accessory nerve, to repair the suprascapular nerve for restoration of shoulder abduction, and to observe its therapeutic effect.Methods From January to October 2003, a total of 11 patients with a brachial plexus injury and an intact or nearly intact spinal accessory nerve were treated by transferring the spinal accessory nerve to the suprascapular nerve through dorsal approach. The patients were followed up for 18 to 26 months [mean (23.5 ±5.2) months] to evaluate their shoulder abduction and function of the trapezius muscle. The outcomes were compared with those of 26 patients treated with traditional anterior approach. And the data were analyzed by Student's t test using SPSS 10.5.Results In the 11 patients, the spinal accessory nerves were transferred to the suprascapular nerve through the dorsal approach successfully. Intact function of the upper trapezius was achieved in all of them. In the patients,the location of the two nerves was relatively stable at the level of superior margin of the scapula, the mean distance between them was (4.2±1.4) cm, both the nerves could be easily dissected and end-to-end anastomosed without any tension. During the follow-up, the first electrophysiological sign of recovery of the infraspinatus appeared at (6.8±2.7) months and the first sign of restoration of the shoulder abduction at (7.6±2.9) months after the operation, which were earlier than that after the traditional operation [(8.7±2.4) months and (9.9±2.8)months, respectively; P<0.05]. The postoperative shoulder abduction was 62.8°± 12

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

    Science.gov (United States)

    2015-01-01

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

  1. Nerve cross-bridging to enhance nerve regeneration in a rat model of delayed nerve repair.

    Science.gov (United States)

    Gordon, Tessa; Hendry, Michael; Lafontaine, Christine A; Cartar, Holliday; Zhang, Jennifer J; Borschel, Gregory H

    2015-01-01

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

  2. APOPTOSIS AFTER SPINAL CORD INJURY IN RATS

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    Objective To confirm the role played by apoptosis in spinal cord injury. Methods 36 rats models of spinal cord injury were made by Allen method. Histological examinations using HE staining and in situ end-labeling were used to observe apoptosis in spinal cord tissues from 1h to 21d after injury. Results HE staining sections showed hemorrhage and necrosis, neuronal degeneration and gliai cell proliferation. In situ end-labeling sections showed the appearance of apoptosis in both gray and white matter as well as in both central and surrounding region. The number of apoptotic cells increased from 12h after injury, increased to the peak at 4d and declined to normal at 21d. Conclu sion The results suggest that apoptosis, especially glial apoptosis, plays a role in the pathogenesis of spinal cord in jury.

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

    Science.gov (United States)

    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.

  4. Phrenic nerve afferents elicited cord dorsum potential in the cat cervical spinal cord

    Directory of Open Access Journals (Sweden)

    Davenport Paul W

    2005-05-01

    Full Text Available Abstract Background The diaphragm has sensory innervation from mechanoreceptors with myelinated axons entering the spinal cord via the phrenic nerve that project to the thalamus and somatosensory cortex. It was hypothesized that phrenic nerve afferent (PnA projection to the central nervous system is via the spinal dorsal column pathway. Results A single N1 peak of the CDP was found in the C4 and C7 spinal segments. Three peaks (N1, N2, and N3 were found in the C5 and C6 segments. No CDP was recorded at C8 dorsal spinal cord surface in cats. Conclusion These results demonstrate PnA activation of neurons in the cervical spinal cord. Three populations of myelinated PnA (Group I, Group II, and Group III enter the cat's cervical spinal segments that supply the phrenic nerve

  5. Nerve excitability in the rat forelimb

    DEFF Research Database (Denmark)

    Arnold, Ria; Moldovan, Mihai; Rosberg, Mette Romer;

    2017-01-01

    Background Nerve excitability testing by threshold-tracking is the only available method to study axonal ion channel function and membrane potential in the clinical setting. The measures are, however, indirect and the interpretation of neuropathic changes remains challenging. The same multiple...... measures of axonal excitability were adapted to further explore the pathophysiological changes in rodent disease models under pharmacologic and genetic manipulations. These studies are typically limited to the investigation of the “long nerves” such as the tail or the tibial nerves. New method We introduce...... a novel setup to explore the ulnar nerve excitability in rodents. We provide normative ulnar data in 11 adult female Long Evans rats under anaesthesia by comparison with tibial and caudal nerves. Additionally, these measures were repeated weekly on 3 occasions to determine the repeatability of these tests...

  6. Ligation of mouse L4 and L5 spinal nerves produces robust allodynia without major motor function deficit.

    Science.gov (United States)

    Ye, Gui-Lan; Savelieva, Katerina V; Vogel, Peter; Baker, Kevin B; Mason, Sara; Lanthorn, Thomas H; Rajan, Indrani

    2015-01-01

    Spinal nerve L5/L6 ligation (SNL) in rats has become the standard for mechanistic studies of peripheral neuropathy and screening for novel analgesics. Conventional SNL in our hybrid mice resulted in a wide range of allodynia. Anatomical evaluation indicated that a variable number of lumbar vertebrae existed, resulting in L4/L5 or L5/L6 being ligated. Surprisingly, L4/L5 ligation did not result in ipsilateral hind limb paralysis and produced robust allodynia. Following a recent report that the mouse L4 neural segment is homologous with rat L5 we generated L4, L5 or both L4 and L5 (L4/L5) ligations in C57 mice after establishing a modified set of surgical landmarks. In contrast to rats, L4 ligation in these mice did not result in hind limb paralysis. Robust allodynia was observed in all three ligation groups. Nerve degeneration confirmed that L4 and L5, respectively, are primary contributors to the tibial and sural branches of the sciatic nerve in mice. A larger von Frey sensitive area reflected the wider distribution of Wallerian degeneration in the hindlimb of L4- compared to L5-ligated mice. Ligation of mouse L4 and L5 spinal nerves produces consistent, robust neuropathic pain behaviors and is suitable as a model for investigating mechanisms of neuropathic pain and for testing of novel analgesics. Gabapentin, used as a validation drug in neuropathic pain models and as a reference compound for novel analgesics, significantly reduced allodynia in the mice tested (L4/L5 ligations). Given the ease of surgery, robust allodynia, and larger von Frey sensitive area, we conclude that combined ligation of spinal nerves L4 and L5 optimizes the SNL model in mice.

  7. Hippocampal plasticity after a vagus nerve injury in the rat

    Institute of Scientific and Technical Information of China (English)

    Giulia Ronchi; Vitaly Ryu; ong ling; Krzysztof Czaja

    2012-01-01

    Stimulation of the vagus nerve has been previously reported to promote neural plasticity and neurogenesis in the brain. Several studies also revealed plastic changes in the spinal cord after injuries to somatosensory nerves originating from both the brachial and lumbo-sacral plexuses. However, the neurogenic responses of the brain to the injury of the viscerosensory innervation are not as yet well understood. In the present study, we investigated whether cells in the dentate gyrus of the hippocampus respond to a chemical and physical damage to the vagus nerve in the adult rat. Intraperitoneal capsaicin administration was used to damage non-myelinated vagal afferents while subdiaphragmatic vagotomy was used to damage both the myelinated and non-myelinated vagal afferents. The 5-bromo-2-deoxyuridine (BrdU) incorporation together with cell-specific markers was used to study neural proliferation in subgranular zone, granule cell layer, molecular layer and hilus of the dentate gyrus. Microglia activation was determined by quantifying changes in the intensity of fluorescent staining with a primary antibody against ionizing calcium adapter-binding molecule 1. Results revealed that vagotomy decreased BrdU incorporation in the hilus 15 days after injury compared to the capsaicin group. Capsaicin administration decreased BrdU incorporation in the granular cell layer 60 days after the treatment. Capsaicin decreased the number of doublecortin-expressing cells in the dentate gyrus, whereas vagotomy did not alter the expression of doublecortin in the hippocampus. Both the capsaicin- and the vagotomy-induced damage to the vagus nerve decreased microglia activation in the hippocampus at 15 days after the injury. At 30 days post injury, capsaicin-treated and vagotomized rats revealed significantly more activated microglia. Our findings show that damage to the subdiaphragmatic vagus in adult rats is followed by microglia activation and long-lasting changes in the dentate gyrus

  8. Combination of acellular nerve graft and schwann cells-like cells for rat sciatic nerve regeneration.

    Science.gov (United States)

    Gao, Songtao; Zheng, Yan; Cai, Qiqing; Deng, Zhansheng; Yao, Weitao; Wang, Jiaqiang; Wang, Xin; Zhang, Peng

    2014-01-01

    To investigate the effect of tissue engineering nerve on repair of rat sciatic nerve defect. Forty-five rats with defective sciatic nerve were randomly divided into three groups. Rats in group A were repaired by acellular nerve grafts only. Rats in group B were repaired by tissue engineering nerve. In group C, rats were repaired by autogenous nerve grafts. After six and twelve weeks, sciatic nerve functional index (SFI), neural electrophysiology (NEP), histological and transmission electron microscope observation, recovery ratio of wet weight of gastrocnemius muscle, regenerated myelinated nerve fibers number, nerve fiber diameter, and thickness of the myelin sheath were measured to assess the effect. After six and twelve weeks, the recovery ratio of SFI and wet weight of gastrocnemius muscle, NEP, and the result of regenerated myelinated nerve fibers in groups B and C were superior to that of group A (P 0.05). The tissue engineering nerve composed of acellular allogenic nerve scaffold and Schwann cells-like cells can effectively repair the nerve defect in rats and its effect was similar to that of the autogenous nerve grafts.

  9. Nerve transfer for treatment of brachial plexus injury: comparison study between the transfer of partial median and ulnar nerves and that of phrenic and spinal accessary nerves

    Institute of Scientific and Technical Information of China (English)

    侯之启; 徐中和

    2002-01-01

    Objective: To compare the effect of using partial median and ulnar nerves for treatment of C5-6 or C5-7 avulsion of the brachial plexus with that of using phrenic and spinal accessary nerves.Methods: The patients were divided into 2 groups randomly according to different surgical procedures. Twelve cases were involved in the first group. The phrenic nerve was transferred to the musculocutaneous nerve or through a sural nerve graft, and the spinal accessary nerve was to the suprascapular nerve. Eleven cases were classified into the second group. A part of the fascicles of median nerve was transferred to be coapted with the motor fascicle of musculocutaneous nerve and a part of fascicles of ulnar nerve was transferred to the axillary nerve. The cases were followed up from 1 to 3 years and the clinical outcome was compared between the two groups. Results: There were 2 cases (16.6%) who got the recovery of M4 strength of biceps muscle in the first group but 7 cases (63.6%) in the second group, and the difference was statistically significant (P<0.025). However, it was not statistically different in the recovery of shoulder function between the two groups. Conclusions: Partial median and ulnar nerve transfer, phrenic and spinal accessary nerve transfer were all effective for the reconstruction of elbow or shoulder function in brachial plexus injury, but the neurotization using a part of median nerve could obtain more powerful biceps muscle strength than that of phrenic nerve transfer procedure.

  10. Rat-derived processed nerve allografts support more axon regeneration in rat than human-derived processed nerve xenografts.

    Science.gov (United States)

    Wood, Matthew D; Kemp, Stephen W P; Liu, Edward H; Szynkaruk, Mark; Gordon, Tessa; Borschel, Gregory H

    2014-04-01

    Processed nerve allografts are increasingly used as "off the shelf" nerve replacements for surgically bridging nerve gaps. Benchmarking the regenerative capacity of a commercially available human-derived nerve or xenograft in a rat nerve injury model would provide a convenient platform for future studies seeking to modify the processed nerve graft. Human and rat processed nerve grafts were used to bridge a 14 mm defect in a Sprague-Dawley rat sciatic nerve. Reversed autografts served as a positive control group. Twelve weeks following surgery, the distal nerve stumps were retrograde labeled and harvested for histology and histomorphometry. The cross-sectional areas of the human- and rat-derived processed nerve grafts were similar. Neuron counts and myelinated axon counts following use of the human-derived processed xenografts were decreased compared with those obtained from both the rat-derived processed nerve allografts and the autografts; the rat-derived processed nerve allografts were statistically equivalent to autografts. Measures of nerve fiber diameter and myelination revealed inferior axon regeneration maturity in both processed nerve grafts compared with autografts. Processed xenografts showed significantly reduced regeneration compared with autografts or processed allografts indicating that cross-species immunological reactions are important considerations in this rat model. Copyright © 2013 Wiley Periodicals, Inc.

  11. Comparison of nerve graft integration after segmentar resection versus epineural burying in crushed rat sciatic nerves

    Directory of Open Access Journals (Sweden)

    Cunha Marco Túlio Rodrigues da

    1997-01-01

    Full Text Available The aim of the present paper is to compare and correlate the take of nerve segments in a severely crushed nerve. Forty adult Wistar rats had their right sciatic nerve by a "Péan-Murphy" forceps for 40 minutes. In Group 1 (n=20, a segmentar serection in the crushed sciatic nerve was made. A sural nerve segment from the opposite hindpaw was placed in the gap. In Group 2 (n=20, a lontudinal insision in the epineurium of the lesioned sciatic nerve was made. A sural nerve segment was buried underneath the epineurium. The crushed sciatic nerves undergone Wallerian degeneration and endoneurial fibrosis. Sciatic nerves from Group 2 had significant better histological aspects than those from Group 1. Sural nerve grafts presented better degrees of regeneration than crushed sciatic nerves. Sural nerve grafts from Group 2 (burying method integrated as well as those from Group 1 (segmentar resection.

  12. Neuroprotective effect of estrogen after chronic spinal cord injury in ovariectomized rats

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    BACKGROUND: At present, there is still lack of effective drugs for chronic spinal cord injury, whereas it is found recently that estrogen has a neuroprotective effect on brain and spinal cord injuries.OBJECTIVE: To observe the effect of estrogen on the apoptosis of nerve cells after gradual chronic spinal cord injury in ovariectomized rats.DESIGN: A randomized controlled animal trial.SETTING: Institute of Orthopaedics, the Second Hospital of Lanzhou University.MATERIALS: Sixty-five female Wistar rats of common degree, weighing 220 - 250 g, were provided by the experimental animal center of Lanzhou University. The rats were randomly divided into sham-operated group (n =5), estrogen-treated group (n =30) and saline control group (n =30), and the latter two groups were observed at 1, 3, 7, 14, 28 and 60 days respectively, and 5 rats for each time point.METHODS: All the rats were treated with bilateral oophorectomy 2 weeks before the experiment. T10 vertebral lamina was revolved into using plastic screw. The spinal canal impingement was not induced initially. After that, the original incision was opened to expose the screw every 7 - 10 days.MAIN OUTCOME MEASURES: The apoptosis and Caspase-3 positive cells in the damaged spinal cord were detected using terminal deoxynucleotidal transferase-mediated dUTP-biotin nick end labeling (TUNEL) method and Caspase-3 immunohistochemical staining at 1, 3, 7, 14, 28 and 60 days after chronic spinal cord injury respectively.RESULTS: Totally 65 rats were used, and the deleted ones during the experiment were supplemented by others. Changes of Caspase-3 expression after spinal cord injury: In the sham-operated group, only a small amount of Caspase-3 proteins were observed in the rat spinal cord, mainly located in motor neurons of spinal cord anterior horn. In the estrogen-treated group and saline control group, positive cells expressed occasionally at 1 day postoperatively, began to increase obviously at 7 days after injury, strongly

  13. Anatomical mechanism of spontaneous recovery in regions caudal to thoracic spinal cord injury lesions in rats

    Science.gov (United States)

    Li, Lu-sheng; Yu, Hao; Raynald, Raynald; Wang, Xiao-dong; Dai, Guang-hui; Cheng, Hong-bin; Liu, Xue-bin

    2017-01-01

    Background The nerve fibre circuits around a lesion play a major role in the spontaneous recovery process after spinal cord hemisection in rats. The aim of the present study was to answer the following question: in the re-control process, do all spinal cord nerves below the lesion site participate, or do the spinal cord nerves of only one vertebral segment have a role in repair? Methods First we made a T7 spinal cord hemisection in 50 rats. Eight weeks later, they were divided into three groups based on distinct second operations at T7: ipsilateral hemisection operation, contralateral hemisection, or transection. We then tested recovery of hindlimbs for another eight weeks. The first step was to confirm the lesion had role or not in the spontaneous recovery process. Secondly, we performed T7 spinal cord hemisections in 125 rats. Eight weeks later, we performed a second single hemisection on the ipsilateral side at T8–T12 and then tested hindlimb recovery for another six weeks. Results In the first part, the Basso, Beattie, Bresnahan (BBB) scores and the electrophysiology tests of both hindlimbs weren’t significantly different after the second hemisection of the ipsilateral side. In the second part, the closer the second hemisection was to T12, the more substantial the resulting impairment in BBB score tests and prolonged latency periods. Conclusions The nerve regeneration from the lesion area after hemisection has no effect on spontaneous recovery of the spinal cord. Repair is carried out by all vertebrae caudal and ipsilateral to the lesion, with T12 being most important. PMID:28097067

  14. In-vivo spinal nerve sensing in MISS using Raman spectroscopy

    Science.gov (United States)

    Chen, Hao; Xu, Weiliang; Broderick, Neil

    2016-04-01

    In modern Minimally Invasive Spine Surgery (MISS), lack of visualization and haptic feedback information are the main obstacles. The spinal cord is a part of the central nervous system (CNS). It is a continuation of the brain stem, carries motor and sensory messages between CNS and the rest of body, and mediates numerous spinal reflexes. Spinal cord and spinal nerves are of great importance but vulnerable, once injured it may result in severe consequences to patients, e.g. paralysis. Raman Spectroscopy has been proved to be an effective and powerful tool in biological and biomedical applications as it works in a rapid, non-invasive and label-free way. It can provide molecular vibrational features of tissue samples and reflect content and proportion of protein, nucleic acids lipids etc. Due to the distinct chemical compositions spinal nerves have, we proposed that spinal nerves can be identified from other types of tissues by using Raman spectroscopy. Ex vivo experiments were first done on samples taken from swine backbones. Comparative spectral data of swine spinal cord, spinal nerves and adjacent tissues (i.e. membrane layer of the spinal cord, muscle, bone and fatty tissue) are obtained by a Raman micro-spectroscopic system and the peak assignment is done. Then the average spectra of all categories of samples are averaged and normalized to the same scale to see the difference against each other. The results verified the feasibility of spinal cord and spinal nerves identification by using Raman spectroscopy. Besides, a fiber-optic Raman sensing system including a miniature Raman sensor for future study is also introduced. This Raman sensor can be embedded into surgical tools for MISS.

  15. Selective targeting of TRPV1 expressing sensory nerve terminals in the spinal cord for long lasting analgesia.

    Directory of Open Access Journals (Sweden)

    Joseph A Jeffry

    Full Text Available Chronic pain is a major clinical problem and opiates are often the only treatment, but they cause significant problems ranging from sedation to deadly respiratory depression. Resiniferatoxin (RTX, a potent agonist of Transient Receptor Potential Vanilloid 1 (TRPV1, causes a slow, sustained and irreversible activation of TRPV1 and increases the frequency of spontaneous excitatory postsynaptic currents, but causes significant depression of evoked EPSCs due to nerve terminal depolarization block. Intrathecal administration of RTX to rats in the short-term inhibits nociceptive synaptic transmission, and in the long-term causes a localized, selective ablation of TRPV1-expressing central sensory nerve terminals leading to long lasting analgesia in behavioral models. Since RTX actions are selective for central sensory nerve terminals, other efferent functions of dorsal root ganglion neurons can be preserved. Preventing nociceptive transmission at the level of the spinal cord can be a useful strategy to treat chronic, debilitating and intractable pain.

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

    Science.gov (United States)

    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.

  17. Large A-fiber activity is required for microglial proliferation and p38 MAPK activation in the spinal cord: different effects of resiniferatoxin and bupivacaine on spinal microglial changes after spared nerve injury

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    Decosterd Isabelle

    2009-09-01

    Full Text Available Abstract Background After peripheral nerve injury, spontaneous ectopic activity arising from the peripheral axons plays an important role in inducing central sensitization and neuropathic pain. Recent evidence indicates that activation of spinal cord microglia also contributes to the development of neuropathic pain. In particular, activation of p38 mitogen-activated protein kinase (MAPK in spinal microglia is required for the development of mechanical allodynia. However, activity-dependent activation of microglia after nerve injury has not been fully addressed. To determine whether spontaneous activity from C- or A-fibers is required for microglial activation, we used resiniferatoxin (RTX to block the conduction of transient receptor potential vanilloid subtype 1 (TRPV1 positive fibers (mostly C- and Aδ-fibers and bupivacaine microspheres to block all fibers of the sciatic nerve in rats before spared nerve injury (SNI, and observed spinal microglial changes 2 days later. Results SNI induced robust mechanical allodynia and p38 activation in spinal microglia. SNI also induced marked cell proliferation in the spinal cord, and all the proliferating cells (BrdU+ were microglia (Iba1+. Bupivacaine induced a complete sensory and motor blockade and also significantly inhibited p38 activation and microglial proliferation in the spinal cord. In contrast, and although it produced an efficient nociceptive block, RTX failed to inhibit p38 activation and microglial proliferation in the spinal cord. Conclusion (1 Blocking peripheral input in TRPV1-positive fibers (presumably C-fibers is not enough to prevent nerve injury-induced spinal microglial activation. (2 Peripheral input from large myelinated fibers is important for microglial activation. (3 Microglial activation is associated with mechanical allodynia.

  18. Effect of low-frequency transcutaneous electrical nerve stimulation on the action potential of spinal cord posterior horn cells in rats after peripheral nerve injury%低频电疗对白鼠周围神经损伤后脊髓后角神经细胞活动电位的影响

    Institute of Scientific and Technical Information of China (English)

    崔松彪; 赵和荣; 吴光; 朴虎男; 许梅花

    2006-01-01

    度刺激所引发的脊髓后角神经细胞的膜电位明显高于注射前[每10 s(174.5±0.41),(235.4±1.41)次,P<0.01].结论:低频电刺激能有效抑制被无害刺激所引发的脊髓后角神经细胞的活动电位,且静脉注射纳洛酮(8 mg/kg)可使之逆转到治疗前的水平,说明低频电疗可能是刺激中枢神经系统使其分泌内源鸦片物质,作用于脊髓后角细胞使其活性降低,从而达到缓解疼痛的目的.%BACKGROUND: Up to now, few studies related to the mechanism of low-frequency transcutaneous electrical nerve stimulation (TENS) in relieving pain, and the effect of low-frequency TENS on the activity potential of dorsal horn cells in rats after peripheral nerve injury. OBJECTIVE: To observe the effects of low-frequency TENS on the activity potential of dorsal horn cells induced by mechanical allodynia and thermal allodynia by using animal models of peripheral nerve injury, and observe the efficacy after interfering of naloxone. DESIGN: A randomized control animal study. SETTING: Department of Neurology, Affiliated Hospital of Medical College, Yanbian University. MATERIALS: The experiment was carried out in the central laboratory of Medical College, Yanbian University between February and October 2004. Eighty male Sprague-Dawley rats were used, and 60 random selected ones were operated to separate sciatic nerve, two branch tibial nerves and sural nerves of sciatic nerve were amputated after ligation, and peroneal nerve was left as the experimental group; the other 20 rats were placed at the origin after sciatic nerve was separated, and then the skin was sutured as the control group. METHODS: ① Pain detection (Behavioral test): At 1 week postoperatively, the rats were given mechanical allodynia and thermal allodynia once every 5 seconds for 10 times, and then the frequency of foot withdrawal was detected (0%-40% for mild pain, 40%-70% for moderate pain; 70% and above for severe pain). ② The spontaneous

  19. Shoulder complaints after neck dissection; is the spinal accessory nerve involved?

    NARCIS (Netherlands)

    van Wilgen, C.P.; Dijkstra, P.U.; van der Laan, B.F.; Plukker, J.T.; Roodenburg, J.L.

    The purpose of the current study was to investigate the relation between shoulder morbidity (pain and range of motion), and the function of the spinal accessory nerve after neck dissection. Identifying dysfunction of the nerve gives insight in the mechanisms of post-operative shoulder complaints. In

  20. Functional nerve recovery after bridging a 15 mm gap in rat sciatic nerve with a biodegradable nerve guide

    NARCIS (Netherlands)

    Meek, MF; Klok, F; Robinson, PH; Nicolai, JPA; Gramsbergen, A; van der Werf, J.F.A.

    2003-01-01

    Recovery of nerve function was evaluated after bridging a 15 mm sciatic nerve gap in 51 rats with a biodegradable poly(DL-lactide-epsilon-caprolactone) nerve guide. Recovery of function was investigated by analysing the footprints, by analysing video recordings of gait, by electrically eliciting the

  1. Functional nerve recovery after bridging a 15 mm gap in rat sciatic nerve with a biodegradable nerve guide

    NARCIS (Netherlands)

    Meek, MF; Klok, F; Robinson, PH; Nicolai, JPA; Gramsbergen, A; van der Werf, J.F.A.

    2003-01-01

    Recovery of nerve function was evaluated after bridging a 15 mm sciatic nerve gap in 51 rats with a biodegradable poly(DL-lactide-epsilon-caprolactone) nerve guide. Recovery of function was investigated by analysing the footprints, by analysing video recordings of gait, by electrically eliciting the

  2. Isolated long thoracic nerve paralysis - a rare complication of anterior spinal surgery: a case report

    Directory of Open Access Journals (Sweden)

    Ameri Ebrahim

    2009-06-01

    Full Text Available Abstract Introduction Isolated long thoracic nerve injury causes paralysis of the serratus anterior muscle. Patients with serratus anterior palsy may present with periscapular pain, weakness, limitation of shoulder elevation and scapular winging. Case presentation We present the case of a 23-year-old woman who sustained isolated long thoracic nerve palsy during anterior spinal surgery which caused external compressive force on the nerve. Conclusion During positioning of patients into the lateral decubitus position, the course of the long thoracic nerve must be attended to carefully and the nerve should be protected from any external pressure.

  3. Differential astroglial responses in the spinal cord of rats submitted to a sciatic nerve double crush treated with local injection of cultured Schwann cell suspension or lesioned spinal cord extract: implications on cell therapy for nerve repair Respostas astrocitárias na medula espinal do rato submetido ao esmagamento duplo do nervo ciático e tratado com injeção local de suspensão de células de Schwann cultivadas ou de extrato de medula espinal lesada: implicações na terapia celular para o reparo do nervo

    Directory of Open Access Journals (Sweden)

    João Gabriel Martins Dallo

    2007-12-01

    Full Text Available PURPOSE: Reactive astrocytes are implicated in several mechanisms after central or peripheral nervous system lesion, including neuroprotection, neuronal sprouting, neurotransmission and neuropathic pain. Schwann cells (SC, a peripheral glia, also react after nerve lesion favoring wound/repair, fiber outgrowth and neuronal regeneration. We investigated herein whether cell therapy for repair of lesioned sciatic nerve may change the pattern of astroglial activation in the spinal cord ventral or dorsal horn of the rat. METHODS: Injections of a cultured SC suspension or a lesioned spinal cord homogenized extract were made in a reservoir promoted by a contiguous double crush of the rat sciatic nerve. Local injection of phosphate buffered saline (PBS served as control. One week later, rats were euthanized and spinal cord astrocytes were labeled by immunohistochemistry and quantified by means of quantitative image analysis. RESULTS: In the ipsilateral ventral horn, slight astroglial activations were seen after PBS or SC injections, however, a substantial activation was achieved after cord extract injection in the sciatic nerve reservoir. Moreover, SC suspension and cord extract injections were able to promote astroglial reaction in the spinal cord dorsal horn bilaterally. Conclusion: Spinal cord astrocytes react according to repair processes of axotomized nerve, which may influence the functional outcome. The event should be considered during the neurosurgery strategies.OBJETIVO: Astrócitos reativos participam de vários mecanismos após lesões do sistema nervoso central e periférico, os quais incluem neuroproteção, brotamento neuronal, neurotransmissão e dor neuropática. As células de Schwann (CS, um tipo de glia periférica, também reagem com a lesão do nervo, podendo interferir com o reparo e cicatrização, crescimento de fibras e regeneração neuronais. Investigamos aqui a possibilidade da terapia celular para o reparo do nervo ci

  4. Pannexin 1: a novel participant in neuropathic pain signaling in the rat spinal cord.

    Science.gov (United States)

    Bravo, David; Ibarra, Paula; Retamal, Jeffri; Pelissier, Teresa; Laurido, Claudio; Hernandez, Alejandro; Constandil, Luis

    2014-10-01

    Pannexin 1 (panx1) is a large-pore membrane channel expressed in many tissues of mammals, including neurons and glial cells. Panx1 channels are highly permeable to calcium and adenosine triphosphatase (ATP); on the other hand, they can be opened by ATP and glutamate, two crucial molecules for acute and chronic pain signaling in the spinal cord dorsal horn, thus suggesting that panx1 could be a key component for the generation of central sensitization during persistent pain. In this study, we examined the effect of three panx1 blockers, namely, 10panx peptide, carbenoxolone, and probenecid, on C-reflex wind-up activity and mechanical nociceptive behavior in a spared nerve injury neuropathic rat model involving sural nerve transection. In addition, the expression of panx1 protein in the dorsal horn of the ipsilateral lumbar spinal cord was measured in sural nerve-transected and sham-operated control rats. Sural nerve transection resulted in a lower threshold for C-reflex activation by electric stimulation of the injured hindpaw, together with persistent mechanical hypersensitivity to pressure stimuli applied to the paw. Intrathecal administration of the panx1 blockers significantly depressed the spinal C-reflex wind-up activity in both neuropathic and sham control rats, and decreased mechanical hyperalgesia in neuropathic rats without affecting the nociceptive threshold in sham animals. Western blotting showed that panx1 was similarly expressed in the dorsal horn of lumbar spinal cord from neuropathic and sham rats. The present results constitute the first evidence that panx1 channels play a significant role in the mechanisms underlying central sensitization in neuropathic pain. Copyright © 2014 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.

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

    Science.gov (United States)

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

    2014-03-05

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

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

    Science.gov (United States)

    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.

  7. Electrical nerve stimulation to promote micturition in spinal cord injury patients: A review of current attempts.

    Science.gov (United States)

    Ren, Jian; Chew, Daniel J; Biers, Suzanne; Thiruchelvam, Nikesh

    2016-03-01

    In this review, we focus on the current attempts of electrical nerve stimulation for micturition in spinal cord injury (SCI) patients. A literature search was performed through PubMed using "spinal cord injury," "electrical nerve stimulation AND bladder," "sacral anterior root stimulation/stimulator" and "Brindley stimulator" from January 1975 to January 2014. Twenty studies were selected for this review. Electrical nerve stimulation is a clinical option for promoting micturition in SCI patients. Well-designed, randomized and controlled studies are essential for further investigation. © 2015 Wiley Periodicals, Inc.

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

    Directory of Open Access Journals (Sweden)

    Aurora Messina

    2016-09-01

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

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

    Science.gov (United States)

    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.

  10. Paralysis following stereotactic spinal irradiation in pigs suggests a tolerance constraint for single-session irradiation of the spinal nerve

    NARCIS (Netherlands)

    Medin, P.M.; Foster, R.D.; Kogel, A.J. van der; Meyer, J.; Sayre, J.W.; Huang, H.; Oz, O.K.

    2013-01-01

    BACKGROUND AND PURPOSE: Paralysis observed during a study of vertebral bone tolerance to single-session irradiation led to further study of the dose-related incidence of motor peripheral neuropathy. MATERIALS AND METHODS: During a bone tolerance study, cervical spinal nerves of 15 minipigs received

  11. Rat sciatic nerve crush injury and recovery tracked by plantar test and immunohistochemistry analysis.

    Science.gov (United States)

    Pavić, Roman; Pavić, Michele L; Tvrdeić, Ante; Tot, Ozana K; Heffer, Marija

    2011-01-01

    An experimental crush injury to the sciatic nerve, with a crush force of 49.2 N (pressure p=1.98x10(8) Pa), was inflicted in 30 male rats (Wistar). A control group (sham), with the same number of rats, was also operated upon exactly as the experimental group but without the crush injury. We tested the sensory and motor recovery of the sciatic nerve with Hargreaves method, using an apparatus from Ugo Basile, Italy. Testing was continued for both legs of each rat, injured and uninjured, starting preoperatively (0 day), and then 1, 7, 14, 21, and 28 days postoperatively. The same experiment was run simultaneously with the sham group. The Plantar test showed recovery of the sensory and motor function of the sciatic nerve, though not complete recovery, by 28 days. An immunohistochemical experiment was run in parallel with the plantar test on L3-L6 segments of the spinal cord from where the sciatic nerve extends. We used antibodies for Myelin-associated glycoprotein (MAG), and gangliosides GD1a and GT1b on the aforesaid part of the spinal cord. The immunohistochemical methods showed changes in sensory and motor axons in the spinal cord segment L3-L6 which suggest correspondence with the results of the Plantar test, in terms of recovery of the sensory and motor function after injury of the sciatic nerve. The immunohistochemical results also show ipsilateral and contralateral changes following injury. Results of the plantar test are suggestive that the rat shows compensation for an injury in its contralateral leg.

  12. Altered acetylcholinesterase levels in the spinal cord anterior horn and dorsal root ganglion following sciatic nerve ischemia

    Institute of Scientific and Technical Information of China (English)

    Zhenjun Yang; Pei Wang; Songhe Yang; Jingfeng Xue

    2009-01-01

    BACKGROUND: Peripheral nerve ischemia has been shown to result in ischemic fiber degeneration and axoplasmic transport disturbance. However, the effect on acetylcholinesterase (AChE) expression in relevant cells following sciatic nerve ischemia remains unclear. OBJECTIVE: To observe AChE concentration changes following peripheral nerve ischemia. DESIGN, TIME AND SETTING: The present comparative observation, neuroanatomical experiment was performed at the Central Laboratory Animal of Chengde Medical College between 2006 and 2007. MATERIALS: A total of 20 healthy, adult, Wistar rats were randomized into two groups (n = 10): 8-day ischemia and 14-day ischemia. METHODS: Ischemia injury was induced in the unilateral sciatic nerve (experimental side) through ligation of the common iliac artery. The contralateral side received no intervention, and served as the control side. Rats in the 8-day ischemia and 14-day ischemia groups were allowed to survive for 8 and 14 days, respectively. MAIN OUTCOME MEASURES: The L5 lumbar spinal cord and the L5 dorsal root ganglion were removed from both sides and sectioned utilizing a Leica vibrating slicer. AChE cellular expression was detected using Karnovsky-Root, and the number of AChE-positive cells and average gray value were analyzed using a MiVnt image analysis system. RESULTS: In the 8-day ischemia group, AChE-positive cell numbers were significantly less in the dorsal root ganglion and spinal cord anterior horn of the experimental side, but the average gray value was significantly greater, compared with the control side (P < 0.05). These changes were more significant in the 14-day ischemia group than in the 8-day ischemia group (P < 0.01). CONCLUSION: Peripheral nerve ischemia leads to decreased AChE expression in the associated cells in a time-dependent manner.

  13. Effects of xenotransplantation of microencapsulated sciatic nerve tissue cells on the expression of calcitonin gene-related peptide after spinal cord injury in rats%异种细胞移植对大鼠损伤脊髓降钙素基因相关肽表达的影响

    Institute of Scientific and Technical Information of China (English)

    段平国; 孙贵才; 刘德明

    2011-01-01

    Objective: To observe the effects of xenotransplantation of the microencapsulated sciatic nerve tissue/cella on the expression of calcitonin gene-related peptide (CGRP) after spinal cord injury (SCI) in rats.Methods: Bilateral sciatic nerves of rabbits were preconditioned for 1 week were dissected under sterile conditions and made into nerve tissue/cells suspension which was mixed with 1.5% sodium alginate solution.The mixture was then extruded using a droplet generation device into 20 mmol/L barium chloride solution to form barium-alginate capsules.Microencapsulated nerve tissue/cells suspension was implanted into the injured sites of the spinal cord in rats.By immunohistochernstry, the expressions of CGRP were observed.Results: The number of CGRP-positive cells in the right ventral horn of spinal cord of rats reduced remarkably in each group after SCI, and it gradually recovered in varying degrees 1 week later.The difference of the number of CGRP-positive cells between the microcapsule group and the cell group was not remarkable, but both of them existed in the distinction when compared with the injury group (P <0.05).At 2, 4 weeks and 8 weeks after SCI, compared to the cell group and injury group,the number of CGRP-positive cells in the microcapsule group increased obviotrsly.Conclusion: The xenotransplantation of the microencapsulated sciatic nerve tissue/cells promotes the expression of CGRP after SCI in rats, benefiting the regeneration of neuron.%目的:观察微囊化异种坐骨神经组织细胞移植对脊髓损伤大鼠降钙素基因相关肽(CGRP)表达的影响.方法:取家兔预变性处理1周的坐骨神经制成组织细胞悬液,与1.5%海藻酸钠溶液混合并喷入20mmol/L氯化钡溶液中制成微囊化的组织细胞悬液.将其植入SD大鼠脊髓损伤处,通过免疫组织化学显色观察CGRP的表达情况.结果:SCI后各组大鼠右侧脊髓前角CGRP阳性细胞数减少,1周后均不同程度地逐渐恢复.SCI后1周,细

  14. Inhibition of spinal reflexes by acetylsalicylate and metamizol (dipyrone) in rats.

    Science.gov (United States)

    Genç, O; Turgut, S; Turgut, G; Kortunay, S

    2003-11-01

    The effects of acetylsalicylate and metamizol on spinal monosynaptic reflexes were tested in spinal rats. Adult rats were anesthetized with ketamine, artificially ventilated, and spinalized at the C1 level. A laminectomy was performed in the lumbosacral region. Following electrical stimulation of the sciatic nerve by single pulses, the reflex potentials were recorded from the ipsilateral L5 ventral root. Acetylsalicylate was administered orally via nasogastric tube and metamizol intramuscularly. Acetylsalicylate (50 and 100 mg/kg) and metamizol (15 mg/kg) significantly decreased the amplitude of the reflex response (p metamizol dose did not significantly decrease the amplitude of the reflex response. The cyclooxygenase products of arachidonic acid may play an important role in regulating the reflex potential. Copyright 2003 S. Karger AG, Basel

  15. Deferoxamine improves neurological function in a rat model of experimental spinal cord injury

    Institute of Scientific and Technical Information of China (English)

    Yanting Wang; Shaoji Yuan; Fachen Wang; Rong Hu; Jiangkai Lin; Zisheng Liu; Hua Feng

    2011-01-01

    A rat model of spinal cord injury was established using modified Allen's method and treated with the ferric iron-chelating agent, deferoxamine. Hematoxylin-eosin, Nissl and Perl's Prussian blue staining, at 7-14 days following spinal cord injury, showed that following deferoxamine treatment, glial cells proliferation increased significantly, nerve cell morphology was improved and hemosiderin was significantly reduced in the injury region. At 1-56 days following injury, Basso, Beattie, and Bres nahan Locomotor Rating Scale scores were increased, while latencies of somatosensory-evoked potentials and motor-evoked potentials were decreased. Results demonstrate that deferoxamine can promote neurological functional recovery after experi-mental spinal cord injury in rats.

  16. Protective Effect of Interleukin-1β on Motor Neurons after Sciatic Nerve Injury in Rats

    Institute of Scientific and Technical Information of China (English)

    翁雨雄; 巴拉特; 洪光祥; 王发斌; 陈振斌; 黄启顺

    2004-01-01

    Summary: Protective effect of interleukin-lβ (IL-1β) on motor neurons was studied after peripheral nerve injury. Twenty Wistar rats were divided into 2 groups randomly. The right sciatic nerve of each rat was resected. After silicon tubulization of sciatic nerve in rat, 15 μl 1 ng/ml IL-1β and PBS solution were injected into the silicon capsule respectively. Enzyme histochemistry was performed to show acetyle cholesterase (AchE) and nitric oxide staining (NOS) activity of spinal a motor neurons in spinal segments 2 weeks later. Neurons were counted and the diameter and cross sectional (c/s) area of neurons were analyzed by using computer image analysis system. The results showed that as compared with the normal side, both enzyme activities significantly changed in motor neurons in PBS group. The diameter and c/s area of both neurons changed significantly too (P<0.01). These results suggest that exogenous IL-1β protects a-motor neurons from degeneration and necrosis after peripheral nerve injury.

  17. Drug distribution in spinal cord during administration with spinal loop dialysis probes in anaesthetized rats

    DEFF Research Database (Denmark)

    Uustalu, Maria; Abelson, Klas S P

    2007-01-01

    The present investigation aimed to study two methodological concerns of an experimental model, where a spinal loop dialysis probe is used for administration of substances to the spinal cord and sampling of neurotransmitters by microdialysis from the same area of anaesthetized rats. [(3)H]Epibatid......The present investigation aimed to study two methodological concerns of an experimental model, where a spinal loop dialysis probe is used for administration of substances to the spinal cord and sampling of neurotransmitters by microdialysis from the same area of anaesthetized rats. [(3)H...... over time. Then, the distribution of the different [(3)H]epibatidine concentrations along the spinal cord was studied. It was found that the percentage of [(3)H]epibatidine entering the spinal cord did not differ between different administered concentrations after a stabilization period of 60 min...... intraspinal administration of substances through the spinal loop dialysis probe....

  18. Nerve Transfers to Restore Upper Extremity Function in Cervical Spinal Cord Injury: Update and Preliminary Outcomes.

    Science.gov (United States)

    Fox, Ida K; Davidge, Kristen M; Novak, Christine B; Hoben, Gwendolyn; Kahn, Lorna C; Juknis, Neringa; Ruvinskaya, Rimma; Mackinnon, Susan E

    2015-10-01

    Cervical spinal cord injury can result in profound loss of upper extremity function. Recent interest in the use of nerve transfers to restore volitional control is an exciting development in the care of these complex patients. In this article, the authors review preliminary results of nerve transfers in spinal cord injury. Review of the literature and the authors' cases series of 13 operations in nine spinal cord injury nerve transfer recipients was performed. Representative cases were reviewed to explore critical concepts and preliminary outcomes. The nerve transfers used expendable donors (e.g., teres minor, deltoid, supinator, and brachialis) innervated above the level of the spinal cord injury to restore volitional control of missing function such as elbow extension, wrist extension, and/or hand function (posterior interosseous nerve or anterior interosseous nerve/finger flexors reinnervated). Results from the literature and the authors' patients (after a mean postsurgical follow-up of 12 months) indicate gains in function as assessed by both manual muscle testing and patients' self-reported outcomes measures. Nerve transfers can provide an alternative and consistent means of reestablishing volitional control of upper extremity function in people with cervical level spinal cord injury. Early outcomes provide evidence of substantial improvements in self-reported function despite relatively subtle objective gains in isolated muscle strength. Further work to investigate the optimal timing and combination of nerve transfer operations, the combination of these with traditional treatments (tendon transfer and functional electrical stimulation), and measurement of outcomes is imperative for determining the precise role of these operations. Therapeutic, IV.

  19. Bacterial melanin promotes recovery after sciatic nerve injury in rats

    Institute of Scientific and Technical Information of China (English)

    Olga V Gevorkyan; Irina B Meliksetyan; Tigran R Petrosyan; Anichka S Hovsepyan

    2015-01-01

    Bacterial melanin, obtained from the mutant strain ofBacillus Thuringiensis, has been shown to promote recovery after central nervous system injury. It is hypothesized, in this study, that bacterial melanin can promote structural and functional recovery after peripheral nerve injury. Rats subjected to sciatic nerve transection were intramuscularly administered bacterial melanin. The sciatic nerve transected rats that did not receive intramuscular administration of bacterial melanin served as controls. Behavior tests showed that compared to control rats, the time taken for instrumental conditioned relfex recovery was signiifcantly shorter and the ability to keep the balance on the rotating bar was signiifcantly better in bacterial melanin-treated rats. Histomor-phological tests showed that bacterial melanin promoted axon regeneration after sciatic nerve injury. These ifndings suggest that bacterial melanin exhibits neuroprotective effects on injured sciatic nerve, contributes to limb motor function recovery, and therefore can be used for rehabil-itation treatment of peripheral nerve injury.

  20. Minocycline treatment inhibits microglial activation and alters spinal levels of endocannabinoids in a rat model of neuropathic pain

    Directory of Open Access Journals (Sweden)

    Elphick Maurice R

    2009-07-01

    Full Text Available Abstract Activation of spinal microglia contributes to aberrant pain responses associated with neuropathic pain states. Endocannabinoids (ECs are present in the spinal cord, and inhibit nociceptive processing; levels of ECs may be altered by microglia which modulate the turnover of endocannabinoids in vitro. Here, we investigate the effect of minocycline, an inhibitor of activated microglia, on levels of the endocannabinoids anandamide and 2-arachidonoylglycerol (2-AG, and the related compound N-palmitoylethanolamine (PEA, in neuropathic spinal cord. Selective spinal nerve ligation (SNL in rats resulted in mechanical allodynia and the presence of activated microglia in the ipsilateral spinal cord. Chronic daily treatment with minocycline (30 mg/kg, ip for 14 days significantly reduced the development of mechanical allodynia at days 5, 10 and 14 post-SNL surgery, compared to vehicle-treated SNL rats (P P P P P

  1. Minocycline treatment inhibits microglial activation and alters spinal levels of endocannabinoids in a rat model of neuropathic pain.

    Science.gov (United States)

    Guasti, Leonardo; Richardson, Denise; Jhaveri, Maulik; Eldeeb, Khalil; Barrett, David; Elphick, Maurice R; Alexander, Stephen P H; Kendall, David; Michael, Gregory J; Chapman, Victoria

    2009-07-01

    Activation of spinal microglia contributes to aberrant pain responses associated with neuropathic pain states. Endocannabinoids (ECs) are present in the spinal cord, and inhibit nociceptive processing; levels of ECs may be altered by microglia which modulate the turnover of endocannabinoids in vitro. Here, we investigate the effect of minocycline, an inhibitor of activated microglia, on levels of the endocannabinoids anandamide and 2-arachidonoylglycerol (2-AG), and the related compound N-palmitoylethanolamine (PEA), in neuropathic spinal cord. Selective spinal nerve ligation (SNL) in rats resulted in mechanical allodynia and the presence of activated microglia in the ipsilateral spinal cord. Chronic daily treatment with minocycline (30 mg/kg, ip for 14 days) significantly reduced the development of mechanical allodynia at days 5, 10 and 14 post-SNL surgery, compared to vehicle-treated SNL rats (P pain states.

  2. [Modern aspects of pathogenesis of the trauma of the spinal cord and trunks of peripheral nerves].

    Science.gov (United States)

    Shul'ga, A E; Norkin, I A; Ninel', V G; Puchin'ian, D M; Zaretskov, V V; Korshunova, G A; Ostrovskiĭ, V V; Smol'kin, A A

    2014-02-01

    In pathogenesis of the traumatic disease of the spinal cord, two mechanisms of the injuries of its neuronal apparatus are defined: primary (necrosis) and secondary (apoptosis). In the work a participation of a number of internal causes in the progression of apoptosis in injury of the spinal cord and peripheral nerve trunks, the role of those remains little-studied up to date, is discussed.

  3. Nerve-pathways of acupoint Fengch'ih in rat by anterograde transport of HRP

    Institute of Scientific and Technical Information of China (English)

    Gang-Ming Xi; Hua-Qiao Wang; Guo-Hou He; Chao-Feng Huang; Qun-Fang Yuan; Guo-Yao Wei; Hua Li; Wen-Wen Liu; Hua-Yan Fan

    2005-01-01

    AIM: To study the nervous-pathways of Fengchih acupuncture by means of anterograde transport of aqueous solution of horseradish peroxidase (HRP).METHODS: Fifty Wistar rats were randomly divided into 1,2, 3, 4, and 5 d groups, and every group had 10 animals. HRP(30% aqueous solution) was injected into a Fengchih. Serial, transverse or capital, 40 μm sections of the cervical spinal ganglia, cervical and thoracic spinal cord segment and brain were cut on a cryotome. Sections were incubated for HRP histochemistry according to the tetramethylbenzidine (TMB). Part of the sections were counterstained with neutral red. RESULTS: After 1 d of survival times, many labeled cell bodies were found in 1-4 cervical spinal ganglia, anterior horn of 1-4 cervical spinal cord, ventromedial division of facial nucleus, accessory facial nucleus ipsilaterally. With increasing survival times, the intensity of labeled cells were slightly decreased. CONCLUSION: Fengchih may bring into full play its effect by correlation of posterior ear branch of facial nerve and anterior branch of 2-3 cervical nerve with 1-4 cervical the anterior horn of the spinal cord, ventromedial division of facial nucleus, accessory facial nucleus.

  4. Effects of Co-grafts Mesenchymal Stem Cells and Nerve Growth Factor Suspension in the Repair of Spinal Cord Injury

    Institute of Scientific and Technical Information of China (English)

    FANG Huang; WANG Junfang; CHEN Anmin

    2006-01-01

    To investigate effect of the transplantation of mesenchymal stem cells (MSCs) in combination with nerve growth factor (NGF) on the repair of spinal cord injury (SCI) in adult rats, spinal cord of adult rats (n= 32) was injured by using the modified Allen' s method. One week after the injury, the injured cords were injected with Dubecco-modified Eagles medium (DMEM , Group Ⅰ), MSCs (Group Ⅱ), NGF (Group Ⅲ), and MSCs plus NGF (Group Ⅳ). One month and two months after the injury, rats were sacrificed and their injured cord tissues were sectioned for the identification of the transplanted cells. The axonal regeneration and the differentiation of MSCs were examined by immunocytochemical staining. At the same time, rats were subjected to behavioral tests by using the open-field BBB scoring system. Immunocytochemical staining showed that axonal regeneration and the transplanted cells partially expressed neuron-specific nuclear protein (NeuN) and glial fibrillary acidic protein (GFAP). At the same time, significant improvement in BBB locomotor rating scale (P<0.05) were observed in the treatment group. More importantly, further functional improvement were noted in the combined treatment group. MSCs could differentiate into neurons and astrocytes. MSCs and NGF can promote axonal regeneration and improve functional recovery. There might exist a synergistic effect between MSCs and NGF.

  5. Normal Distribution of VGLUT1 Synapses on Spinal Motoneuron Dendrites and Their Reorganization after Nerve Injury

    OpenAIRE

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

    2014-01-01

    Peripheral nerve injury induces permanent alterations in spinal cord circuitries that are not reversed by regeneration. Nerve injury provokes the loss of many proprioceptive IA afferent synapses (VGLUT1-IR boutons) from motoneurons, the reduction of IA EPSPs in motoneurons, and the disappearance of stretch reflexes. After motor and sensory axons successfully reinnervate muscle, lost IA VGLUT1 synapses are not re-established and the stretch reflex does not recover; however, electrically evoked...

  6. Expression of neurotrophic factors in injured spinal cord after transplantation of human-umbilical cord blood stem cells in rats.

    Science.gov (United States)

    Chung, Hyo-jin; Chung, Wook-hun; Lee, Jae-Hoon; Chung, Dai-Jung; Yang, Wo-Jong; Lee, A-Jin; Choi, Chi-Bong; Chang, Hwa-Seok; Kim, Dae-Hyun; Suh, Hyun Jung; Lee, Dong-Hun; Hwang, Soo-Han; Do, Sun Hee; Kim, Hwi-Yool

    2016-03-01

    We induced percutaneous spinal cord injuries (SCI) using a balloon catheter in 45 rats and transplanted human umbilical cord blood derived mesenchymal stem cells (hUCB-MSCs) at the injury site. Locomotor function was significantly improved in hUCB-MSCs transplanted groups. Quantitative ELISA of extract from entire injured spinal cord showed increased expression of brain-derived neurotrophic factor (BDNF), nerve growth factor (NGF) and neurotrophin-3 (NT-3). Our results show that treatment of SCI with hUCB-MSCs can improve locomotor functions, and suggest that increased levels of BDNF, NGF and NT-3 in the injured spinal cord were the main therapeutic effect.

  7. Effects of polarization in low-level laser therapy of spinal cord injury in rats

    Science.gov (United States)

    Ando, Takahiro; Sato, Shunichi; Kobayashi, Hiroaki; Nawashiro, Hiroshi; Ashida, Hiroshi; Hamblin, Michael R.; Obara, Minoru

    2012-03-01

    Low-level laser therapy (LLLT) is a promising approach to treat the spinal cord injury (SCI). Since nerve fibers have optical anisotropy, propagation of light in the spinal tissue might be affected by its polarization direction. However, the effect of polarization on the efficacy of LLLT has not been elucidated. In the present study, we investigated the effect of polarization on the efficacy of near-infrared LLLT for SCI. Rat spinal cord was injured with a weight-drop device. The lesion site was irradiated with an 808-nm diode laser beam that was transmitted through a polarizing filter immediately after injury and daily for five consecutive days. The laser power at the injured spinal cord surface was 25 mW, and the dosage per day was 9.6 J/cm2 (spot diameter, 2 cm; irradiation duration, 1200 s). Functional recovery was assessed daily by an open-field test. The results showed that the functional scores of the SCI rats that were treated with 808-nm laser irradiation were significantly higher than those of the SCI alone group (Group 1) from day 5 after injury, regardless of the polarization direction. Importantly, as compared to the locomotive function of the SCI rats that were treated with the perpendicularly-polarized laser parallel to the spinal column (Group 2), that of the SCI rats that were irradiated with the linearly aligned polarization (Group 3) was significantly improved from day 10 after injury. In addition, the ATP contents in the injured spinal tissue of Group 3, which were measured immediately after laser irradiation, were moderately higher than those of Group 2. These observations are attributable to the deeper penetration of the parallelpolarized light in the anisotropic spinal tissue, suggesting that polarization direction significantly affects the efficacy of LLLT for SCI.

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

    Science.gov (United States)

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

    2016-01-01

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

  9. Trigeminal nerve injury induced thrombospondin-4 upregulation contributes to orofacial neuropathic pain states in a rat model

    Science.gov (United States)

    Li, Kang-Wu; Kim, Doo-Sik; Zaucke, Frank; Luo, Z. David

    2013-01-01

    Background Injury to the trigeminal nerve often results in the development of chronic pain states including tactile allodynia, or hypersensitivity to light touch, in orofacial area, but its underlying mechanisms are poorly understood. Peripheral nerve injury has been shown to cause upregulation of thrombospondin-4 (TSP4) in dorsal spinal cord that correlates with neuropathic pain development. In this study, we examined whether injury-induced TSP4 is critical in mediating orofacial pain development in a rat model of chronic constriction injury to the infraorbital nerve (CCI-ION). Methods Orofacial sensitivity to mechanical stimulation was examined in a unilateral infraorbital nerve ligation rat model. The levels of TSP4 in trigeminal ganglia and associated spinal subnucleus caudalis and C1/C2 spinal cord (Vc/C2) from injured rats were examined at time points correlating with the initiation and peak orofacial hypersensitivity. TSP4 antisense and mismatch oligodeoxynucleotides were intrathecally injected into injured rats to see if antisense oligodeoxynucleotide treatment could reverse injury-induced TSP4 upregulation and orofacial behavioral hypersensitivity. Results Our data indicated that trigeminal nerve injury induced TSP4 upregulation in Vc/C2 at a time point correlated with orofacial tactile allodynia. In addition, intrathecal treatment with TSP4 antisense, but not mismatch, oligodeoxynucleotides blocked both injury-induced TSP4 upregulation in Vc/C2 and behavioral hypersensitivity. Conclusions Our data support that infraorbital nerve injury leads to TSP4 upregulation in trigeminal spinal complex that contributes to orofacial neuropathic pain states. Blocking this pathway may provide an alternative approach in management of orofacial neuropathic pain states. PMID:24019258

  10. Trigeminal nerve injury-induced thrombospondin-4 up-regulation contributes to orofacial neuropathic pain states in a rat model.

    Science.gov (United States)

    Li, K-W; Kim, D-S; Zaucke, F; Luo, Z D

    2014-04-01

    Injury to the trigeminal nerve often results in the development of chronic pain states including tactile allodynia, or hypersensitivity to light touch, in orofacial area, but its underlying mechanisms are poorly understood. Peripheral nerve injury has been shown to cause up-regulation of thrombospondin-4 (TSP4) in dorsal spinal cord that correlates with neuropathic pain development. In this study, we examined whether injury-induced TSP4 is critical in mediating orofacial pain development in a rat model of chronic constriction injury to the infraorbital nerve. Orofacial sensitivity to mechanical stimulation was examined in a unilateral infraorbital nerve ligation rat model. The levels of TSP4 in trigeminal ganglia and associated spinal subnucleus caudalis and C1/C2 spinal cord (Vc/C2) from injured rats were examined at time points correlating with the initiation and peak orofacial hypersensitivity. TSP4 antisense and mismatch oligodeoxynucleotides were intrathecally injected into injured rats to see if antisense oligodeoxynucleotide treatment could reverse injury-induced TSP4 up-regulation and orofacial behavioural hypersensitivity. Our data indicated that trigeminal nerve injury induced TSP4 up-regulation in Vc/C2 at a time point correlated with orofacial tactile allodynia. In addition, intrathecal treatment with TSP4 antisense, but not mismatch, oligodeoxynucleotides blocked both injury-induced TSP4 up-regulation in Vc/C2 and behavioural hypersensitivity. Our data support that infraorbital nerve injury leads to TSP4 up-regulation in trigeminal spinal complex that contributes to orofacial neuropathic pain states. Blocking this pathway may provide an alternative approach in management of orofacial neuropathic pain states. © 2013 European Pain Federation - EFIC®

  11. Ependymal cell proliferation and apoptosis following acute spinal cord injury in the adult rat

    Institute of Scientific and Technical Information of China (English)

    Xu Wang; Jun Qian; Yanchao Ma; Guoxin Nan; Shuanke Wang; Yayi Xia; Youcheng Zhang

    2008-01-01

    BACKGROUND: Studies have reported that spinal cord injury can induce the reactive proliferation of ependymal cells and secondarily cause the apoptosis of nerve cells. However, there is no generally accepted theory on the apoptotic characteristics of ependymal cells in the injured spinal cord.OBJECTIVE: To observe the reactive proliferation and apoptosis of ependymal cells in adult rats following acute spinal cord injury.DESIGN, TIME AND SETTING: A randomized control study based on neuropathology was performed in the Third Military Medical University of Chinese PLA between 2005 and 2007.MATERIALS: Forty healthy, adult, Wistar rats were included in the present study.METHODS: Moderate spinal cord injury was established in twenty rats using Feeney's method, while the remaining 20 rats served as controls and were only treated with laminectomy. All rats were injected intraperitoneally with 1.25 mL of BrdU solution (10 mg BrdU/mL saline) 3 times at 4 hours intervals during the 12 hours prior to sacrifice.MAIN OUTCOME MEASURES: Ependymal cell proliferation and apoptosis in the rat spinal cord were determined by BrdU and nestin immunofluorescence double-labeling, as well as the TUNEL method, at 1, 3, 7, and 14 days after operation.RESULTS: In the moderate spinal cord injury rats, nestin expression was observed in the cytoplasm of ependymal cells. One day immediately following surgery, ependymal cells were BrdU-labeled. The number of BrdU-positive cells increased at 3 days, reached a peak at 7 days, and gradually reduced thereafter. The ependyma developed ti'om a constitutive monolayer cells to a multi-layer cell complex. Some BrdU/Nestin double-positive ependymal cells migrated out from the ependyma. TUNEL-positive cells were also detected in the ependyma in the central region, as well as ischemic regions of the injured spinal cord. In addition, TUNEL-positive cells were visible in the ependyma. No TUNEL-positive ependymal cells were observed in the normal spinal cord

  12. Label-free imaging of rat spinal cords based on multiphoton microscopy

    Science.gov (United States)

    Liao, Chenxi; Wang, Zhenyu; Zhou, Linquan; Zhu, Xiaoqin; Liu, Wenge; Chen, Jianxin

    2016-10-01

    As an integral part of the central nervous system, the spinal cord is a communication cable between the body and the brain. It mainly contains neurons, glial cells, nerve fibers and fiber tracts. The recent development of the optical imaging technique allows high-resolution imaging of biological tissues with the great potential for non-invasively looking inside the body. In this work, we evaluate the imaging capacity of multiphoton microscopy (MPM) based on second harmonic generation (SHG) and two-photon excited fluorescence (TPEF) for the cells and extracellular matrix in the spinal cord at molecular level. Rat spinal cord tissues were sectioned and imaged by MPM to demonstrate that MPM is able to show the microstructure including white matter, gray matter, ventral horns, dorsal horns, and axons based on the distinct intrinsic sources in each region of spinal cord. In the high-resolution and high-contrast MPM images, the cell profile can be clearly identified as dark shadows caused by nuclei and encircled by cytoplasm. The nerve fibers in white matter region emitted both SHG and TPEF signals. The multiphoton microscopic imaging technique proves to be a fast and effective tool for label-free imaging spinal cord tissues, based on endogenous signals in biological tissue. It has the potential to extend this optical technique to clinical study, where the rapid and damage-free imaging is needed.

  13. Convergent nociceptive input to spinal dorsal horn neurons after peripheral nerve injury.

    Science.gov (United States)

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

    2015-03-01

    The number of c-Fos protein-like immunoreactive (c-Fos-IR) neurons in the spinal dorsal horn evoked by noxious stimulation was previously shown to be increased following peripheral nerve injury, and this increase was proposed to reflect the neuropathic pain state. The aim of this study was to investigate whether anomalous convergent primary afferent input to spinal dorsal horn neurons contributed to nerve injury-induced c-Fos hyperinducibility. Double immunofluorescence labeling for c-Fos and phosphorylated extracellular signal-regulated kinase (p-ERK) was performed to detect convergent synaptic input from different branches of the sciatic nerve after injury to the tibial nerve. c-Fos expression and the phosphorylation of ERK were induced by noxious heat stimulation of the hindpaw and also by electrical stimulation (ES) of the injured tibial nerve, respectively. The number of c-Fos-IR neurons was significantly decreased 3 days after the injury. However, the number of c-Fos-IR neurons returned to the control level 14 days after the injury. P-ERK immunoreactive (p-ERK-IR) neurons were induced in the central terminal field of the tibial nerve by ES of the tibial nerve. The topographic distribution pattern and number of such p-ERK-IR neurons remained unchanged after the nerve injury. The time course of changes in the number of double-labeled neurons, that presumably received convergent primary afferent input, showed a pattern similar to that of c-Fos-IR neurons after the injury. These results indicate that convergent primary nociceptive input through neighboring intact nerves may contribute to c-Fos hyperinducibility in the spinal dorsal horn.

  14. Effects of Alcohol Injection in Rat Sciatic Nerve

    Science.gov (United States)

    Mazoch, Mathew J.; Cheema, Gulraiz A.; Suva, Larry J.; Thomas, Ruth L.

    2015-01-01

    Background Previous studies have shown that the injection of dehydrated alcohol has been successful for the treatment of Morton's neuroma in the foot. In this study, we determined the cellular effect of injection of alcohol into and around the sciatic nerve of rats, and measured the extent of cell necrosis and/or any associated histologic or inflammatory changes. Methods Twenty-two male (~375g) Wistar rats were randomized into two groups each receiving alcohol injections into or around the sciatic nerve after nerve exposure under sterile technique. Group 1 rats were injected with a 0.5ml solution of 0.5% Marcaine in the left sciatic nerve as a control group. In the right sciatic nerve a 0.5ml solution of 4% ethanol with 0.5% Marcaine was injected. Group 2 rats received 0.5ml of 20%ethanol with 0.5% Marcaine injected into the left sciatic nerve and 0.5 ml of 30% ethanol with 0.5% Marcaine injected into the right sciatic nerve. In each group, the rats were placed in 3 subgroups: intraneural, perineural, perimuscular injections. All rats were sacrificed and tissue harvested for histologic evaluation at day 10 post injection. Results No evidence of alcohol-associated cell necrosis, apoptosis or apparent inflammation was observed in histologic specimens of any injected nerves, perineural tissue, or muscles in controls or experimental groups regardless of concentration of ethanol injected on day 10. Conclusion We concluded that alcohol injection (≤30% ethanol) into and/or around the sciatic nerve or the adjacent muscle of rats has no histologic evidence of necrosis or inflammation to the nerve or surrounding tissue. There was no observable histological change in apoptosis, or cell number, in response to the alcohol injection. PMID:25097192

  15. Neural stem cell transplantation combined with erythropoietin for the treatment of spinal cord injury in rats.

    Science.gov (United States)

    Zhao, Yan; Zuo, Yuan; Jiang, Jianming; Yan, Huibo; Wang, Xiliang; Huo, Hunjun; Xiao, Yulong

    2016-10-01

    Spinal cord injury (SCI) comprises nerve and motor function disorders that may be caused by a variety of damaging factors and is challenging to treat. The aim of the present study was to investigate the regenerative effects of neural stem cell (NSC) transplantation combined with intraperitoneal injection of erythropoietin (EPO) on cross-sectional SCI in rats. A model of SCI was induced in 40 adult Wistar rats via the complete transection of the 10th thoracic vertebra (T10). The rats were allocated at random into 4 groups: Control, NSC, EPO and NSC + EPO groups (n=10 per group). Morphological alterations associated with axonal regeneration were detected using neurofilament (NF)-200 immunohistochemistry and immunofluorescence staining after 8 weeks. Basso, Beattie and Bresnahan (BBB) scoring was used to evaluate the recovery of hindlimb function. A total of 5 rats died following surgery, including 2 control rats and 1 rat each in the EPO, NSC and NSC + EPO groups. NSCs labeled with bromodeoxyuridine were observed to have survived and migrated in the spinal cord tissue after 8 weeks. Significant histomorphological differences were observed in the NSC and NSC + EPO groups compared with the EPO and control groups. Furthermore, the rats of the NSC + EPO group exhibited significantly enhanced axonal regeneration in the SCI area compared with the NSC group rats. The rats of the NSC and NSC + EPO groups exhibited significantly improved BBB scores compared with the EPO and control group rats at 7 days after treatment (PEPO group were significantly improved compared with those of the three other groups at 7 days after surgery (PEPO may benefit the survival and regeneration of injured axons, and accelerate the repair of injured spinal cord tissue, thus facilitating the functional recovery of hindlimb locomotor function in rats.

  16. Influences of olfactory ensheathing cells transplantation on axonal regeneration in spinal cord of adult rats

    Institute of Scientific and Technical Information of China (English)

    沈慧勇; 唐勇; 吴燕峰; 陈燕涛; 程志安

    2002-01-01

    To observe whether olfactory ensheathing cells could be used to promote axonal regeneration in a spontaneously nonregenerating system. Methods: After laminectomy at the lower thoracic level, the spinal cords of adult rats were exposed and completely transected at T10. A suspension of ensheathing cells was injected into the lesion site in 12 adult rats, and control D/F-12 (1∶1 mixture of DMEM and Hams F-12) was injected in 12 adult rats. Six weeks and ten weeks after cell transplantation, the rats were evaluated by climbing test and motor evoked potentials (MEPs) monitoring. The samples were procured and studied with histologicl and immunohistochemical methods. Results: At the 6th week after cell transplantation, all the rats in both the transplanted and control groups were paraplegic and the MEPs could not be recorded. At the 10th week after cell transplantation, of 7 rats in the control group, 2 rats had muscles contraction of the lower extremities, 2 rats had hips and/or knees active movement; and 5 rats MEPs could be recorded in the hind limbs in the transplanted group (n=7). None of the rats in the control group had functional improvement and no MEPs recorded (n=7). Numerous regenerating axons were observed through the transplantation and continued to regenerate into the denervated host tract. Cell labelling using anti-Myelin Basic Protein (MBP) and anti-Nerve Growth Factor Receptor (anti-NGFR) indicated that the regenerated axons were derived from the appropriate neuronal source and that donor cells migrated into the denervated host tract. But axonal degeneration existed and regenerating axons were not observed within the spinal cords of the adult rats with only D/F-12 injection. Conclusions: The axonal regeneration in the transected adult rat spinal cord is possible after ensheathing cells transplantation.

  17. Presence of neuropeptide FF receptors on primary afferent fibres of the rat spinal cord

    Energy Technology Data Exchange (ETDEWEB)

    Zajac, J.-M. [Laboratoire de Pharmacologie et de Toxicologie Fondamentales, C.N.R.S., 205 Route de Narbonne, 31077 Toulouse Cedex (France); Kar, S. [Douglas Hospital Research Centre and Department of Psychiatry, McGill University, 6875 LaSalle Blvd, Verdun, Quebec H4H1R3 (Canada); Gouarderes, C. [Laboratoire de Pharmacologie et de Toxicologie Fondamentales, C.N.R.S., 205 Route de Narbonne, 31077 Toulouse Cedex (France)

    1996-09-01

    A radioiodinated analogue of neuropeptide FF, [{sup 125}I][d.Tyr{sup 1},(NMe)Phe{sup 3}]neuropeptide FF, was used as a selective probe to label neuropeptide FF receptors in the rat spinal cord. Following neonatal capsaicin treatment, dorsal rhizotomy or sciatic nerve section, the distribution and possible alterations of spinal cord specific [{sup 125}I][d.Tyr{sup 1},(NMe)Phe{sup 3}]neuropeptide FF binding sites were evaluated using in vitro quantitative receptor autoradiography. In normal rats, the highest densities of sites were observed in the superficial layers of the dorsal horn (laminae I-II) whereas moderate to low amounts of labelling were seen in the deeper (III-VI) laminae, around the central canal, and in the ventral horn. Capsaicin-treated rats showed a bilateral decrease (47%) in [{sup 125}I][d.Tyr{sup 1},(NMe)Phe{sup 3}]neuropeptide FF binding in all spinal areas. Unilateral sciatic nerve section and unilateral dorsal rhizotomy induced significant depletions (15-27%) in [{sup 125}I][d.Tyr{sup 1},(NMe)Phe{sup 3}]neuropeptide FF labelling in the ipsilateral dorsal horn.These results suggest that a proportion of neuropeptide FF receptors is located on primary afferent terminals of the dorsal horn and could thus play a role in the modulation of nociceptive transmission. (Copyright (c) 1996 Elsevier Science B.V., Amsterdam. All rights reserved.)

  18. Effect of glial cell line-derived neurotrophic factor on peripheral nerve regeneration in adult rat

    Institute of Scientific and Technical Information of China (English)

    CHEN Zhe-yu; LI Jian-hong; ZHENG Xing-dong; LU Chang-lin; HE Cheng

    2001-01-01

    Objective: To study the effect of glial cell line-derived neurotrophic (GDNF) on adult peripheral nerve regeneration. Methods: Transectioned sciatic nerve in adult rats was sutured into silicone channel. GDNF or SAL solution was injected into the silicone channels during operation. Four weeks later, the effect of GDNF on axonal regeneration was evaluated by degenerative neurofiber staining and HRP retrograde tracing. Results: Compared with SAL group, the percentage of degenerative neurofiber areas decreased from 17.3% to 1.9% ( P<0.01 ) and the ratio of labeled spinal somas number was significantly increased from 43.5% to 68.3% ( P<0.01 ) in GDNF group. Conclusion: The results suggest that exogenous GDNF can obviously enhance adult peripheral nerve regeneration.

  19. 七叶皂甙钠对坐骨神经结扎术后大鼠热痛觉及脊髓神经细胞凋亡的影响%Effects of Sodium aescinate on heat pain and spinal neural apoptosis in rats after sciatic nerve ligation

    Institute of Scientific and Technical Information of China (English)

    于亚亮; 伊红丽; 李海波

    2012-01-01

    目的 探讨七叶皂甙钠对坐骨神经结扎术后大鼠热痛觉及脊髓神经细胞凋亡的影响.方法 90只SD大鼠随机分为正常对照组、坐骨神经慢性压迫损伤(CCI)模型组(CCI组)和药物治疗组(药物组),每组30只大鼠.采用坐骨神经中段结扎法制作大鼠CCI模型.药物组大鼠术后给予腹腔注射0.1%七叶皂甙钠5 mg/(kg·d)治疗,CCI组给予等量生理盐水替代.各组于术前1d取5只大鼠测定热痛觉,于术后8h、1d、3d、7d、14 d及21 d时分别取5只大鼠测定热痛觉后处死.分别应用TUNEL法及免疫组化染色法检测大鼠相应损伤段脊髓组织中凋亡神经细胞数及肿瘤坏死因子-α(TNF-α)的表达.结果 各组大鼠术前1d时热痛觉的比较差异无统计学意义.CCI组及药物组大鼠术后热痛觉均较正常对照组更敏感(均P<0.05);药物组大鼠术后热痛觉较CCI组迟钝(均P<0.05).CCI组及药物组大鼠术后各时间点脊髓组织中凋亡细胞数均明显多于正常对照组(均P <0.05);药物组大鼠术后各时间点脊髓组织中凋亡细胞数均明显少于CCI组(均P<0.05).CCI组大鼠术后8h~14d,药物组术后8h~7d脊髓组织TNF-α的表达均明显高于正常对照组(均P<0.05);两组TNF-α的表达均于术后8h起逐渐增高,至术后3d时达最高,其后逐渐减少(均P<0.05);并分别于术后21 d及14 d时降至正常对照组水平.结论 结扎大鼠坐骨神经可产生神经病理性疼痛,并可诱发脊髓神经细胞凋亡.七叶皂甙钠能缓解坐骨神经结扎术后大鼠热痛觉增敏,这可能与其降低TNF-α在脊髓后角的表达及抑制神经细胞的凋亡有关.%Objective To observe the effects of Sodium aescinate on heat pain and spinal neural apoptosis in rats after sciatic nerve ligation. Methods Ninty SD rats were randomly divided into normal control group ( NC group) , chronic constriction injury (CCI) model group (CCI group) and therapy group, with 30 rats

  20. Perineural tumor spread - Interconnection between spinal and cranial nerves.

    Science.gov (United States)

    Kozić, Duško; Njagulj, Vesna; Gaćeša, Jelena Popadić; Semnic, Robert; Prvulović, Nataša

    2012-12-15

    The secondary neoplastic involvement of the cervical plexus in patients with head and neck malignancies is extremely rare. MR examination of the neck revealed the diffuse neoplastic infiltration of the right C2 root, in a 57-year-old patient with several months long pain in the right ear region and a history of the tongue squamous cell carcinoma. Associated perineural tumor spread and consequent distal involvement of great auricular nerve and vagus nerve were evident. Best of our knowledge, this is the first reported involvement of the cervical plexus in patients with head and neck cancers, associated with the clearly documented interconnection between the cervical plexus and cranial nerves via great auricular nerve.

  1. Spinal cord stimulation-induced analgesia: electrical stimulation of dorsal column and dorsal roots attenuates dorsal horn neuronal excitability in neuropathic rats.

    Science.gov (United States)

    Guan, Yun; Wacnik, Paul W; Yang, Fei; Carteret, Alene F; Chung, Chih-Yang; Meyer, Richard A; Raja, Srinivasa N

    2010-12-01

    The sites of action and cellular mechanisms by which spinal cord stimulation reduces neuropathic pain remain unclear. We examined the effect of bipolar electrical-conditioning stimulation (50 Hz, 0.2 ms, 5 min) of the dorsal column and lumbar dorsal roots on the response properties of spinal wide dynamic range (WDR) neurons in rats after L5 spinal nerve injury. The conditioning stimulation intensity was set at the lowest current that evoked a peak antidromic sciatic Aα/β-compound action potential without inducing an Aδ- or C-compound action potential. Within 15 min of the dorsal column or root conditioning stimulation, the spontaneous activity rate of WDR neurons was significantly reduced in nerve-injured rats. Conditioning stimulation also significantly attenuated WDR neuronal responses to mechanical stimuli in nerve-injured rats and inhibited the C-component of the neuronal response to graded intracutaneous electrical stimuli applied to the receptive field in nerve-injured and sham-operated rats. It is noteworthy that dorsal column stimulation blocked windup of WDR neuronal response to repetitive intracutaneous electrical stimulation (0.5 Hz) in nerve-injured and sham-operated rats, whereas dorsal root stimulation inhibited windup only in sham-operated rats. Therefore, stimulation of putative spinal substrates at A-fiber intensities with parameters similar to those used by patients with spinal cord stimulators attenuated established WDR neuronal hyperexcitability in the neuropathic condition and counteracted activity-dependent increase in neuronal excitability (i.e., windup). These results suggest a potential cellular mechanism underlying spinal cord stimulation-induced pain relief. This in vivo model allows the neurophysiologic basis for spinal cord stimulation-induced analgesia to be studied.

  2. Serial Neu rophysiologieal Changes in Experimental Selective Lumbar Spinal Nerve Root Compression in a Feline Model

    Institute of Scientific and Technical Information of China (English)

    Zhou Hui; XH He; HK Wong

    2000-01-01

    The spinal nerve root may be subjected to compression in a variety of clinical conditions which may lead to disabling leg pain and disability. The objective documentation of the clinical symptoms by electrophysiological tests could be procedure dependent. In the experimental study of nerve root compression in animal models, electrophytsiological tests are one of the few available methods to assess the effects of in nerve root compression. The purpose of this study is to evaluate the effects of compression of the spinal nerve root on the motor conduction velocity(MCV) and cortical somatosensory evoked potentials(SCEP) over a period of 6 weeks in a feline model. Ten cats were used in this study. Under anaesthesia, a laminectomy at L6 and L7 was performed. The right L6 nerve root was exposed and compressed by a Surg i-loop around nerve root and maintained by a Ligacap. MCV was recorded by stimulating the proximal end of nerve root before and after compression. Stimulating the right posterior tibial nerve and recording at the skull performed CSEP. After nerve root compression, MCV showed a significant reduction of amplitudes (immediate:64 ± 11%; 3-week: 73± 13%; 6-week: 73± 12% p<0.01 ) . The lateneies of MCV were not significant changed. The amplitudes of CSEP were also reduced significantly (immediate:56±9%; 5-minute:74± 12%). The N1 peak disappeared and latencies prolonged. We conclude that amplitude changes of MCV and CSEP could be used for diagnosis of acute peripheral nerve injury in the feline model, which may have clinical implication.

  3. High rat food vitamin E content improves nerve function in streptozotocin-diabetic rats

    NARCIS (Netherlands)

    Gispen, W.H.; Dam, P.S. van; Bravenboer, B.; Asbeck, B.S. van; Marx, J.J.

    1999-01-01

    Antioxidants can improve nerve dysfunction in hyperglycaemic rats. We evaluated whether the standard supplementation of rat food with vitamin E (normally added for preservation purposes) or high-dose vitamin E treatment improves nerve conduction in maturing streptozotocin-diabetic rats, a model

  4. Coordinated Respiratory Motor Activity in Nerves Innervating the Upper Airway Muscles in Rats.

    Science.gov (United States)

    Tachikawa, Satoshi; Nakayama, Kiyomi; Nakamura, Shiro; Mochizuki, Ayako; Iijima, Takehiko; Inoue, Tomio

    2016-01-01

    Maintaining the patency of the upper airway during breathing is of vital importance. The activity of various muscles is related to the patency of the upper airway. In the present study, we examined the respiratory motor activity in the efferent nerves innervating the upper airway muscles to determine the movements of the upper airway during respiration under normocapnic conditions (pH = 7.4) and in hypercapnic acidosis (pH = 7.2). Experiments were performed on arterially perfused decerebrate rats aged between postnatal days 21-35. We recorded the efferent nerve activity in a branch of the cervical spinal nerve innervating the infrahyoid muscles (CN), the hypoglossal nerve (HGN), the external branch of the superior laryngeal nerve (SLN), and the recurrent laryngeal nerve (RLN) with the phrenic nerve (PN). Inspiratory nerve discharges were observed in all these nerves under normocapnic conditions. The onset of inspiratory discharges in the CN and HGN was slightly prior to those in the SLN and RLN. When the CO2 concentration in the perfusate was increased from 5% to 8% to prepare for hypercapnic acidosis, the peak amplitudes of the inspiratory discharges in all the recorded nerves were increased. Moreover, hypercapnic acidosis induced pre-inspiratory discharges in the CN, HGN, SLN, and RLN. The onset of pre-inspiratory discharges in the CN, HGN, and SLN was prior to that of discharges in the RLN. These results suggest that the securing of the airway that occurs a certain time before dilation of the glottis may facilitate ventilation and improve hypercapnic acidosis.

  5. Sciatic nerve regeneration in rats by a nerve conduit engineering with a membrane derived from natural latex.

    Science.gov (United States)

    Ganga, Marcos Vinícius Muniz; Coutinho-Netto, Joaquim; Colli, Benedicto Oscar; Marques Junior, Wilson; Catalão, Carlos Henrique Rocha; Santana, Ricardo Torres; Oltramari, Marcos Roberto Pedron; Carraro, Kleber Tadeu; Lachat, João-José; Lopes, Luiza da Silva

    2012-12-01

    To evaluate the capacity of natural latex membrane to accelerate and improve the regeneration quality of the of rat sciatic nerves. Forty male adult Wistar rats were used, anesthetized and operated to cut the sciatic nerve and receive an autograft or a conduit made with a membrane derived from natural latex (Hevea brasiliensis). Four or eight weeks after surgery, to investigate motor nerve recovery, we analyzed the neurological function by walking pattern (footprints analysis and computerized treadmill), electrophysiological evaluation and histological analysis of regenerated nerve (autologous nerve graft or tissue cables between the nerve stumps), and anterior tibial and gastrocnemius muscles. All functional and morphological analysis showed that the rats transplanted with latex conduit had a better neurological recovery than those operated with autologous nerve: quality of footprints, performance on treadmill (pregeneration. The data reported showed behavioral and functional recovery in rats implanted with latex conduit for sciatic nerve repair, supporting a complete morphological and physiological regeneration of the nerve.

  6. Optical coherence tomography of the rat cavernous nerves

    Science.gov (United States)

    Fried, Nathaniel M.; Rais-Bahrami, Soroush; Lagoda, Gwen A.; Chuang, Ying; Burnett, Arthur L.; Su, Li-Ming

    2007-02-01

    Improvements in identification, imaging, and visualization of the cavernous nerves during radical prostatectomy, which are responsible for erectile function, may improve nerve preservation and postoperative potency. Optical coherence tomography (OCT) is capable of real-time, high-resolution, cross-sectional, in vivo tissue imaging. The rat prostate serves as an excellent model for studying the use of OCT for imaging the cavernous nerves, as the rat cavernous nerve is a large, visible, and distinct bundle allowing for easy identification with OCT in addition to histologic confirmation. Imaging was performed with the Niris OCT system and a handheld 8 Fr probe, capable of acquiring real-time images with 11-μm axial and 25-μm lateral resolution in tissue. Open surgical exposure of the prostate was performed on a total of 6 male rats, and OCT images of the prostate, cavernous nerve, pelvic plexus ganglion, seminal vesicle, blood vessels, and periprostatic fat were acquired. Cavernous nerve electrical stimulation with simultaneous intracorporeal pressure measurements was performed to confirm proper identification of the cavernous nerves. The prostate and cavernous nerves were also processed for histologic analysis and further confirmation. Cross-sectional and longitudinal OCT images of the cavernous nerves were acquired and compared with histologic sections. The cavernous nerve and ganglion could be differentiated from the surrounding prostate gland, seminal vesicle, blood vessels, bladder, and fatty tissue. We report preliminary results of OCT images of the rat cavernous nerves with histologic correlation and erectile stimulation measurements, thus providing interpretation of prostate structures as they appear in OCT images.

  7. The distribution of nicotinamide adenine dinucleotide phosphate-diaphorase (NADPH-d) in the medulla oblongata, spinal cord, cranial and spinal nerves of frog, Microhyla ornata.

    Science.gov (United States)

    Jadhao, Arun G; Biswas, Saikat P; Bhoyar, Rahul C; Pinelli, Claudia

    2017-04-01

    Nicotinamide adenine dinucleotide phosphate-diaphorase (NADPH-d) enzymatic activity has been reported in few amphibian species. In this study, we report its unusual localization in the medulla oblongata, spinal cord, cranial nerves, spinal nerves, and ganglions of the frog, Microhyla ornata. In the rhombencephalon, at the level of facial and vagus nerves, the NADPH-d labeling was noted in the nucleus of the abducent and facial nerves, dorsal nucleus of the vestibulocochlear nerve, the nucleus of hypoglossus nerve, dorsal and lateral column nucleus, the nucleus of the solitary tract, the dorsal field of spinal grey, the lateral and medial motor fields of spinal grey and radix ventralis and dorsalis (2-10). Many ependymal cells around the lining of the fourth ventricle, both facial and vagus nerves and dorsal root ganglion, were intensely labeled with NADPH-d. Most strikingly the NADPH-d activity was seen in small and large sized motoneurons in both medial and lateral motor neuron columns on the right and left sides of the brain. This is the largest stained group observed from the caudal rhombencephalon up to the level of radix dorsalis 10 in the spinal cord. The neurons were either oval or elongated in shape with long processes and showed significant variation in the nuclear and cellular diameter. A massive NADPH-d activity in the medulla oblongata, spinal cord, and spinal nerves implied an important role of this enzyme in the neuronal signaling as well as in the modulation of motor functions in the peripheral nervous systems of the amphibians.

  8. Locally transplanted enteric gila improve functional and structural recovery in a rat model of spinal cord injury

    Institute of Scientific and Technical Information of China (English)

    Shucui Jiang; Mohammad I.Khan; James R.Bain; Cai Jiang; Christopher R.Hansebout; Zesheng Yu; Yuqing Liu; Michel P.Rathbone

    2009-01-01

    BACKGROUND: We have previously reported that adult enteric gila (EG) facilitate the growth of transected dorsal root axons into the uninjured spinal cord to form functional connections with their targets. OBJECTIVE: The present study investigated the effects of EG on spinal cord function, tissue injury, and axonal regeneration following transplantation into injured rat spinal cords, according to histological and functional outcomes. DESIGN, TIME AND SETTING: A randomized controlled animal experiment was performed at McMaster University, Canada from January 2006 to March 2008.MATERIALS: EG were isolated from rat intestine. METHODS: One week following spinal cord crush, female Wistar rats were injected with an EG suspension (2 μL, 1 x 10 5/μL, n=10) or with the same volume of fresh culture medium alone (control animals, n=11). The third group did not receive any injection following laminectomy and served as the sham-operated controls (n=5). MAIN OUTCOME MEASURES: Behavior was tested prior to transplantation and weekly following transplantation, with nine behavioral examinations in total. Open field, hind limb placement response, foot orientation response, and inclined plane test were utilized. Immediately following the final behavioral examination, spinal cord T9 to L1 segments were harvested for immunohistochemical and hematoxylin-eosin staining to determine astroglial scarring, axonal regeneration and spinal cord lesion size. RESULTS: Rats with EG transplantation exhibited significantly better locomotor function with reduced tissue damage, compared with the control rats. Cystic cavities were present 2 months after injury in spinal cords from both control groups. In contrast, rats injected with EG did not present with cystic lesions. In addition, the injury site consisted of cellular material and nerve fibers, and axonal regeneration was apparent, with dense labeling of neurofilament-positive axons within the injury site. Moreover, regenerating axons were

  9. Rewarding electrical brain stimulation in rats after peripheral nerve injury: decreased facilitation by commonly abused prescription opioids.

    Science.gov (United States)

    Ewan, Eric E; Martin, Thomas J

    2011-12-01

    Prescription opioid abuse is a significant concern in treating chronic pain, yet few studies examine how neuropathic pain alters the abuse liability of commonly abused prescription opioids. Normal and spinal nerve ligated (SNL) rats were implanted with electrodes into the left ventral tegmental area (VTA). Rats were trained to lever press for intracranial electrical stimulation (VTA ICSS), and the effects of methadone, fentanyl, hydromorphone, and oxycodone on facilitation of VTA ICSS were assessed. A second group of neuropathic rats were implanted with intrathecal catheters, and the effects of intrathecal clonidine, adenosine, and gabapentin on facilitation of VTA ICSS were assessed. The effects of electrical stimulation of the VTA on mechanical allodynia were assessed in SNL rats. Responding for VTA ICSS was similar in control and SNL rats. Methadone, fentanyl, and hydromorphone were less potent in facilitating VTA ICSS in SNL rats. Oxycodone produced a significant facilitation of VTA ICSS in control (maximum shift 24.10 ± 6.19 Hz) but not SNL rats (maximum shift 16.32 ± 7.49 Hz), but also reduced maximal response rates in SNL rats. Intrathecal administration of clonidine, adenosine, and gabapentin failed to facilitate VTA ICSS in SNL rats, and electrical stimulation of the VTA did not alter mechanical allodynia following nerve injury. The present data suggests that the positive reinforcing effects of commonly abused prescription opioids are diminished following nerve injury. In addition, alleviation of mechanical allodynia with nonopioid analgesics does not appear to stimulate limbic dopamine pathways originating from the VTA in SNL rats.

  10. Improved Neural Regeneration with Olfactory Ensheathing Cell Inoculated PLGA Scaffolds in Spinal Cord Injury Adult Rats

    Directory of Open Access Journals (Sweden)

    Changxing Wang

    2017-03-01

    Full Text Available Background/Aims: Every year, around the world, between 250000 and 500000 people suffer from spinal cord injury (SCI. This study investigated the potential for poly (lactic-co-glycolic acid (PLGA complex inoculated with olfactory ensheathing cells (OECs to treat spinal cord injury in a rat model. Methods: OECs were identified by immunofluorescence based on the nerve growth factor receptor (NGFR p75. The Basso, Beattie, and Bresnahan (BBB score, together with an inclined plane (IP test were used to detect functional recovery. Nissl staining along with the luxol fast blue (LFB staining were independently employed to illustrate morphological alterations. More so, immunofluorescence labeling of the glial fibrillary acidic protein (GFAP and the microtubule-associated protein-2 (MAP-2, representing astrocytes and neurons respectively, were investigated at time points of weeks 2 and 8 post-operation. Results: The findings showed enhanced locomotor recovery, axon myelination and better protected neurons post SCI when compared with either PLGA or untreated groups (P < 0.05. Conclusion: PLGA complexes inoculated with OECs improve locomotor functional recovery in transected spinal cord injured rat models, which is most likely due to the fact it is conducive to a relatively benevolent microenvironment, has nerve protective effects, as well as the ability to enhance remyelination, via a promotion of cell differentiation and inhibition of astrocyte formation.

  11. An experimental study of retrograde axonal plasmatic flow in the peripheral nerves of rats.

    Science.gov (United States)

    Sanguinetti, C; Tranquilli Leali, P; Grispigni, C

    1986-12-01

    Retrograde axonal flow (R.A.F.) in the sciatic nerve of Sprague Dowley rats was studied by injecting horseradish peroxidase (H.R.P.) peripherally and identifying its appearance in the related segment of the spinal cord. This called for a precise identification of the vertebro-medullary topography, the afferant root levels of the sciatic nerve, and the transport velocity of the H.R.P. Our study revealed a clear difference of neuromuscular end plate permeability as between new-born and adult animals. The vertebral column of the rat consists of 8 cervical metameres, 13 dorsal, 6 lumbar, 4 sacral, and 3 coccygeal. The sciatic nerve is derived principally from the roots L4, L5, L6 and in part from L3 and S1. The injection of H.R.P. in the sural triceps of the new-born rat produced granules in the anterior horn cells as early as 12 hours later. In similar experiments with adult rats H.R.P. in the motorneurons was never detected. In our experimental model the transport velocity of H.R.P. from the point of injection to the anterior horn cells was approximately 68 mm per day. These findings provide a foundation on which to base future studies of retrograde flows in conditions of induced pathology.

  12. Spinal Cord Blood Flow after Ischemic Preconditioning in a Rat Model of Spinal Cord Ischemia

    Directory of Open Access Journals (Sweden)

    David Zvara

    2004-01-01

    Full Text Available Spinal cord blood flow after ischemic preconditioning is poorly characterized. This study is designed to evaluate spinal cord blood flow patterns in animals after acute ischemic preconditioning. Experiment 1: After a laminectomy and placement of a laser Doppler probe over the lumbar spinal cord to measure spinal cord blood flow, 16 male Sprague-Dawley rats were randomized into two groups: ischemic preconditioning (IPC, n = 8, and control (CTRL, n = 8. Rats in the CTRL and the IPC groups were subjected to 12 min of ischemia directly followed by 60 min of reperfusion. IPC rats received 3 min of IPC and 30 min of reperfusion prior to the 12-min insult period. Experiment 2: After instrumentation, the rats were randomized into three groups: control (CTRL, n = 7, ischemic preconditioning (IPC, n = 7, and time control (TC, n = 4. Rats in the CTRL and the IPC groups were subjected to the same ischemia and reperfusion protocol as above. The TC group was anesthetized for the same time period as the CTRL and the IPC groups, but had no ischemic intervention. Microspheres were injected at baseline and at 15 and 60 min into the final reperfusion. All rats were euthanized and tissue harvested for spinal cord blood flow analysis. In Experiment 1, there was a slight, significant difference in spinal cord blood flow during the ischemic period; however, this difference soon disappeared during reperfusion. In experiment 2, there was no difference in blood flow at any experimental time. The results of these experiments demonstrate that IPC slightly enhances blood flow to the spinal cord during ischemia; however, this effect is not sustained during the reperfusion period.

  13. Nerve protective effect of Baicalin on newborn HIBD rats

    Institute of Scientific and Technical Information of China (English)

    Xue-Mei Liu; Yi Feng; Ai-Min Li

    2014-01-01

    Objective:To investigate the nerve protective effect and mechanism of baicalin on newborn rats with hypoxic ischemic brain damage(HIBD).Methods:A total of64SD newborn rats were randomly divided into control group, model group, nerve growth factor group and baicalin group, with16 in each group.Left carotid artery ligation method was adopted to establish theHIBD model except for in control group, which was treated with intraperitoneal injection of salin e10 mL/kg for3 d.After oxygen recovery on hypoxia ischemia rats, intraperitoneal injection of saline10 mL/kg was adopted in model group for3 d.Intraperitoneal injection of nerve growth factor injection 50μg/kg per day was adopted in nerve growth factor group for3 d; intraperitoneal injection of radix scutellariae16 mg/kg per day was adopted in baicalin group for3 d after modeling.Four rats of each group were sacrificed atDay1,2,3,7 for microscopic observation of pathological morphological changes in brain tissue afterHE staining,S-P immunohistochemical method was used for observation ofFas andFasL expression in brain cells.Results:Neat structure of cells was observed in control group; edema cells in disordered arrangement was observed in model group, with some cells necrosis and cavity change; tissue injury in nerve growth factor group and baicalin group was significantly lighter than that in model group;Fas andFasL expression in model group, nerve growth factor group and baicalin group were significantly higher than that in control group at different time points(P0.05).Conclusions:Baicalin can reduce expression ofFas andFasL inHIBD rats, inhibit apoptosis of nerve cells, thus achieve the protective effect onHIBD rat nerves.

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

    Institute of Scientific and Technical Information of China (English)

    Yu Feng; Yan Gao; Wendong Yang; Tianyou Feng

    2013-01-01

    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.

  15. EFFECTS OF BOTH GDNF AND HSV-GDNF ON Bcl-2 EXPRESSION IN SPINAL CORD MOTOR NEURONS AFTER SCIATIC NERVE INJURY IN RATS%GDNF及HSV-GDNF对坐骨神经损伤大鼠脊髓运动神经元 Bcl-2表达的影响

    Institute of Scientific and Technical Information of China (English)

    王常利; 苏剑斌; 鄂玲玲; 周长满

    2001-01-01

    目的 观察胶质细胞源性神经营养因子(GDNF)及单纯疱疹病毒(HSV)载体介导的GDNF(HSV-GDNF)对坐骨神经损伤大鼠脊髓运动神经元Bcl-2表达的影响。 方法 分别取坐骨神经损伤后4d、7d和14d大鼠(分成对照组、GDNF组和HSV-GDNF组)的腰段脊髓(L4~6),行石蜡包埋、切片;用抗Bcl-2抗血清进行免疫组织化学染色,观察Bcl-2免疫反应(Bcl-2-IR)神经元数目,并在图像分析仪上对Bcl-2-IR阳性神经元作光密度的色谱分析。 结果1.坐骨神经损伤后4d、7d时,GDNF组和HSV-GDNF组损伤侧脊髓运动神经元Bcl-2-IR阳性神经元的数量和平均光密度均明显高于对照组损伤侧。2.坐骨神经损伤后14d时,对照组、GDNF组和HSV-GDNF组损伤侧脊髓运动神经元对Bcl-2的表达已无明显差别。 结论 GDNF与HSV-GDNF能够增强坐骨神经损伤大鼠脊髓运动神经元Bcl-2的表达,减少神经元的退化死亡。%Objective To observe the effects of GDNF and HSV-GDNF on B cl-2expression in spinal cord motor neurons after sciatic nerve injury in rats . Methods Lumbar of spinal cord was immunohistochemically stained b y using the antiserum of Bcl-2.The number and mean optical densities of Bcl-2 i mmunoreactive(Bcl-2-IR)positive neurons were counted and observed. Results The number and mean optical densities of Bcl-2-IR positi ve neurons were significantly increased in GDNF and HSV-GDNF 4 days and 7 days after sciatic nerve injury.But differences of the number and the mean optical de nsities of Bcl-2-IR positive neurons were not obvious in three groups 14 days after sciatic nerve injury. Conclusion Local application of GDNF and HSV-GDNF to transected s ciatic nerve can prevent the massive neuron apoptosis or programmed cell death i nduced by nerve injury.

  16. Motor recovery following olfactory ensheathing cell transplantation in rats with spinal cord injury

    Directory of Open Access Journals (Sweden)

    George Tharion

    2011-01-01

    Full Text Available Background: Olfactory ensheathing cells (OEC are considered to be the most suitable cells for transplantation therapy in the central nervous system (CNS because of their unique ability to help axonal regrowth and remyelination in the CNS. However, there are conflicting reports about the success rates with OEC. Aim: This study was undertaken to evaluate the therapeutic effect of OEC in rat models using different cell dosages. Material and Methods: OECs harvested from the olfactory mucosa of adult white Albino rats were cultured. Spinal cord injury (SCI was inflicted at the lower thoracic segment in a control and test group of rats. Two weeks later, OECs were delivered in and around the injured spinal cord segment of the test group of the rats. The outcome in terms of locomotor recovery of limb muscles was assessed on a standard rating scale and by recording the motor-evoked potentials from the muscles during transcranial electrical stimulation. Finally, the animals were sacrificed to assess the structural repair by light microscopy. Statistical Analysis: Wilcoxon signed rank test and Mann-Whitney U-test were used to compare the data in the control and the test group of animals. A P value of <0.05 was considered significant. Results: The study showed a moderate but significant recovery of the injured rats after OEC transplantation (P=0.005. Conclusion: Transplantation of OECs along with olfactory nerve fibroblasts improved the motor recovery in rat models with SCI.

  17. Simulation of spinal nerve blocks for training anesthesiology residents

    Science.gov (United States)

    Blezek, Daniel J.; Robb, Richard A.; Camp, Jon J.; Nauss, Lee A.; Martin, David P.

    1998-06-01

    Deep nerve regional anesthesiology procedures, such as the celiac plexus block, are challenging to learn. The current training process primarily involves studying anatomy and practicing needle insertion is cadavers. Unfortunately, the training often continues on the first few patients subjected to the care of the new resident. To augment the training, we have developed a virtual reality surgical simulation designed to provide an immersive environment in which an understanding of the complex 3D relationships among the anatomic structures involved can be obtained and the mechanics of the celiac block procedure practiced under realistic conditions. Study of the relevant anatomy is provided by interactive 3D visualization of patient specific data nd the practice simulated using a head mounted display, a 6 degree of freedom tracker, and a haptic feedback device simulating the needle insertion. By training in a controlled environment, the resident may practice procedures repeatedly without the risks associated with actual patient procedures, and may become more adept and confident in the ability to perform nerve blocks. The resident may select a variety of different nerve block procedures to practice, and may place the virtual patient in any desired position and orientation. The preliminary anatomic models used in the simulation have been computed from the Visible Human Male; however, patient specific models may be generated from patient image data, allowing the physician to evaluate, plan, and practice difficult blocks and/or understand variations in anatomy before attempting the procedure on any specific patient.

  18. The influence of cervical spinal cord compression and vertebral displacement on somatosympathetic reflexes in the rat.

    Science.gov (United States)

    Bigland, Mark J; Budgell, Brian S; Bolton, Philip S

    2015-06-01

    One theory within chiropractic proposes that vertebral subluxation in the upper cervical region induces spinal cord compression sufficient to alter spinal cord efferent output. We report on the feasibility of three different experimental approaches to test this theory. A high threshold electrical-evoked somatosympathetic reflex was recorded in adrenal or renal nerves of 10 anaesthetized adult male rats before and after (1) graded pressure was applied directly to the C1/C2 spinal cord segment in eight rats by the use of either direct compression or inflation of an extradural balloon and (2) displacement, less than a dislocation applied posterior to anterior, to the C2 vertebra in two rats. The latency and amplitude of the pre- and postintervention reflex responses were compared. The reflex amplitude was not significantly changed by pressure (26 mmHg) from an extra-dural balloon or direct compression of the dura mater onto the dorsal spinal cord. Additional pressure, at least sufficient to occlude the dorsal vessels, induced a significant reduction in the amplitude of the reflex, and this reduction persisted for 20 minutes after removal of the pressure (Dunn's method for all pairwise multiple comparison Q stat=3.437; critical value for k=6 with α=0.05 is 2.936). Maximal vertebral (C2) displacement (4 mm), without dislocation did not induce significant changes compared with the control period. Although this feasibility study suggests it is unlikely that upper cervical vertebral subluxation, displacement less than a dislocation, compromises the sympathetic outflow in the adrenal or renal nerves, further vertebral displacement studies are necessary to formally test this. Copyright © 2015 Elsevier Inc. All rights reserved.

  19. Electrophysiological functional recovery in a rat model of spinal cord hemisection injury following bone marrow-derived mesenchymal stem cell transplantation under hypothermia

    Institute of Scientific and Technical Information of China (English)

    Dong Wang; Jianjun Zhang

    2012-01-01

    Following successful establishment of a rat model of spinal cord hemisection injury by resecting right spinal cord tissues, bone marrow stem cells were transplanted into the spinal cord lesions via the caudal vein while maintaining rectal temperature at 34 ± 0.5°C for 6 hours (mild hypothermia). Hematoxylin-eosin staining showed that astrocytes gathered around the injury site and formed scars at 4 weeks post-transplantation. Compared with rats transplanted with bone marrow stem cells under normal temperature, rats transplanted with bone marrow stem cells under hypothermia showed increased numbers of proliferating cells (bromodeoxyuridine-positive cells), better recovery of somatosensory-evoked and motor-evoked potentials, greater Basso, Beattie, and Bresnahan locomotor rating scores, and an increased degree of angle in the incline plate test. These findings suggested that hypothermia combined with bone marrow mesenchymal stem cells transplantation effectively promoted electrical conduction and nerve functional repair in a rat model of spinal cord hemisection injury.

  20. Dopamine is produced in the rat spinal cord and regulates micturition reflex after spinal cord injury.

    Science.gov (United States)

    Hou, Shaoping; Carson, David M; Wu, Di; Klaw, Michelle C; Houlé, John D; Tom, Veronica J

    2016-11-01

    Dopamine (DA) neurons in the mammalian central nervous system are thought to be restricted to the brain. DA-mediated regulation of urinary activity is considered to occur through an interaction between midbrain DA neurons and the pontine micturition center. Here we show that DA is produced in the rat spinal cord and modulates the bladder reflex. We observed numerous tyrosine hydroxylase (TH)(+) neurons in the autonomic nuclei and superficial dorsal horn in L6-S3 spinal segments. These neurons are dopamine-β-hydroxylase (DBH)(-) and some contain detectable dopamine decarboxylase (DDC), suggesting their capacity to produce DA. Interestingly, following a complete thoracic spinal cord injury (SCI) to interrupt supraspinal projections, more TH(+) neurons emerged in the lumbosacral spinal cord, coincident with a sustained, low level of DA expression there and a partially recovered micturition reflex. Non-selective blockade of spinal DA receptors reduced bladder activity whereas activation of spinal D2-like receptors increased bladder activity and facilitated voiding. Additionally, depletion of lumbosacral TH(+) neurons with 6-hydroxydopamine (6-OHDA) decreased bladder non-voiding contractions and voiding efficiency. Furthermore, injecting the transsynaptic neuronal tracer pseudorabies virus (PRV) into the bladder detrusor labeled TH(+) cells in the lumbosacral cord, confirming their involvement in spinal micturition reflex circuits. These results illustrate that DA is synthesized in the rat spinal cord; plasticity of lumbosacral TH(+) neurons following SCI may contribute to DA expression and modulate the spinal bladder reflex. Thus, spinally-derived DA and receptors could be a novel therapeutic target to improve micturition recovery after SCI. Published by Elsevier Inc.

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

    Science.gov (United States)

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

    2001-01-01

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

  2. Effects of methyl prednisolone, dimethyl sulphoxide and naloxone in experimental spinal cord injuries in rats.

    Science.gov (United States)

    Zileli, M; Ovül, I; Dalbasti, T

    1988-12-01

    The effects of methyl prednisolone (MPD), dimethyl sulphoxide (DMSO), and naloxone were examined in 38 albino rats after making an impact spinal cord injury on the midthoracic segments with a modified Allen's weight dropping trauma method. Somatosensorial evoked potentials (SEPs) were recorded before and 12 h and 14 d after the injury from epidurally inserted electrodes on the parietal cortex with sciatic nerve stimulations. Lower extremity motor functions of the animals were also examined. It may be concluded that in this study model, DMSO has a moderate effect which can be demonstrated clinically and through SEPs. Naloxone has no effect on the clinical outcome but causes reasonable improvement electrophysiologically.

  3. Raman spectroscopic investigation of spinal cord injury in a rat model

    Science.gov (United States)

    Saxena, Tarun; Deng, Bin; Stelzner, Dennis; Hasenwinkel, Julie; Chaiken, Joseph

    2011-02-01

    Raman spectroscopy was used to study temporal molecular changes associated with spinal cord injury (SCI) in a rat model. Raman spectra of saline-perfused, injured, and healthy rat spinal cords were obtained and compared. Two injury models, a lateral hemisection and a moderate contusion were investigated. The net fluorescence and the Raman spectra showed clear differences between the injured and healthy spinal cords. Based on extensive histological and biochemical characterization of SCI available in the literature, these differences were hypothesized to be due to cell death, demyelination, and changes in the extracellular matrix composition, such as increased expression of proteoglycans and hyaluronic acid, at the site of injury where the glial scar forms. Further, analysis of difference spectra indicated the presence of carbonyl containing compounds, hypothesized to be products of lipid peroxidation and acid catalyzed hydrolysis of glycosaminoglycan moieties. These results compared well with in vitro experiments conducted on chondroitin sulfate sugars. Since the glial scar is thought to be a potent biochemical barrier to nerve regeneration, this observation suggests the possibility of using near infrared Raman spectroscopy to study injury progression and explore potential treatments ex vivo, and ultimately monitor potential remedial treatments within the spinal cord in vivo.

  4. Sciatic nerve regeneration in rats subjected to ketogenic diet.

    Science.gov (United States)

    Liśkiewicz, Arkadiusz; Właszczuk, Adam; Gendosz, Daria; Larysz-Brysz, Magdalena; Kapustka, Bartosz; Łączyński, Mariusz; Lewin-Kowalik, Joanna; Jędrzejowska-Szypułka, Halina

    2016-01-01

    Ketogenic diet (KD) is a high-fat-content diet with insufficiency of carbohydrates that induces ketogenesis. Besides its anticonvulsant properties, many studies have shown its neuroprotective effect in central nervous system, but its influence on peripheral nervous system has not been studied yet. We examined the influence of KD on regeneration of peripheral nerves in adult rats. Fifty one rats were divided into three experimental (n = 15) and one control (n = 6) groups. Right sciatic nerve was crushed and animals were kept on standard (ST group) or ketogenic diet, the latter was introduced 3 weeks before (KDB group) or on the day of surgery (KDA group). Functional (CatWalk) tests were performed once a week, and morphometric (fiber density, axon diameter, and myelin thickness) analysis of the nerves was made after 6 weeks. Body weight and blood ketone bodies level were estimated at the beginning and the end of experiment. Functional analysis showed no differences between groups. Morphometric evaluation showed most similarities to the healthy (uncrushed) nerves in KDB group. Nerves in ST group differed mostly from all other groups. Ketone bodies were elevated in both KD groups, while post-surgery animals' body weight was lower as compared to ST group. Regeneration of sciatic nerves was improved in KD - preconditioned rats. These results suggest a neuroprotective effect of KD on peripheral nerves.

  5. Vascular endothelial growth factor promotes peripheral nerve regeneration after sciatic nerve transection in rat

    Directory of Open Access Journals (Sweden)

    Mohammadi Rahim

    2013-12-01

    Full Text Available 【Abstract】Objective: To evaluate the local effect of vascular endothelial growth factor (VEGF on transected sciatic nerve regeneration. Methods: Sixty male white Wistar rats were divided into four experimental groups randomly (n=15. In transected group the left sciatic nerve was transected and the stump was fixed to adjacent muscle. In treatment group the defect was bridged using a silicone graft filled with 10 µL VEGF. In silicone group the graft was filled with phosphate-buffered saline. In sham-operated group the sciatic nerve was ex- posed and manipulated. Each group was subdivided into three subgroups with five animals in each and nerve fibers were studied 4, 8 and 12 weeks after operation. Results: Behavioral test, functional study of sciatic nerve, gastrocnemius muscle mass and morphometric indi- ces confirmed a faster recovery of regenerated axons in VEGF group than in silicone group (P<0.05. In immunohistochemi- cal assessment, reactions to S-100 in VEGF group were more positive than that in silicone group. Conclusion: Local administration of VEGF will im- prove functional recovery and morphometric indices of sci- atic nerve. Key words: Peripheral nerves; Nerve regeneration; Sciatic nerve; Vascular endothelial growth factor

  6. Repairing peripheral nerve defects with tissue engineered artificial nerves in rats

    Institute of Scientific and Technical Information of China (English)

    WEI Ai-lin; LIU Shi-qing; TAO Hai-ying; PENG Hao

    2008-01-01

    Objective: To observe the effect of tissue engineered nerves in repairing peripheral nerve defects ( about 1. 5 cm in length) in rats to provide data for clinical application.Methods: Glycerinated sciatic nerves (2 cm in length) from 10 Sprague Dawley ( SD) rats ( aged 4 months) were used to prepare homologous dermal acellular matrix. Other 10 neonate SD rats (aged 5-7 days) were killed by neck dislocation. After removing the epineurium, the separated sciatic nerve tracts were cut into small pieces, then digested by 2.5 g/L trypsin and 625 U/ml collagenase and cultured in Dulbecco's modified Eagle's medium (DMEM) for 3 weeks. After proliferation, the Schwann cells ( SCs) were identified and prepared for use. And other 40 female adult SD rats (weighing 200 g and aged 3 months) with sciatic nerve defects of 1.5 cm in length were randomly divided into four groups: the defects of 10 rats bridged with proliferated SCs and homologous dermal acellular matrix (the tissue engineered nerve group, Group A), 10 rats with no SCs but homologous dermal acellular matrix with internal scaffolds ( Group B ), 10 with autologous nerves ( Group C) , and the other 10 with nothing (the blank control group, Group D). The general status of the rats was observed, the wet weight of triceps muscle of calf was monitored, and the histological observation of the regenerated nerves were made at 12 weeks after operation.Results: The wounds of all 40 rats healed after operation and no death was found. No foot ulceration was found in Groups A, B and C, but 7 rats suffered from foot ulceration in Group D. The triceps muscles of calf were depauperated in the experimental sides in all the groups compared with the uninjured sides,which was much more obvious in Group D. The wet weight of triceps muscle of calf and nerve electrophysiologic monitoring showed no statistical difference between Group A and Group C,but statistical difference was found between Groups A and B and Groups B and D. And significant

  7. Impaired Prosaposin Secretion During Nerve Regeneration in Diabetic Rats and Protection of Nerve Regeneration by a Prosaposin-Derived Peptide

    Science.gov (United States)

    Jolivalt, Corinne G.; Vu, Yvonne; Mizisin, Leah M.; Mizisin, Andrew P.; Calcutt, Nigel A.

    2009-01-01

    Prosaposin is both a precursor of sphingolipid activator proteins and a secreted neurotrophic and myelinotrophic factor. Because peripheral nerve regeneration is impaired in diabetes mellitus, we measured prosaposin protein levels from control and streptozotocin-diabetic rats by collecting endoneurial fluid secreted into a bridging tube connecting the ends of transected sciatic nerve. Prosaposin protein levels were significantly reduced in endoneurial fluid from diabetic rats and increased in the proximal nerve stump compared to controls. To investigate whether a prosaposin-derived peptide could improve nerve regeneration, rats were treated with prosaptide TX14(A) following sciatic nerve crush. In control rats, TX14(A) was without effect in the uninjured nerve but shortened toe spread recovery time after nerve crush. In diabetic rats, efficacy of prosaptide TX14(A) was confirmed by correction of thermal hypoalgesia, formalin-evoked hyperalgesia and conduction slowing in the uninjured nerve. The peptide also prevented diabetes-induced abnormalities in nerve regeneration distance and mean axonal diameter of regenerated axons, whereas delayed recovery of toe spread was not improved. Muscle denervation atrophy was attenuated by TX14(A) in both control and diabetic rats. These results suggest that reduced prosaposin secretion after nerve injury may contribute to impaired regeneration rates in diabetic rats and that prosaptide TX14(A) can improve aspects of nerve regeneration. PMID:18596543

  8. Impaired prosaposin secretion during nerve regeneration in diabetic rats and protection of nerve regeneration by a prosaposin-derived peptide.

    Science.gov (United States)

    Jolivalt, Corinne G; Vu, Yvonne; Mizisin, Leah M; Mizisin, Andrew P; Calcutt, Nigel A

    2008-07-01

    Prosaposin is both a precursor of sphingolipid activator proteins and a secreted neurotrophic and myelinotrophic factor. Because peripheral nerve regeneration is impaired in diabetes mellitus, we measured prosaposin protein levels from control and streptozotocin-diabetic rats by collecting endoneurial fluid secreted into a bridging tube connecting the ends of transected sciatic nerve. Prosaposin protein levels were significantly reduced in endoneurial fluid from diabetic rats and increased in the proximal nerve stump compared to controls. To investigate whether a prosaposin-derived peptide could improve nerve regeneration, rats were treated with prosaptide TX14(A) after sciatic nerve crush. In control rats, TX14(A) was without effect in the uninjured nerve but shortened toe spread recovery time after nerve crush. In diabetic rats, efficacy of prosaptide TX14(A) was confirmed by correction of thermal hypoalgesia, formalin-evoked hyperalgesia, and conduction slowing in the uninjured nerve. The peptide also prevented diabetes-induced abnormalities in nerve regeneration distance and mean axonal diameter of regenerated axons, whereas delayed recovery of toe spread was not improved. Muscle denervation atrophy was attenuated by TX14(A) in both control and diabetic rats. These results suggest that reduced prosaposin secretion after nerve injury may contribute to impaired regeneration rates in diabetic rats, and that prosaptide TX14(A) can improve aspects of nerve regeneration.

  9. Substance P mRNA expression in the rat spinal cord following selective brachial plexus injury

    Institute of Scientific and Technical Information of China (English)

    Na Liu; Longju Chen; Feng Li; Wutian Wu

    2008-01-01

    BACKGROUND: The neuropeptide, substance P, has various bioactivities and is widely distributed in the central nervous system. Substance P participates in neural transmission in the spinal cord and plays an important role in regeneration and repair of nerve injury.OBJECTIVE: To investigate substance P mRNA expression in the anterior horn of the spinal cord following brachial plexus injury.DESIGN, TIME AND SETTING: A molecular cell biology randomized controlled study was performed at the Department of Anatomy, Zhongshan Medical College, Sun Yat-sen University and the DaAn Gene Laboratory in May 2005.MATERIALS: A total of 29 adult male Sprague Dawley rats were randomly assigned to a control group (n=5) and an injury group (n = 24).METHODS: The injury group was divided into three subgroups. In subgroup A, the right seventh cervical vertebra (C7) anterior root was avulsed, and the residual nerve root at the distal end was removed. In subgroup B, the right C7 anterior root was avulsed, and the right C5 first thoracic vertebrae (TO posterior root was incised. Thus afferent pathways of the posterior root that connected with the anterior horn motor neurons were blocked. In subgroup C, the right C7 anterior root was avulsed, and a right C5-6 hemisection was performed. Thus the descending fiber pathways of the cortex that connected with anterior horn motor neurons were blocked. In the control group, the C5-T1 vertebral plate was opened, and then the skin was sutured.MAIN OUTCOME MEASURE: Substance P mRNA expression in the anterior horn of the spinal cord was quantified using fluorescent quantitative reverse transcription-polymerase chain reaction.RESULTS: Substance P mRNA expression was low in the anterior horn of the rat spinal cord in the control group. Substance P mRNA expression in the anterior horn of the spinal cord was upregulated and was significantly higher in the injury group compared with the control group (P < 0.01 ). Substance P mRNA expression was highest in

  10. Establishment of intramedullary spinal cord glioma model in rats

    Institute of Scientific and Technical Information of China (English)

    REN Tian-jian; WANG Zhong-cheng; ZHANG Ya-zhuo; LI Dan; WANG Hong-yun; LI Zhen-zong

    2010-01-01

    Background Treating intramedullary spinal cord gliomas is a big challenge because of limited options, high recurrence rate and poor prognosis. An intramedullary glioma model is prerequisite for testing new treatments. This paper describes the establishment of a rodent intramedullary glioma model and presents functional progression, neuroimaging and histopathological characterization of the tumour model.Methods Fischer344 rats (n=24) were randomized into two groups. Group 1 (n=16) received a 5 μl intramedullary implantation of 9L gliosarcomal (105) cells. Group 2 (n=8) received a 5 μl intramedullary injection of Dulbecco's modified Eagle medium. The rats were anesthetized, the spinous process of the T10 vertebra and the ligamentum flavum were removed to expose the T10-11 intervertebral space and an intramedullary injection was conducted into the spinal cord. The rats were evaluated preoperatively and daily postoperatively for neurological deficits using the Basso, Beattie and Bresnahan scale. High resolution magnetic resonance images were acquired preoperatively and weekly postoperatively.When score equal to 0, rats were sacrificed for histopathological examination.Results Rats implanted with 9L gliosarcoma cells had a statistically significant median onset of hind limb paraplegia at (16.0±0.4) days, compared with rats in the control group in which neurological deficits were absent. Imaging and pathological cross sections confirmed intramedullary 9L gliosarcoma invading the spinal cord. Rats in the control group showed no significant functional, radiological or histopathological findings of tumour.Conclusions Rats implanted with 9L cells regularly develop paraplegia in a reliable and reproducible manner. The progression of neurological deficits, neuroimaging and histopathological characteristics of intramedullary spinal cord gliomas in rats is comparable with the behaviour of infiltrative intramedullary spinal cord gliomas in patients.

  11. A polylactic acid non-woven nerve conduit for facial nerve regeneration in rats.

    Science.gov (United States)

    Matsumine, Hajime; Sasaki, Ryo; Yamato, Masayuki; Okano, Teruo; Sakurai, Hiroyuki

    2014-06-01

    This study developed a biodegradable nerve conduit with PLA non-woven fabric and evaluated its nerve regeneration-promoting effect. The buccal branch of the facial nerve of 8 week-old Lewis rats was exposed, and a 7 mm nerve defect was created. A nerve conduit made of either PLA non-woven fabric (mean fibre diameter 460 nm), or silicone tube filled with type I collagen gel, or an autologous nerve, was implanted into the nerve defect, and their nerve regenerative abilities were evaluated 13 weeks after the surgery. The number of myelinated neural fibres in the middle portion of the regenerated nerve was the highest for PLA tubes (mean ± SD, 5051 ± 2335), followed by autologous nerves (4233 ± 590) and silicone tubes (1604 ± 148). Axon diameter was significantly greater in the PLA tube group (5.17 ± 1.69 µm) than in the silicone tube group (4.25 ± 1.60 µm) and no significant difference was found between the PLA tube and autograft (5.53 ± 1.93 µm) groups. Myelin thickness was greatest for the autograft group (0.65 ± 0.24 µm), followed by the PLA tube (0.54 ± 0.18 µm) and silicone tube (0.38 ± 0.12 µm) groups, showing significant differences among the three groups. The PLA non-woven fabric tube, composed of randomly-connected PLA fibres, is porous and has a number of advantages, such as sufficient strength to maintain luminal structure. The tube has demonstrated a comparable ability to induce peripheral nerve regeneration following autologous nerve transplantation.

  12. Effect of morphine on synaptic long-term potentiation in spinal dorsal horn evoked by electric stimulation of sciatic nerve in rats%吗啡对电刺激坐骨神经诱发大鼠脊髓背角突触长时程增强的影响

    Institute of Scientific and Technical Information of China (English)

    吴江; 黄德樱; 程洁; 上官守琴; 胡祁生

    2009-01-01

    Objective To evaluate the effect of morphine on synaptic long-term potentiation (LTP) in the spinal dorsal horn evoked by electric stimulation of sciatic nerve in rats. Methods Twenty-seven healthy male SD rats aged 60-90 d weighing 180-200 g were randomly divided into 4 groups: group Ⅰ control (group C, n=7), group Ⅱ morphine (group M, n=7), group Ⅲ naloxone (group N, n=6), and group Ⅳ morphine + naloxone (group MN, n=7). The animals were anesthetized with intraperitoneal 10% urethane 1 g/kg, intubated and then mechanically ventilated. The bipolar insulated stainless steel recording electrode (impedance 0.5-1 MΩ, diameter 0.1 mm) was inserted into the left side of the spinal dorsal horn at T13-L1 to stimulate the left side of the sciatic nerve. Single square pulses (15 V, 0.5 ms, 1/60 Hz for 30 min) was applied to evoke spinal field potentials. Normal saline 10 μl, morphine 10 μl (15 μg/μl), naloxone 10 μl (2.5 μg/μl), and the mixture 10 μl of naloxone 5 μl (2.5 μg/μl) and morphine 5 μl (15 μg/μl) was gradually instilled over 2 rain in the 4 groups respectively. Five minutes later, high-frequency and intensity tetanic stimulation (30-40 V, 0.5 ms, 100 Hz, given in 4 trains of 1-s duration at 10-s intervals) was used to induce LTP. Then single square stimuli (15 V, 5 ms, 1/60 Hz) were applied to the sciatic nerve for 210 min. The amplitude and latency period of the field potential were recorded 30 min before tetanic stimulation, and 0-30, 35-60, 65-120 and 125-210 min after titanic stimulation. Results Compared with group C, the amplitude of the field potential was significantly decreased and the latency period prolonged in group M and MN, but there was no significant difference in the above indices between group N and C. Compared with group M, the amplitude of the field potential was significantly increased and the latency period shortened in group MN. Compared with those 30 min before the tetanic stimulation, the amplitude of the field

  13. Effect of intravenous transplantation of bone marrow mesenchymal stem cells on neurotransmitters and synapsins in rats with spinal cord injury

    Institute of Scientific and Technical Information of China (English)

    Shaoqiang Chen; Bilian Wu; Jianhua Lin

    2012-01-01

    Bone marrow mesenchymal stem cells were isolated,purified and cultured in vitro by Percoll density gradient centrifugation combined with the cell adherence method.Passages 3-5 bone marrow mesenchymal stem cells were transplanted into rats with traumatic spinal cord injury via the caudal vein.Basso-Beattie-Bresnahan scores indicate that neurological function of experimental rats was significantly improved over transplantation time (1-5 weeks).Expressions of choline acetyltransferase,glutamic acid decarboxylase and synapsins in the damaged spinal cord of rats was significantly increased after transplantation,determined by immunofluorescence staining and laser confocal scanning microscopy.Bone marrow mesenchymal stem cells that had migrated into the damaged area of rats in the experimental group began to express choline acetyltransferase,glutamic acid decarboxylase and synapsins,3 weeks after transplantation.The Basso-Beattie-Bresnahan scores positively correlated with expression of choline acetyltransferase and synapsins.Experimental findings indicate that intravenously transplanted bone marrow mesenchymal stem cells traverse into the damaged spinal cord of rats,promote expression of choline acetyltransferase,glutamic acid decarboxylase and synapsins,and improve nerve function in rats with spinal cord injury.

  14. Purinergic Modulation of Spinal Neuroglial Maladaptive Plasticity Following Peripheral Nerve Injury.

    Science.gov (United States)

    Cirillo, Giovanni; Colangelo, Anna Maria; Berbenni, Miluscia; Ippolito, Vita Maria; De Luca, Ciro; Verdesca, Francesco; Savarese, Leonilde; Alberghina, Lilia; Maggio, Nicola; Papa, Michele

    2015-12-01

    Modulation of spinal reactive gliosis following peripheral nerve injury (PNI) is a promising strategy to restore synaptic homeostasis. Oxidized ATP (OxATP), a nonselective antagonist of purinergic P2X receptors, was found to recover a neuropathic behavior following PNI. We investigated the role of intraperitoneal (i.p.) OxATP treatment in restoring the expression of neuronal and glial markers in the mouse spinal cord after sciatic spared nerve injury (SNI). Using in vivo two-photon microscopy, we imaged Ca(2+) transients in neurons and astrocytes of the dorsal horn of spinal cord at rest and upon right hind paw electrical stimulation in sham, SNI, and OxATP-treated mice. Neuropathic behavior was investigated by von Frey and thermal plantar test. Glial [glial fibrillary acidic protein (GFAP), ionized calcium-binding adaptor molecule 1 (Iba1)] and GABAergic [vesicular GABA transporter (vGAT) and glutamic acid decarboxylase 65/76 (GAD65/67)] markers and glial [glutamate transporter (GLT1) and GLAST] and neuronal amino acid [EAAC1, vesicular glutamate transporter 1 (vGLUT1)] transporters have been evaluated. In SNI mice, we found (i) increased glial response, (ii) decreased glial amino acid transporters, and (iii) increased levels of neuronal amino acid transporters, and (iv) in vivo analysis of spinal neurons and astrocytes showed a persistent increase of Ca(2+) levels. OxATP administration reduced glial activation, modulated the expression of glial and neuronal glutamate/GABA transporters, restored neuronal and astrocytic Ca(2+) levels, and prevented neuropathic behavior. In vitro studies validated that OxATP (i) reduced levels of reactive oxygen species (ROS), (ii) reduced astrocytic proliferation, (iii) increase vGLUT expression. All together, these data support the correlation between reactive gliosis and perturbation of the spinal synaptic homeostasis and the role played by the purinergic system in modulating spinal plasticity following PNI.

  15. Intraoperative monitoring during decompression of the spinal cord and spinal nerves using transcranial motor-evoked potentials: The law of twenty percent.

    Science.gov (United States)

    Tanaka, Satoshi; Hirao, Jun; Oka, Hidehiro; Akimoto, Jiro; Takanashi, Junko; Yamada, Junichi

    2015-09-01

    Motor-evoked potential (MEP) monitoring was performed during 196 consecutive spinal (79 cervical and 117 lumbar) surgeries for the decompression of compressive spinal and spinal nerve diseases. MEP monitoring in spinal surgery has been considered sensitive to predict postoperative neurological recovery. In this series, transcranial stimulation consisted of trains of five pulses at a constant voltage (200-600 V). For the normalization of MEP, we recorded compound muscle action potentials (CMAP) after peripheral nerve stimulation, usually on the median nerve at the wrist 2 seconds before or after each transcranial stimulation of the motor area, for all operations. The sensitivity and specificity of MEP monitoring was 100% and 97.4%, respectively, or 96.9% with or without CMAP compensation (if the threshold of postoperative motor palsy was defined as 20% relative amplitude rate [RAR]). The mean RAR after CMAP normalization, of the most affected muscle in the patient group with excellent postoperative results (recovery rate of a Japan Orthopedic Association score of more than 50%) was significantly higher than that in the other groups (p=0.0224). All patients with an amplitude increase rate (AIR) with CMAP normalization of more than 20% achieved neurological recovery postoperatively. Our results suggest that if the RAR is more than 20%, postoperative motor palsy can be avoided in spinal surgery. If the AIR with normalization by CMAP after peripheral nerve stimulation is more than 20%, neurological recovery can be expected in spinal surgery.

  16. Successful Reinnervation of the Diaphragm After Intercostal to Phrenic Nerve Neurotization in Patients With High Spinal Cord Injury.

    Science.gov (United States)

    Nandra, Kulvir S; Harari, Martin; Price, Thea P; Greaney, Patrick J; Weinstein, Michael S

    2017-08-01

    Our objective in this study was to extend diaphragmatic pacing therapy to include paraplegic patients with high cervical spinal cord injuries between C3 and C5. Diaphragmatic pacing has been used in patients experiencing ventilator-dependent respiratory failure due to spinal cord injury as a means to reduce or eliminate the need for mechanical ventilation. However, this technique relies on intact phrenic nerve function. Recently, phrenic nerve reconstruction with intercostal nerve grafting has expanded the indications for diaphragmatic pacing. Our study aimed to evaluate early outcomes and efficacy of intercostal nerve transfer in diaphragmatic pacing. Four ventilator-dependent patients with high cervical spinal cord injuries were selected for this study. Each patient demonstrated absence of phrenic nerve function via external neck stimulation and laparoscopic diaphragm mapping. Each patient underwent intercostal to phrenic nerve grafting with implantation of a phrenic nerve pacer. The patients were followed, and ventilator dependence was reassessed at 1 year postoperatively. Our primary outcome was measured by the amount of time our patients tolerated off the ventilator per day. We found that all 4 patients have tolerated paced breathing independent of mechanical ventilation, with 1 patient achieving 24 hours of tracheostomy collar. From this study, intercostal to phrenic nerve transfer seems to be a promising approach in reducing or eliminating ventilator support in patients with C3 to C5 high spinal cord injury.

  17. Expression of VEGF and neural repair after alprostadil treatment in a rat model of sciatic nerve crush injury

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    Tang Jinrong

    2009-01-01

    Full Text Available Background: Vasoactive drug alprostadil improves microcirculation and can be effective in treating disorders of peripheral nerves. Vascular endothelial growth factor (VEGF has been shown to have protective action in cerebral ischemia, disorders of spinal cord, and also peripheral nerves. However, the mechanism of action of VEGF in peripheral nerve injuries is uncertain. Objectives: To study the effect of application of alprostadil on the pathological and functional repair of crush nerve injuries and also the expression of VEGF. Materials and Methods: Rat sciatic nerves were crushed by pincers to establish the model of crush injury. All of the 400 sprague dawley (SD rats were randomly divided into: Control; saline; saline + VEGF-antibody; alprostadil; and alprostadil + VEGF antibody groups. The SPSS 11.5 software was used for statistical analysis. The expression of VEGF in dorsal root ganglia (DRGs, following crush injury to sciatic nerves, was studied by reverse transcribed-polymerase chain reaction (RT-PCR, immunohistochemistry, electromicroscope, and electrophysiology. The effects of alprostadil on expression of VEGF, repair of neural pathology, and recovery of neural function were also evaluated. Results: We found that VEGF messenger ribonucleic acid (mRNA was significantly increased in alprostadil and alprostadil + VEGF-antibody groups, compared to the saline and saline + VEGF antibody groups. The number of VEGF-positive neurons was significantly increased in the alprostadil group, compared to the saline, saline + VEGF antibody, and alprostadil + VEGF antibody groups. Besides, addition of this drug also caused less pathological changes in DRGs, better improvement of nerve conduction velocities of sciatic nerves, and more increase of toe spaces of right hind limbs of rats. Conclusions: The vasoactive agent alprostadil may reduce the pathological lesion of peripheral nerves and improve the rehabilitation of the neural function, which may

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

    Science.gov (United States)

    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.

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

    OpenAIRE

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

    2016-01-01

    Wallerian degeneration is a sequence of events in the distal stump of axotomized nerves. Despite large numbers of researches concentrating on WD, the biological mechanism still remains unclear. Hence we constructed a rat model with both motor and sensory nerves injury and then conducted a RNA-seq analysis. Here the rats were divided into the 4 following groups: normal motor nerves (NMN), injured motor nerves (IMN), normal sensory nerves (NSN) and injured sensory nerves (ISN). The transcriptom...

  20. Effect of neurotrophic factor, MDP, on rats' nerve regeneration.

    Science.gov (United States)

    Fornazari, A A; Rezende, M R de; Mattar Jr, R; Taira, R I; Santos, G B dos; Paulos, R G

    2011-04-01

    Our objective was to determine the immune-modulating effects of the neurotrophic factor N-acetylmuramyl-L-alanyl-D-isoglutamine (MDP) on median nerve regeneration in rats. We used male Wistar rats (120-140 days of age, weighing 250-332 g) and compared the results of three different techniques of nerve repair: 1) epineural neurorrhaphy using sutures alone (group S - 10 rats), 2) epineural neurorrhaphy using sutures plus fibrin tissue adhesive (FTA; group SF - 20 rats), and 3) sutures plus FTA, with MDP added to the FTA (group SFM - 20 rats). Functional assessments using the grasp test were performed weekly for 12 weeks to identify recovery of flexor muscle function in the fingers secondary to median nerve regeneration. Histological analysis was also utilized. The total number and diameter of myelinated fibers were determined in each proximal and distal nerve segment. Two indices, reported as percentage, were calculated from these parameters, namely, the regeneration index and the diameter change index. By the 8th week, superiority of group SFM over group S became apparent in the grasping test (P = 0.005). By the 12th week, rats that had received MDP were superior in the grasping test compared to both group S (P MDP obtained better function, in the absence of any significant histological differences.

  1. Immune Responses Following Mouse Peripheral Nerve Xenotransplantation in Rats

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    Lai-Jin Lu

    2009-01-01

    Full Text Available Xenotransplantation offers a potentially unlimited source for tissues and organs for transplantation, but the strong xenoimmune responses pose a major obstacle to its application in the clinic. In this study, we investigate the rejection of mouse peripheral nerve xenografts in rats. Severe intragraft mononuclear cell infiltration, graft distension, and necrosis were detected in the recipients as early as 2 weeks after mouse nerve xenotransplantation. The number of axons in xenografts reduced progressively and became almost undetectable at week 8. However, mouse nerve xenotransplantation only led to a transient and moderate increase in the production of Th1 cytokines, including IL-2, IFN-γ, and TNF-α. The data implicate that cellular immune responses play a critical role in nerve xenograft rejection but that further identification of the major effector cells mediating the rejection is required for developing effective means to prevent peripheral nerve xenograft rejection.

  2. Disruption of spinal cord white matter and sciatic nerve geometry inhibits axonal growth in vitro in the absence of glial scarring

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    Crutcher Keith A

    2001-05-01

    Full Text Available Abstract Background Axons within the mature mammalian central nervous system fail to regenerate following injury, usually resulting in long-lasting motor and sensory deficits. Studies involving transplantation of adult neurons into white matter implicate glial scar-associated factors in regeneration failure. However, these studies cannot distinguish between the effects of these factors and disruption of the spatial organization of cells and molecular factors (disrupted geometry. Since white matter can support or inhibit neurite growth depending on the geometry of the fiber tract, the present study sought to determine whether disrupted geometry is sufficient to inhibit neurite growth. Results Embryonic chick sympathetic neurons were cultured on unfixed longitudinal cryostat sections of mature rat spinal cord or sciatic nerve that had been crushed with forceps ex vivo then immediately frozen to prevent glial scarring. Neurite growth on uncrushed portions of spinal cord white matter or sciatic nerve was extensive and highly parallel with the longitudinal axis of the fiber tract but did not extend onto crushed portions. Moreover, neurite growth from neurons attached directly to crushed white matter or nerve tissue was shorter and less parallel compared with neurite growth on uncrushed tissue. In contrast, neurite growth appeared to be unaffected by crushed spinal cord gray matter. Conclusions These observations suggest that glial scar-associated factors are not necessary to block axonal growth at sites of injury. Disruption of fiber tract geometry, perhaps involving myelin-associated neurite-growth inhibitors, may be sufficient to pose a barrier to regenerating axons in spinal cord white matter and peripheral nerves.

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

    Science.gov (United States)

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

    2016-01-01

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

  4. Sericin protects against diabetes-induced injuries in sciatic nerve and related nerve cells

    Institute of Scientific and Technical Information of China (English)

    Chengjun Song; Zhenjun Yang; Meirong Zhong; Zhihong Chen

    2013-01-01

    Sericin from discarded silkworm cocoons of silk reeling has been used in different fields, such as cosmetology, skin care, nutrition, and oncology. The present study established a rat model of type 2 diabetes by consecutive intraperitoneal injections of low-dose (25 mg/kg) streptozotocin. After intragastrical perfusion of sericin for 35 days, blood glucose levels significantly declined, and the expression of neurofilament protein in the sciatic nerve and nerve growth factor in L4–6 spinal ganglion and anterior horn cells significantly increased. However, the expression of neuropeptide Y in spinal ganglion and anterior horn cells significantly decreased in model rats. These findings indicate that sericin protected the sciatic nerve and related nerve cells against injury in a rat type 2 diabetic model by upregulating the expression of neurofilament protein in the sciatic nerve and nerve growth factor in spinal ganglion and anterior horn cells, and downregulating the expression of neuropeptide Y in spinal ganglion and anterior horn cells.

  5. Spinal stimulation of the upper lumbar spinal cord modulates urethral sphincter activity in rats after spinal cord injury.

    Science.gov (United States)

    Abud, Edsel M; Ichiyama, Ronaldo M; Havton, Leif A; Chang, Huiyi H

    2015-05-01

    After spinal cord injury (SCI), the neurogenic bladder is observed to develop asynchronous bladder and external urethral sphincter (EUS) contractions in a condition known as detrusor-sphincter dyssnergia (DSD). Activation of the EUS spinal controlling center located at the upper lumbar spinal cord may contribute to reduce EUS dyssynergic contractions and decrease urethral resistance during voiding. However, this mechanism has not been well studied. This study aimed at evaluating the effects of epidural stimulation (EpS) over the spinal EUS controlling center (L3) in combination with a serotonergic receptor agonist on EUS relaxation in naive rats and chronic (6-8 wk) T8 SCI rats. Cystometrogram and EUS electromyography (EMG) were obtained before and after the intravenous administration of 5HT-1A receptor agonist and antagonist. The latency, duration, frequency, amplitude, and area under curve of EpS-evoked EUS EMG responses were analyzed. EpS on L3 evoked an inhibition of EUS tonic contraction and an excitation of EUS intermittent bursting/relaxation correlating with urine expulsion in intact rats. Combined with a 5HT-1A receptor agonist, EpS on L3 evoked a similar effect in chronic T8 SCI rats to reduce urethral contraction (resistance). This study examined the effect of facilitating the EUS spinal controlling center to switch between urine storage and voiding phases by using EpS and a serotonergic receptor agonist. This novel approach of applying EpS on the EUS controlling center modulates EUS contraction and relaxation as well as reduces urethral resistance during voiding in chronic SCI rats with DSD. Copyright © 2015 the American Physiological Society.

  6. Serotonin(2) receptors mediate respiratory recovery after cervical spinal cord hemisection in adult rats.

    Science.gov (United States)

    Zhou, S Y; Basura, G J; Goshgarian, H G

    2001-12-01

    The aim of the present study was to specifically investigate the involvement of serotonin [5-hydroxytryptamine (5-HT(2))] receptors in 5-HT-mediated respiratory recovery after cervical hemisection. Experiments were conducted on C(2) spinal cord-hemisected, anesthetized (chloral hydrate, 400 mg/kg ip), vagotomized, pancuronium- paralyzed, and artificially ventilated female Sprague-Dawley rats in which CO(2) levels were monitored and maintained. Twenty-four hours after spinal hemisection, the ipsilateral phrenic nerve displayed no respiratory-related activity indicative of a functionally complete hemisection. Intravenous administration of the 5-HT(2A/2C)-receptor agonist (+/-)-2,5-dimethoxy-4-iodoamphetamine hydrochloride (DOI) induced respiratory-related activity in the phrenic nerve ipsilateral to hemisection under conditions in which CO(2) was maintained at constant levels and augmented the activity induced under conditions of hypercapnia. The effects of DOI were found to be dose dependent, and the recovery of activity could be maintained for up to 2 h after a single injection. DOI-induced recovery was attenuated by the 5-HT(2)-receptor antagonist ketanserin but not with the 5-HT(2C)-receptor antagonist RS-102221, suggesting that 5-HT(2A) and not necessarily 5-HT(2C) receptors may be involved in the induction of respiratory recovery after cervical spinal cord injury.

  7. EXCITATORY CONNECTIONS BETWEEN SPINAL MOTONEURONS IN THE ADULT RAT

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    Objectives. Dendro-dendritic and dendro-somatic projections are common between spinal motoneurons. We attempted to clarify whether there are functional connections through these projections.Methods. Motoneurons were antidromically stimulated by the muscle nerve and recorded intracellularly to examine the direct interaction between them, after the related dorsal roots had been cut.Results. Excitatory connections, demonstrated by depolarizing potentials in response to muscle nerve stimulation, were found between motoneurons innervating the same muscle or synergistic muscles, but never between motoneurons innervating antagonistic muscles. These potentials were finely graded in response to a series of increasing stimuli and resistant to high frequency (50Hz) stimulation.Conclusions.These results indicate that excitatory connections, with certain specificity of spatial and temporal distribution, occur in the spinal motoneurons. It is also suggested that electrical coupling should be involved in these connections and this mechanism should improve the excitability of the motoneurons in the same column.

  8. Gene transfer of GLT-1, a glial glutamate transporter, into the spinal cord by recombinant adenovirus attenuates inflammatory and neuropathic pain in rats

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    Nakagawa Takayuki

    2008-12-01

    Full Text Available Abstract Background The glial glutamate transporter GLT-1 is abundantly expressed in astrocytes and is crucial for glutamate removal from the synaptic cleft. Decreases in glutamate uptake activity and expression of spinal glutamate transporters are reported in animal models of pathological pain. However, the lack of available specific inhibitors and/or activators for GLT-1 makes it difficult to determine the roles of spinal GLT-1 in inflammatory and neuropathic pain. In this study, we examined the effect of gene transfer of GLT-1 into the spinal cord with recombinant adenoviruses on the inflammatory and neuropathic pain in rats. Results Intraspinal infusion of adenoviral vectors expressing the GLT-1 gene increased GLT-1 expression in the spinal cord 2–21 days after the infusion. Transgene expression was primarily localized to astrocytes. The spinal GLT-1 gene transfer had no effect on acute mechanical and thermal nociceptive responses in naive rats, whereas it significantly reduced the inflammatory mechanical hyperalgesia induced by hindlimb intraplantar injection of carrageenan/kaolin. Spinal GLT-1 gene transfer 7 days before partial sciatic nerve ligation recovered the extent of the spinal GLT-1 expression in the membrane fraction that was decreased following the nerve ligation, and prevented the induction of tactile allodynia. However, the partial sciatic nerve ligation-induced allodynia was not reversed when the adenoviruses were infused 7 or 14 days after the nerve ligation. Conclusion These results suggest that overexpression of GLT-1 on astrocytes in the spinal cord by recombinant adenoviruses attenuates the induction, but not maintenance, of inflammatory and neuropathic pain, probably by preventing the induction of central sensitization, without affecting acute pain sensation. Upregulation or functional enhancement of spinal GLT-1 could be a novel strategy for the prevention of pathological pain.

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

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    Xiaowen Jiang

    2016-01-01

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

  10. Effect of gabapentin on activation of glial cells in spinal cord after chronic constrictive injury to sciatic nerve in rats%加巴喷丁对神经病理性痛大鼠脊髓胶质细胞活化的影响

    Institute of Scientific and Technical Information of China (English)

    林福清; 杨小虎; 侯冷晨; 傅舒昆

    2010-01-01

    Objective To investigate the effect of gabapentin on the activation of glial cells in the spinal cord after chronic constrictive injury (CCI) to sciatic nerve in rats.Methods Twenty-four male SD rats weighing 180-220 g were randomly divided into 3 groups (n = 8 each): group Ⅰ sham operation (group S), group Ⅱ CCI and group Ⅲ gabapentin + CCI. Right sciatic nerve was exposed and 4 loose ligatures were placed with 6-0chromic catgut. Seven days after operation gabapentin 50 mg/kg in 5 ml was given by intragastric gavage twice a day for 5 days in group Ⅲ. Paw withdrawal threshold to mechanical stimulation with von Frey filaments was measured one day before (baseline) and at 7, 15 d after operation. The animals were killed at 15 d after operation. The lumbar segment L4-5 of the spinal cord was removed. Immunohistochemical double mark technique was used to detect the activation of astrocytes and microglias in the spinal cord. Results Paw withdrawal threshold to mechanical stimulation was significantly decreased on the 7th and 15th day after CCI operation in group CCI as compared with group S. After 5 day treatment with gabapentin, the withdrawal threshold to von Frey hair stimulation was significantly higher in group Ⅲ than in group Ⅱ . The activation of astrocytes and microglias in the spinal cord was significantly enhanced in group CCI as compared with group S. Treatment with gabapentin significantly inhibited CCI-induced activation of astrocytes and microglias in the spinal cord. ConclusionGabapentin reduces neuropathic pain by inhibiting activation of glial cells in the spinal cord.%目的 评价加巴喷丁对神经病理性痛大鼠脊髓胶质细胞活化的影响.方法 雄性SD大鼠24只,体重180~220 g,随机分为3组(n=8):假手术组(S组)、坐骨神经慢性压迫性损伤组(CCI组)和加巴喷丁组(G组).CCI组和G组采用坐骨神经慢性压迫性损伤法建立大鼠神经病理性痛模型;S组只暴露坐

  11. Altered prosaposin expression in the rat facial nerve nucleus following facial nerve transection and repair

    Institute of Scientific and Technical Information of China (English)

    Dong Wang; Wenlong Luo; Cuiying Zhou; Jingjing Li

    2009-01-01

    BACKGROUND: Studies have demonstrated that damaged facial nerves synthesize prosaposin to promote repair of facial neurons.OBJECTIVE: To observe time-course changes of prosaposin expression in the facial nerve nucleus of Sprague Dawley rats following facial nerve transection and repair.DESIGN, TIME AND SETTING: A randomized control neuropathological animal experiment was performed in Chongqing Medical University between March 2007 and September 2008.MATERIALS: A total of 48 adult, male, Sprague Dawley rats were selected and randomly divided into transection and transection + end-to-end anastomosis groups (n =24). Rabbit anti-rat prosaposin antibody, instant SABC immunohistochemical kit, and antibody dilution solution were purchased from Wuhan Uscn Science Co., Ltd., China.METHODS: In the transection group, the nerve trunk of the distal retroauricular branch of the left facial nerves was ligated in Sprague Dawley rats, and a 5-mm nerve trunk at the distal end of the ligation site was removed. In the transection + end-to-end anastomosis group, epineurial anastomosis was performed immediately following transection of the left facial nerves. The right facial nerves in the two groups sewed as the normal control group.MAIN OUTCOME MEASURES: The number of prosaposin-positive neurons, as well as intensity of immunostaining in facial nerve nucleus, following transection and end-to-end anastomosis were determined by immunohistochemistry at 1,3, 7, 14, 21, and 35 days after injury.RESULTS: Transection group: transection of facial nerves resulted in increased number of prosaposin-positive neurons and immunoreactivity intensity in the facial nucleus on day 1. These values significantly increased by day 3. Expression was greater than in the control side. The peak of the reduction was reached at 7 days post-surgery. Transection + end-to-end anastomosis group: the number of prosaposin-positive neurons and immunoreactivity intensity was reduced in the facial nerve nucleus following

  12. Degeneration and regeneration of motor and sensory nerves: a stereological study of crush lesions in rat facial and mental nerves

    DEFF Research Database (Denmark)

    Barghash, Ziad; Larsen, Jytte Overgaard; Al-Bishri, Awad

    2013-01-01

    The aim of this study was to evaluate the degeneration and regeneration of a sensory nerve and a motor nerve at the histological level after a crush injury. Twenty-five female Wistar rats had their mental nerve and the buccal branch of their facial nerve compressed unilaterally against a glass rod...... in the degenerative pattern; however, at day 19 the buccal branch had regenerated to the normal number of axons, whereas the mental nerve had only regained 50% of the normal number of axons. We conclude that the regenerative process is faster and/or more complete in the facial nerve (motor function) than...... for 30 s. Specimens of the compressed nerves and the corresponding control nerves were dissected at 3, 7, and 19 days after surgery. Nerve cross-sections were stained with osmium tetroxide and toluidine blue and analysed using two-dimensional stereology. We found differences between the two nerves both...

  13. High-frequency transcutaneous electrical nerve stimulation alters thermal but not mechanical allodynia following chronic constriction injury of the rat sciatic nerve.

    Science.gov (United States)

    Somers, D L; Clemente, F R

    1998-11-01

    To determine if daily transcutaneous electrical nerve stimulation (TENS) can alter the thermal and mechanical allodynia that develops after chronic constriction injury (CCI) to the right sciatic nerve of rats. A completely randomized experimental design was used. Four groups of rats underwent CCI surgery to the right sciatic nerve and either were not treated with TENS or received TENS starting at different times after the CCI surgery. TENS was delivered daily for 1 hour to CCI rats through self-adhesive electrodes applied to skin innervated by the right dorsal rami of lumbar spinal nerves L1-6. Rats of different groups received daily TENS starting immediately, 20 to 30 hours, or 3 days after the CCI surgery. Thermal and mechanical pain thresholds of hind paws were assessed bilaterally in all rats twice before the CCI surgery (baseline) and then 2, 7, 12, and 14 days after surgery. Thermal and mechanical allodynia were expressed as difference scores between the pain thresholds of right and left hind paws. These values were normalized to differences that existed between the two paws at baseline. Daily TENS beginning immediately after CCI surgery prevented the development of thermal allodynia at all assessment times (p < .05). Daily TENS starting 1 day after surgery reduced thermal allodynia, but only on days 2 and 14 (p < .05). Daily TENS beginning 3 days after surgery had no effect on the development of thermal allodynia. Regardless of when it was started, daily TENS did not consistently alter mechanical allodynia in CCI rats. It appears that daily TENS can prevent thermal but not mechanical allodynia in this model. However, early intervention with the treatment is critical if it is to be effective at all.

  14. Influence of tail vein administration of bone marrow mesenchymal stem cells on expression of brain-derived neurotrophic factor and nerve growth factor after spinal cord injury in rats%骨髓间充质干细胞尾静脉移植脊髓损伤大鼠脑源性神经营养因子及神经生长因子的表达

    Institute of Scientific and Technical Information of China (English)

    董锋; 林建华; 吴朝阳

    2011-01-01

    BACKGROUND: Transplantation of bone marrow mesenchymal stem cells has an effect on the treatment of spinal cord injury, but the mechanism is not fully understood.OBJECTIVE: To explore the influence of intravenous administration of bone marrow mesenchymal stem cells on expression of brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) after spinal cord injury in rats and to study possible mechanism of intravenous administration of bone marrow mesenchymal stem cells after spinal cord injury in adult rats.METHODS: Modified Allen method was applied to induce T 10 spinal cord injury to prepare rat models of paraplegia. There were 6 rats in sham operation group and 24 rats in injury group. Then, the injury group was randomly divided into transplantation group and control group. Rats in the sham operation and transplantation groups received tail vein transplantation of 1 mL bone marrow mesenchymal stem cells (1×106 cells), while those in the control group were treated with PBS.RESULTS AND CONCLUSION: After spinal cord injury in rats, the expression of BDNF and NGF was improved and advanced to increase via intravenous administration of bone marrow mesenchymal stem cells. Maybe it is one of the mechanisms of promoting restoration of injured spinal cord and improving motor function.%背景:骨髓间充质干细胞移植对脊髓损伤有治疗作用,但其机制尚不完全清楚.目的:应用免疫组织化学方法观察骨髓间充质干细胞静脉移植损伤脊髓局部脑源性神经营养因子及神经生长因子的表达,分析骨髓间充质干细胞移植治疗大鼠脊髓损伤的作用途径.方法:运用改良Allen 法制备T10 脊髓外伤性截瘫大鼠模型,假手术组6 只,脊髓损伤组24 只随机分为对照组和骨髓间充质干细胞移植组.骨髓间充质干细胞移植组、假手术组接受骨髓间充质干细胞单细胞悬液1 mL(1×106 cells)自大鼠尾静脉缓慢注射移植,对照组静脉注射PBS 1 mL.结果

  15. Ginsenoside Rg1 promotes peripheral nerve regeneration in rat model of nerve crush injury.

    Science.gov (United States)

    Ma, Junxiong; Li, Wenxian; Tian, Ruifeng; Lei, Wei

    2010-07-05

    Searching for effective drugs which are capable of promoting nerve regeneration after nerve injuries has gained extensive attention. Ginsenoside Rg1 (GRg1) is one of the bioactive compounds extracted from ginseng. GRg1 has been shown to be neuroprotective in many in vitro studies, which raises the possibility of using GRg1 as a neuroprotective agent after nerve injuries. However, such a possibility has never been tested in in vivo studies. The present study was designed to investigate the efficacy of GRg1 in promoting nerve regeneration after nerve crush injury in rats. All rats were randomly divided into four groups (n=8 in each group) after crush injury and were intraperitoneally administrated daily for 4 weeks with 1mg/kg, or 5mg/kg GRg1 (low or high dose GRg1 groups), or 100mug/kg mecobalamin or normal saline, respectively. The axonal regeneration was investigated by retrograde labeling and morphometric analysis. The motor functional recovery was evaluated by electrophysiological studies, behavioral tests and histological appearance of the target muscles. Our data showed that high dose GRg1 achieved better axonal regeneration and functional recovery than those achieved by low dose GRg1 and mecobalamin. The final outcome of low dose GRg1 and mecobalamin was similar in both morphological and functional items, which was significantly better than that in saline group. These findings show that GRg1 is capable of promoting nerve regeneration after nerve injuries, suggesting the possibility of developing GRg1 a neuroprotective drug for peripheral nerve repair applications.

  16. Vitamin A deficiency induces congenital spinal deformities in rats.

    Directory of Open Access Journals (Sweden)

    Zheng Li

    Full Text Available Most cases of congenital spinal deformities were sporadic and without strong evidence of heritability. The etiology of congenital spinal deformities is still elusive and assumed to be multi-factorial. The current study seeks to elucidate the effect of maternal vitamin A deficiency and the production of congenital spinal deformities in the offsping. Thirty two female rats were randomized into two groups: control group, which was fed a normal diet; vitamin A deficient group, which were given vitamin A-deficient diet from at least 2 weeks before mating till delivery. Three random neonatal rats from each group were killed the next day of parturition. Female rats were fed an AIN-93G diet sufficient in vitamin A to feed the rest of neonates for two weeks until euthanasia. Serum levels of vitamin A were assessed in the adult and filial rats. Anteroposterior (AP spine radiographs were obtained at week 2 after delivery to evaluate the presence of the skeletal abnormalities especially of spinal deformities. Liver and vertebral body expression of retinaldehyde dehydrogenase (RALDHs and RARs mRNA was assessed by reverse transcription-real time PCR. VAD neonates displayed many skeletal malformations in the cervical, thoracic, the pelvic and sacral and limbs regions. The incidence of congenital scoliosis was 13.79% (8/58 in the filial rats of vitamin A deficiency group and 0% in the control group. Furthermore, vitamin A deficiency negatively regulate the liver and verterbral body mRNA levels of RALDH1, RALDH2, RALDH3, RAR-α, RAR-β and RAR-γ. Vitamin A deficiency in pregnancy may induce congenital spinal deformities in the postnatal rats. The decreases of RALDHs and RARs mRNA expression induced by vitamin A deprivation suggest that vertebral birth defects may be caused by a defect in RA signaling pathway during somitogenesis.

  17. Neuroprotective effects of N-acetyl-cysteine and acetyl-L-carnitine after spinal cord injury in adult rats.

    Directory of Open Access Journals (Sweden)

    Amar Karalija

    Full Text Available Following the initial acute stage of spinal cord injury, a cascade of cellular and inflammatory responses will lead to progressive secondary damage of the nerve tissue surrounding the primary injury site. The degeneration is manifested by loss of neurons and glial cells, demyelination and cyst formation. Injury to the mammalian spinal cord results in nearly complete failure of the severed axons to regenerate. We have previously demonstrated that the antioxidants N-acetyl-cysteine (NAC and acetyl-L-carnitine (ALC can attenuate retrograde neuronal degeneration after peripheral nerve and ventral root injury. The present study evaluates the effects of NAC and ALC on neuronal survival, axonal sprouting and glial cell reactions after spinal cord injury in adult rats. Tibial motoneurons in the spinal cord were pre-labeled with fluorescent tracer Fast Blue one week before lumbar L5 hemisection. Continuous intrathecal infusion of NAC (2.4 mg/day or ALC (0.9 mg/day was initiated immediately after spinal injury using Alzet 2002 osmotic minipumps. Neuroprotective effects of treatment were assessed by counting surviving motoneurons and by using quantitative immunohistochemistry and Western blotting for neuronal and glial cell markers 4 weeks after hemisection. Spinal cord injury induced significant loss of tibial motoneurons in L4-L6 segments. Neuronal degeneration was associated with decreased immunostaining for microtubular-associated protein-2 (MAP2 in dendritic branches, synaptophysin in presynaptic boutons and neurofilaments in nerve fibers. Immunostaining for the astroglial marker GFAP and microglial marker OX42 was increased. Treatment with NAC and ALC rescued approximately half of the motoneurons destined to die. In addition, antioxidants restored MAP2 and synaptophysin immunoreactivity. However, the perineuronal synaptophysin labeling was not recovered. Although both treatments promoted axonal sprouting, there was no effect on reactive astrocytes

  18. Localization of Brain Natriuretic Peptide Immunoreactivity in Rat Spinal Cord

    Directory of Open Access Journals (Sweden)

    Essam M Abdelalim

    2016-12-01

    Full Text Available Brain natriuretic peptide (BNP exerts its functions through natriuretic peptide receptors. Recently, BNP has been shown to be involved in a wide range of functions. Previous studies reported BNP expression in the sensory afferent fibers in the dorsal horn of the spinal cord. However, BNP expression and function in the neurons of the central nervous system are still controversial. Therefore, in this study, we investigated BNP expression in the rat spinal cord in detail using RT-PCR and immunohistochemistry. RT-PCR analysis showed that BNP mRNA was present in the spinal cord and DRG. BNP immunoreactivity was observed in different structures of the spinal cord, including the neuronal cell bodies and neuronal processes. BNP immunoreactivity was observed in the dorsal horn of the spinal cord and in the neurons of the intermediate column and ventral horn. Double-immunolabeling showed a high level of BNP expression in the afferent fibers (laminae I-II labeled with calcitonin gene-related peptide (CGRP, suggesting BNP involvement in sensory function. In addition, BNP was co-localized with CGRP and choline acetyltransferase in the motor neurons of the ventral horn. Together, these results indicate that BNP is expressed in sensory and motor systems of the spinal cord, suggesting its involvement in several biological actions on sensory and motor neurons via its binding to NPR-A and/or NPR-B in the DRG and spinal cord.

  19. NERVE REGENERATION THROUGH A 2-PLY BIODEGRADABLE NERVE GUIDE IN THE RAT AND THE INFLUENCE OF ACTH4-9 NERVE GROWTH-FACTOR

    NARCIS (Netherlands)

    ROBINSON, PH; VANDERLEI, B; HOPPEN, HJ; LEENSLAG, JW; PENNINGS, AJ; NIEUWENHUIS, P

    1991-01-01

    Biodegradable polyurethane-based (PU) nerve guides, instilled with or without ACTH4-9 analog (a melanocortin) were used for bridging an 8 mm gap in the rat sciatic nerve and were evaluated for function and histological appearance after 16 weeks of implantation. Autologous nerve grafts functioned as

  20. Spinal pharmacology of tactile allodynia in diabetic rats

    OpenAIRE

    1997-01-01

    Rats develop tactile allodynia to stimulation of the plantar surface of the hindpaw with von Frey filaments within days of the onset of streptozotocin-induced diabetes. This is prevented by insulin and alleviated by systemic lignocaine, but the aetiology is unknown.Using indwelling lumbar intrathecal catheters to deliver pharmacological agents, we have investigated whether tactile allodynia in streptozotocin-diabetic rats is dependent on mechanisms associated with spinal sensitization, by ass...

  1. Mandibular branch of the facial nerve in wistar rats: new experimental model to assess facial nerve regeneration.

    Science.gov (United States)

    Bento, Ricardo Ferreira; Salomone, Raquel; Nascimento, Silvia Bona do; Ferreira, Ricardo Jose Rodriguez; Silva, Ciro Ferreira da; Costa, Heloisa Juliana Zabeu Rossi

    2014-07-01

    Introduction The ideal animal model for nerve regeneration studies is the object of controversy, because all models described by the literature have advantages and disadvantages. Objective To describe the histologic and functional patterns of the mandibular branch of the facial nerve of Wistar rats to create a new experimental model of facial nerve regeneration. Methods Forty-two male rats were submitted to a nerve conduction test of the mandibular branch to obtain the compound muscle action potential. Twelve of these rats had the mandibular branch surgically removed and submitted to histologic analysis (number, partial density, and axonal diameter) of the proximal and distal segments. Results There was no statistically significant difference in the functional and histologic variables studied. Conclusion These new histologic and functional standards of the mandibular branch of the facial nerve of rats establish an objective, easy, and greatly reproducible model for future facial nerve regeneration studies.

  2. Excitability changes in the sciatic nerve and triceps surae muscle after spinal cord injury in mice

    Directory of Open Access Journals (Sweden)

    Freedland Robert

    2010-04-01

    Full Text Available Abstract Background From the onset to the chronic phase of spinal cord injury (SCI, peripheral axons and muscles are subjected to abnormal states of activity. This starts with very intense spasms during the first instant of SCI, through a no activity flaccidity phase, to a chronic hyperactivity phase. It remains unclear how the nature of this sequence may affect the peripheral axons and muscles. Methods We set out to investigate the changes in excitability of the sciatic nerve and to characterize the properties of muscle contractility after contusive injury of the mouse thoracic spinal cord. Results The following changes were observed in animals after SCI: 1 The sciatic nerve compound action potential was of higher amplitudes and lower threshold, with the longer strength-duration time constant and faster conduction velocity; 2 The latency of the onset of muscle contraction of the triceps surae muscle was significantly shorter in animals with SCI; 3 The muscle twitches expressed slower rising and falling slopes, which were accompanied by prolonged contraction duration in SCI animals compared to controls. Conclusion These findings suggest that in peripheral nerves SCI promotes hyperexcitability, which might contribute to mechanisms of spastic syndrome.

  3. Electroacupuncture improves microcirculation and neuronal morphology in the spinal cord of a rat model of intervertebral disc extrusion

    Directory of Open Access Journals (Sweden)

    Dai-xun Jiang

    2015-01-01

    Full Text Available Most studies on spinal cord neuronal injury have focused on spinal cord tissue histology and the expression of nerve cell damage and repair-related genes. The importance of the microcirculation is often ignored in spinal cord injury and repair research. Therefore, in this study, we established a rat model of intervertebral disc extrusion by inserting a silica gel pad into the left ventral surface of T 13 . Electroacupuncture was used to stimulate the bilateral Zusanli point (ST36 and Neiting point (ST44 for 14 days. Compared with control animals, blood flow in the first lumbar vertebra (L 1 was noticeably increased in rats given electroacupuncture. Microvessel density in the T 13 segment of the spinal cord was increased significantly as well. The number of normal neurons was higher in the ventral horn of the spinal cord. In addition, vacuolation in the white matter was lessened. No obvious glial cell proliferation was visible. Furthermore, hindlimb motor function was improved significantly. Collectively, our results suggest that electroacupuncture can improve neuronal morphology and microcirculation, and promote the recovery of neurological functions in a rat model of intervertebral disc extrusion.

  4. Spinal pharmacology of tactile allodynia in diabetic rats

    Science.gov (United States)

    Calcutt, Nigel A; Chaplan, Sandra R

    1997-01-01

    Rats develop tactile allodynia to stimulation of the plantar surface of the hindpaw with von Frey filaments within days of the onset of streptozotocin-induced diabetes. This is prevented by insulin and alleviated by systemic lignocaine, but the aetiology is unknown.Using indwelling lumbar intrathecal catheters to deliver pharmacological agents, we have investigated whether tactile allodynia in streptozotocin-diabetic rats is dependent on mechanisms associated with spinal sensitization, by assessing the efficacy of agents that inhibit specific components of spinal nociceptive processing.Dose-dependent inhibition of tactile allodynia in diabetic rats was noted with the N-type calcium channel antagonist SNX 239, the α2-adrenoceptor agonist dexmedetomidine, the μ-opioid receptor agonist morphine, the N-methyl-D-aspartate (NMDA) receptor antagonist AP5 and the non-NMDA receptor antagonist NBQX.No effect on tactile allodynia was noted after intrathecal administration of the nitric oxide synthase inhibitor NG-nitro-L-arginine methyl ester (L-NAME), the cyclo-oxygenase inhibitor ketorolac, the L-type calcium channel inhibitor diltiazem or any vehicle.These data suggest that the tactile allodynia of diabetic rats involves spinal glutamatergic pathways but is not associated with spinal release of nitric oxide or prostaglandins. PMID:9421298

  5. Brief transvertebral electrical stimulation of the spinal cord improves the specificity of femoral nerve reinnervation.

    Science.gov (United States)

    Franz, Colin K; Singh, Bhagat; Martinez, Jose A; Zochodne, Douglas W; Midha, Rajiv

    2013-01-01

    Functional outcomes are generally poor following peripheral nerve injury (PNI). The reason is multifactorial but includes the misdirection of regenerating axons to inappropriate end organs. It has been shown that brief electrical stimulation (Estim) of nerves has the potential to improve the accuracy and rate of peripheral axon regeneration. The present study explores a novel percutaneous transvertebral approach to Estim, which was tested in the mouse femoral nerve model. Inspired by the protocol of Gordon and colleagues (ie, 20 Hz, for 1 hour), we applied Estim to the cervicothoracic spinal cord (SC-Estim) to remotely activate lumbar motor neurons following transection and repair of the femoral nerve. Fluorescent dyes were applied to the distal nerve to label reinnervating cells. Sections of nerve were taken to quantify the numbers of reinnervating axons as well as to stain for a known femoral axon guidance molecule-polysialylated neural cell adhesion molecule (PSA-NCAM). In comparison to sham treatment, SC-Estim led to significantly greater expression of PSA-NCAM as well as improved the specificity of motor reinnervation. Interestingly, although SC-Estim did not alter the number of early reinnervating (ie, pioneer) axons, there was a reduction in the number of retrogradely labeled neurons at 2 weeks postrepair. However, by 6 weeks postrepair, there was no difference in the number of neurons that had reinnervated the femoral nerve. The present findings support the development of SC-Estim as a novel approach to enhance the specificity of reinnervation and potentially improve functional outcomes following PNI.

  6. Antioxidation of melatonin against spinal cord injury in rats

    Institute of Scientific and Technical Information of China (English)

    刘锦波; 唐天驷; 杨惠林; 肖德生

    2004-01-01

    Background The iron catalyzed lipid peroxidation plays an important role in the autodestruction of the injured spinal cord. This study was to detect the antioxidation of melatonin against spinal cord injury (SCI) in rats.Methods Sity Sprague-Dawley rats were randomly divided into four groups: group A (n = 15) for laminectomyanly, group B (n = 15) for laminectomy with SCI, group C (n = 15) for SCI and intraperitoneal injection of a bolus of 100 mg/kg melatonin, and group D (n = 15) for SCI and intraperitoneal injection of saline containing 5% ethanol. The SCI of animal model was made using modified Allen's method on T12. Six rats of each group were sacrificed 4 hours after injury, and the levels of free iron and malondialdehyde (MDA) of the involved spinal cord segments were measured by the bleomycin assay and thiobarbituric acid (TBA) separately. Functional recovery of the spinal cord was assessed by Modified Tarlov's scale and the inclined plane method at 1,3, 7, 14, 21 days after SCI. The histologic changes of the damaged spinal cord were also examined at 7 days after SCl.Results After SCI, the levels of free iron and MDA were increased significantly and the modified Tarlov's score and inclined plane angle decreased significantly in groups B and D. In group C, the Tarlov's score and inclined plane angle were increased significantly at 7, 14 and 21 days, with histological improvement.Conclusion: Melatonin can reduce the level of lipid peroxidation and prevent damage to the spinal cord of rat.

  7. Transplantation of low-power laser-irradiated olfactory ensheathing cells to promote repair of spinal cord injury in rats

    Institute of Scientific and Technical Information of China (English)

    Haoxian Chen; Xinfeng Zheng; Weibin Sheng; Qin Wei; Tao Jiang; Gele Jin

    2009-01-01

    BACKGROUND: Previous studies have demonstrated that low-power laser (LPL) irradiation can promote the regeneration of peripheral nerves and central nerves, as well as influence cellular proliferation. Therefore, it is thought to be a potential treatment for spinal cord injury.OBJECTIVE: Utilizing histological observations and behavioral evaluations, the aim of this study was to investigate the influence of transplanted olfactory ensheathing cells (OECs), irradiated by LPL, on functional repair of rats following transversal spinal cord injury.DESIGN, TIME AND SETTING: A randomized, controlled, animal experiment was performed at the animal experimental center in the First Affiliated Hospital of Xinjiang Medical University between January 2007 and February 2008.MATERIALS: A total of 52 Sprague Dawley rats were included in this experiment. Twelve rats were used to harvest OECs, some of which were irradiated by LPL on days 3, 5, and 7 in culture.The remaining 40 rats were used to establish T12 complete spinal cord transection injury.DMEM/F12 medium was purchased from Sigma, USA, Fluorogold was provided by Chemicon,USA, and the LY/JG650-D500-16 low-power laser was produced by Xi'an Lingyue Electromechanical Science And Technology Co., Ltd., China.METHODS: The successful rat models were randomly divided into three groups: OEC transplantation, LPL-irradiated OEC transplantation, and control. These animals were microinjected with OEC suspension, LPL-irradiated OEC suspension, and DMEM/F12 medium(10 μL) respectively 4 weeks after spinal cord was completely transected at the T12 level.MAIN OUTCOME MEASURES: Spinal cord injury was observed using hematoxylin-eosin staining.Expression of nerve growth factor receptor p75 and glial fibrillary acidic protein were determined using immunohistochemical staining. Regeneration of spinal nerve fibers in rats was assayed by Fluorogold retrograde labeling method. Basso, Beattie and Bresnahan (BBB) scores were used to evaluate motor

  8. Histochemical discrimination of fibers in regenerating rat infraorbital nerve

    Science.gov (United States)

    Wilke, R. A.; Riley, D. A.; Sanger, J. R.

    1992-01-01

    In rat dorsal root ganglia, histochemical staining of carbonic anhydrase (CA) and cholinesterase (CE) yields a reciprocal pattern of activity: Sensory processes are CA positive and CE negative, whereas motor processes are CA negative and CE positive. In rat infraorbital nerve (a sensory peripheral nerve), we saw extensive CA staining of nearly 100% of the myelinated axons. Although CE reactivity in myelinated axons was extremely rare, we did observe CE staining of unmyelinated autonomic fibers. Four weeks after transection of infraorbital nerves, CA-stained longitudinal sections of the proximal stump demonstrated 3 distinct morphological zones. A fraction of the viable axons retained CA activity to within 2 mm of the distal extent of the stump, and the stain is capable of resolving growth sprouts being regenerated from these fibers. Staining of unmyelinated autonomic fibers in serial sections shows that CE activity was not retained as far distally as is the CA sensory staining.

  9. 早期干预ERK在脊髓的激活可阻断外周神经损伤引起的神经病理性疼痛的发生%Early intervention of ERK activation in the spinal cord can block initiation of peripheral nerve injury-induced neuropathic pain in rats

    Institute of Scientific and Technical Information of China (English)

    韩梅; 黄如一; 杜逸旻; 赵志奇; 张玉秋

    2011-01-01

    本文采用大鼠坐骨神经慢性压迫损伤引起的神经病理痛模型,研究脊髓背角细胞外信号调节激酶(extracellular signal-regulatedkinase,ERK)在外周神经损伤引起的神经病理疼痛发生中的作用.结果显示,单侧坐骨神经压迫性损伤后1天,大鼠损伤侧脊髓背角ERK的磷酸化(激活)水平显著上调,其下游转录因子cAMP反应原件结合蛋白(cAMP response elementbindingprotein,CREB)在双侧脊髓背角的激活水平也同时上调,而此时由神经损伤引起的痛觉敏化行为尚未出现.神经损伤之前和损伤后早期鞘内给予促分裂原活化蛋白激酶激酶(mitogen-activated protein kinase kinase,MEK)的抑制剂UO126,可阻断和延迟坐骨神经损伤引起的触诱发痛和热痛觉过敏行为的发生.这些结果提示,脊髓背角ERK-CREB信号的激活参与外周神经损伤引起的神经病理疼痛的发生,对该信号通路的早期十预可能是控制神经病理性疼痛的重要手段.%The present study is to investigate whether the extracellular signal-regulated kinase (ERK) and cAMP response element binding protein (CREB) signaling pathway contributes to the initiation of chronic constriction injury (CCI)-induced neuropathic pain in rats. Mechanical allodynia was assessed by measuring the hindpaw withdrawal threshold in response to a calibrated series of von Frey hairs. Thermal hyperalgesia was assessed by measuring the latency of paw withdrawal in response to a radiant heat source. The expressions of phosphor-ERK (pERK) and phosphor-CREB (pCREB) were examined using Western blot analysis and immunohistochemistry. An early robust increase in the expression of pERK on the spinal cords ipsilateral to injury was observed on day 1 after CCI, when the CCl-induced behavioral hypersensitivity had not developed yet. Moreover, the upregulation of pERK expression in ip-silateral spinal cord was associated with the increase in pCREB expression in bilateral spinal cord

  10. Nerve Growth Factor Decreases in Sympathetic and Sensory Nerves of Rats with Chronic Heart Failure

    Science.gov (United States)

    Lu, Jian

    2014-01-01

    Nerve growth factor (NGF) plays a critical role in the maintenance and survival of both sympathetic and sensory nerves. Also, NGF can regulate receptor expression and neuronal activity in the sympathetic and sensory neurons. Abnormalities in NGF regulation are observed in patients and animals with heart failure (HF). Nevertheless, the effects of chronic HF on the levels of NGF within the sympathetic and sensory nerves are not known. Thus, the ELISA method was used to assess the levels of NGF in the stellate ganglion (SG) and dorsal root ganglion (DRG) neurons of control rats and rats with chronic HF induced by myocardial infarction. Our data show for the first time that the levels of NGF were significantly decreased (P < 0.05) in the SG and DRG neurons 6–20 weeks after ligation of the coronary artery. In addition, a close relation was observed between the NGF levels and the left ventricular function. In conclusion, chronic HF impairs the expression of NGF in the sympathetic and sensory nerves. Given that sensory afferent nerves are engaged in the sympathetic nervous responses to somatic stimulation (i.e. muscle activity during exercise) via a reflex mechanism, our data indicate that NGF is likely responsible for the development of muscle reflex-mediated abnormal sympathetic responsiveness observed in chronic HF. PMID:24913185

  11. H-reflex up-conditioning encourages recovery of EMG activity and H-reflexes after sciatic nerve transection and repair in rats.

    Science.gov (United States)

    Chen, Yi; Wang, Yu; Chen, Lu; Sun, Chenyou; English, Arthur W; Wolpaw, Jonathan R; Chen, Xiang Yang

    2010-12-01

    Operant conditioning of the spinal stretch reflex or its electrical analog, the H-reflex, produces spinal cord plasticity and can thereby affect motoneuron responses to primary afferent input. To explore whether this conditioning can affect the functional outcome after peripheral nerve injury, we assessed the effect of up-conditioning soleus (SOL) H-reflex on SOL and tibialis anterior (TA) function after sciatic nerve transection and repair. Sprague Dawley rats were implanted with EMG electrodes in SOL and TA and stimulating cuffs on the posterior tibial nerve. After control data collection, the sciatic nerve was transected and repaired and the rat was exposed for 120 d to continued control data collection (TC rats) or SOL H-reflex up-conditioning (TU rats). At the end of data collection, motoneurons that had reinnervated SOL and TA were labeled retrogradely. Putative primary afferent terminals [i.e., terminals containing vesicular glutamate transporter-1 (VGLUT1)] on SOL motoneurons were studied immunohistochemically. SOL (and probably TA) background EMG activity recovered faster in TU rats than in TC rats, and the final recovered SOL H-reflex was significantly larger in TU than in TC rats. TU and TC rats had significantly fewer labeled motoneurons and higher proportions of double-labeled motoneurons than untransected rats. VGLUT1 terminals were significantly more numerous on SOL motoneurons of TU than TC rats. Combined with the larger H-reflexes in TU rats, this anatomical finding supports the hypothesis that SOL H-reflex up-conditioning strengthened primary afferent reinnervation of SOL motoneurons. These results suggest that H-reflex up-conditioning may improve functional recovery after nerve injury and repair.

  12. Somatic modulation of spinal reflex bladder activity mediated by nociceptive bladder afferent nerve fibers in cats.

    Science.gov (United States)

    Xiao, Zhiying; Rogers, Marc J; Shen, Bing; Wang, Jicheng; Schwen, Zeyad; Roppolo, James R; de Groat, William C; Tai, Changfeng

    2014-09-15

    The goal of the present study was to determine if supraspinal pathways are necessary for inhibition of bladder reflex activity induced by activation of somatic afferents in the pudendal or tibial nerve. Cats anesthetized with α-chloralose were studied after acute spinal cord transection at the thoracic T9/T10 level. Dilute (0.25%) acetic acid was used to irritate the bladder, activate nociceptive afferent C-fibers, and trigger spinal reflex bladder contractions (amplitude: 19.3 ± 2.9 cmH2O). Hexamethonium (a ganglionic blocker, intravenously) significantly (P irritation. Understanding the sites of action for PNS or TNS inhibition is important for the clinical application of pudendal or tibial neuromodulation to treat bladder dysfunctions. Copyright © 2014 the American Physiological Society.

  13. Electrical stimulation modulates injury potentials in rats after spinal cord injury*

    Institute of Scientific and Technical Information of China (English)

    Guanghao Zhang; Xiaolin Huo; Aihua Wang; Changzhe Wu; Cheng Zhang; Jinzhu Bai

    2013-01-01

    An injury potential is the direct current potential difference between the site of spinal cord injury and the healthy nerves. Its initial amplitude is a significant indicator of the severity of spinal cord injury, and many cations, such as sodium and calcium, account for the major portion of injury potentials. This injury potential, as wel as injury current, can be modulated by direct current field stimulation;however, the appropriate parameters of the electrical field are hard to define. In this paper, injury potential is used as a parameter to adjust the intensity of electrical stimulation. Injury potential could be modulated to slightly above 0 mV (as the anode-centered group) by placing the anodes at the site of the injured spinal cord and the cathodes at the rostral and caudal sections, or around-70 mV, which is resting membrane potential (as the cathode-centered group) by reversing the polarity of electrodes in the anode-centered group. In addition, rats receiving no electrical stimulation were used as the control group. Results showed that the absolute value of the injury potentials acquired after 30 minutes of electrical stimulation was higher than the control group rats and much lower than the initial absolute value, whether the anodes or the cathodes were placed at the site of injury. This phenomenon il ustrates that by changing the polarity of the electrical field, electrical stimulation can effectively modulate the injury potentials in rats after spinal cord injury. This is also beneficial for the spontaneous repair of the cel membrane and the reduction of cation influx.

  14. Electrical stimulation modulates injury potentials in rats after spinal cord injury.

    Science.gov (United States)

    Zhang, Guanghao; Huo, Xiaolin; Wang, Aihua; Wu, Changzhe; Zhang, Cheng; Bai, Jinzhu

    2013-09-25

    An injury potential is the direct current potential difference between the site of spinal cord injury and the healthy nerves. Its initial amplitude is a significant indicator of the severity of spinal cord injury, and many cations, such as sodium and calcium, account for the major portion of injury potentials. This injury potential, as well as injury current, can be modulated by direct current field stimulation; however, the appropriate parameters of the electrical field are hard to define. In this paper, injury potential is used as a parameter to adjust the intensity of electrical stimulation. Injury potential could be modulated to slightly above 0 mV (as the anode-centered group) by placing the anodes at the site of the injured spinal cord and the cathodes at the rostral and caudal sections, or around -70 mV, which is resting membrane potential (as the cathode-centered group) by reversing the polarity of electrodes in the anode-centered group. In addition, rats receiving no electrical stimulation were used as the control group. Results showed that the absolute value of the injury potentials acquired after 30 minutes of electrical stimulation was higher than the control group rats and much lower than the initial absolute value, whether the anodes or the cathodes were placed at the site of injury. This phenomenon illustrates that by changing the polarity of the electrical field, electrical stimulation can effectively modulate the injury potentials in rats after spinal cord injury. This is also beneficial for the spontaneous repair of the cell membrane and the reduction of cation influx.

  15. Variable spatial magnetic field influences peripheral nerves regeneration in rats.

    Science.gov (United States)

    Suszyński, Krzysztof; Marcol, Wiesław; Szajkowski, Sebastian; Pietrucha-Dutczak, Marita; Cieślar, Grzegorz; Sieroń, Aleksander; Lewin-Kowalik, Joanna

    2014-09-01

    Generator of spatial magnetic field is one of most recent achievements among the magnetostimulators. This apparatus allows to obtain the rotating magnetic field. This new method may be more effective than other widely used techniques of magnetostimulation and magnetotherapy. We investigated the influence of alternating, spatial magnetic field on the regeneration of the crushed rat sciatic nerves. Functional and morphological evaluations were used. After crush injury of the right sciatic nerve, Wistar C rats (n = 80) were randomly divided into four groups (control and three experimental). The experimental groups (A, B, C) were exposed (20 min/day, 5 d/week, 4 weeks) to alternating spatial magnetic field of three different intensities. Sciatic Functional Index (SFI) and tensometric assessments were performed every week after nerve crush. Forty-eight hours before the sacrificing of animals, DiI (1,1'-di-octadecyl-3,3,3',3'-tetramethyloindocarbocyanine perchlorate) was applied 5 mm distally to the crush site. Collected nerves and dorsal root ganglia (DRG) were subjected to histological and immunohistochemical staining. The survival rate of DRG neurons was estimated. Regrowth and myelination of the nerves was examined. The results of SFI and tensometric assessment showed improvement in all experimental groups as compared to control, with best outcome observed in group C, exposed to the strongest magnetic field. In addition, DRG survival rate and nerve regeneration intensity were significantly higher in the C group. Above results indicate that strong spatial alternating magnetic field exerts positive effect on peripheral nerve regeneration and its application could be taken under consideration in the therapy of injured peripheral nerves.

  16. Impaired formalin-evoked changes of spinal amino acid levels in diabetic rats.

    Science.gov (United States)

    Malmberg, Annika B; O'Connor, William T; Glennon, Jeffery C; Ceseña, Rose; Calcutt, Nigel A

    2006-10-18

    To investigate mechanisms by which diabetes alters sensory processing, we measured levels of amino acid neurotransmitters in spinal dialysates from awake, unrestrained control and diabetic rats under resting conditions and following hind paw formalin injection. Under resting conditions, glutamate concentrations in spinal dialysates were significantly (Phyperalgesia in diabetic rats does not appear to be secondary to enhanced glutamatergic input to the spinal cord.

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

    Science.gov (United States)

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

    2016-09-01

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

  18. Repetitive magnetic stimulation affects the microenvironment of nerve regeneration and evoked potentials after spinal cord injury.

    Science.gov (United States)

    Jiang, Jin-Lan; Guo, Xu-Dong; Zhang, Shu-Quan; Wang, Xin-Gang; Wu, Shi-Feng

    2016-05-01

    Repetitive magnetic stimulation has been shown to alter local blood flow of the brain, excite the corticospinal tract and muscle, and induce motor function recovery. We established a rat model of acute spinal cord injury using the modified Allen's method. After 4 hours of injury, rat models received repetitive magnetic stimulation, with a stimulus intensity of 35% maximum output intensity, 5-Hz frequency, 5 seconds for each sequence, and an interval of 2 minutes. This was repeated for a total of 10 sequences, once a day, 5 days in a week, for 2 consecutive weeks. After repetitive magnetic stimulation, the number of apoptotic cells decreased, matrix metalloproteinase 9/2 gene and protein expression decreased, nestin expression increased, somatosensory and motor-evoked potentials recovered, and motor function recovered in the injured spinal cord. These findings confirm that repetitive magnetic stimulation of the spinal cord improved the microenvironment of neural regeneration, reduced neuronal apoptosis, and induced neuroprotective and repair effects on the injured spinal cord.

  19. Repetitive magnetic stimulation affects the microenvironment of nerve regeneration and evoked potentials after spinal cord injury

    Directory of Open Access Journals (Sweden)

    Jin-lan Jiang

    2016-01-01

    Full Text Available Repetitive magnetic stimulation has been shown to alter local blood flow of the brain, excite the corticospinal tract and muscle, and induce motor function recovery. We established a rat model of acute spinal cord injury using the modified Allen′s method. After 4 hours of injury, rat models received repetitive magnetic stimulation, with a stimulus intensity of 35% maximum output intensity, 5-Hz frequency, 5 seconds for each sequence, and an interval of 2 minutes. This was repeated for a total of 10 sequences, once a day, 5 days in a week, for 2 consecutive weeks. After repetitive magnetic stimulation, the number of apoptotic cells decreased, matrix metalloproteinase 9/2 gene and protein expression decreased, nestin expression increased, somatosensory and motor-evoked potentials recovered, and motor function recovered in the injured spinal cord. These findings confirm that repetitive magnetic stimulation of the spinal cord improved the microenvironment of neural regeneration, reduced neuronal apoptosis, and induced neuroprotective and repair effects on the injured spinal cord.

  20. Glatiramer acetate immune system augmentation for peripheral nerve regeneration in rat crushed sciatic nerve model.

    Science.gov (United States)

    Luria, Shai; Waitayawinyu, Thanapong; Conniff, James; Morton, H Josette; Nemechek, Nicholas M; Sonnen, Joshua A; Katolik, Leonid I; Trumble, Thomas E

    2010-02-01

    Protective antiself response to nervous system injury has been reported to be mediated by a T-cell subpopulation that can recognize self-antigens. Immune cells have been shown to play a role in the regulation of motor neuron survival after a peripheral nerve injury. The objective of the present study was to evaluate the effects of immune system augmentation with use of the antigen glatiramer acetate, which is known to affect T-cell immunity, on peripheral nerve regeneration. Wild-type and nude-type (T-cell-deficient) rats underwent crush injury of the sciatic nerve. Three and six weeks after the injury, the sciatic nerve was examined, both functionally (on the basis of footprint analysis and the tibialis anterior muscle response and weight) and histologically (on the basis of axon count). Significantly greater muscle responses were measured after three weeks in the group of wild-type rats that were treated with glatiramer acetate (control limb:injured limb ratio, 0.05 for the glatiramer acetate group [n = 9], compared with 0.51 for the saline solution group [n = 8]; p < 0.05). Higher axon counts were also found in this group (control limb:injured limb ratio, -0.07 for the glatiramer acetate group [n = 10], compared with 0.29 for the saline solution group [n = 8]; p < 0.05). The nude-type rats showed no response to the intervention after three weeks but showed a delayed response after six weeks. A second dose of glatiramer acetate, delivered forty-eight hours after the injury, did not result in an improved response as compared with the control groups. We found that a single treatment with glatiramer acetate resulted in accelerated functional and histological recovery after sciatic nerve crush injury. The role of T-cell immunity in the mechanism of glatiramer acetate was suggested by the partial and late response found in the T-cell-deficient rats.

  1. Percutaneous peripheral nerve stimulation for treatment of shoulder pain after spinal cord injury: A case report.

    Science.gov (United States)

    Mehech, Daniela; Mejia, Melvin; Nemunaitis, Gregory A; Chae, John; Wilson, Richard D

    2017-03-17

    This describes the first person with spinal cord injury (SCI) treated with percutaneous peripheral nerve stimulation for chronic shoulder pain. From baseline to one-week after treatment, the subject's worst pain in the last week, rated on a 0-10 numerical rating scale (BPI-SF3), decreased by 44%. Pain interference decreased and remained below baseline 12 weeks after the end of treatment. There was an associated improvement in the mental component of quality of life. This case demonstrates the feasibility of treating shoulder pain in patients with SCI with percutaneous PNS. To demonstrate efficacy further studies are required.

  2. Morphological differences in skeletal muscle atrophy of rats with motor nerve and/or sensory nerve injury

    Institute of Scientific and Technical Information of China (English)

    Lei Zhao; Guangming Lv; Shengyang Jiang; Zhiqiang Yan; Junming Sun; Ling Wang; Donglin Jiang

    2012-01-01

    Skeletal muscle atrophy occurs after denervation. The present study dissected the rat left ventral root and dorsal root at L4-6 or the sciatic nerve to establish a model of simple motor nerve injury, sensory nerve injury or mixed nerve injury. Results showed that with prolonged denervation time, rats with simple motor nerve injury, sensory nerve injury or mixed nerve injury exhibited abnormal behavior, reduced wet weight of the left gastrocnemius muscle, decreased diameter and cross-sectional area and altered ultrastructure of muscle cells, as well as decreased cross-sectional area and increased gray scale of the gastrocnemius muscle motor end plate. Moreover, at the same time point, the pathological changes were most severe in mixed nerve injury, followed by simple motor nerve injury, and the changes in simple sensory nerve injury were the mildest. These findings indicate that normal skeletal muscle morphology is maintained by intact innervation. Motor nerve injury resulted in larger damage to skeletal muscle and more severe atrophy than sensory nerve injury. Thus, reconstruction of motor nerves should be considered first in the clinical treatment of skeletal muscle atrophy caused by denervation.

  3. Combining peripheral nerve grafts and chondroitinase promotes functional axonal regeneration in the chronically injured spinal cord.

    Science.gov (United States)

    Tom, Veronica J; Sandrow-Feinberg, Harra R; Miller, Kassi; Santi, Lauren; Connors, Theresa; Lemay, Michel A; Houlé, John D

    2009-11-25

    Because there currently is no treatment for spinal cord injury, most patients are living with long-standing injuries. Therefore, strategies aimed at promoting restoration of function to the chronically injured spinal cord have high therapeutic value. For successful regeneration, long-injured axons must overcome their poor intrinsic growth potential as well as the inhibitory environment of the glial scar established around the lesion site. Acutely injured axons that regenerate into growth-permissive peripheral nerve grafts (PNGs) reenter host tissue to mediate functional recovery if the distal graft-host interface is treated with chondroitinase ABC (ChABC) to cleave inhibitory chondroitin sulfate proteoglycans in the scar matrix. To determine whether a similar strategy is effective for a chronic injury, we combined grafting of a peripheral nerve into a highly relevant, chronic, cervical contusion site with ChABC treatment of the glial scar and glial cell line-derived neurotrophic factor (GDNF) stimulation of long-injured axons. We tested this combination in two grafting paradigms: (1) a peripheral nerve that was grafted to span a chronic injury site or (2) a PNG that bridged a chronic contusion site with a second, more distal injury site. Unlike GDNF-PBS treatment, GDNF-ChABC treatment facilitated axons to exit the PNG into host tissue and promoted some functional recovery. Electrical stimulation of axons in the peripheral nerve bridge induced c-Fos expression in host neurons, indicative of synaptic contact by regenerating fibers. Thus, our data demonstrate, for the first time, that administering ChABC to a distal graft interface allows for functional axonal regeneration by chronically injured neurons.

  4. The inhibitory effects of pudendal nerve stimulation on bladder overactivity in spinal cord injury dogs: is early stimulation necessary?

    Science.gov (United States)

    Chen, Guoqing; Liao, Limin; Dong, Qian; Ju, Yanhe

    2012-01-01

    To determine the inhibitory effects of pudendal nerve stimulation (5 Hz) on bladder overactivity at early and late stages of spinal cord injury in dogs. The study was performed in eight dogs with chronic spinal cord transection at the T9-T10 level. Group 1 (four dogs) underwent electrical stimulation of pudendal nerve one month after spinal cord transection. Group 2 (four dogs) underwent stimulation six months after spinal cord transection. The bladders were removed for histological examination of fibrosis after the stimulation. The bladder capacity and the compliance were significantly increased (p stimulation in group 1, but not in group 2. The nonvoiding contractions were inhibited in both groups by electrical stimulation. Collagen fiber was increased, while elastic fiber was significantly decreased (p stimulation can increase the bladder capacity and compliance only during the early period before the bladder wall becomes fibrosit and can inhibit the nonvoiding contraction during two stages. © 2012 International Neuromodulation Society.

  5. Antinociceptive effect of ambroxol in rats with neuropathic spinal cord injury pain

    Science.gov (United States)

    Hama, Aldric T.; Plum, Ann Woodhouse; Sagen, Jacqueline

    2010-01-01

    Symptoms of neuropathic spinal cord injury (SCI) pain include evoked cutaneous hypersensitivity and spontaneous pain, which can be present below the level of the injury. Adverse side-effects obtained with currently available analgesics complicate effective pain management in SCI patients. Voltage-gated Na+ channels expressed in primary afferent nociceptors have been identified to mediate persistent hyperexcitability in dorsal root ganglia (DRG) neurons, which in part underlies the symptoms of nerve injury-induced pain. Ambroxol has previously demonstrated antinociceptive effects in rat chronic pain models and has also shown to potently block Na+ channel current in DRG neurons. Ambroxol was tested in rats that underwent a mid-thoracic spinal cord compression injury. Injured rats demonstrated robust hind paw (below-level) heat and mechanical hypersensitivity. Orally administered ambroxol significantly attenuated below-level hypersensitivity at doses that did not affect performance on the rotarod test. Intrathecal injection of ambroxol did not ameliorate below-level hypersensitivity. The current data suggest that ambroxol could be effective for clinical neuropathic SCI pain. Furthermore, the data suggests that peripherally expressed Na+ channels could lend themselves as targets for the development of pharmacotherapies for SCI pain. PMID:20732348

  6. Spinal translocator protein (TSPO) modulates pain behavior in rats with CFA-induced monoarthritis.

    Science.gov (United States)

    Hernstadt, Hayley; Wang, Shuxing; Lim, Grewo; Mao, Jianren

    2009-08-25

    Translocator protein 18 kDa (TSPO), previously known as the peripheral benzodiazepine receptor (PBR), is predominantly located in the mitochondrial outer membrane and plays an important role in steroidogenesis, immunomodulation, cell survival and proliferation. Previous studies have shown an increased expression of TSPO centrally in neuropathology, as well as in injured nerves. TSPO has also been implicated in modulation of nociception. In the present study, we examined the hypothesis that TSPO is involved in the initiation and maintenance of inflammatory pain using a rat model of Complete Freund's Adjuvant (CFA)-induced monoarthritis of the tibio-tarsal joint. Immunohistochemistry was performed using Iba-1 (microglia), NeuN (neurons), anti-Glial Fibrillary Acidic Protein, GFAP (astrocytes) and anti-PBR (TSPO) on Days 1, 7 and 14 after CFA-induced arthritis. Rats with CFA-induced monoarthritis showed mechanical allodynia and thermal hyperalgesia on the ipsilateral hindpaw, which correlated with the increased TSPO expression in ipsilateral laminae I-II on all experimental days. Iba-1 expression in the ipsilateral dorsal horn was also increased on Days 7 and 14. Moreover, TSPO was colocalized with Iba-1, GFAP and NeuN within the spinal cord dorsal horn. The TSPO agonist Ro5-4864, given intrathecally, dose-dependently retarded or prevented the development of mechanical allodynia and thermal hyperalgesia in rats with CFA-induced monoarthritis. These findings provide evidence that spinal TSPO is involved in the development and maintenance of inflammatory pain behaviors in rats. Thus, spinal TSPO may present a central target as a complementary therapy to reduce inflammatory pain.

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

    Science.gov (United States)

    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.

  8. Spinal cord decompression reduces rat neural cell apoptosis secondary to spinal cord injury

    Institute of Scientific and Technical Information of China (English)

    Kan XU; Qi-xin CHEN; Fang-cai LI; Wei-shan CHEN; Min LIN; Qiong-hua WET

    2009-01-01

    Objective: To determine whether spinal cord decompression plays a role in neural cell apoptosis after spinal cord injury. Study design: We used an animal model of compressive spinal cord injury with incomplete paraparesis to evaluate neural cell apoptosis after decompression. Apoptosis and cellular damage were assessed by staining with terminal deoxynucleotidyl transferase (TdT)-mediated deoxyuridine triphosphate nick-end labelling (TUNEL) and immunostaining for caspase-3, Bcl-2 and Bax. Methods: Experiments were conducted in male Spragne-Dawley rats (n=78) weighing 300-400 g. The spinal cord was compressed posteriorly at T10 level using a custom-made screw for 6 h, 24 h or continuously, followed by decompression by removal of the screw. The rats were sacrificed on Day 1 or 3 or in Week 1 or 4 post-decompression. The spinal cord was removed en bloc and examined at lesion site, rostral site and caudal site (7.5 mm away from the lesion). Results: The numbers of TUNEL-positive cells were significantly lower at the site of decompression on Day l, and also at the rostral and caudal sites between Day 3 and Week 4 post-decompression, compared with the persistently compressed group. The numbers of cells between Day 1 and Week 4 were immunoreactive to caspase-3 and B-cell lymphoma-2 (Bcl-2)-associated X-protein (Bax), but not to Bcl-2, correlated with those of TUNEL-positive cells. Conclusion: Our results suggest that decompression reduces neural cell apoptosis following spinal cord injury.

  9. Effects of Epidural Spinal Cord Stimulation and Treadmill Training on Locomotion Function and Ultrastructure of Spinal Cord Anterior Horn after Moderate Spinal Cord Injury in Rats

    Institute of Scientific and Technical Information of China (English)

    WANG Yizhao; HUANG Xiaolin; XU Jiang; XU Tao; FANG Zhengyu; XU Qi; TU Xikai; YANG Peipei

    2009-01-01

    Objective:To investigate the effects of epidural spinal cord stimulation (ESCS) and treadmill training on the locomotion function and ultrastructure of spinal cord anterior horn after moderate spinal cord injury in rats. (IT, n=3). All rats received a moderate spinal cord injury surgery. Four weeks after surgery, rats in SE group received an electrode implantation procedure, with the electrode field covering spinal cord segments L2-S1. Four weeks after electrode implantation, rats received subthreshold ESCS for 30 min/d. Rats in TY group received 4cm/s treadmill training for 30min/d. Rats in SI group received no intervention, as a control group. All procedures in these three groups lasted four weeks.The open field Basso,Beattie and Bresnahan (BBB) scale was used before and after intervention to evaluate rats' hindlimb motor function. Result:After four weeks intervention, rats in TT group improved their open field locomotion scores to 20. In contrast, no significant improvement was observed in groups SI and SE. The morphology of synapses and neurons were similar regardless of whether rats had undergone ESCS, treadmill training or not. Conclusion:ESCS alone was not sufficient to improve the walking ability of spinal cord injured rats. ESCS or treadmill training alone might not contribute to the changes of ultrastructure in anterior horn of spinal cord that underlie the recovery of walking ability. Further research is needed to understand the contributions of combination of ESCS and treadmill training to the rehabilitation of spinal cord injured rats.

  10. The comparison of combined femoral-sciatic nerve block with spinal anesthesia at lower extremity surgery

    Directory of Open Access Journals (Sweden)

    Selim Almaz

    2014-06-01

    Full Text Available Introduction: In this study, we aimed to compare the spinal anesthesia technique with combined femoral-sciatic block technique in patients undergoing lower limb surgery. Methods: In this study, after obtaining the approval of the Dicle University Faculty of Medicine Ethics Committee, scheduled for elective lower extremity surgery, the ASA 1-2 groups, between the ages of 18-65, 60 patients were enrolled. Study was planned as a prospective, randomized and controlled. Patients were randomly divided into 2 groups as the spinal anesthesia (Group S and combined sciatic-femoral nerve block (Group CSF to be. Results: Demographic data similar between the groups (p> 0.05. The implementation period of the technique was long in the Group CSF compared with in the Group S (p <0.001. Surgery delivery time was shorter in the Group S compared with in the Group CSF (p <0.001. The time of motor block occurrence was longer in the Group CSF compared with in the Group S (p <0.001. The duration of motor block was long in the Group CSF compared with in the Group S (p <0.001. Conclusion: The each of two methods is safe and effective in lower extremity orthopedic surgery, but the application of peripheral nerve block to provide the long-term advantages such as postoperative analgesia and reducing postoperative analgesic consumption. J Clin Exp Invest 2014; 5 (2: 443-446

  11. Impulse magnetic stimulation facilitates synaptic regeneration in rats following sciatic nerve injury

    Institute of Scientific and Technical Information of China (English)

    Sergey A. Zhivolupov; Miroslav M. Odinak; Nariman A. Rashidov; Ludmila S. Onischenko; Igor N. Samartsev; Anton A. Jurin

    2012-01-01

    The current studies describing magnetic stimulation for treatment of nervous system diseases mainly focus on transcranial magnetic stimulation and rarely focus on spinal cord magnetic stimula-tion. Spinal cord magnetic stimulation has been confirmed to promote neural plasticity after injuries of spinal cord, brain and peripheral nerve. To evaluate the effects of impulse magnetic stimulation of the spinal cord on peripheral nerve regneration, we compressed a 3 mm segment located in the middle third of the hip using a sterilized artery forceps to induce ischemia. Then, all animals un-derwent impulse magnetic stimulation of the lumbar portion of spinal crod and spinal nerve roots daily for 1 month. Electron microscopy results showed that in and below the injuryed segment, the inflammation and demyelination of neural tissue were alleviated, apoptotic cells were reduced, and injured Schwann cells and myelin fibers were repaired. These findings suggest that high-frequency impulse magnetic stimulation of spinal cord and corresponding spinal nerve roots promotes synaptic regeneration following sciatic nerve injury.

  12. Synergistic effects of bone mesenchymal stem cells and chondroitinase ABC on nerve regeneration after acellular nerve allograft in rats.

    Science.gov (United States)

    Wang, Ying; Jia, Hua; Li, Wen-Yuan; Tong, Xiao-Jie; Liu, Gui-Bo; Kang, Si-Wen

    2012-04-01

    This study aimed to evaluate whether combination therapy of bone marrow stromal cells (BMSCs) transplantation and chondroitinase ABC (ChABC) treatment further enhances axonal regeneration and functional recovery after acellular nerve allograft repair of the sciatic nerve gap in rats. Eight Sprague-Dawley rats were used as nerve donors, and 32 Wistar rats were randomly divided into four groups: Group I: acellular rat sciatic nerve (ARSN) group; Group II: ChABC treatment; Group III: BMSCs transplantation; and Group IV: ChABC treatment and BMSCs transplantation. The results showed that compared with ARSN control group, BMSC transplantation promoted axonal regeneration, the secretion of neural trophic factors NGF, BDNF and axon angiogenesis in nerve graft. ChABC treatment degraded chondroitin sulfate proteoglycans in ARSN in vitro and in vivo and improved BMSCs survival in ARSN. The combination therapy caused much better beneficial effects evidenced by increasing sciatic function index, nerve conduction velocity, restoration rate of tibialis anterior wet muscle weight, and myelinated nerve number, but did not further boost the therapeutic effects on neurotrophic factor production, axon angiogenesis, and sensory functional recovery by BMSC transplantation. Taken together, for the first time, we demonstrate the synergistic effects of BMSC transplantation and BMSCs treatment on peripheral nerve regeneration, and our findings may help establish novel strategies for cell transplantation therapy for peripheral nerve injury.

  13. 不同传入神经损伤对大鼠神经病理性痛形成的影响及其与脊髓和背根神经节BDNF的关系%Effects of different afferent nerve injury on development of neuropathic pain and its relationship with brain-derived neurotrophic factor in spinal cord and dorsal root ganglion in rats

    Institute of Scientific and Technical Information of China (English)

    杨涛; 叶西就; 王志; 彭书凌

    2010-01-01

    Objective To investigate the effects of different afferent nerve injury on development of neuropathic pain and its relationship with brain-derived neurotrophic factor (BDNF) in spinal cord and dorsal root ganglion (DRG) in rats. Methods Twenty-four male SD rats aged 2 months weighing 200-250 g were randomly divided into 3 groups:group Ⅰ sham operation (group S); group Ⅱ sural nerve injury (group SUR) and group Ⅲ gastrocnemius-soleus nerve injury (group GS). Sural nerve and gastrocnemius-soleus nerve were transected in group SUR and GS respectively. Paw withdrawal threshold to von Frey filament stimulation was measured the day before and at day 3 and 7 after operation. The animals were killed at postoperative day 7 after the measurement of paw withdrawal threshold. The ipsllateral L5 DRG and L5 segment of the spinal cord were removed. BDNF expression in the spinal dorsal horn was determined. The percentage of BDNF positive neurons and ATF-3 positive neurons in the total DRG neurons and the percentage of BDNF positive neurons in the damaged neurons (ATF-3 positive) were calculated. Results Mechanical hyperalgesia developed after transection of gastrocnemius-soleus muscle in group GS. Mechanical pain threshold was sinificantly lower, while BDNF expression in the spinal dorsal horn and the percentage of BDNF positive neurons in total DRG neurons were significantly higher in group GS than in group S and SUR (P < 0.01). There was no significant difference in all variables between group SUR and S (P>0.05). There was no significant difference in the percentage of ATF-3 positive neurons in the total DRG neurons between group GS and SUR (P > 0.05), but the percentage of BDNF positive neurons in the damaged neurons (ATF-3 positive) was significantly higher in group GS than in group SUR (P < 0.05). Conclusion Transection of the afferent nerve innervating muscle can produce neuropathic pain through up-regulation of BDNF expression in spinal dorsal horn and DRG in

  14. Spinal analgesic action of endomorphins in acute, inflammatory and neuropathic pain in rats.

    Science.gov (United States)

    Przewłocka, B; Mika, J; Labuz, D; Toth, G; Przewłocki, R

    1999-02-19

    We studied spinal analgesic and antiallodynic effects of endomorphin-1 and endomorphin-2 administered i.t. in comparison with Tyr-D-Ala-Gly-MePhe-Gly-ol (DAMGO) or morphine, during acute, inflammatory and neuropathic pain in rats chronically implanted with intrathecal cannulas. Endomorphin-1 and endomorphin-2 (2.5, 5, 10 microg i.t.) increased the tail-flick latency and, to the lesser extent, the paw pressure latency. The range of potencies in both those models of acute pain was as follows: DAMGO > morphine = endomorphin-1 > endomorphin-2. In a model of inflammatory pain, the number of formalin-induced flinching episodes was decreased by endomorphin-1. The effect of endomorphin-2 was much less pronounced. Both DAMGO and morphine significantly inhibited the pain-related behavior evoked by formalin. In a neuropathic pain model (sciatic nerve crushing in rats), endomorphin-1 and -2 (5 microg i.t.) had a statistically significant effect on the tail-flick latency and on the cold-water tail flick latency. Morphine, 5 microg, was found to be ineffective. Endomorphin-1 and -2 (2.5 and 5 microg i.t.) dose-dependently antagonized allodynia. Those effects of endomorphins were antagonized in acute (30 microg), inflammatory (30 microg) and neuropathic pain models (60 microg) by cyprodime, a selective mu-opioid receptor antagonist. In conclusion, our results show a strong analgesic action of endomorphins at the spinal cord level. The most interesting finding is a strong, stronger than in the case of morphine, antiallodynic effect of endomorphins in rats subjected to sciatic nerve crushing, which suggests a possible use of these compounds in a very difficult therapy of neuropathic pain.

  15. Effects of Valproic Acid on Axonal Regeneration and Recovery of Motor Function after Peripheral Nerve Injury in the Rat

    Directory of Open Access Journals (Sweden)

    Ting Rao

    2014-03-01

    Full Text Available Background:   Valproic acid (VPA is used to be an effective anti-epileptic drug and mood stabilizer. It has recently been demonstrated that VPA could promote neurite outgrowth, activate the extracellular signal regulated kinase pathway, and increases bcl-2 and growth cone-associated protein 43 levels in spinal cord. In the present research we demonstrate the effect of VPA on peripheral nerve regeneration and recovery of motor function following sciatic nerve transaction in rats. Methods:   The rats in VPA group and control group were administered with valproic acid (300mg/kg and sodium chloride respectively after operation. Each animal was observed sciatic nerve index (SFI at 2-week intervals and studied electrophysiology at 4-week intervals for 12 weeks. Histological and morphometrical analyses were performed 12 weeks after operation. Using the digital image-analysis system, thickness of the myelin sheath was measured, and total numbers of regenerated axons were counted. Results:   There was a significant difference in SFI, electrophysiological index (motor-nerve conduct velocity, and morphometrical results (regenerated axon number and thickness of myelin sheath in nerve regeneration between the VPA group and controls (   P

  16. Fos protein-like immunoreactive neurons induced by electrical stimulation in the trigeminal sensory nuclear complex of rats with chronically injured peripheral nerve.

    Science.gov (United States)

    Fujisawa, Naoko; Terayama, Ryuji; Yamaguchi, Daisuke; Omura, Shinji; Yamashiro, Takashi; Sugimoto, Tomosada

    2012-06-01

    The rat trigeminal sensory nuclear complex (TSNC) was examined for Fos protein-like immunoreactive (Fos-LI) neurons induced by electrical stimulation (ES) of the lingual nerve (LN) at 2 weeks after injury to the LN or the inferior alveolar nerve (IAN). Intensity-dependent increase in the number of Fos-LI neurons was observed in the subnucleus oralis (Vo) and caudalis (Vc) of the spinal trigeminal tract nucleus irrespective of nerve injury. The number of Fos-LI neurons induced by ES of the chronically injured LN at A-fiber intensity (0.1 mA) was significantly increased in the Vo but not the Vc. On the other hand, in rats with chronically injured IAN, the number of Fos-LI neurons induced by ES of the LN at C-fiber intensity (10 mA) was significantly increased in the Vc but not the Vo. These results indicated that injury of a nerve innervating intraoral structures increased the c-Fos response of Vo neurons to A-fiber intensity ES of the injured nerve. A similar nerve injury enhanced the c-Fos response of Vc neurons to C-fiber intensity ES of a spared uninjured nerve innervating an intraoral territory neighboring that of the injured nerve. The present result show that nerve injury causes differential effects on c-Fos expression in the Vo and Vc, which may explain complexity of neuropathic pain symptoms in clinical cases.

  17. Characterization of postsynaptic potentials evoked by sural nerve stimulation in hindlimb motoneurons from acute and chronic spinal cats.

    Science.gov (United States)

    Baker, L L; Chandler, S H

    1987-09-15

    The purpose of this study was to characterize the changes in postsynaptic potentials recorded in ankle extensor motoneurons resulting from activation of the sural nerve after spinal cord transection in the adult cat. Eight acute and nine chronic animals were spinalized at T12. Intracellular recordings from motoneurons innervating the triceps surae were performed. Sural nerve stimulation evoked complex synaptic potentials consisting of early and late components in all motoneurons. Early excitatory and inhibitory postsynaptic potentials (PSPs), as well as long latency excitatory postsynaptic potentials were recorded and averaged for assessment of PSP amplitude and duration. Early PSPs, both excitatory and inhibitory, were significantly larger in the motoneurons of cats spinalized 4-6 months earlier. Central latency of excitatory potentials were similar in the two samples of motoneurons, but the central latency associated with the initial inhibitory PSP was significantly shorter in the recordings from motoneurons of chronic spinal cats. In most recordings, an additional inhibitory PSP followed the initial excitatory PSP in motoneurons, and this secondary inhibitory PSP was similar in peak amplitude and duration in both samples of motoneurons. Also, a long latency excitatory PSP was recorded in a large percentage of motoneurons from both samples. This potential was typically of greater amplitude and longer duration in the motoneurons from chronic animals, when compared to recordings from acute animals. Although changes in amplitude and duration of PSP activity could be documented, there was no marked alteration in the frequency of occurrence of each PSP pattern recorded from the two preparations. This suggests that the synaptic pathways mediating the sural nerve reflexes have not qualitatively changed in the chronic spinal animal. The changes in amplitudes and durations of the PSPs in the chronic spinal cat indicate, however, that quantitative changes have occurred

  18. Degeneration and regeneration of motor and sensory nerves: a stereological study of crush lesions in rat facial and mental nerves.

    Science.gov (United States)

    Barghash, Z; Larsen, J O; Al-Bishri, A; Kahnberg, K-E

    2013-12-01

    The aim of this study was to evaluate the degeneration and regeneration of a sensory nerve and a motor nerve at the histological level after a crush injury. Twenty-five female Wistar rats had their mental nerve and the buccal branch of their facial nerve compressed unilaterally against a glass rod for 30s. Specimens of the compressed nerves and the corresponding control nerves were dissected at 3, 7, and 19 days after surgery. Nerve cross-sections were stained with osmium tetroxide and toluidine blue and analysed using two-dimensional stereology. We found differences between the two nerves both in the normal anatomy and in the regenerative pattern. The mental nerve had a larger cross-sectional area including all tissue components. The mental nerve had a larger volume fraction of myelinated axons and a correspondingly smaller volume fraction of endoneurium. No differences were observed in the degenerative pattern; however, at day 19 the buccal branch had regenerated to the normal number of axons, whereas the mental nerve had only regained 50% of the normal number of axons. We conclude that the regenerative process is faster and/or more complete in the facial nerve (motor function) than it is in the mental nerve (somatosensory function).

  19. Compound action potential of sensory tail nerves in the rat.

    Science.gov (United States)

    Leandri, Massimo; Saturno, Moreno; Cilli, Michele; Bisaglia, Michela; Lunardi, Gianluigi

    2007-01-01

    Assessment of the conduction velocity of motor fibers of the rat tail nerves has been used by some authors in the past, but very little is known about the sensory fibers. In 10 adult rats, weighing between 320 and 380 g, responses from the nerves and muscles of the tail have been recorded after stimulation at its root and tip. It was found that stimulation of the tip involved mainly sensory fibers, of which two main groups could be identified. One faster group, conducting within the range of 38-27 m/s, and one slower group with range 14-7 m/s. The bipolar recording configuration was found to be optimal for sensory recording. Stimulation of the tail root evoked a motor response, which was preceded by a very small neurographic activity, due to the fastest sensory fibers conducting antidromically. The conduction velocity of motor fibers was calculated to be approximately 19 m/s. Distance traveled by the volley can be assessed with excellent precision on the tail nerves; hence the calculated conduction velocities are highly reliable and reproducible. We propose that the tail nerves may be a useful tool for evaluation of conduction velocity of Abeta and Adelta afferents. As the technique is just minimally invasive, the test can be repeated a number of times in animals under chronic experimental conditions.

  20. Adhesion to carbon nanotube conductive scaffolds forces action-potential appearance in immature rat spinal neurons.

    Science.gov (United States)

    Fabbro, Alessandra; Sucapane, Antonietta; Toma, Francesca Maria; Calura, Enrica; Rizzetto, Lisa; Carrieri, Claudia; Roncaglia, Paola; Martinelli, Valentina; Scaini, Denis; Masten, Lara; Turco, Antonio; Gustincich, Stefano; Prato, Maurizio; Ballerini, Laura

    2013-01-01

    In the last decade, carbon nanotube growth substrates have been used to investigate neurons and neuronal networks formation in vitro when guided by artificial nano-scaled cues. Besides, nanotube-based interfaces are being developed, such as prosthesis for monitoring brain activity. We recently described how carbon nanotube substrates alter the electrophysiological and synaptic responses of hippocampal neurons in culture. This observation highlighted the exceptional ability of this material in interfering with nerve tissue growth. Here we test the hypothesis that carbon nanotube scaffolds promote the development of immature neurons isolated from the neonatal rat spinal cord, and maintained in vitro. To address this issue we performed electrophysiological studies associated to gene expression analysis. Our results indicate that spinal neurons plated on electro-conductive carbon nanotubes show a facilitated development. Spinal neurons anticipate the expression of functional markers of maturation, such as the generation of voltage dependent currents or action potentials. These changes are accompanied by a selective modulation of gene expression, involving neuronal and non-neuronal components. Our microarray experiments suggest that carbon nanotube platforms trigger reparative activities involving microglia, in the absence of reactive gliosis. Hence, future tissue scaffolds blended with conductive nanotubes may be exploited to promote cell differentiation and reparative pathways in neural regeneration strategies.

  1. Neurotoxic effects of levobupivacaine and fentanyl on rat spinal cord

    Directory of Open Access Journals (Sweden)

    Yesim Cokay Abut

    2015-02-01

    Full Text Available BACKGROUND: The purpose of the study was to compare the neurotoxic effects of intrathecally administered levobupivacaine, fentanyl and their mixture on rat spinal cord. METHODS: In experiment, there were four groups with medication and a control group. Rats were injected 15 µL saline or fentanyl 0.0005 µg/15 µL, levobupivacaine 0.25%/15 µL and fentanyl 0.0005 µg + levobupivacaine 0.25%/15 µL intrathecally for four days. Hot plate test was performed to assess neurologic function after each injection at 5th, 30th and 60th min. Five days after last lumbal injection, spinal cord sections between the T5 and T6 vertebral levels were obtained for histologic analysis. A score based on subjective assessment of number of eosinophilic neurons - Red neuron - which means irreversible neuronal degeneration. They reflect the approximate number of degenerating neurons present in the affected neuroanatomic areas as follows: 1, none; 2, 1-20%; 3, 21-40%; 4, 41-60%; and 5, 61-100% dead neurons. An overall neuropathologic score was calculated for each rat by summating the pathologic scores for all spinal cord areas examined. RESULTS: In the results of HPT, comparing the control group, analgesic latency statistically prolonged for all four groups.In neuropathologic investment, the fentanyl and fentanyl + levobupivacaine groups have statistically significant high degenerative neuron counts than control and saline groups. CONCLUSIONS: These results suggest that, when administered intrathecally in rats, fentanyl and levobupivacaine behave similar for analgesic action, but fentanyl may be neurotoxic for spinal cord. There was no significant degeneration with levobupivacaine, but fentanyl group has had significant degeneration.

  2. Wnt/Ryk signaling contributes to neuropathic pain by regulating sensory neuron excitability and spinal synaptic plasticity in rats.

    Science.gov (United States)

    Liu, Su; Liu, Yue-Peng; Huang, Zhi-Jiang; Zhang, Yan-Kai; Song, Angela A; Ma, Ping-Chuan; Song, Xue-Jun

    2015-12-01

    Treating neuropathic pain continues to be a major clinical challenge and underlying mechanisms of neuropathic pain remain elusive. We have recently demonstrated that Wnt signaling, which is important in developmental processes of the nervous systems, plays critical roles in the development of neuropathic pain through the β-catenin-dependent pathway in the spinal cord and the β-catenin-independent pathway in primary sensory neurons after nerve injury. Here, we report that Wnt signaling may contribute to neuropathic pain through the atypical Wnt/Ryk signaling pathway in rats. Sciatic nerve injury causes a rapid-onset and long-lasting expression of Wnt3a, Wnt5b, and Ryk receptors in primary sensory neurons, and dorsal horn neurons and astrocytes. Spinal blocking of the Wnt/Ryk receptor signaling inhibits the induction and persistence of neuropathic pain without affecting normal pain sensitivity and locomotor activity. Blocking activation of the Ryk receptor with anti-Ryk antibody, in vivo or in vitro, greatly suppresses nerve injury-induced increased intracellular Ca and hyperexcitability of the sensory neurons, and also the enhanced plasticity of synapses between afferent C-fibers and the dorsal horn neurons, and activation of the NR2B receptor and the subsequent Ca-dependent signals CaMKII, Src, ERK, PKCγ, and CREB in sensory neurons and the spinal cord. These findings indicate a critical mechanism underlying the pathogenesis of neuropathic pain and suggest that targeting the Wnt/Ryk signaling may be an effective approach for treating neuropathic pain.

  3. Chronic spinal infusion of loperamide alleviates postsurgical pain in rats.

    Science.gov (United States)

    Kumar, Rakesh; Reeta, K H; Ray, Subrata Basu

    2014-04-01

    Plantar incision in rat generates spontaneous pain behaviour. The opioid drug, morphine used to treat postsurgical pain produces tolerance after long-term administration. Loperamide, a potent mu-opioid agonist, has documented analgesic action in various pain conditions. However, loperamide analgesia and associated tolerance following continuous spinal administration in postsurgical pain has not been reported. Chronic spinal infusion of drugs was achieved using intrathecal catheters connected to osmotic minipump. Coinciding with the onset of spinal infusion of loperamide or morphine, rats were subjected to plantar incision. Pain-related behaviour was assessed by Hargreaves apparatus (thermal hyperalgesia) and von Frey filaments (mechanical allodynia). Morphine and loperamide (0.5, 1 and 2 microL/h) induced analgesia was observed until 7th day post-plantar incision in Sprague-Dawley rats. Morphine and loperamide produced dose-dependent analgesia. Loperamide, in the highest dose, produced analgesia till 7th day. However, the highest dose of morphine produced inhibition of thermal hyperalgesia till 5th day and mechanical allodynia only till 3rd day post-plantar incision. Morphine and loperamide produced analgesia in postsurgical pain, which may be mediated through different mechanisms. Longer duration of analgesia with loperamide could probably be due sustained blockade of calcium channels.

  4. Antioxidation of quercetin against spinal cord injury in rats

    Institute of Scientific and Technical Information of China (English)

    LIU Jin-bo; TANG Tian-si; YANG Hui-lin

    2006-01-01

    Objective: To observe the effect of quercetin on experimental spinal cord injury (SCI) in rats.Methods: Sixty Sprague-Dawley rats were randomly divided into four groups: Group A only for laminectomy,Group B for laminectomy with SCI, Group C for SCI and intraperitoneal injection with a bolus of 200 mg/kg quercetin and Group D for SCI and intraperitoneal injection of saline. SCI model was made by using modified Allen's method on T12. Six rats of each group were killed at4 h after injury and the levels of free iron and malondialdehyde (MDA) of the involved spinal cord segments were measured by bleomycin and thiobarbituric acid (TBA) assays separately. The recovery of hind limb function was assessed by Modified Tarlov's scale and inclined plane method at 7 d,14 d and 21 d after SCI. The histological changes of the damaged spinal cord were also examined at 7 d after SCI.Results: After SCI, the levels of free iron and MDA were significantly increased in Groups B and D, while not in Group C. The Modified Tarlov's score and the inclined plane angles were significantly decreased in Groups B, C and D. The histological findings were not improved.Conclusions: After SCI, quercetin can reduce the level of lipid peroxidation, but not improve recovery of function.

  5. Anatomical Study of the Intercostobrachial Nerve in Sprague-Dawlay Rats

    Institute of Scientific and Technical Information of China (English)

    Liansheng Ning; Xin Wang; Kai Zhao; Zhenfang Yang; Hui Sun; Jie Ge

    2006-01-01

    OBJECTIVE The aim of the study was to explore the anatomy of the intercostobrachial nerve in rats.METHODS Dissections of 8 Sprague-dawley rats were performed to examine the intercostobrachial nerve. Fifteen dissections were successful.The position of the nerve, origin, termination, length and diameter were measured and recorded.RESULTS 1) 80% of the nerves originated from the second intercostal space and 20% from the first intercostal space; 2) 60% of the nerves terminated in the latissimus dorsi and 40% in the axillary skin 3) the branches of the nerves only were divided into 2 types, single and double; 4) the length of the nerves ranged from 2.4 to 3.4 cm with an average of 2.97±0.90 cm; 5) the diameter of the nerves was thicker at their origin compared to their termination.CONCLUSION The intercostobrachial nerve is simple in rats with 60%terminating in the latissimus dorsi.

  6. Sciatic nerve regeneration in rats by a promising electrospun collagen/poly(ε-caprolactone nerve conduit with tailored degradation rate

    Directory of Open Access Journals (Sweden)

    Jiang Xinquan

    2011-07-01

    Full Text Available Abstract Background To cope with the limitations faced by autograft acquisitions particularly for multiple nerve injuries, artificial nerve conduit has been introduced by researchers as a substitute for autologous nerve graft for the easy specification and availability for mass production. In order to best mimic the structures and components of autologous nerve, great efforts have been made to improve the designation of nerve conduits either from materials or fabrication techniques. Electrospinning is an easy and versatile technique that has recently been used to fabricate fibrous tissue-engineered scaffolds which have great similarity to the extracellular matrix on fiber structure. Results In this study we fabricated a collagen/poly(ε-caprolactone (collagen/PCL fibrous scaffold by electrospinning and explored its application as nerve guide substrate or conduit in vitro and in vivo. Material characterizations showed this electrospun composite material which was made of submicron fibers possessed good hydrophilicity and flexibility. In vitro study indicated electrospun collagen/PCL fibrous meshes promoted Schwann cell adhesion, elongation and proliferation. In vivo test showed electrospun collagen/PCL porous nerve conduits successfully supported nerve regeneration through an 8 mm sciatic nerve gap in adult rats, achieving similar electrophysiological and muscle reinnervation results as autografts. Although regenerated nerve fibers were still in a pre-mature stage 4 months postoperatively, the implanted collagen/PCL nerve conduits facilitated more axons regenerating through the conduit lumen and gradually degraded which well matched the nerve regeneration rate. Conclusions All the results demonstrated this collagen/PCL nerve conduit with tailored degradation rate fabricated by electrospinning could be an efficient alternative to autograft for peripheral nerve regeneration research. Due to its advantage of high surface area for cell attachment, it

  7. Exercise training improves functional recovery and motor nerve conduction velocity after sciatic nerve crush lesion in the rat

    NARCIS (Netherlands)

    Gispen, W.H.; Meeteren, N.L.U.; Brakkee, J.H.; Hamers, F.P.T.; Helders, P.J.M.

    1997-01-01

    Objective: To observe the effects of exercise training on recuperation of sensorimotor function in the early phase of regeneration, and to monitor the long-term effects of exercise on electrophysiological aspects of the regenerating nerve. Design: After sciatic nerve crush in 20 male Wistar rats, o

  8. Variation in nerve autograft length increases fibre misdirection and decreases pruning effectiveness: an experimental study in the rat median nerve.

    Science.gov (United States)

    Bertelli, J A; Taleb, M; Mira, J C; Ghizoni, M F

    2005-09-01

    In the clinical set, autologus nerve grafts are the current option for reconstruction of nerve tissue losses. The length of the nerve graft has been suggested to affect outcomes. Experiments were performed in the rat in order to test this assumption and to detect a possible mechanism to explain differences in recovery. The rat median nerve was repaired by ulnar nerve grafts of different lengths. Rats were evaluated for 12 months by behavioural assessment and histological studies, including ATPase myofibrillary histochemistry and retrograde neuronal labelling. It was demonstrated that graft length interferes in behavioural functional recovery that here correlates to muscle weight recovery. Short nerve grafts recovered faster and better. Reinnervation was not specific either at the trunk level or in the muscle itself. The normal mosaic pattern of Type I muscle fibres was never restored and their number remained largely augmented. An increment in the number of motor fibres was observed after the nerve grafting in a predominantly sensory branch in all groups. This increment was more pronounced in the long graft group. In the postoperative period, about a 20% reduction in the number of misdirected motor fibres occurred in the short nerve graft group only. Variation in the length of nerve grafts interferes in behavioural recovery and increases motor fibres misdirection. Early recovery onset was related to a better outcome, which occurs in the short graft group.

  9. Late changes in human sural nerves in Minamata disease and in nerves of rats with experimental organic mercury poisoning.

    Science.gov (United States)

    Miyakawa, T; Murayama, E; Sumiyoshi, S; Deshimaru, M; Fujimoto, T

    1976-06-15

    The sural nerves of 2 human cases with Minamata disease and poisoned rats were examined histopathologically. Both showed similar findings: the myelinated nerve fibres were decreased in number, but small myelinated nerve fibres were increased: The latter were irregular in shape and their Schwann cells showed regressive changes, with high electron density of the cytoplasms and many glycogen granules. Onion bulb formation was not found. According to fibre diameter histograms, the ratio of small myelinated nerve fibres of 2-5 mum showed a high percentage. A large number of the small myelinated nerve fibres were presumed to be regenerated nerve fibres. These findings are different from other peripheral neuropathies and may be characteristics of the late changes of the sural nerve induced by organic mercury compound.

  10. Extensive molecular differences between anterior- and posterior-half-sclerotomes underlie somite polarity and spinal nerve segmentation

    Directory of Open Access Journals (Sweden)

    Keynes Roger J

    2009-05-01

    Full Text Available Abstract Background The polarization of somite-derived sclerotomes into anterior and posterior halves underlies vertebral morphogenesis and spinal nerve segmentation. To characterize the full extent of molecular differences that underlie this polarity, we have undertaken a systematic comparison of gene expression between the two sclerotome halves in the mouse embryo. Results Several hundred genes are differentially-expressed between the two sclerotome halves, showing that a marked degree of molecular heterogeneity underpins the development of somite polarity. Conclusion We have identified a set of genes that warrant further investigation as regulators of somite polarity and vertebral morphogenesis, as well as repellents of spinal axon growth. Moreover the results indicate that, unlike the posterior half-sclerotome, the central region of the anterior-half-sclerotome does not contribute bone and cartilage to the vertebral column, being associated instead with the development of the segmented spinal nerves.

  11. Impaired Prosaposin Secretion During Nerve Regeneration in Diabetic Rats and Protection of Nerve Regeneration by a Prosaposin-Derived Peptide

    OpenAIRE

    2008-01-01

    Prosaposin is both a precursor of sphingolipid activator proteins and a secreted neurotrophic and myelinotrophic factor. Because peripheral nerve regeneration is impaired in diabetes mellitus, we measured prosaposin protein levels from control and streptozotocin-diabetic rats by collecting endoneurial fluid secreted into a bridging tube connecting the ends of transected sciatic nerve. Prosaposin protein levels were significantly reduced in endoneurial fluid from diabetic rats and increased in...

  12. Photochemically induced spinal ischaemia: a model of spinal cord trauma in the rat

    Science.gov (United States)

    Olby, Natasha J.; Blakemore, W. F.

    1995-05-01

    Focal thrombosis was induced in the dorsal funiculus of the rat spinal cord by exposing the cord to light following intravenous injection of the photoactive dye, rose bengal. The light source was a 599 standing wave dye laser, pumped by an Innova 70 - 4 argon ion laser (Coherent Ltd, Cambridge, UK) and the light was delivered to the operative site via an optical fiber. The histological characteristics of the development and resolution of the lesion have been studied. Forty rats were examined with light and electron microscopy at various time points between 30 minutes and one month after irradiation and the lesion length was measured. Platelet aggregation, increased extracellular space in the white matter and vacuolation of the neurones and glia of the grey matter were present 30 minutes after injury. Progressive necrosis of the white and grey matter developed over the subsequent 24 hours to produce a fusiform lesion that occupied the dorsal funiculus and dorsal horns of the spinal cord at its center and tapered cranially and caudally along the dorsal columns for a total distance of seven millimeters. By one month after injury the area of necrosis had become a cyst lined by astrocytes ventrolaterally and meningeal cells dorsally. Measurements of lesion length showed a variability of 26%. This model of spinal cord trauma produces a lesion that is sufficiently reproducible to be suitable for performing studies aimed at tissue preservation and repair.

  13. Recovery of spinal cord function induced by direct current stimulation of the injured rat spinal cord.

    Science.gov (United States)

    Wallace, M C; Tator, C H; Piper, I

    1987-06-01

    Direct current stimulation has been shown by others to enhance the regeneration of several types of tissues, including nervous tissue in some species. The purpose of the present experiment was to assess the value of direct current stimulation for enhancing the recovery of spinal cord function after clip compression injury of the rat spinal cord. Twenty Wistar rats underwent a 1-minute, 50-g clip compression injury at T-1, after which electrodes were placed epidurally with the anode proximal and the cathode distal to the injury site. These electrodes were attached to a stimulator implanted subcutaneously. Ten animals received stimulators that produced a constant current of 14 microA, and the remainder received stimulators with no electrical output and served as controls. Assignment of stimulators was random, and the treatment group was not identified until sacrifice. Neurological function was tested weekly for 15 weeks by the inclined plane technique, after which the animals were killed and the injured cords were examined for histological evidence of regeneration. The mean inclined plane result for the treatment group (39 +/- 5 degrees) was significantly better than that for the control group (31 +/- 6 degrees) (P less than 0.02), although there was no significant difference in histological findings between the two groups. Thus, direct current stimulation of the injured mammalian spinal cord produced improvement in neurological function and warrants further investigation.

  14. [Effects of electroacupuncture on glutamate and aspartic acid contents in the dorsal root ganglion and spinal cord in rats with neuropathic pain].

    Science.gov (United States)

    Ma, Cheng; Li, Cui-xian; Yi, Jian-liang; Yan, Li-ping

    2008-08-01

    To observe the effect of electroacupuncture (EA) on pain threshold and contents of excitatory amino acids (EAA) in dorsal root ganglia (DRG) and spinal cord in rats with neuropathic pain. Fifty SD rats were randomly divided into control (C),model (M), sham-model (SM), EA, and sham-EA groups, with 10 cases in each. Neuropathic pain (spared nerve injury, SNI) model was established by cutting off the right common peroneal nerve and proso-tibial nerve (with the sural nerve reserved intact). Before and after surgery, the mechanical pain threshold (MPT) and thermal pain threshold (TPT) were measured respectively on the injured side under consciousness state. EA (2 Hz, 1-3 mA, adding 1 mA/10 min) was applied to "Huantiao" (GB 30) and "Weizhong" (BL 40) on the affected side for 30 min. For rats of sham-EA group, filiform needles were inserted into GB30 and BL40 simply without manipulation or electrical stimulation. The treatment was given once daily for 7 days. On the 15th day, the rats were sacrificed for sampling right L4-L6 DRG and spinal cord. The contents of neurotransmitters, glutamate (Glu) and aspartic acid (Asp) in DRG and spinal cord were detected with high performance liquid chromatography (HPLC). Micro-dialysis technique was used to collect the dialysate from the spinal cord, homogenated for measuring EAA by HPLC. In comparison with control group, after SNI, MPT decreased significantly from the 1st day on in model group. Compared with model group, on the 15th day, MPT increased significantly in both EA and sham-EA groups (P 0.05). It suggested that sham EA still had an analgesic effect in spite of being lower than that of true EA. Compared with control group, the contents of Glu and Asp in the spinal cord tissue and micro-dialysate in model group increased significantly after SNI (P spinal cord tissue and micro-dialysate, and Asp in the spinal cord tissue and micro-dialysate in both sham-EA and EA groups decreased considerably (P spinal cord tissue Asp contents

  15. Alterations in the neural circuits from peripheral afferents to the spinal cord: possible implications for diabetic polyneuropathy in streptozotocin-induced type 1 diabetic rats

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    Zhen-Zhen eKou

    2014-01-01

    Full Text Available Diabetic polyneuropathy (DPN presents as a wide variety of sensorimotor symptoms and affects approximately 50% of diabetic patients. Changes in the neural circuits may occur in the early stages in diabetes and are implicated in the development of DPN. Therefore, we aimed to detect changes in the expression of isolectin B4 (IB4, the marker for nonpeptidergic unmyelinated fibers and their cell bodies and calcitonin gene-related peptide (CGRP, the marker for peptidergic fibers and their cell bodies in the dorsal root ganglion (DRG and spinal cord of streptozotocin (STZ-induced type 1 diabetic rats showing alterations in sensory and motor function. We also used cholera toxin B subunit (CTB to show the morphological changes of the myelinated fibers and motor neurons. STZ-induced diabetic rats exhibited hyperglycemia, decreased body weight gain, mechanical allodynia and impaired locomotor activity. In the DRG and spinal dorsal horn, IB4-labeled structures decreased, but both CGRP immunostaining and CTB labeling increased from day 14 to day 28 in diabetic rats. In spinal ventral horn, CTB labeling decreased in motor neurons in diabetic rats. Treatment with intrathecal injection of insulin at the early stages of DPN could alleviate mechanical allodynia and impaired locomotor activity in diabetic rats. The results suggest that the alterations of the neural circuits between spinal nerve and spinal cord via the DRG and ventral root might be involved in DPN.

  16. Effect of nitric oxide on spinal evoked potentials and survival rate in rats with decompression sickness

    DEFF Research Database (Denmark)

    Randsøe, Thomas; Meehan, Claire Francesca; Broholm, Helle

    2015-01-01

    evaluated by means of spinal evoked potentials (SEPs). Anesthetized rats were decompressed from a 1-h hyperbaric air dive at 506.6 kPa (40 m of seawater) for 3 min and 17 s, and spinal cord conduction was studied by measurements of SEPs. Histological samples of the spinal cord were analyzed for lesions...

  17. Low-Level Laser Irradiation Improves Functional Recovery and Nerve Regeneration in Sciatic Nerve Crush Rat Injury Model

    Science.gov (United States)

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

    2014-01-01

    The development of noninvasive approaches to facilitate the regeneration of post-traumatic nerve injury is important for clinical rehabilitation. In this study, we investigated the effective dose of noninvasive 808-nm low-level laser therapy (LLLT) on sciatic nerve crush rat injury model. Thirty-six male Sprague Dawley rats were divided into 6 experimental groups: a normal group with or without 808-nm LLLT at 8 J/cm2 and a sciatic nerve crush injury group with or without 808-nm LLLT at 3, 8 or 15 J/cm2. Rats were given consecutive transcutaneous LLLT at the crush site and sacrificed 20 days after the crush injury. Functional assessments of nerve regeneration were analyzed using the sciatic functional index (SFI) and hindlimb range of motion (ROM). Nerve regeneration was investigated by measuring the myelin sheath thickness of the sciatic nerve using transmission electron microscopy (TEM) and by analyzing the expression of growth-associated protein 43 (GAP43) in sciatic nerve using western blot and immunofluorescence staining. We found that sciatic-injured rats that were irradiated with LLLT at both 3 and 8 J/cm2 had significantly improved SFI but that a significant improvement of ROM was only found in rats with LLLT at 8 J/cm2. Furthermore, the myelin sheath thickness and GAP43 expression levels were significantly enhanced in sciatic nerve-crushed rats receiving 808-nm LLLT at 3 and 8 J/cm2. Taken together, these results suggest that 808-nm LLLT at a low energy density (3 J/cm2 and 8 J/cm2) is capable of enhancing sciatic nerve regeneration following a crush injury. PMID:25119457

  18. N-acetylcysteine downregulates phosphorylated p-38 expression but does not reverse the increased superoxide anion levels in the spinal cord of rats with neuropathic pain.

    Science.gov (United States)

    Horst, A; de Souza, J A; Santos, M C Q; Riffel, A P K; Kolberg, C; Ribeiro, M F M; de Fraga, L S; Partata, W A

    2017-02-16

    We determined the effect of N-acetylcysteine (NAC) on the expression of the phosphorylated p38 (p-p38) protein and superoxide anion generation (SAG), two important players in the processing of neuropathic pain, in the lumbosacral spinal cord of rats with chronic constriction injury (CCI)-induced neuropathic pain. The sciatic functional index (SFI) was also measured to assess the functional recovery post-nerve lesion. Thirty-six male Wistar rats were divided equally into the following groups: Naive (rats did not undergo surgical manipulation); Sham (rats in which all surgical procedures involved in CCI were used except the ligature), and CCI (rats in which four ligatures were tied loosely around the right common sciatic nerve), which received 2, 4, or 8 intraperitoneal injections of NAC (150 mg·kg-1·day-1) or saline beginning 4 h after CCI. Rats were sacrificed 1, 3, and 7 days after CCI. The SFI was measured on these days and the lumbosacral spinal cord was used for analysis of p-p38 expression and SAG. CCI induced a decrease in SFI as well as an increase in p-p38 expression and SAG in the spinal cord. The SFI showed a partial recovery at day 7 in saline-treated CCI rats, but recovery was improved in NAC-treated CCI rats. NAC induced a downregulation in p-p38 expression at all time-points evaluated, but did not reverse the increased SAG induced by CCI. Since p-p38 is a mediator in neuropathic pain and/or nerve regeneration, modulation of this protein may play a role in NAC-induced effects in CCI rats.

  19. Transient long thoracic nerve injury during posterior spinal fusion for adolescent idiopathic scoliosis: A report of two cases

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    Athanasios I Tsirikos

    2013-01-01

    Full Text Available We present the transient long thoracic nerve (LTN injury during instrumented posterior spinal arthrodesis for idiopathic scoliosis. The suspected mechanism of injury, postoperative course and final outcome is discussed. The LTN is susceptible to injury due to its long and relatively superficial course across the thoracic wall through direct trauma or tension. Radical mastectomies with resection of axillary lymph nodes, first rib resection to treat thoracic outlet syndrome and cardiac surgery can be complicated with LTN injury. LTN injury producing scapular winging has not been reported in association with spinal deformity surgery. We reviewed the medical notes and spinal radiographs of two adolescent patients with idiopathic scoliosis who underwent posterior spinal arthrodesis and developed LTN neuropraxia. Scoliosis surgery was uneventful and intraoperative spinal cord monitoring was stable throughout the procedure. Postoperative neurological examination was otherwise normal, but both patients developed winging of the scapula at 4 and 6 days after spinal arthrodesis, which did not affect shoulder function. Both patients made a good recovery and the scapular winging resolved spontaneously 8 and 11 months following surgery with no residual morbidity. We believe that this LTN was due to positioning of our patients with their head flexed, tilted and rotated toward the contralateral side while the arm was abducted and extended. The use of heavy retractors may have also applied compression or tension to the nerve in one of our patients contributing to the development of neuropraxia. This is an important consideration during spinal deformity surgery to prevent potentially permanent injury to the nerve, which can produce severe shoulder dysfunction and persistent pain.

  20. Research progress in three-dimensional reconstruction of the rat spinal tract

    Institute of Scientific and Technical Information of China (English)

    Huiqun Wu; Guangming Lü

    2008-01-01

    BACKGROUND: Recently, three-dimensional (3D) reconstruction of the corticospinal tract has been attempted in treatment for corticospinal tract injury. However, results remain unsatisfactory. OBJECTIVE: This manuscript reviews technique progress and problems in 3D reconstruction of rat spinal tracts, as well as 3D reconstruction of human spinal tracts. RETRIEVAL STRATEGY: Using the keywords "rat, spinal tracts, three-dimensional reconstruction", the PubMed database was searched for English articles pertaining to 3D reconstruction of the rat spinal tract that were published between January 1996 and January 2007. Meanwhile, the above-mentioned keywords in Chinese were also used to search the CNKI database for articles that were published between January 1999 and January 2007. Inclusion criteria: manuscripts that addressed the study of 3D reconstruction of the rat spinal tract and review articles. Exclusion criteria: old and repetitive articles. All manuscripts were initially evaluated, followed by extensive review.LITERATURE EVALUATION: A total of 154 related manuscripts were collected; a total of 27 were evaluated and reviewed for the present review. One manuscript assessed rat behavioral functions, four were experimental reports addressing micro-3D reconstruction techniques, ten were experiment reports about image analysis of rat corticospinal tracts, and twelve were experiment articles related to image processing of serial spinal cord sections. DATA SYNTHESIS: Rat spinal cord sections were obtained through section staining or magnetic resonance imaging (MRI) techniques, specifically localizing the inner tracts. Software was used to construct 3D reconstruction from the serial sections to observe and analyze rat spinal cord structures. The rat spinal cord is small, with complicated inner tracts, which makes accurate 3D reconstruction difficult.CONCLUSION: The assembly of 3D reconstructions from rat spinal cord serial sections and the visualization of the inner tracts

  1. The Role of Nerve Growth Factor in Ginsenoside Rg1-Induced Regeneration of Injured Rat Sciatic Nerve.

    Science.gov (United States)

    Huo, Dong-Sheng; Zhang, Ming; Cai, Zhi-Ping; Dong, Chao-Xuan; Wang, He; Yang, Zhan-Jun

    2015-01-01

    Sciatic nerve injury is commonly seen in clinical practice predominantly associated with trauma or sports injuries. Recent studies indicated that ginsenoside Rg1 (Gs Rg1), extracted from Chinese herbs, was found to promote regeneration of injured rat sciatic nerve and that nerve growth factor (NGF) may be involved in this process. The aim of this study was to examine the role that NGF may play in ginsenoside Rg1-induced regeneration of rat sciatic nerve following injury. Animals following surgical right sciatic nerve injury were subsequently administered intraperitoneally either saline (sham control) or different doses of 2, 4, 8, or 12 mg/kg daily GsRg1 for 2 to 8 wk. In addition, 100 μg/kg mecobalamin, a drug utilized to treat nerve injuries, was employed as a positive control. After 2, 4, or 8 wk, sciatic functional index (SFI) and mean nerve conduction velocity (MNCV), markers of sciatic nerve function, were assessed to determine whether recovery of injured sciatic nerve occurred. In addition, immunohistochemistry and Western blot methods were used to examine NGF protein expression changes. Results showed that all doses of GsRg1 significantly increased SFI and MNCV in injured sciatic-nerve-damaged rats in a manner similar to that noted with mecobalamin. It is of interest that the intermediate 4- and 8-mg/kg doses were more effective in restoring nerve functions. Immunohistochemistry and Western blot results also demonstrated a similar pattern with enhanced NGF protein expression at all doses, but greater effects were noted at 4 and 8 mg/kg GsRg1. Data suggest that GsRg1 promotes recovery of injured sciatic nerve functions within a specific dose range and that NGF may be involved in this physiological process.

  2. Immediate effect of transcutaneous electrical nerve stimulation on spasticity in patients with spinal cord injury.

    Science.gov (United States)

    Ping Ho Chung, Bryan; Kam Kwan Cheng, Benson

    2010-03-01

    To investigate the immediate effect of transcutaneous electrical nerve stimulation (TENS) on spasticity in patients with spinal cord injury. Randomized controlled trial. Extended rehabilitation centre. Eighteen subjects with spinal cord injury and symptoms of spasticity over lower limbs were randomly assigned to receive either 60 minutes of active TENS (0.25 ms, 100 Hz, 15 mA) or 60 minutes of placebo non-electrically stimulated TENS over the common peroneal nerve. Composite Spasticity Score was used to assess the spasticity level of ankle plantar flexors immediately before and after TENS application. Composite Spasticity Score consisted of Achilles tendon jerks, resistance to full-range passive ankle dorsiflexion and ankle clonus. Between-group statistical differences of reduction of Composite Spasticity Score, Achilles tendon jerks, resistance to full-range passive ankle dorsiflexion and ankle clonus were calculated using the Mann-Whitney test. Within-group statistical differences of Composite Spasticity Score, Achilles tendon jerks, resistance to full-range passive ankle dorsiflexion and ankle clonus were calculated using the Wilcoxon signed ranks test. Significant reductions were shown in Composite Spasticity Score by 29.5% (p = 0.017), resistance to full-range passive ankle dorsiflexion by 31.0% (p = 0.024) and ankle clonus by 29.6% (p = 0.023) in the TENS group but these reductions were not found in the placebo TENS group. The between-group differences of both Composite Spasticity Score and resistance to full-range passive ankle dorsiflexion were significant (p = 0.027 and p = 0.024, respectively). This study showed that a single session of TENS could immediately reduce spasticity.

  3. Diffusion Tensor Imaging in Rat Spinal Cord In-Vivo

    Science.gov (United States)

    Al-Rekabi, Zeinab

    2008-05-01

    Diffusion Tensor Imaging (DTI), an MRI technique based on probing the structure of tissues at a microscopic level is used to determine regional values of Fractional Anisotropy (FA) and mean diffusivity (Dav) of excised and in-vivo rat spinal cords. Two pulse sequences: Spin Echo (SE) and Echo Planar Imaging (EPI) are optimized to provide the best image quality, signal-to-noise ratio (SNR) and the greatest spatial resolution at reasonable acquisition times in the rat spinal cord. The study was conducted using a 7T BRUKER BioSpec MRI animal scanner. In the ex-vivo experiments images with the spatial resolution of 100 μm and the SNR of 1.938 ± 0.010 were acquired in 2 minutes. After optimization both methods were applied in-vivo. The values of FA and Dav acquired in this study showed good correlation with the literature values. Furthermore, results from these studies should provide the necessary baseline data for serial DTI in injured spinal cord in future studies.

  4. Comparative evaluation of femoral nerve block and intravenous fentanyl for positioning during spinal anaesthesia in surgery of femur fracture

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    Ashok Jadon

    2014-01-01

    Full Text Available Background: Spinal anaesthesia is the preferred technique to fix fracture of the femur. Extreme pain does not allow ideal positioning for this procedure. Intravenous fentanyl and femoral nerve block are commonly used techniques to reduce the pain during position for spinal anaesthesia however; results are conflicting regarding superiority of femoral nerve block over intravenous fentanyl. Aims: We conducted this study to compare the analgesic effect provided by femoral nerve block (FNB and intra- venous (IV fentanyl prior to positioning for central neuraxial block in patients undergoing surgery for femur fracture. Patients and Methods: In this randomized prospective study 60 patients scheduled for fracture femur operation under spinal were included. Patients were distributed in two groups through computer generated random numbers table; Femoral nerve block group (FNB and Intravenous fentanyl group (FENT. In FNB group patients received FNB guided by a peripheral nerve stimulator (Stimuplex; B Braun, Melsungen, AG 5 minutes prior to positioning. 20mL, 1.5% lidocaine with adrenaline (1:200,000 was injected incrementally after a negative aspiration test. Patients in the fentanyl group received injection fentanyl 1 μg/kg IV 5 mins prior to positioning. Spinal block was performed and pain scores before and during positioning were recorded. Statistical analysis was done with Sigmaplot version-10 computer software. Student t-test was applied to compare the means and P < 0.05 was taken as significant. Results: VAS during positioning in group FNB: 0.57 ± 0.31 versus FENT 2.53 ± 1.61 (P = 0.0020. Time to perform spinal anesthesia in group FNB: 15.33 ± 1.64 min versus FENT 19.56 ± 3.09 min (P = 0.000049. Quality of patient positioning for spinal anesthesia in group FNB 2.67± 0.606 versus FENT 1.967 ± 0.85 (P = 0.000027. Patient acceptance was less in group FENT (P = 0.000031. Conclusion: Femoral nerve block provides better analgesia, patient

  5. Pharmacological switch in Aβ-fiber stimulation-induced spinal transmission in mice with partial sciatic nerve injury

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    Ma Lin

    2008-07-01

    Full Text Available Abstract Background We have previously demonstrated that different spinal transmissions are involved in the nociceptive behavior caused by electrical stimulation of Aβ-, Aδ- or C-fibers using a Neurometer® in naïve mice. In this study, we attempted to pharmacologically characterize the alteration in spinal transmission induced by partial sciatic nerve injury in terms of nociceptive behavior and phosphorylation of extracellular signal-regulated kinase (pERK in the spinal dorsal horn. Results Aβ-fiber responses (2000-Hz, which were selectively blocked by the AMPA/kainate antagonist CNQX in naïve mice, were hypersensitized but blocked by the NMDA receptor antagonists MK-801 and AP-5 in injured mice in an electrical stimulation-induced paw withdrawal (EPW test. Although Aδ-fiber responses (250-Hz were also hypersensitized by nerve injury, there was no change in the pharmacological characteristics of Aδ-fiber responses through NMDA receptors. On the contrary, C-fiber responses (5-Hz were hyposensitized by nerve injury. Moreover, Aδ- and C-, but not Aβ-fiber stimulations significantly increased the number of pERK-positive neurons in the superficial spinal dorsal horns of naïve mice, and corresponding antagonists used in the EPW test inhibited this increase. In mice with nerve injury, Aβ- as well as Aδ-fiber stimulations significantly increased the number of pERK-positive neurons in the superficial spinal dorsal horn, whereas C-fiber stimulation decreased this number. The nerve injury-specific pERK increase induced by Aβ-stimulation was inhibited by MK-801 and AP-5, but not by CNQX. However, Aβ- and Aδ-stimulations did not affect the number or size of pERK-positive neurons in the dorsal root ganglion, whereas C-fiber-stimulation selectively decreased the number of pERK-positive neurons. Conclusion These results suggest that Aβ-fiber perception is newly transmitted to spinal neurons, which originally receive only Aδ- and C

  6. Gait analysis in rats with peripheral nerve injury.

    Science.gov (United States)

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

    2001-02-01

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

  7. Effects of electrode geometry and combination on nerve fibre selectivity in spinal cord stimulation.

    Science.gov (United States)

    Holsheimer, J; Struijk, J J; Tas, N R

    1995-09-01

    The differential effects of the geometry of a rostrocaudal array of electrode contacts on dorsal column fibre and dorsal root fibre activation in spinal cord stimulation are analysed theoretically. 3-D models of the mid-cervical and mid-thoracic vertebral areas are used for the computation of stimulation induced field potentials, whereas a cable model of myelinated nerve fibre is used for the calculation of the excitation thresholds of large dorsal column and dorsal root fibres. The size and spacing of 2-D rectangular electrode contacts are varied while mono-, bi- and tripolar stimulation are applied. The model predicts that the highest preferential stimulation of dorsal root fibres is obtained in monopolar stimulation with a large cathode, whereas dorsal column fibre preference is highest in tripolar stimulation with small contacts and small contact spacings. Fibre type preference is most sensitive to variations of rostrocaudal contact size and least sensitive to variations of lateral contact size. Dorsal root fibre preference is increased and sensitivity to lead geometry is reduced as the distance from contacts to spinal cord is increased.

  8. General anesthesia plus ilioinguinal nerve block versus spinal anesthesia for ambulatory inguinal herniorrhapy

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    Lucía Vizcaíno-Martínez

    2014-01-01

    Full Text Available Objective: The aim was to evaluate general anesthesia (GA plus ilioinguinal nerve block (IIB versus spinal anesthesia (SA in patients scheduled for ambulatory inguinal hernia repair regarding pain management, anesthesia recovery and reducing potential complications. Materials and Methods: A double-blind, prospective, randomized, controlled study in patients American Society of Anesthesiologists I-III randomized into two groups: GA plus IIB group, induction of anesthesia with propofol, maintenance with sevoflurane, airway management with laryngeal mask allowing spontaneous ventilation and ultrasound-guided IIB; SA group, patients who underwent spinal block with 2% mepivacaine. The study variables were pain intensity, assessed by visual analog scale, analgesic requirements until hospital discharge, time to ambulation and discharge, postoperative complications-related to both techniques and satisfaction experienced. Results: Thirty-two patients were enrolled; 16 patients in each group. The differences regarding pain were statistically significant at 2 h of admission (P < 0.001 and at discharge (P < 0.001 in favor of the GA plus ilioinguinal block group. In addition in this group, analgesic requirements were lower than SA group (P < 0.001, with times of ambulation and discharge significantly shorter. The SA group had a higher tendency to develop complications and less satisfaction. Conclusion: General anesthesia plus IIB is better than SA regarding postoperative analgesia, time to mobilization and discharge, side-effect profile and satisfaction experienced by the patients.

  9. Transfer of the brachialis to the anterior interosseous nerve as a treatment strategy for cervical spinal cord injury: technical note.

    Science.gov (United States)

    Hawasli, Ammar H; Chang, Jodie; Reynolds, Matthew R; Ray, Wilson Z

    2015-04-01

    Study Design Technical report. Objective To provide a technical description of the transfer of the brachialis to the anterior interosseous nerve (AIN) for the treatment of tetraplegia after a cervical spinal cord injury (SCI). Methods In this technical report, the authors present a case illustration of an ideal surgical candidate for a brachialis-to-AIN transfer: a 21-year-old patient with a complete C7 spinal cord injury and failure of any hand motor recovery. The authors provide detailed description including images and video showing how to perform the brachialis-to-AIN transfer. Results The brachialis nerve and AIN fascicles can be successfully isolated using visual inspection and motor mapping. Then, careful dissection and microsurgical coaptation can be used for a successful anterior interosseous reinnervation. Conclusion The nerve transfer techniques for reinnervation have been described predominantly for the treatment of brachial plexus injuries. The majority of the nerve transfer techniques have focused on the upper brachial plexus or distal nerves of the lower brachial plexus. More recently, nerve transfers have reemerged as a potential reinnervation strategy for select patients with cervical SCI. The brachialis-to-AIN transfer technique offers a potential means for restoration of intrinsic hand function in patients with SCI.

  10. Differential expression of Cathepsin S and X in the spinal cord of a rat neuropathic pain model

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    Schmitz Beate

    2008-08-01

    Full Text Available Abstract Background Ample evidence suggests a substantial contribution of cellular and molecular changes in the spinal cord to the induction and persistence of chronic neuropathic pain conditions. While for a long time, proteases were mainly considered as protein degrading enzymes, they are now receiving growing interest as signalling molecules in the pain pathology. In the present study we focused on two cathepsins, CATS and CATX, and studied their spatiotemporal expression and activity during the development and progression of neuropathic pain in the CNS of the rat 5th lumbar spinal nerve transection model (L5T. Results Immediately after the lesion, both cathepsins, CATS and CATX, were upregulated in the spinal cord. Moreover, we succeeded in measuring the activity of CATX, which was substantially increased after L5T. The differential expression of these proteins exhibited the same spatial distribution and temporal progression in the spinal cord, progressing up to the medulla oblongata in the late phase of chronic pain. The cellular distribution of CATS and CATX was, however, considerably different. Conclusion The cellular distribution and the spatio-temporal development of the altered expression of CATS and CATX suggest that these proteins are important players in the spinal mechanisms involved in chronic pain induction and maintenance.

  11. Expression of PirB in Normal and Injured Spinal Cord of Rats

    Institute of Scientific and Technical Information of China (English)

    周迎春; 迁荣军; 饶竞; 翁密霞; 易序霞

    2010-01-01

    The expression of paired immunoglobulin-like receptor B (PirB) in normal and injured spinal cord of rats was investigated. The SD rat hemi-sectioned spinal cord injury (SCI) model was established. Before and 1, 3, 7, 10 days after SCI, the spinal cord tissues were harvested, and Western blot and immunohistochemistry were used to examine the expression and location of PirB. The results showed that the expression level of PirB in the normal spinal cord of SD rats was low. At the first day after SCI, the expre...

  12. Axonal autophagy during regeneration of the rat sciatic nerve

    Institute of Scientific and Technical Information of China (English)

    Kangrong Lu; Zhongxian Piao; Zhenxi Liu; Weiwang Gu; Wanshan Wang; Nngjie Piao

    2008-01-01

    BACKGROUND: The removal of degenerated axonal debris during Wallerian degeneration is very important for nerve regeneration. However, the mechanism by which debris is removed is not been completely understood. Considerable controversy remains as to the clearance pathway and cells that are involved. OBJECTIVE: To investigate axonal autophagy during removal of degenerated axonal debris by transecting the sciatic nerve in a rat Wallerian degeneration model.DESIGN, TIME AND SETTING: Experimental neuropathological analysis. The experiment was conducted at the Laboratory Animal Service Center of the Southern Medical University between January and June 2005. MATERIALS: Fifty-four adult, Wistar rats of either sex, weighing 180-250 g, were obtained from the Laboratory Animal Service Center of the Southern Medical University. Animals were randomly divided into nine groups of six rats. METHODS: Wallerian degeneration was induced by transecting the rat sciatic nerve, and tissue samples from the distal stump were obtained 0.2, 0.4, 1, 2, 3, 4, 7, 10, and 15 days post-transection. Ultrathin sections were prepared for electron microscopy to study ultrastructure and enzyme cytochemistry staining. MAIN OUTCOME MEASURES: Ultrastructure (axon body, autophagic body, and cystoskeleton) of axons and myelin sheaths observed with electron microscopy; acidic phosphatase activity detected by Gomori staining using electron microscopy. RESULTS: The major changes of degenerating axons after transection were axoplasm swelling and separation of axons from their myelin sheath between five hours and two days post-transection. At four days post-transection, the axoplasm condensed and axons were completely separated from the myelin sheath, forming dissociative axon bodies. Vacuoles of different sizes formed in axons during the early phase after lesion. Larger dissociative axon bodies were formed when the axons were completely separated from the myelin sheath during a late phase. The axolemma

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

    Science.gov (United States)

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

    2015-05-01

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

  14. Propofol combined with bone marrow mesenchymal stem cell transplantation improves electrophysiological function in the hindlimb of rats with spinal cord injury better than monotherapy

    Directory of Open Access Journals (Sweden)

    Yue-xin Wang

    2015-01-01

    Full Text Available The repair effects of bone marrow mesenchymal stem cell transplantation on nervous system damage are not satisfactory. Propofol has been shown to protect against spinal cord injury. Therefore, this study sought to explore the therapeutic effects of their combination on spinal cord injury. Rat models of spinal cord injury were established using the weight drop method. Rats were subjected to bone marrow mesenchymal stem cell transplantation via tail vein injection and/or propofol injection via tail vein using an infusion pump. Four weeks after cell transplantation and/or propofol treatment, the cavity within the spinal cord was reduced. The numbers of PKH-26-positive cells and horseradish peroxidase-positive nerve fibers apparently increased in the spinal cord. Latencies of somatosensory evoked potentials and motor evoked potentials in the hindlimb were noticeably shortened, amplitude was increased and hindlimb motor function was obviously improved. Moreover, the combined effects were better than cell transplantation or propofol injection alone. The above data suggest that the combination of propofol injection and bone marrow mesenchymal stem cell transplantation can effectively improve hindlimb electrophysiological function, promote the recovery of motor funtion, and play a neuroprotective role in spinal cord injury in rats.

  15. Antiallodynic effect of tianeptine via modulation of the 5-HT7 receptor of GABAergic interneurons in the spinal cord of neuropathic rats.

    Science.gov (United States)

    Lin, Hai; Heo, Bong Ha; Kim, Woong Mo; Kim, Yong Chul; Yoon, Myung Ha

    2015-06-26

    Although tianeptine, an atypical antidepressant has been reported to have antinociceptive effects, the mode of action is different from that of tricyclic antidepressants despite structural similarities. We examined the antiallodynic effect of intrathecal tianeptine in neuropathic pain rats and determined the involvement of 5-hydroxytryptamine type 7 (5-HT7) receptor of the GABAergic interneurons in the spinal cord. Neuropathic pain was induced by spinal nerve ligation (SNL). After observation of the effect from intrathecal tianeptine, a 5-HT7 receptor antagonist (SB-269970) was administered intrathecally 10 min before delivery of tianeptine, to determine the contribution of spinal 5-HT7 receptor on the activity of tianeptine. GAD expression and GABA concentrations were assessed. Intrathecal tianeptine dose-dependently attenuated mechanical allodynia in SNL rats. Pre-treatment with intrathecal SB-269970 reversed the antiallodynic effect of tianeptine. Both GAD65 expression and the GABA concentration in the spinal cord were decreased in neuropathic rats but were increased by tianeptine. Additionally, 5-HT7 receptor and GAD65 were co-localized in the spinal cord. Intrathecal tianeptine reduces neuropathic pain. 5-HT7 receptor of the GABAergic interneurons together with GAD65 plays a role in the activity of tianeptine at the spinal cord level.

  16. Propofol injection combined with bone marrow mesenchymal stem cell transplantation better improves electrophysiological function in the hindlimb of rats with spinal cord injury than monotherapy

    Institute of Scientific and Technical Information of China (English)

    Yue-xin Wang; Jing-jing Sun; Mei Zhang; Xiao-hua Hou; Jun Hong; Ya-jing Zhou; Zhi-yong Zhang

    2015-01-01

    The repair effects of bone marrow mesenchymal stem cell transplantation on nervous system damage are not satisfactory. Propofol has been shown to protect against spinal cord injury. Therefore, this study sought to explore the therapeutic effects of their combination on spinal cord injury. Rat models of spinal cord injury were established using the weight drop method. Rats were subjected to bone marrow mesenchymal stem cell transplantationvia tail vein injection and/or propofol injectionvia tail vein using an infusion pump. Four weeks after cell transplan-tation and/or propofol treatment, the cavity within the spinal cord was reduced. The numbers of PKH-26-positive cells and horseradish peroxidase-positive nerve ifbers apparently increased in the spinal cord. Latencies of somatosensory evoked potentials and motor evoked potentials in the hindlimb were noticeably shortened, amplitude was increased and hindlimb motor function was obviously improved. Moreover, the combined effects were better than cell transplantation or propofol injection alone. The above data suggest that the combination of propofol injection and bone marrow mesenchymal stem cell transplantation can effectively improve hindlimb electro-physiological function, promote the recovery of motor funtion, and play a neuroprotective role in spinal cord injury in rats.

  17. Pre-differentiation of mesenchymal stromal cells in combination with a microstructured nerve guide supports peripheral nerve regeneration in the rat sciatic nerve model.

    Science.gov (United States)

    Boecker, Arne Hendrik; van Neerven, Sabien Geraldine Antonia; Scheffel, Juliane; Tank, Julian; Altinova, Haktan; Seidensticker, Katrin; Deumens, Ronald; Tolba, Rene; Weis, Joachim; Brook, Gary Anthony; Pallua, Norbert; Bozkurt, Ahmet

    2016-02-01

    Many bioartificial nerve guides have been investigated pre-clinically for their nerve regeneration-supporting function, often in comparison to autologous nerve transplantation, which is still regarded as the current clinical gold standard. Enrichment of these scaffolds with cells intended to support axonal regeneration has been explored as a strategy to boost axonal regeneration across these nerve guides Ansselin et al. (1998). In the present study, 20 mm rat sciatic nerve defects were implanted with a cell-seeded microstructured collagen nerve guide (Perimaix) or an autologous nerve graft. Under the influence of seeded, pre-differentiated mesenchymal stromal cells, axons regenerated well into the Perimaix nerve guide. Myelination-related parameters, like myelin sheath thickness, benefitted from an additional seeding with pre-differentiated mesenchymal stromal cells. Furthermore, both the number of retrogradely labelled sensory neurons and the axon density within the implant were elevated in the cell-seeded scaffold group with pre-differentiated mesenchymal stromal cells. However, a pre-differentiation had no influence on functional recovery. An additional cell seeding of the Perimaix nerve guide with mesenchymal stromal cells led to an extent of functional recovery, independent of the differentiation status, similar to autologous nerve transplantation. These findings encourage further investigations on pre-differentiated mesenchymal stromal cells as a cellular support for peripheral nerve regeneration. © 2015 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

  18. The reparative response to cross-linked collagen-based scaffolds in a rat spinal cord gap model.

    Science.gov (United States)

    Cholas, Rahmatullah H; Hsu, Hu-Ping; Spector, Myron

    2012-03-01

    Prior work demonstrated the improvement of peripheral nerve regeneration in gaps implanted with collagen scaffold-filled collagen tubes, compared with nerve autografts, and the promise of such implants for treating gaps in spinal cord injury (SCI) in rats. The objective of this study was to investigate collagen implants alone and incorporating select therapeutic agents in a 5-mm full-resection gap model in the rat spinal cord. Two studies were performed, one with a 6-week time point and one with a 2-week time point. For the 6-week study the groups included: (1) untreated control, (2) dehydrothermally (DHT)-cross-linked collagen scaffold, (3) DHT-cross-linked collagen scaffold seeded with adult rat neural stem cells (NSCs), and (4) DHT-cross-linked collagen scaffold incorporating plasmid encoding glial cell line-derived neurotropic factor (pGDNF). The 2-week study groups were: (1) nontreated control, (2) DHT-cross-linked collagen scaffold; (3) DHT-cross-linked collagen scaffold containing laminin; and (4) carbodiimide-cross-linked collagen scaffold containing laminin. The tissue filling the defect of all groups at 6 weeks was largely composed of fibrous scar; however, the tissue was generally more favorably aligned with the long axis of the spinal cord in all of the treatment groups, but not in the control group. Quantification of the percentage of animals per group containing cystic cavities in the defect showed a trend toward fewer rats with cysts in the groups in which the scaffolds were implanted compared to control. All of the collagen implants were clearly visible and mostly intact after 2 weeks. A band of fibrous tissue filling the control gaps was not seen in the collagen implant groups. In all of the groups there was a narrowing of the spinal canal within the gap as a result of surrounding soft tissue collapse into the defect. The narrowing of the spinal canal occurred to a greater extent in the control and DHT scaffold alone groups compared to the DHT

  19. 减重步行训练对脊髓损伤大鼠干细胞移植后神经细胞诱导分化的影响%Body weight supported treadmill training on nerve cells differentiation after stem cells transplantation in rats of spinal cord injury

    Institute of Scientific and Technical Information of China (English)

    董春磊; 王宝兰; 李忠伟; 谢冲; 赵学飞; 杨春生; 张小宁

    2015-01-01

    ,联合治疗组神经特异性标志物(NSE、MAP-1 β、VIM)荧光表达明显强于其余3组,同时可见明显的神经纤维增生和分化.结论 干细胞移植结合减重步行训练可有效促进SCI大鼠神经功能的恢复,且效果明显优于单纯干细胞移植组和减重步行训练组.%Objective To investigate the effect of bone marrow stem cells (BMSCs) transplantation combined with body weight supported treadmill training on neural functional recovery of rats with spinal cord injury.Methods T11 complete spinal cord injury (SCI) was introduced into 40 Sprague-Dawley male rats using an improved simple device,imitating the Allen method.The rats were randomly divided into a stem cell transplantation group,a body weight support treadmill training group,a combined treatment group and a control group,each of 10 assigned according to a random number table.One week after the SCI operation,stem cell transplantation was performed on the rats in the stem cell transplantation group and the combined treatment group.One day before their transplantation,the third passage BMSCs were labeled with 5-ethynyl-2'-deoxyuridine (Edu).The rats in body weight support treadmill training group and combined treatment group were received body weight support treadmill training,while the other two groups were not given any training.At the 1 st,2nd,3rd,4th and 5th week after SCI modeling,Basso-Beattie-Bresnahan (BBB) movement function score was used to evaluate the motor function recovery of all rats.At the 5 th week after SCI,immunohistochemical staining and immunofluorescence staining was applied to detect neural specific markers including the neuron specific enolase (NSE),microtubule associated protein (MAP-1 β) and vimentin (VIM).The survival and differentiation of the transplanted cells,as well as the nerve fiber recovery in the lesion were also observed.Results The average BBB score of the combined treatment group was (6.60 ± 0.97) at the 2nd week after SCI operation

  20. Muscarinic excitatory and inhibitory mechanisms involved in afferent fibre-evoked depolarization of motoneurones in the neonatal rat spinal cord.

    Science.gov (United States)

    Kurihara, T.; Suzuki, H.; Yanagisawa, M.; Yoshioka, K.

    1993-01-01

    1. The involvement of acetylcholine and muscarinic receptors in spinal synaptic responses evoked by electrical and noxious sensory stimuli was investigated in the neonatal rat spinal cord in vitro. 2. Potentials were recorded extracellularly from a ventral root (L3-L5) of the isolated spinal cord, spinal cord-cutaneous nerve, and spinal cord-skin preparations of 1- to 4-day-old rats. Spinal reflexes were elicited by electrical stimulation of the ipsilateral dorsal root or the cutaneous saphenous nerve, or by noxious skin stimulation. 3. Single shock stimulation of supramaximum intensity of a dorsal root induced a mono-synaptic reflex in the corresponding ventral root. Bath-application of the muscarinic agonists, muscarine (0.3-30 microM) and (+)-cis-dioxolane (0.1-100 microM), produced an inhibition of the mono-synaptic reflex and a depolarization of motoneurones. Other muscarinic agonists, arecoline (10 nM-10 microM) and oxotremorine (10 nM-1 microM), inhibited the mono-synaptic reflex with little or no depolarization of motoneurones. Repetitive stimulation of the saphenous nerve at C-fibre strength induced a slow depolarizing response lasting about 30 s of the L3 ventral root. This slow ventral root potential (VRP) was also inhibited by arecoline (10 nM-10 microM) and oxotremorine (10 nM-1 microM). 4. In the spinal cord-saphenous nerve-skin preparation, a slow VRP was evoked by application of capsaicin (0.5 microM), bradykinin (3 microM), or noxious heat (47 degrees C) to skin. This slow VRP was depressed by the muscarinic agonists, arecoline (3 microM) and oxotremorine (1 microM). 5. Of the (+)-cis-dioxolane-induced inhibition of mono-synaptic reflex and motoneurone depolarization, the M2 antagonists, AF-DX 116 (0.1-1 microM) and methoctramine (100-300 nM), preferentially blocked the former response, whereas the M3 antagonists, 4-DAMP (3-10 nM) and p-F-HHSiD (0.3-3 microM), preferentially blocked the latter response. AF-DX 116 (0.1-1 microM) and methoctramine

  1. Altered distribution of interstitial cells and innervation in the rat urinary bladder following spinal cord injury.

    Science.gov (United States)

    Johnston, Louise; Cunningham, Rebecca M J; Young, John S; Fry, Christopher H; McMurray, Gordon; Eccles, Rachel; McCloskey, Karen D

    2012-07-01

    Changes in the distribution of interstitial cells (IC) are reportedly associated with dysfunctional bladder. This study investigated whether spinal cord injury (SCI) resulted in changes to IC subpopulations (vimentin-positive with the ultrastructural profile of IC), smooth muscle and nerves within the bladder wall and correlated cellular remodelling with functional properties. Bladders from SCI (T8/9 transection) and sham-operated rats 5 weeks post-injury were used for ex vivo pressure-volume experiments or processed for morphological analysis with transmission electron microscopy (TEM) and light/confocal microscopy. Pressure-volume relationships revealed low-pressure, hypercompliance in SCI bladders indicative of decompensation. Extensive networks of vimentin-positive IC were typical in sham lamina propria and detrusor but were markedly reduced post-SCI; semi-quantitative analysis showed significant reduction. Nerves labelled with anti-neurofilament and anti-vAChT were notably decreased post-SCI. TEM revealed lamina propria IC and detrusor IC which formed close synaptic-like contacts with vesicle-containing nerve varicosities in shams. Lamina propria and detrusor IC were ultrastructurally damaged post-SCI with retracted/lost cell processes and were adjacent to areas of cellular debris and neuronal degradation. Smooth muscle hypertrophy was common to SCI tissues. In conclusion, IC populations in bladder wall were decreased 5 weeks post-SCI, accompanied with reduced innervation, smooth muscle hypertrophy and increased compliance. These novel findings indicate that bladder wall remodelling post-SCI affects the integrity of interactions between smooth muscle, nerves and IC, with compromised IC populations. Correlation between IC reduction and a hypercompliant phenotype suggests that disruption to bladder IC contribute to pathophysiological processes underpinning the dysfunctional SCI bladder.

  2. Rat whisker movement after facial nerve lesion: Evidence for autonomic contraction of skeletal muscle.

    NARCIS (Netherlands)

    Heaton, J.T.; Sheu, S.H.; Hohman, M.H.; Knox, C.J.; Weinberg, J.S.; Kleiss, I.J.; Hadlock, T.A.

    2014-01-01

    Vibrissal whisking is often employed to track facial nerve regeneration in rats; however, we have observed similar degrees of whisking recovery after facial nerve transection with or without repair. We hypothesized that the source of non-facial nerve-mediated whisker movement after chronic denervati

  3. Near infrared Raman spectroscopic study of reactive gliosis and the glial scar in injured rat spinal cords

    Science.gov (United States)

    Saxena, Tarun; Deng, Bin; Lewis-Clark, Eric; Hoellger, Kyle; Stelzner, Dennis; Hasenwinkel, Julie; Chaiken, Joseph

    2010-02-01

    Comparative Raman spectra of ex vivo, saline-perfused, injured and healthy rat spinal cord as well as experiments using enzymatic digestion suggest that proteoglycan over expression may be observable in injured tissue. Comparison with authentic materials in vitro suggest the occurrence of side reactions between products of cord digestion with chondroitinase (cABC) that produce lactones and similar species with distinct Raman features that are often not overlapped with Raman features from other chemical species. Since the glial scar is thought to be a biochemical and physical barrier to nerve regeneration, this observation suggests the possibility of using near infrared Raman spectroscopy to study disease progression and explore potential treatments ex vivo and if potential treatments can be designed, perhaps to monitor potential remedial treatments within the spinal cord in vivo.

  4. Morphological and electrophysiological evidence for regeneration of transected spinal cord fibers and restoration of motor functions in adult rats

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    After 2/3 transection of the right ninth thoracic spinal cord of an adult rat, a chitosan tube seeded with L-poly-lysine was implanted between the rostral and caudal end of the lesioned cord. Twelve months after the operation, regeneration of myelinated and non-myelinated axons and new blood vessels were observed along the wall of the chitosan tube implanted under an electron microscope. Somatosensory evoked potentials (SEP) could be consistently recorded from the left somatosensory cortex following electrical stimulation of the right hind limb, while transcranial magnetic stimulation of the left motor cortex could also evoke motor activity from the right hind limb. The present result suggests that implanted chitosan tube might be useful in regeneration of injured nerve fibers of the spinal cord resulting in a long-term restoration of motor functions.

  5. Effects of Afferent Stimulation of the Lingual Nerve on Gastrointestinal Motility in the Rat

    Directory of Open Access Journals (Sweden)

    Sugimoto,Masaharu

    1987-06-01

    Full Text Available Effects of afferent stimulation of the lingual nerve (LNAS on gastrointestinal motility and the reflex pathways which mediate the response to LNAS were investigated in rats. LNAS induced excitatory, inhibitory or biphasic responses in the stomach, duodenum and proximal colon. These responses continued after bilateral vagotomy, but were abolished after additional bilateral splanchnicotomy or transection of the spinal cord between Th4 and Th5. The inhibitory, excitatory and biphasic responses induced by LNAS were not affected by decerebration. Both after administration of atropine (0.2 mg/kg, i.v. and guanethidine (3-5 mg/kg, i.v., LNAS-induced excitatory and inhibitory responses were abolished in most cases, but the slight inhibitory response in the stomach and duodenum to LNAS remained in a few cases. These results suggest that the reflex centers which cause LNAS-induced excitatory and inhibitory responses are located in the dorsal nucleus of vagus and that the reflex pathways include the vagus and splanchnic nerves.

  6. The promotion of functional recovery and nerve regeneration after spinal cord injury by lentiviral vectors encoding Lingo-1 shRNA delivered by Pluronic F-127.

    Science.gov (United States)

    Wu, Hong-Fu; Cen, Jing-Sheng; Zhong, Qian; Chen, Luming; Wang, Jue; Deng, David Y B; Wan, Yong

    2013-02-01

    Lingo-1 is selectively expressed on both oligodendrocytes and neurons in the central nervous system (CNS) and serves as a key negative regulator of nerve regeneration, implying a therapeutic target for spinal cord injury (SCI). Here we described a strategy to knock-down Lingo-1 expression in vivo using lentiviral vectors encoding Lingo-1 short harpin interfering RNA (shRNA) delivered by Pluronic F-127 (PF-127) gel, a non-cytotoxic scaffold and gene delivery carrier, after the complete transection of the T10 spinal cord in adult rats. We showed administration of PF-127 encapsulating Lingo-1 shRNA lentiviral vectors efficiently down-regulated the expression of Lingo-1, and exhibited transduction efficiency comparable to using vectors alone in oligodendrocyte culture in vitro. Furthermore, similar silencing effects and higher transfection efficiency were observed in vivo when Lingo-1 shRNA was co-delivered to the injured site by PF-127 gel with lower viral concentrations. Cografting of gel and Lingo-1 RNAi significantly promoted functional recovery and nerve regeneration, enhanced neurite outgrowth and synapses formation, preserved myelinated axons, and induced the proliferation of glial cells. In addition, the combined implantation also improved neuronal survival and inhibited cell apoptosis, which may be associated with the attenuation of endoplasmic reticulum (ER) stress after SCI. Together, our data indicated that delivering Lingo-1 shRNA by gel scaffold was a valuable treatment approach to SCI and PF-127 delivery of viral vectors to the spinal cord may provide strategy to study and develop therapies for SCI.

  7. Survival of transplanted neurotrophin-3 expressing human neural stem cells and motor function in a rat model of spinal cord injury

    Institute of Scientific and Technical Information of China (English)

    Peiqiang Cai; Guangyun Sun; Peishu Cai; Martin Oudega; Rui Xiao; Xuewen Wang; Wei Li; Yunbing Shu; Cheng Cai; Haihao Yang; Xuebing Shan; Wuhua Luo

    2009-01-01

    BACKGROUND: Many methods have been attempted to repair nerves following spinal cord injury,including peripheral nerve transplantation, Schwann cell transplantation, olfactory ensheathing cell transplantation, and embryonic neural tissue transplantation. However, there is a need for improved outcomes.OBJECTIVE: To investigate the repair feasibility for rat spinal cord injury using human neural stem cells (hNSCs) genetically modified by lentivirus to express neurotrophin-3.DESIGN, TIME AND SETTING: In vitro cell biological experiment and in vivo randomized, controlled,genetic engineering experiment were performed at the Third Military Medical University of Chinese PLA and First People's Hospital of Yibin, China from March 2006 to December 2007.MATERIALS: A total of 64 adult, female, Wistar rats were used for the in vivo study. Of them, 48 rats were used to establish models of spinal cord hemisection, and were subsequently equally and randomly assigned to model, genetically modified hNSC, and normal hNSC groups. The remaining 16 rats served as normal controls.METHODS: hNSCs were in vitro genetically modified by lentivirus to secrete both green fluorescence protein and neurotrophin-3. Neurotrophin-3 expression was measured by Westem blot.Genetically modified hNSC or normal hNSC suspension (5×105) was injected into the rat spinal cord following T10 spinal cord hemisection. A total of 5μL Dulbecco's-modified Eagle's medium was infused into the rat spinal cord in the model group. Transgene expression and survival of transplanted hNSCs were determined by immunohistochemistry. Motor function was evaluatedusing the Basso, Beattie, and Bresnahan (BBB) scale.MAIN OUTCOME MEASURES: The following parameters were measured: expression ofneurotrophin-3 produced by genetically modified hNSCs, transgene expression and survival ofhNSCs in rats, motor function in rats.RESULTS: hNSCs were successfully genetically modified by lentivirus to stably express neurotrophin-3. The

  8. L-carnitine alleviates sciatic nerve crush injury in rats:functional and electron microscopy assessments

    Institute of Scientific and Technical Information of China (English)

    Ümmü Zeynep Avsar; Umit Avsar; Ali Aydin; Muhammed Yayla; Berna Ozturkkaragoz; Harun Un; Murat Saritemur; Tolga Mercantepe

    2014-01-01

    Several studies have demonstrated that L-carnitine exhibits neuroprotective effects on injured sciatic nerve of rats with diabetes mellitus. It is hypothesized that L-carnitine exhibits neuro-protective effects on injured sciatic nerve of rats. Rat sciatic nerve was crush injured by a forceps and exhibited degenerative changes. After intragastric administration of 50 and 100 mg/kg L-carnitine for 30 days, axon area, myelin sheath area, axon diameter, myelin sheath diameter, and numerical density of the myelinated axons of injured sciatic nerve were similar to normal, and the function of injured sciatic nerve also improved signiifcantly. These ifndings suggest that L-carnitine exhibits neuroprotective effects on sciatic nerve crush injury in rats.

  9. Concentration-dependent neurotoxicity of articaine: an electrophysiological and stereological study of the rat sciatic nerve

    DEFF Research Database (Denmark)

    Hillerup, Søren; Bakke, Merete; Larsen, Jytte Overgaard;

    2011-01-01

    We performed this study to quantify the detrimental effect of intraneural injection of 50 μL of saline, articaine 2%, or articaine 4% in the rat sciatic nerve.......We performed this study to quantify the detrimental effect of intraneural injection of 50 μL of saline, articaine 2%, or articaine 4% in the rat sciatic nerve....

  10. Functional evaluation of peripheral nerve regeneration in the rat : walking track analysis

    NARCIS (Netherlands)

    Varejao, ASP; Meek, MF; Patricio, JAB; Cabrita, AMS

    2001-01-01

    The experimental model of choice for many peripheral nerve investigators is the rat. Walking track analysis is a useful tool in the evaluation of functional peripheral nerve recovery in the rat. This quantitative method of analyzing hind limbs performance by examining footprints, known as the sciati

  11. Semaphorin 3A expression in spinal cord injured rats after olfactory ensheathing cell transplantation

    Institute of Scientific and Technical Information of China (English)

    Guoyu Wang; Xijing He; Puwei Yuan; Haopeng Li; Rui Chang

    2011-01-01

    Semaphorin 3A expression is thought to increase following spinal cord injury. The impact of olfactory ensheathing cell transplantation remains unclear. The current study demonstrated that spinal cord hemorrhage, edema, degeneration, necrosis, cyst formation, proliferation of glial cells, regeneration of nerve fibers and various pathological reactions occurred following a simple cross-section of spinal cord injury. Transplantation of olfactory ensheathing cells was found to significantly relieve the pathological reactions in the spinal cord described above, decrease the extent of necrosis in damaged neurons and nerve fibers, and downregulate semaphorin 3A expression in the injured zone. The results confirmed that olfactory ensheathing cell transplantation plays a protective role on the injured spinal cord by reducing the expression of semaphorin 3A.

  12. Mats made from fibronectin support oriented growth of axons in the damaged spinal cord of the adult rat.

    Science.gov (United States)

    King, Von R; Henseler, Manuel; Brown, Robert A; Priestley, John V

    2003-08-01

    A variety of biological as well as synthetic implants have been used to attempt to promote regeneration into the damaged spinal cord. We have implanted mats made from fibronectin (FN) into the damaged spinal cord to determine their effectiveness as a substrate for regeneration of axons. These mats contain oriented pores and can take up and release growth factors. Lesion cavities 1 mm in width and depth and 2 mm in length were created on one side of the spinal cord of adult rats. FN mats containing neurotrophins or saline were placed into the lesion. Mats were well integrated into surrounding tissue and showed robust well-oriented growth of calcitonin gene-related peptide, substance P, GABAergic, cholinergic, glutamatergic, and noradrenergic axons into FN mats. Transganglionic tracing using cholera toxin B indicated large-diameter primary afferents had grown into FN implants. Schwann cells had also infiltrated FN mats. Electron microscopy confirmed the presence of axons within implants sites, with most axons either ensheathed or myelinated by Schwann cells. Mats incubated in brain-derived neurotrophic factor and neurotrophin-3 showed significantly more neurofilament-positive and glutamatergic fibers compared to saline- and nerve growth factor-incubated mats, while mats incubated with nerve growth factor showed more calcitonin gene-related peptide-positive axons. In contrast, neurotrophin treatment had no effect on PGP 9.5-positive axons. In addition, in some animals with neurotrophin-3-incubated mats, cholera toxin B-labelled fibers had grown from the mat into adjoining intact areas of spinal cord. The results indicate that FN mats provide a substrate that is permissive for robust oriented axonal growth in the damaged spinal cord, and that this growth is supported by Schwann cells.

  13. LIN28 expression in rat spinal cord after injury.

    Science.gov (United States)

    Yue, Ying; Zhang, Dongmei; Jiang, Shengyang; Li, Aihong; Guo, Aisong; Wu, Xinming; Xia, Xiaopeng; Cheng, Hongbing; Tao, Tao; Gu, Xingxing

    2014-05-01

    LIN28, an RNA-binding protein, is known to be involved in the regulation of many cellular processes, such as embryonic stem cell proliferation, cell fate succession, developmental timing, and oncogenesis. However, its expression and function in central nervous system still unclear. In this study, we performed an acute spinal cord contusion injury (SCI) model in adult rats and investigated the dynamic changes of LIN28 expression in spinal cord. Western blot and immunohistochemistry analysis revealed that LIN28 was present in normal spinal cord. It gradually increased, reached a peak at 3 day, and then nearly declined to the basal level at 14 days after SCI. Double immunofluorescence staining showed that LIN28 immunoreactivity was found in neurons, astrocytes and a handful of microglia. Interestingly, LIN28 expression was increased predominantly in astrocytes but not in neurons. Moreover, the colocalization of LIN28 and proliferating cell nuclear antigen was detected after injury. Western blot showed that LIN28 participated in lipopolysaccharide (LPS) induced astrocytes inflammatory responses by NF-κB signaling pathway. These results suggested that LIN28 may be involved in the pathologic process of SCI, and further research is needed to have a good understanding of its function and mechanism.

  14. Isobolographic analysis of caramiphen and lidocaine on spinal anesthesia in rats.

    Science.gov (United States)

    Chen, Yu-Wen; Chu, Chin-Chen; Chen, Yu-Chung; Wang, Jhi-Joung; Hung, Ching-Hsia

    2010-01-18

    The aims of the study were to evaluate the spinal anesthetic effect of caramiphen and also assess spinal anesthetic interactions of caramiphen with lidocaine. Lidocaine, a common local anesthetic, was used as control. Dose-dependent responses of intrathecal caramiphen on spinal anesthesia were compared with lidocaine in rats. The interactions of caramiphen with lidocaine were evaluated via an isobolographic analysis. Caramiphen and lidocaine produced a dose-dependent local anesthetic effect as spinal anesthesia. On a 50% effective dose (ED(50)) basis, the spinal anesthetic effect of caramiphen was more potent than lidocaine (P<0.01 for each comparison). Co-administration of caramiphen with lidocaine produced an additive effect. Caramiphen and lidocaine are known to have local anesthetic effects as spinal anesthesia in rats. The spinal anesthetic effects of adding caramiphen to lidocaine are similar to the combinations of other anesthetics with lidocaine.

  15. FUNCTIONAL AND STRUCTURAL RECOVERY OF INJURED SPINAL CORD FOLLOWING DELAYED X-IRRADIATION IN RATS

    Institute of Scientific and Technical Information of China (English)

    Xin-gang Li; De-ze Jia; Dong-hai Wang; Yu-hang Su; Qing-lin Zhang

    2007-01-01

    Objective To test the hypothesis that delayed X-irradiation can enhance the functional and structural recovery of the injured spinal cord in rats,Methods Seventy Sprague-Dawley rats were randomly divided into two groups, 35 rats in each. The control group sustained a one-minute clip compression (force of clip was 30 g) injury of the spinal cord at the T2 level, without X-irradiation. The experimental group received X-irradiation 14 days after injury. Neurological function was assessed by the modified Tarlov method, including hind limbs movement, inclined plane, and pain withdrawal. These tests were performed in a blinded fashion at 3, 7, 14, 21, 28, 35 , and 42 days after injury. At 43 days after injury, histological examination of the injured spinal cord was performed following decapitation of the rats.Results Sixty-two rats met the experimental requirements (spinal cord injury was similar), 32 rats in experimental group and 30 rats in control group. Statistically significant difference was observed between the two groups in hind limbs movement and inclined plane (P <0.01), but not in the pain withdrawal test The edema and necrosis areas of injured spinal cords in experimental group were less than those in control group, and axons in experimental group were significantly more than those in control group (P < 0.01).Conclusion Delayed X-irradiation following spinal cord injury may enhance functional recovery by improving and restoring structural integrity of the injured spinal cord in rats.

  16. Long-lasting neonatal inflammation enhances pain responses to subsequent inflammation, but not peripheral nerve injury in adult rats.

    Science.gov (United States)

    Lim, Eun Jeong; Back, Seung Keun; Kim, Myung Ah; Li, Chengjin; Lee, Jaehee; Jeong, Keun Yeong; Na, Heung Sik

    2009-05-01

    The early postnatal period has been suggested to be the vulnerable time for structural and functional reorganization of sensory systems, and painful stimuli at this time may alter neuronal circuits, thereby leading to changes in an individual's response to pain later in life. In the present study, we examined whether inflammatory experience in the early life can affect pain responses to subsequent noxious insults later in life. The two groups of neonatal rats, treated with an inflammatory irritant and untreated, were subjected to inflammation and peripheral nerve injury in adulthood. Neonatal inflammation was induced by injection of complete Freund's adjuvant (CFA, 25 microl) into the hindpaw or tail of newborn rat pups. Adult rats which had suffered from neonatal paw inflammation at P0 were subjected to re-injection of CFA into the paw neonatally exposed to CFA or L5 spinal nerve ligation. Paw thickness and histology of inflamed paw were examined to assess the neonatal inflammation. Adult animals whose tail had been subjected to CFA injection on P3 received tail-innervating nerve injury. The results showed that the neonatal CFA-treated rats suffered from chronic inflammation, confirmed by persistent increase of paw thickness and histological result of inflamed paw. These animals showed enhanced pain responses to re-inflammatory challenge by injection of CFA (200 microl) into the neonatally inflamed paw 8 weeks after birth compared with the neonatally untreated animals. However, neuropathic pain on the hindpaw and the tail which had been induced by peripheral nerve injury in the neonatal CFA-treated group were not different from those of the untreated group. The present data suggest that early neonatal long-lasting inflammation differentially affects pain responses later in life, depending on the types of subsequent noxious insults.

  17. Histopathological Analysis Of Gangliosides Use In Peripheral Nerve Regeneration After Axonotmesis In Rats

    OpenAIRE

    Camila Maria Beder Ribeiro; Belmiro Cavalcanti do Egito Vasconcelos; Joaquim Celestino da Silva Neto; Valdemiro Amaro da Silva Júnior; Nancy Gurgel Figueiredo

    2008-01-01

    PURPOSE: To analyze the action of gangliosides in peripheral nerve regeneration in the sciatic nerve of the rat. METHODS: The sample was composed of 96 male Wistar rats. The animals were anaesthetized and, after identification of the anaesthesic plane, an incision was made in the posterior region of the thigh, followed by skin and muscle divulsion. The right sciatic nerve was isolated and compressed for 2 minutes. Continuous suture of the skin was performed. The animals were randomly divided ...

  18. [REACTIVE CHANGES IN SPINAL CORD MOTONEURONS AFTER SCIATIC NERVE INJURY AFTER HIGH-FREQUENCY ELECTROSURGICAL INSTRUMENT APPLICATION].

    Science.gov (United States)

    Korsak, A; Chaikovsky, Yu; Sokurenko, L; Likhodiievskyi, V; Neverovskyi, A

    2016-02-01

    A new experimental model for tissues connection at peripheral nerve injury site in form of tissues welding was designed. In current study we investigated motoneuron state 1, 3, 6 and 12 weeks after peripheral nerve injury and surgical repair with high-frequency electrosurgical technology. Spinal cord sections was stained by Nissl method and observed with light microscopy. We found that postoperative period in animals from experimental groups characterized by qualitative changes in neurons from spinal motor centers that can be interpreted as compensatory processes as response to alteration. In animals from group with high-frequency electrosurgical technology usage stabilization processes passes more quickly comparatively to animals with epineural sutures. High-frequency electrosurgical technology usage provides less harmful effects on motoneurons than epineural suturing.

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

    Science.gov (United States)

    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.

  20. Palmitoylethanolamide Inhibits Glutamate Release in Rat Cerebrocortical Nerve Terminals

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    Tzu-Yu Lin

    2015-03-01

    Full Text Available The effect of palmitoylethanolamide (PEA, an endogenous fatty acid amide displaying neuroprotective actions, on glutamate release from rat cerebrocortical nerve terminals (synaptosomes was investigated. PEA inhibited the Ca2+-dependent release of glutamate, which was triggered by exposing synaptosomes to the potassium channel blocker 4-aminopyridine. This release inhibition was concentration dependent, associated with a reduction in cytosolic Ca2+ concentration, and not due to a change in synaptosomal membrane potential. The glutamate release-inhibiting effect of PEA was prevented by the Cav2.1 (P/Q-type channel blocker ω-agatoxin IVA or the protein kinase A inhibitor H89, not affected by the intracellular Ca2+ release inhibitors dantrolene and CGP37157, and partially antagonized by the cannabinoid CB1 receptor antagonist AM281. Based on these results, we suggest that PEA exerts its presynaptic inhibition, likely through a reduction in the Ca2+ influx mediated by Cav2.1 (P/Q-type channels, thereby inhibiting the release of glutamate from rat cortical nerve terminals. This release inhibition might be linked to the activation of presynaptic cannabinoid CB1 receptors and the suppression of the protein kinase A pathway.

  1. Early applied electric field stimulation attenuates secondary apoptotic responses and exerts neuroprotective effects in acute spinal cord injury of rats.

    Science.gov (United States)

    Zhang, C; Zhang, G; Rong, W; Wang, A; Wu, C; Huo, X

    2015-04-16

    Injury potential, which refers to a direct current voltage between intact and injured nerve ends, is mainly caused by injury-induced Ca2+ influx. Our previous studies revealed that injury potential increased with the onset and severity of spinal cord injury (SCI), and an application of applied electric field stimulation (EFS) with the cathode distal to the lesion could delay and attenuate injury potential formation. As Ca2+ influx is also considered as a major trigger for secondary injury after SCI, we hypothesize that EFS would protect an injured spinal cord from secondary injury and consequently improve functional and pathological outcomes. In this study, rats were divided into three groups: (1) sham group, laminectomy only; (2) control group, subjected to SCI only; and (3) EFS group, received EFS immediately post-injury with the injury potential modulated to 0±0.5 mV by EFS. Functional recovery of the hind limbs was assessed using the Basso, Beattie, and Bresnahan (BBB) locomotor scale. Results revealed that EFS-treated rats exhibited significantly better locomotor function recovery. Luxol fast blue staining was performed to assess the spared myelin area. Immunofluorescence was used to observe the number of myelinated nerve fibers. Ultrastructural analysis was performed to evaluate the size of myelinated nerve fibers. Findings showed that the EFS group rats exhibited significantly less myelin loss and had larger and more myelinated nerve fibers than the control group rats in dorsal corticospinal tract (dCST) 8 weeks after SCI. Furthermore, we found that EFS inhibited the activation of calpain and caspase-3, as well as the expression of Bax, as detected by Western blot analysis. Moreover, EFS decreased cellular apoptosis, as measured by TUNEL, within 4 weeks post-injury. Results suggest that early EFS could significantly reduce spinal cord degeneration and improve functional and historical recovery. Furthermore, these neuroprotective effects may be related to

  2. Chitosan-cross-linked nanofibrous PHBV nerve guide for rat sciatic nerve regeneration across a defect bridge.

    Science.gov (United States)

    Biazar, Esmaeil; Keshel, Saeed Heidari

    2013-01-01

    The aim of this study was to produce a chitosan-cross-linked nanofibrous biodegradable poly (3-hydroxybutyrate-co-3-hydroxyvalerate) nerve conduit. The artificial nerve scaffold designed by electrospinning method and cross-linked with chitosan by chemical method. Afterwards, the scaffolds were evaluated by microscopic, physical, and mechanical analyses and cell culture assays with Schwann cells. The conduits were implanted into a 10 mm gap in the sciatic nerves of the rats. Four months after surgery, the regenerated nerves were evaluated by macroscopic assessments and histology. This polymeric conduit had sufficiently good mechanical properties to serve as a nerve guide. Cellular experiments showed a better cell adhesion, growth, and proliferation inside the cross-linked nanofibrous scaffolds compared with un-cross-linked ones, also Schwann cells well attached on chitosan-cross-linked nanofibrous surface. The in vivo results demonstrated that in the nanofibrous graft, the sciatic nerve trunk had been reconstructed with restoration of nerve continuity and formatted nerve fibers with myelination. This neural conduit appears to have the right organization for testing in vivo nerve tissue engineering studies.

  3. Changes in retinal nerve fiber layer thickness after spinal surgery in the prone position: a prospective study

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    Baran Gencer

    2015-02-01

    Full Text Available BACKGROUND AND OBJECTIVES: Changes in ocular perfusion play an important role in the pathogenesis of ischemic optic neuropathy. Ocular perfusion pressure is equal to mean arterial pressure minus intraocular pressure. The aim of this study was to evaluate the changes in the intraocular pressure and the retinal nerve fiber layer thickness in patients undergoing spinal surgery in the prone position. METHODS: This prospective study included 30 patients undergoing spinal surgery. Retinal nerve fiber layer thickness were measured one day before and after the surgery by using optical coherence tomography. Intraocular pressure was measured by tonopen six times at different position and time-duration: supine position (baseline; 10 min after intubation (Supine 1; 10 (Prone 1, 60 (Prone 2, 120 (Prone 3 min after prone position; and just after postoperative supine position (Supine 2. RESULTS: Our study involved 10 male and 20 female patients with the median age of 57 years. When postoperative retinal nerve fiber layer thickness measurements were compared with preoperative values, a statistically significant thinning was observed in inferior and nasal quadrants (p = 0.009 and p = 0.003, respectively. We observed a statistically significant intraocular pressure decrease in Supine 1 and an increase in both Prone 2 and Prone 3 when compared to the baseline. Mean arterial pressure and ocular perfusion pressure were found to be significantly lower in Prone 1, Prone 2 and Prone 3, when compared with the baseline. CONCLUSIONS: Our study has shown increase in intraocular pressure during spinal surgery in prone position. A statistically significant retinal nerve fiber layer thickness thinning was seen in inferior and nasal quadrants one day after the spinal surgery.

  4. Partial epineural burying of nerve grafts with different sizes next to or distant from neurorrhaphy?s site: histological and electrophysiological studies in rat sciatic nerves

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    Cunha Marco Túlio Rodrigues da

    2001-01-01

    Full Text Available The aim of the present study was to compare and correlate histologically and electromyographically the effects of partial epineural burying of sural nerve segments in sectioned and sutured rat sciatic nerves. Sixty adult male Wistar rats were operated on 3 groups: Group 1, sural nerve graft, 9mm long, placed next to neurorrhaphy; Group 2, sural nerve graft, 9mm long, buryied 10mm distant from neurorrhaphy; Group 3, sural nerve graft, 18mm long, set next to neurorrhaphy. The morphological features were examined at light microscope after 3 months in 45 rats. The elements observed were: vascularization, vacuoles in nerve fibers, mastocytes and inflammatory infiltrate. The morphometry was made after 6 months in 15 rats from Group 1, 2 and 3, measuring external nerve fiber diameters and counting myelinated nerve fibers/mm². The electrophysiological study was perfomed after 6 months, registering maximum amplitude and frequency of EMG pontentials, at rest, in extensor digitorum longus muscle. Group 3 rats presented sciatic nerves better conserved morphologically and mean external nerve fiber diameters greater than those from Groups 1 and 2. There were no significant differences in density of nerve fibers/mm², and in the electrophysiological study in rats from Group 1, 2 and 3. The epineural burying of sural nerve grafts with greater length and placed next to the neurorrhaphy?s site had a significantly better regeneration of the histological features than the smaller ones distant from neurorrhaphy.

  5. Developmental Changes In Pain And Spinal Immune Gene Expression After Radicular Trauma In The Rat

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    Gordon Alfred Barr

    2016-12-01

    Full Text Available Neuropathic pain is an example of chronic pain that develops after nerve injury and is less frequent in infants and children than in adults. Likewise, in animal models of neuropathic pain, allodynia and hyperalgesia are non-existent or attenuated in the infant, with a switch during development by which acute nerve injury transitions to chronic pain. Concomitant with the delay in neuropathic pain, there is a parallel delay in the ability of nerve injury to activate the immune system. Models of neuropathic pain in the infant have used various ligation methods and find that neuropathic pain does not occur under after postnatal day 21-28 (PN21-PN28, linked to activation of immune processes and developmental regulation of anti-inflammatory cytokines. We applied a model of neuropathic pain in the adult using a transient compression of the cervical nerve or nerve root in infant rats (injured at 10, 14, 21 or 28 days of age to define transition periods during which injury results in no change in thermal and mechanical pain sensitivity or in short term changes in pain. There was little to no hyperalgesia when the injury was imposed at PN10, but significant thermal hyperalgesia and mechanical allodynia one day after compression injury when performed at PN14, 21 or 28. Thermal withdrawal latencies return to near baseline by 7 days post-surgery (PS7 when the injuries were at PN14, and lasted up to 14 days when imposed at PN28. There was mechanical allodynia following nerve injury at 7 or 14 days after injury at PN14. Measurements of mRNA from spinal cord at 1, 7 and 14 days post-injury at PN14, 21, and 28 showed that both the magnitude and duration of elevated immune markers and chemokines/cytokines were greater in the older animals, corresponding to the development of hyperalgesia. Thus we confirm the late onset of neuropathic pain but found no evidence of emergent hyperalgesia if the injury was before PN21/28. This may be due to the use of a transient

  6. Effect of neural stem cell transplantation combined with erythropoietin injection on axon regeneration in adult rats with transected spinal cord injury.

    Science.gov (United States)

    Zhao, Y; Zuo, Y; Wang, X L; Huo, H J; Jiang, J M; Yan, H B; Xiao, Y L

    2015-12-22

    We investigated the effect of neural stem cells (NSC) and erythropoietin (EPO) on axon regeneration in adult rats with transected spinal cord injury, and provided an experimental basis for clinical treatment. Forty Wistar rats with T10-transected spinal cord injury were randomly divided into four groups of ten rats: a control group (group A), an NSC-transplant group (group B), an NSC-transplant and EPO group (group C), and an EPO group (group D). Biotinylated dextran amines (BDA) anterograde corticospinal cord neuronal tracing and Fluoro-Gold (FG) retrograde tracing were carried out at the 8th week after operation to observe the regeneration of nerve fibers. The Basso, Beattie, and Bresnahan (BBB) locomotor score was used to evaluate restoration. 1) BDA and FG immunofluorescence staining: in group C, a large number of regenerated axons were observed and some penetrated the injured area. In group B, only a small number of regenerated axons were observed and none penetrated the injured area. In group D, only sporadic regenerated nerve fibers were observed occasionally, while in group A, no axonal regeneration was observed. In group C, a small number of cones and axons emitted yellow fluorescence, and no FG-labeled cells were observed in the other groups. 2) The BBB scores for group C were higher than those for the other groups, and the differences were statistically significance (P EPO intraperitoneal injection may benefit axon regeneration in rats with transected spinal cord injury, and accelerate the functional recovery of the hindlimb locomotor.

  7. A non-opioid pathway for dynorphin-caused spinal cord injury in rats

    Institute of Scientific and Technical Information of China (English)

    Yu Chen; Liangbi Xiang; Jun Liu; Dapeng Zhou; Hailong Yu; Qi Wang; Wenfeng Han; Mingming Guo

    2012-01-01

    Intrathecal injection of dynorphin into rats via subarachnoid catheter induces damage to spinal cord tissue and motor function. Injection of the kappa opioid receptor antagonist nor-binaltorphine, or the excitatory amino acid N-methyl-D-aspartate receptor antagonist MK-801 into rats alleviated the pathological changes of dynorphin-caused spinal cord tissue injury and reduced the acid phosphatase activity in the spinal cord. The experimental findings indicate that there are opioid and non-opioid pathways for dynorphin-induced spinal cord injury, and that the non-opioid receptor pathway may be mediated by the excitatory amino acid N-methyl-D-aspartate receptor.

  8. Early transcutaneous electrical nerve stimulation reduces hyperalgesia and decreases activation of spinal glial cells in mice with neuropathic pain.

    Science.gov (United States)

    Matsuo, Hideaki; Uchida, Kenzo; Nakajima, Hideaki; Guerrero, Alexander Rodriguez; Watanabe, Shuji; Takeura, Naoto; Sugita, Daisuke; Shimada, Seiichiro; Nakatsuka, Terumasa; Baba, Hisatoshi

    2014-09-01

    Although transcutaneous electrical nerve stimulation (TENS) is widely used for the treatment of neuropathic pain, its effectiveness and mechanism of action in reducing neuropathic pain remain uncertain. We investigated the effects of early TENS (starting from the day after surgery) in mice with neuropathic pain, on hyperalgesia, glial cell activation, pain transmission neuron sensitization, expression of proinflammatory cytokines, and opioid receptors in the spinal dorsal horn. Following nerve injury, TENS and behavioral tests were performed every day. Immunohistochemical, immunoblot, and flow cytometric analysis of the lumbar spinal cord were performed after 8 days. Early TENS reduced mechanical and thermal hyperalgesia and decreased the activation of microglia and astrocytes (PEarly TENS decreased p-p38 within microglia (Pearly TENS relieved hyperalgesia in our mouse model of neuropathic pain by inhibiting glial activation, MAP kinase activation, PKC-γ, and p-CREB expression, and proinflammatory cytokines expression, as well as maintenance of spinal opioid receptors. The findings indicate that TENS treatment is more effective when applied as early after nerve injury as possible. Copyright © 2014 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.

  9. A continuous spinal cord stimulation model attenuates pain-related behavior in vivo following induction of a peripheral nerve injury.

    Science.gov (United States)

    Tilley, Dana M; Vallejo, Ricardo; Kelley, Courtney A; Benyamin, Ramsin; Cedeño, David L

    2015-04-01

    Models that simulate clinical conditions are needed to gain an understanding of the mechanism involved during spinal cord stimulation (SCS) treatment of chronic neuropathic pain. An animal model has been developed for continuous SCS in which animals that have been injured to develop neuropathic pain behavior were allowed to carry on with regular daily activities while being stimulated for 72 hours. Sprague-Dawley rats were randomized into each of six different groups (N = 10-13). Three groups included animals in which the spared nerve injury (SNI) was induced. Animals in two of these groups were implanted with a four-contact electrode in the epidural space. Animals in one of these groups received stimulation for 72 hours continuously. Three corresponding sham groups (no SNI) were included. Mechanical and cold-thermal allodynia were evaluated using von Frey filaments and acetone drops, respectively. Mean withdrawal thresholds were compared. Statistical significance was established using one-way ANOVAs followed by Holm-Sidak post hoc analysis. Continuous SCS attenuates mechanical allodynia in animals with neuropathic pain behavior. Mechanical withdrawal threshold increases significantly in SNI animals after 24 and 72 hours stimulation vs. SNI no stimulation (p = 0.007 and p stimulation (p = 0.001 and p Stimulation did not provide recovery to baseline values. SCS did not seem to attenuate cold-thermal allodynia. A continuous SCS model has been developed. Animals with neuropathic pain behavior that were continuously stimulated showed significant increase in withdrawal thresholds proportional to stimulation time. © 2015 International Neuromodulation Society.

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

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    Cheng, Lei; Liu, Yi; Zhao, Hua; Zhang, Wen; Guo, Ying-Jun; Nie, Lin, E-mail: chengleiyx@126.com

    2013-10-18

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

  11. Peripheral nerve injury increases glutamate-evoked calcium mobilization in adult spinal cord neurons

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    Doolen Suzanne

    2012-07-01

    Full Text Available Abstract Background Central sensitization in the spinal cord requires glutamate receptor activation and intracellular Ca2+ mobilization. We used Fura-2 AM bulk loading of mouse slices together with wide-field Ca2+ imaging to measure glutamate-evoked increases in extracellular Ca2+ to test the hypotheses that: 1. Exogenous application of glutamate causes Ca2+ mobilization in a preponderance of dorsal horn neurons within spinal cord slices taken from adult mice; 2. Glutamate-evoked Ca2+ mobilization is associated with spontaneous and/or evoked action potentials; 3. Glutamate acts at glutamate receptor subtypes to evoked Ca2+ transients; and 4. The magnitude of glutamate-evoked Ca2+ responses increases in the setting of peripheral neuropathic pain. Results Bath-applied glutamate robustly increased [Ca2+]i in 14.4 ± 2.6 cells per dorsal horn within a 440 x 330 um field-of-view, with an average time-to-peak of 27 s and decay of 112 s. Repeated application produced sequential responses of similar magnitude, indicating the absence of sensitization, desensitization or tachyphylaxis. Ca2+ transients were glutamate concentration-dependent with a Kd = 0.64 mM. Ca2+ responses predominantly occurred on neurons since: 1 Over 95% of glutamate-responsive cells did not label with the astrocyte marker, SR-101; 2 62% of fura-2 AM loaded cells exhibited spontaneous action potentials; 3 75% of cells that responded to locally-applied glutamate with a rise in [Ca2+]i also showed a significant increase in AP frequency upon a subsequent glutamate exposure; 4 In experiments using simultaneous on-cell recordings and Ca2+ imaging, glutamate elicited a Ca2+ response and an increase in AP frequency. AMPA/kainate (CNQX- and AMPA (GYKI 52466-selective receptor antagonists significantly attenuated glutamate-evoked increases in [Ca2+]i, while NMDA (AP-5, kainate (UBP-301 and class I mGluRs (AIDA did not. Compared to sham controls, peripheral nerve injury

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

    Science.gov (United States)

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

    2016-05-01

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

  13. Increased Nerve Growth Factor Signaling in Sensory Neurons of Early Diabetic Rats Is Corrected by Electroacupuncture

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    Stefania Lucia Nori

    2013-01-01

    Full Text Available Diabetic polyneuropathy (DPN, characterized by early hyperalgesia and increased nerve growth factor (NGF, evolves in late irreversible neuropathic symptoms with reduced NGF support to sensory neurons. Electroacupuncture (EA modulates NGF in the peripheral nervous system, being effective for the treatment of DPN symptoms. We hypothesize that NGF plays an important pathogenic role in DPN development, while EA could be useful in the therapy of DPN by modulating NGF expression/activity. Diabetes was induced in rats by streptozotocin (STZ injection. One week after STZ, EA was started and continued for three weeks. NGF system and hyperalgesia-related mediators were analyzed in the dorsal root ganglia (DRG and in their spinal cord and skin innervation territories. Our results show that four weeks long diabetes increased NGF and NGF receptors and deregulated intracellular signaling mediators of DRG neurons hypersensitization; EA in diabetic rats decreased NGF and NGF receptors, normalized c-Jun N-terminal and p38 kinases activation, decreased transient receptor potential vanilloid-1 ion channel, and possibly activated the nuclear factor kappa-light-chain-enhancer of activated B cells (Nf-κB. In conclusion, NGF signaling deregulation might play an important role in the development of DPN. EA represents a supportive tool to control DPN development by modulating NGF signaling in diabetes-targeted neurons.

  14. Semiconditional electrical stimulation of pudendal nerve afferents stimulation to manage neurogenic detrusor overactivity in patients with spinal cord injury.

    Science.gov (United States)

    Lee, Young-Hee; Kim, Jung Moon; Im, Hyung Tae; Lee, Kye-Wook; Kim, Sung Hoon; Hur, Dong Min

    2011-10-01

    To evaluate the effect of semiconditional electrical stimulation of the pudendal nerve afferents for the neurogenic detrusor overactivity in patients with spinal cord injury. Forty patients (36 males, 4 males) with spinal cord injury who had urinary incontinence and frequency, as well as felt bladder contraction with bladder filling sense or autonomic dysreflexic symptom participated in this study. Patients with neurogenic detrusor overactivity were subdivided into complete injury and incomplete injury groups by ASIA classification and subdivided into tetraplegia and paraplegia groups by neurologic level of injury. Bladder function, such as bladder volumes infused to the bladder until the first occurrence of neurogenic detrusor overactivity (V(ini)) and the last contraction suppressed by electrical stimulation (V(max)) was measured by water cystometry (CMG) and compared with the results of each subgroup. Among the 40 subjects, 35 patients showed neurogenic detrusor overactivity in the CMG study. Among these 35 patients, detrusor overactivity was suppressed effectively by pudendal nerve afferent electrical stimulation in 32 patients. The infusion volume until the occurrence of the first reflex contraction (V(ini)) was 99.4±80.3 ml. The volume of saline infused to the bladder until the last contraction suppressed by semiconditional pudendal nerve stimulation (V(max)) was 274.3±93.2 ml, which was significantly greater than V(ini). In patients with good response to the pudendal nerve afferent stimulation, the bladder volume significantly increased by stimulation in all the patients. In this study, semiconditional electrical stimulation on the dorsal penile afferent nerve could effectively inhibit neurogenic detrusor overactivity and increase bladder volume in patients with spinal cord injury.

  15. Nerve tissue growth factors as markers of evaluation of neuro-genesis processes in traumatic spinal cord disease

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    Uljanov V.Yu.

    2014-09-01

    Full Text Available Objective: immunological differentiation effects regeneration of nerve tissue in the acute and early periods of traumatic spinal cord disease on the basis of assessment of the dynamics of content neurospecific proteins in serum affected. Material and Methods. Content of neurospecific proteins in the blood serum has been studied by enzyme immunoassay in 40 patients with spinal cord injuries. Results. Dynamics and quantitative changes in the content of chronometric neurospecific proteins in serum of patients in acute and early periods of traumatic spinal cord disease is characterized by two-phase increase in the concentration CNTF; monotonic increase in the content of NT-3 in all periods of observation; biphasic increase in the levels of NT-4 to 1-4th and 14-th day from the date of injury. Conclusion. Complex research of neurospecific levels of proteins in the serum allows one to evaluate selectively the individual components of the process of regeneration of nerve tissue in acute and early periods of traumatic spinal cord disease.

  16. Operant behavioral responses to orofacial cold stimuli in rats with chronic constrictive trigeminal nerve injury: effects of menthol and capsazepine

    Science.gov (United States)

    2013-01-01

    Both spinal and trigeminal somatosensory systems use the TRPM8 channel as a principal transducer for detecting cold stimuli. It is currently unclear whether this cold transducer may play a role in trigeminal neuropathic pain manifesting cold allodynia and hyperalgesia. In the present study, trigeminal neuropathy was induced by chronic constrictive nerve injury of the infraorbital nerve (ION-CCI). Behavioral responses to cold stimuli in orofacial regions were assessed by the newly developed orofacial operant test in the ION-CCI rats. We tested menthol and capsazepine, two compounds that can activate and inhibit TRPM8 respectively, on orofacial operant responses to cold stimuli in ION-CCI rats. Testing animals performed operant tasks by voluntarily contacting their orofacial regions to a cold stimulation module in order to access sweetened milk as a reward, and contact time and number of the operant behaviors were automatically recorded. Total contact time was significantly reduced at the cooling temperatures of 17°C and 12°C in ION-CCI group in comparison with sham group, indicating the presence of cold allodynia and hyperalgesia in ION-CCI rats. When menthol was administered to ION-CCI rats, total contact time was further reduced and total contact number increased at the cooling temperatures. In contrast, after administration of capsazepine to ION-CCI rats, total contact time was significantly increased at the cooling temperatures. The behavioral outcomes support the idea that TRPM8 plays a role in cold allodynia and hyperalgesia following chronic trigeminal nerve injury. PMID:23767981

  17. Functional recovery in spinal cord injured rats using polypyrrole/iodine implants and treadmill training.

    Science.gov (United States)

    Alvarez-Mejia, Laura; Morales, Juan; Cruz, Guillermo J; Olayo, María-Guadalupe; Olayo, Roberto; Díaz-Ruíz, Araceli; Ríos, Camilo; Mondragón-Lozano, Rodrigo; Sánchez-Torres, Stephanie; Morales-Guadarrama, Axayacatl; Fabela-Sánchez, Omar; Salgado-Ceballos, Hermelinda

    2015-07-01

    Currently, there is no universally accepted treatment for traumatic spinal cord injury (TSCI), a pathology that can cause paraplegia or quadriplegia. Due to the complexity of TSCI, more than one therapeutic strategy may be necessary to regain lost functions. Therefore, the present study proposes the use of implants of mesoparticles (MPs) of polypyrrole/iodine (PPy/I) synthesized by plasma for neuroprotection promotion and functional recovery in combination with treadmill training (TT) for neuroplasticity promotion and maintenance of muscle tone. PPy/I films were synthesized by plasma and pulverized to obtain MPs. Rats with a TSCI produced by the NYU impactor were divided into four groups: Vehicle (saline solution); MPs (PPy/I implant); Vehicle-TT (saline solution + TT); and MPs-TT (PPy/I implant + TT). The vehicle or MPs (30 μL) were injected into the lesion site 48 h after a TSCI. Four days later, TT was carried out 5 days a week for 2 months. Functional recovery was evaluated weekly using the BBB motor scale for 9 weeks and tissue protection using histological and morphometric analysis thereafter. Although the MPs of PPy/I increased nerve tissue preservation (P = 0.03) and promoted functional recovery (P = 0.015), combination with TT did not produce better neuroprotection, but significantly improved functional results (P = 0.000) when comparing with the vehicle group. So, use these therapeutic strategies by separately could stimulate specific mechanisms of neuroprotection and neuroregeneration, but when using together they could mainly potentiate different mechanisms of neuronal plasticity in the preserved spinal cord tissue after a TSCI and produce a significant functional recovery. The implant of mesoparticles of polypyrrole/iodine into the injured spinal cord displayed good integration into the nervous tissue without a response of rejection, as well as an increased in the amount of preserved tissue and a better functional recovery than the group without

  18. Cauda equina redundant nerve roots are associated to the degree of spinal stenosis and to spondylolisthesis

    Directory of Open Access Journals (Sweden)

    Leonor Garbin Savarese

    2014-10-01

    Full Text Available To evaluate the association of redundant nerve roots of cauda equina (RNRCE with the degree of lumbar spinal stenosis (LSS and with spondylolisthesis. Method After Institutional Board approval, 171 consecutive patients were retrospectively enrolled, 105 LSS patients and 66 patients without stenosis. The dural sac cross-sectional area (CSA was measured on T2w axial MRI at the level of L2-3, L3-4 and L4-5 intervertebral discs. Two blinded radiologists classified cases as exhibiting or not RNRCE in MRI. Intra- and inter-observer reproducibility was assessed. Results RNRCE were associated with LSS. RRNCE was more frequent when maximum stenosis<55 mm2. Substantial intra- observer agreement and moderate inter-observer agreement were obtained in the classification of RNRCE. Spondylolisthesis was identified in 27 patients and represented increased risk for RRNCE. Conclusion LSS is a risk factor for RNRCE, especially for dural sac CSA<55 mm2. LSS and spondylolisthesis are independent risk factors for RNRCE.

  19. Transcutaneous electrical nerve stimulation for treatment of spinal cord injury neuropathic pain.

    Science.gov (United States)

    Norrbrink, Cecilia

    2009-01-01

    The aim of the study was to assess the short-term effects of high- and low-frequency (HF and LF, respectively) transcutaneous electrical nerve stimulation (TENS) for neuropathic pain following spinal cord injury (SCI). A total of 24 patients participated in the study. According to the protocol, half of the patients were assigned to HF (80 Hz) and half to LF (burst of 2 Hz) TENS. Patients were instructed to treat themselves three times daily for 2 weeks. After a 2-week wash-out period, patients switched stimulation frequencies and repeated the procedure. Results were calculated on an intent-to-treat basis. No differences between the two modes of stimulation were found. On a group level, no effects on pain intensity ratings or ratings of mood, coping with pain, life satisfaction, sleep quality, or psychosocial consequences of pain were seen. However, 29% of the patients reported a favorable effect from HF and 38% from LF stimulation on a 5-point global pain-relief scale. Six of the patients (25%) were, at their request, prescribed TENS stimulators for further treatment at the end of the study. In conclusion, TENS merits consideration as a com plementary treatment in patients with SCI and neuropathic pain.

  20. Nerve regeneration in chitosan conduits and in autologous nerve grafts in healthy and in type 2 diabetic Goto-Kakizaki rats.

    Science.gov (United States)

    Stenberg, Lena; Kodama, Akira; Lindwall-Blom, Charlotta; Dahlin, Lars B

    2016-02-01

    Knowledge about nerve regeneration after nerve injury and reconstruction in appropriate diabetic animal models is incomplete. Short-term nerve regeneration after reconstruction of a 10-mm sciatic nerve defect with either a hollow chitosan conduit or an autologous nerve graft was investigated in healthy Wistar and diabetic Goto-Kakizaki (GK) rats. After 21 days, axonal outgrowth, the presence of activated and apoptotic Schwann cells and the thickness of the formed matrix in the conduits were measured. In general, nerve regeneration was superior in autologous nerve grafts. In chitosan conduits, a matrix, which was thicker in diabetic rats, was formed and was positively correlated with length of axonal outgrowth. Axonal outgrowth in conduits and in nerve grafts extended further in diabetic rats than in healthy rats. There was a higher percentage of activating transcription factor 3 (ATF3)-immunostained cells in nerve segments from healthy rats than in diabetic rats after autologous nerve graft reconstruction. In chitosan conduits, more cleaved caspase 3-stained Schwann cells were generally observed in the matrix from the diabetic rats than in healthy rats. However, there were fewer apoptotic cells in the distal segment in diabetic rats reconstructed with a chitosan conduit. Preoperative glucose levels were positively correlated with axonal outgrowth after both reconstruction methods. Axonal regeneration was better in autologous nerve grafts than in hollow chitosan conduits and was enhanced in diabetic GK rats compared to healthy rats after reconstruction. This study provides insights into the nerve regeneration process in a clinically relevant diabetic animal model. © 2015 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

  1. Propofol promotes spinal cord injury repair by bone marrow mesenchymal stem cell transplantation

    Directory of Open Access Journals (Sweden)

    Ya-jing Zhou

    2015-01-01

    Full Text Available Propofol is a neuroprotective anesthetic. Whether propofol can promote spinal cord injury repair by bone marrow mesenchymal stem cells remains poorly understood. We used rats to investigate spinal cord injury repair using bone marrow mesenchymal stem cell transplantation combined with propofol administration via the tail vein. Rat spinal cord injury was clearly alleviated; a large number of newborn non-myelinated and myelinated nerve fibers appeared in the spinal cord, the numbers of CM-Dil-labeled bone marrow mesenchymal stem cells and fluorogold-labeled nerve fibers were increased and hindlimb motor function of spinal cord-injured rats was markedly improved. These improvements were more prominent in rats subjected to bone marrow mesenchymal cell transplantation combined with propofol administration than in rats receiving monotherapy. These results indicate that propofol can enhance the therapeutic effects of bone marrow mesenchymal stem cell transplantation on spinal cord injury in rats.

  2. Propofol promotes spinal cord injury repair by bone marrow mesenchymal stem cell transplantation

    Institute of Scientific and Technical Information of China (English)

    Ya-jing Zhou; Jian-min Liu; Shu-ming Wei; Yun-hao Zhang; Zhen-hua Qu; Shu-bo Chen

    2015-01-01

    Propofol is a neuroprotective anesthetic. Whether propofol can promote spinal cord injury repair by bone marrow mesenchymal stem cells remains poorly understood. We used rats to investigate spinal cord injury repair using bone marrow mesenchymal stem cell transplantation combined with propofol administrationvia the tail vein. Rat spinal cord injury was clearly alleviated; a large number of newborn non-myelinated and myelinated nerve ifbers appeared in the spinal cord, the numbers of CM-Dil-labeled bone marrow mesenchymal stem cells and lfuorogold-labeled nerve ifbers were increased and hindlimb motor function of spinal cord-injured rats was mark-edly improved. These improvements were more prominent in rats subjected to bone marrow mesenchymal cell transplantation combined with propofol administration than in rats receiving monotherapy. These results indicate that propofol can enhance the therapeutic effects of bone marrow mesenchymal stem cell transplantation on spinal cord injury in rats.

  3. FOS EXPRESSION IN LUMBARSACRAL SPINAL CORD AND MEDULLA OBLONGATA INDUCED BY CHRONIC COLONIC INFLAMMATION IN RATS

    Institute of Scientific and Technical Information of China (English)

    2005-01-01

    Objective To investigate Fos expression in rat lumbarsacral spinal cord and medulla oblongata induced by chronic colonic inflammation. Methods Thirty-three male Sprague-Dawley rats were randomly divided into two groups: experimental group: colonic inflammation was induced in seventeen rats by intraluminal administration of trinitrobenzenesulfonic acid (TNBS); control group: saline was administered intraluminally in sixteen rats; After 3, 7, 14 and 28 days of administration, lumbarsacral spinal cord and medulla oblongata were removed and processed for Fos immunohistochemistry. Results Fos-immunoreactive (Fos-IR) neurons induced by TNBS administration were primarily distributed in deep laminae (laminae Ⅲ-Ⅳ,Ⅴ-Ⅵ) in the spinal dorsal horn and in medullary visceral zone (MVZ) in the medulla oblongata. The number of Fos-IR cells in the spinal cord and MVZ in rats after 7 and 14 days of TNBS administration were significantly higher than that in the control rats (P<0.05). After 28 days of TNBS instillation, the number of Fos-IR neurons in MVZ decreased and became comparable to the control group. However, the number of Fos cells in the spinal cord in some rats were still significantly increased compared with the control rats (P<0.05). Conclusion Fos-IR neurons after colonic inflammation recovery may play an important role in the development of visceral hypersensitivity. Medulla oblongata was a less important structure than the spinal cord in inducing visceral hypersensitivity after chronic colonic inflammation.

  4. Vagus nerve stimulation delivered during motor rehabilitation improves recovery in a rat model of stroke.

    Science.gov (United States)

    Khodaparast, Navid; Hays, Seth A; Sloan, Andrew M; Fayyaz, Tabbassum; Hulsey, Daniel R; Rennaker, Robert L; Kilgard, Michael P

    2014-09-01

    Neural plasticity is widely believed to support functional recovery following brain damage. Vagus nerve stimulation paired with different forelimb movements causes long-lasting map plasticity in rat primary motor cortex that is specific to the paired movement. We tested the hypothesis that repeatedly pairing vagus nerve stimulation with upper forelimb movements would improve recovery of motor function in a rat model of stroke. Rats were separated into 3 groups: vagus nerve stimulation during rehabilitation (rehab), vagus nerve stimulation after rehab, and rehab alone. Animals underwent 4 training stages: shaping (motor skill learning), prelesion training, postlesion training, and therapeutic training. Rats were given a unilateral ischemic lesion within motor cortex and implanted with a left vagus nerve cuff. Animals were allowed 1 week of recovery before postlesion baseline training. During the therapeutic training stage, rats received vagus nerve stimulation paired with each successful trial. All 17 trained rats demonstrated significant contralateral forelimb impairment when performing a bradykinesia assessment task. Forelimb function was recovered completely to prelesion levels when vagus nerve stimulation was delivered during rehab training. Alternatively, intensive rehab training alone (without stimulation) failed to restore function to prelesion levels. Delivering the same amount of stimulation after rehab training did not yield improvements compared with rehab alone. These results demonstrate that vagus nerve stimulation repeatedly paired with successful forelimb movements can improve recovery after motor cortex ischemia and may be a viable option for stroke rehabilitation.

  5. Estrogens Suppress Spinal Endomorphin 2 Release in Female Rats in Phase with the Estrous Cycle

    Science.gov (United States)

    Kumar, Arjun; Storman, Emiliya M.; Liu, Nai-Jiang; Gintzler, Alan R.

    2015-01-01

    Background/Aims Male and female rats differ in their ability to utilize spinal endomorphin 2 (EM2; the predominant mu-opioid receptor ligand in spinal cord) and in the mechanisms that underlie spinal EM2 analgesic responsiveness. We investigated the relevance of spinal estrogen receptors (ERs) to the in vivo regulation of spinal EM2 release. Methods ER antagonists were administered directly to the lumbosacral spinal cord of male and female rats, intrathecal perfusate was collected, and resulting changes in EM2 release were quantified using a plate-based radioimmunoassay. Results Intrathecal application of an antagonist of either estrogen receptor-α (ERα) or the ER GPR30 failed to alter spinal EM2 release. Strikingly, however, the concomitant blockade of ERα and GPR30 enhanced spinal EM2 release. This effect was sexually dimorphic, being absent in males. Furthermore, the magnitude of the enhancement of spinal EM2 release in females was dependent upon estrous cycle stage, suggesting a relationship with circulating levels of 17β-estradiol. The rapid onset of enhanced EM2 release following intrathecal application of ERα/GPR30 antagonists (within 30–40 min) suggests mediation via ERs in the plasma membrane, not the nucleus. Notably, both ovarian and spinally synthesized estrogens are essential for membrane ER regulation of spinal EM2 release. Conclusion These findings underscore the importance of estrogens for the regulation of spinal EM2 activity and, by extension, endogenous spinal EM2 antinoci-ception in females. Components of the spinal estrogenic mechanism(s) that suppress EM2 release could represent novel drug targets for improving utilization of endogenous spinal EM2, and thereby pain management in women. PMID:25925013

  6. Lidocaine for prolonged and intensified spinal anesthesia by coadministration of propranolol in the rat.

    Science.gov (United States)

    Chen, Yu-Wen; Chu, Chin-Chen; Chen, Yu-Chung; Hung, Ching-Hsia; Li, Yung-Tsung; Wang, Jhi-Joung

    2011-09-26

    Although the coadministration of lidocaine with propranolol interferes with the metabolic profile (pharmacokinetics), its pharmacodynamics is still unclear. In this report, we investigate whether propranolol can potentiate the effect of lidocaine. Rats received spinal anesthesia with lidocaine co-injected with propranolol. After intrathecal injections of drugs in rats, three neurobehavioral examinations (motor function, proprioception, and nociception) were performed. We showed that lidocaine and propranolol elicited a spinal blockade in motor function, proprioception, and nociception. Propranolol at the dose of 0.82 μmol/kg produced no spinal anesthesia. Co-administration of lidocaine [50% effective dose (ED(50)) or ED(95)] and propranolol (0.82 μmol/kg) produced greater spinal anesthesia than lidocaine (ED(50) or ED(95)), respectively. These preclinical findings demonstrated that propranolol and lidocaine displayed spinal anesthesia. When combined with propranolol, lidocaine elicited a supra-additive effect of spinal anesthesia.

  7. Elevated spinal cyclooxygenase and prostaglandin release during hyperalgesia in diabetic rats.

    Science.gov (United States)

    Freshwater, Jason D; Svensson, Camilla I; Malmberg, Annika B; Calcutt, Nigel A

    2002-07-01

    Diabetic rats display exaggerated hyperalgesic behavior in response to noxious stimuli that may model aspects of painful diabetic neuropathy. This study examined the contribution of spinal prostaglandin production to this exaggerated hyperalgesic behavior. Rats were implanted with spinal dialysis probes and received noxious stimulation to the hind paw by subcutaneous injection of 0.5% formalin solution. Prostaglandin E(2) (PGE(2)) was measured in dialysates of lumbar spinal cerebrospinal fluid concurrent with behavioral responses to formalin injection. In separate experiments, formalin-evoked behavioral responses were measured after intrathecal delivery of either a cyclooxygenase inhibitor or an EP(1) receptor antagonist, and cyclooxygenase protein was measured in spinal cord homogenates. Diabetic rats exhibited exaggerated behavioral responses to paw formalin injection and a concurrent prolongation of formalin-evoked PGE(2) release. Formalin-evoked behavioral responses were dose-dependently reduced in diabetic rats by spinal delivery of a cyclooxygenase inhibitor or an EP(1) receptor antagonist. Protein levels of cyclooxygenase-2 were elevated in the spinal cord of diabetic rats, whereas cyclooxygenase-1 protein was reduced. Hyperalgesic behavior in diabetic rats is associated with both increased cyclooxygenase-2 protein and cyclooxygenase-mediated PGE(2) release. Spinal delivery of selective inhibitors of cyclooxygenase-2 or antagonists of prostaglandin receptors may have therapeutic potential for treating painful diabetic neuropathy.

  8. Rat hair follicle stem cells differentiate and promote recovery following spinal cord injury

    Institute of Scientific and Technical Information of China (English)

    Nowruz Najafzadeh; Maliheh Nobakht; Bagher Pourheydar; Mohammad Ghasem Golmohammadi

    2013-01-01

    Emerging studies of treating spinal cord injury (SCI) with adult stem cells led us to evaluate the effects of transplantation of hair fol icle stem cells in rats with a compression-induced spinal cord lesion. Here, we proposed a hypothesis that rat hair fol icle stem celltransplantation can promote the recovery of injured spinal cord. Compression-induced spinal cord injury was induced in Wistar rats in this study. The bulge area of the rat vibrissa fol icles was isolated, cultivated and characterized with nestin as a stem cellmarker. 5-Bromo-2′-deoxyuridine (BrdU) labeled bulge stem cells were transplanted into rats with spinal cord injury. Immunohistochemical staining results showed that some of the grafted cells could survive and differentiate into oligodendrocytes (receptor-interacting protein positive cells) and neuronal-like cells (βIII-tubulin positive cells) at 3 weeks after transplantation. In addition, recovery of hind limb locomotor function in spinal cord injury rats at 8 weeks fol owing celltransplantation was assessed using the Basso, Beattie and Bresnahan (BBB) locomotor rating scale. The results demon-strate that the grafted hair fol icle stem cells can survive for a long time period in vivo and differentiate into neuronal- and glial-like cells. These results suggest that hair fol icle stem cells can promote the recovery of spinal cord injury.

  9. Undifferentiated and differentiated adipose-derived stem cells improve nerve regeneration in a rat model of facial nerve defect.

    Science.gov (United States)

    Watanabe, Yorikatsu; Sasaki, Ryo; Matsumine, Hajime; Yamato, Masayuki; Okano, Teruo

    2017-02-01

    Autologous nerve grafting is the current procedure used for repairing facial nerve gaps. As an alternative to this method, tissue engineering cell-based therapy using induced pluripotent stem cells, Schwann cells and bone marrow-derived mesenchymal stem cells has been proposed. However, these cells have major problems, including tumorigenesis in induced pluripotent stem cells and invasiveness and limited tissue associated with harvesting for the other cells. Here, we investigated the therapeutic potential of adipose-derived stem cells (ASCs), which can be harvested easily and repeatedly by a minimally invasive liposuction procedure. The ASCs had characteristics of mesenchymal tissue lineages and could differentiate into Schwann-like cells that were relatively simple to isolate and expand in culture. In an in vivo study, a silicone conduit containing undifferentiated ASCs, differentiated ASCs or Schwann cells were transplanted, embedded in a collagen gel and the efficacy of repair of a 7 mm-gap in the rat facial nerve examined. Morphometric quantification analysis of regenerated facial nerves after a regeneration period of 13 weeks showed that undifferentiated ASCs, differentiated ASCs, and Schwann cells had similar potential for nerve regeneration. Furthermore, the functional recovery of facial nerve regeneration using a rat facial palsy scoring system in the three groups was close to that in autologous nerve graft positive controls. These findings suggest that undifferentiated and differentiated ASCs may both have therapeutic potential in facial nerve regeneration as a source of Schwann cells in cell-based therapy performed as an alternative to autologous nerve grafts. Copyright © 2014 John Wiley & Sons, Ltd. Copyright © 2014 John Wiley & Sons, Ltd.

  10. Long-term effect of ropivacaine nanoparticles for sciatic nerve block on postoperative pain in rats

    Directory of Open Access Journals (Sweden)

    Wang Z

    2016-05-01

    Full Text Available Zi Wang,1,* Haizhen Huang,2,* Shaozhong Yang,1 Shanshan Huang,1 Jingxuan Guo,1 Qi Tang,1 Feng Qi1 1Department of Anesthesiology, Qilu Hospital of Shandong University, 2Department of Anesthesiology, Stomatology Hospital of Shandong University, Jinan, Shandong, People’s Republic of China *These authors contributed equally to this work Purpose: The analgesic effect of ropivacaine (Rop for nerve block lasts only ~3–6 hours for single use. The aim of this study was to develop long-acting regional anesthetic Rop nanoparticles and investigate the effects of sciatic nerve block on postoperative pain in rats.Materials and methods: Rop nanoparticles were developed using polyethylene glycol-co-polylactic acid (PELA. One hundred and twenty adult male Wistar rats were randomly divided into four groups (n=30, each: Con (control group; 0.9% saline, 200 µL, PELA (PELA group; 10 mg, Rop (Rop group; 0.5%, 200 µL, and Rop-PELA (Rop-PELA group; 10%, 10 mg. Another 12 rats were used for the detection of Rop concentration in plasma. The mechanical withdrawal threshold and thermal withdrawal latency were measured at 2 hours, 4 hours, 8 hours, 1 day, 2 days, 3 days, 5 days, and 7 days after incision. The expression of c-FOS was determined by immunohistochemistry at 2 hours, 8 hours, 48 hours, and 7 days. Nerve and organ toxicities were also evaluated at 7 days.Results: The duration of Rop absorption in the plasma of the Rop-PELA group was longer (>8 hours than that of the Rop group (4 hours. Mechanical withdrawal threshold and thermal withdrawal latency in the Rop-PELA group were higher than that in other groups (4 hours–3 days. c-FOS expression in the Rop-PELA group was lower than that in the control group at 2 hours, 8 hours, and 48 hours and lower than that in the Rop group at 8 hours and 48 hours after paw incision. Slight foreign body reactions were observed surrounding the sciatic nerve at 7 days. No obvious pathophysiological

  11. Dexmedetomidine Attenuates Blood-Spinal Cord Barrier Disruption Induced by Spinal Cord Ischemia Reperfusion Injury in Rats

    Directory of Open Access Journals (Sweden)

    Bo Fang

    2015-05-01

    Full Text Available Background/Aims: Dexmedetomidine has beneficial effects on ischemia reperfusion (I/R injury to the spinal cord, but the underlying mechanisms are not fully understood. This study investigated the effects and possible mechanisms of dexmedetomidine on blood-spinal cord barrier (BSCB disruption induced by spinal cord I/R injury. Methods: Rats were intrathecally pretreated with dexmedetomidine or PBS control 30 minutes before undergoing 14-minute occlusion of aortic arch. Hind-limb motor function was assessed using Tarlov criteria, and motor neurons in the ventral gray matter were counted by histological examination. The permeability of the BSCB was examined using Evans blue (EB as a vascular tracer. The spinal cord edema was evaluated using the wet-dry method. The expression and localization of matrix metalloproteinase-9 (MMP-9, Angiopoietin-1 (Ang1 and Tie2 were assessed by western blot, real-time polymerase chain reaction, and immunofluorescence. Results: Intrathecal preconditioning with dexmedetomidine minimized the neuromotor dysfunction and histopathological deficits, and attenuated EB extravasation after spinal cord I/R injury. In addition, dexmedetomidine preconditioning suppressed I/R-induced increase in MMP-9. Finally, Dexmedetomidine preconditioning enhanced the Ang1-Tie2 system activity after spinal cord I/R injury. Conclusions: Dexmedetomidine preconditioning stabilized the BSCB integrity against spinal cord I/R injury by inhibition of MMP-9, and enhancing the Ang1-Tie2 system.

  12. Characterization of upper thoracic spinal neurons responding to esophageal distension in diabetic rats

    DEFF Research Database (Denmark)

    Qin, Chao; Ghorbani, Marie L M; Wu, Mingyuan

    2008-01-01

    The aim of this study was to examine spinal neuronal processing of innocuous and noxious mechanical inputs from the esophagus in diabetic rats. Streptozotocin (50 mg/kg, ip) was used to induce diabetes in 15 male Sprague-Dawley rats, and vehicle (10 mM citrate buffer) was injected into 15 rats...

  13. Thoracic rat spinal cord contusion injury induces remote spinal gliogenesis but not neurogenesis or gliogenesis in the brain.

    Directory of Open Access Journals (Sweden)

    Steffen Franz

    Full Text Available After spinal cord injury, transected axons fail to regenerate, yet significant, spontaneous functional improvement can be observed over time. Distinct central nervous system regions retain the capacity to generate new neurons and glia from an endogenous pool of progenitor cells and to compensate neural cell loss following certain lesions. The aim of the present study was to investigate whether endogenous cell replacement (neurogenesis or gliogenesis in the brain (subventricular zone, SVZ; corpus callosum, CC; hippocampus, HC; and motor cortex, MC or cervical spinal cord might represent a structural correlate for spontaneous locomotor recovery after a thoracic spinal cord injury. Adult Fischer 344 rats received severe contusion injuries (200 kDyn of the mid-thoracic spinal cord using an Infinite Horizon Impactor. Uninjured rats served as controls. From 4 to 14 days post-injury, both groups received injections of bromodeoxyuridine (BrdU to label dividing cells. Over the course of six weeks post-injury, spontaneous recovery of locomotor function occurred. Survival of newly generated cells was unaltered in the SVZ, HC, CC, and the MC. Neurogenesis, as determined by identification and quantification of doublecortin immunoreactive neuroblasts or BrdU/neuronal nuclear antigen double positive newly generated neurons, was not present in non-neurogenic regions (MC, CC, and cervical spinal cord and unaltered in neurogenic regions (dentate gyrus and SVZ of the brain. The lack of neuronal replacement in the brain and spinal cord after spinal cord injury precludes any relevance for spontaneous recovery of locomotor function. Gliogenesis was increased in the cervical spinal cord remote from the injury site, however, is unlikely to contribute to functional improvement.

  14. Thoracic rat spinal cord contusion injury induces remote spinal gliogenesis but not neurogenesis or gliogenesis in the brain.

    Science.gov (United States)

    Franz, Steffen; Ciatipis, Mareva; Pfeifer, Kathrin; Kierdorf, Birthe; Sandner, Beatrice; Bogdahn, Ulrich; Blesch, Armin; Winner, Beate; Weidner, Norbert

    2014-01-01

    After spinal cord injury, transected axons fail to regenerate, yet significant, spontaneous functional improvement can be observed over time. Distinct central nervous system regions retain the capacity to generate new neurons and glia from an endogenous pool of progenitor cells and to compensate neural cell loss following certain lesions. The aim of the present study was to investigate whether endogenous cell replacement (neurogenesis or gliogenesis) in the brain (subventricular zone, SVZ; corpus callosum, CC; hippocampus, HC; and motor cortex, MC) or cervical spinal cord might represent a structural correlate for spontaneous locomotor recovery after a thoracic spinal cord injury. Adult Fischer 344 rats received severe contusion injuries (200 kDyn) of the mid-thoracic spinal cord using an Infinite Horizon Impactor. Uninjured rats served as controls. From 4 to 14 days post-injury, both groups received injections of bromodeoxyuridine (BrdU) to label dividing cells. Over the course of six weeks post-injury, spontaneous recovery of locomotor function occurred. Survival of newly generated cells was unaltered in the SVZ, HC, CC, and the MC. Neurogenesis, as determined by identification and quantification of doublecortin immunoreactive neuroblasts or BrdU/neuronal nuclear antigen double positive newly generated neurons, was not present in non-neurogenic regions (MC, CC, and cervical spinal cord) and unaltered in neurogenic regions (dentate gyrus and SVZ) of the brain. The lack of neuronal replacement in the brain and spinal cord after spinal cord injury precludes any relevance for spontaneous recovery of locomotor function. Gliogenesis was increased in the cervical spinal cord remote from the injury site, however, is unlikely to contribute to functional improvement.

  15. Developmental Changes in Pain and Spinal Immune Gene Expression after Radicular Trauma in the Rat

    Science.gov (United States)

    Barr, Gordon A.; Wang, Shaoning; Weisshaar, Christine L.; Winkelstein, Beth A.

    2016-01-01

    Neuropathic pain is chronic pain that develops after nerve injury and is less frequent in infants and children than in adults. Likewise, in animal models of neuropathic pain, allodynia and hyperalgesia are non-existent or attenuated in the infant, with a “switch” during development by which acute nerve injury transitions to chronic pain. Concomitant with the delay in neuropathic pain, there is a parallel delay in the ability of nerve injury to activate the immune system. Models of neuropathic pain in the infant have used various ligation methods and find that neuropathic pain does not occur under after postnatal days 21–28 (PN21–PN28), linked to activation of immune processes and developmental regulation of anti-inflammatory cytokines. We applied a model of neuropathic pain in the adult using a transient compression of the cervical nerve or nerve root in infant rats (injured at 10, 14, 21, or 28 days of age) to define transition periods during which injury results in no change in thermal and mechanical pain sensitivity or in short-term changes in pain. There was little to no hyperalgesia when the injury was imposed at PN10, but significant thermal hyperalgesia and mechanical allodynia 1 day after compression injury when performed at PN14, 21, or 28. Thermal withdrawal latencies returned to near baseline by 7 days postsurgery when the injuries were at PN14, and lasted up to 14 days when the injury was imposed at PN28. There was mechanical allodynia following injury at 1 day postinjury and at 14 days after injury at PN14. Measurements of mRNA from spinal cord at 1, 7, and 14 days postinjury at PN14, 21, and 28 showed that both the magnitude and duration of elevated immune markers and chemokines/cytokines were greater in the older animals, corresponding to the development of hyperalgesia. Thus, we confirm the late onset of neuropathic pain but found no evidence of emergent hyperalgesia if the injury was before PN21. This may be due to the use of

  16. Developmental Changes in Pain and Spinal Immune Gene Expression after Radicular Trauma in the Rat.

    Science.gov (United States)

    Barr, Gordon A; Wang, Shaoning; Weisshaar, Christine L; Winkelstein, Beth A

    2016-01-01

    Neuropathic pain is chronic pain that develops after nerve injury and is less frequent in infants and children than in adults. Likewise, in animal models of neuropathic pain, allodynia and hyperalgesia are non-existent or attenuated in the infant, with a "switch" during development by which acute nerve injury transitions to chronic pain. Concomitant with the delay in neuropathic pain, there is a parallel delay in the ability of nerve injury to activate the immune system. Models of neuropathic pain in the infant have used various ligation methods and find that neuropathic pain does not occur under after postnatal days 21-28 (PN21-PN28), linked to activation of immune processes and developmental regulation of anti-inflammatory cytokines. We applied a model of neuropathic pain in the adult using a transient compression of the cervical nerve or nerve root in infant rats (injured at 10, 14, 21, or 28 days of age) to define transition periods during which injury results in no change in thermal and mechanical pain sensitivity or in short-term changes in pain. There was little to no hyperalgesia when the injury was imposed at PN10, but significant thermal hyperalgesia and mechanical allodynia 1 day after compression injury when performed at PN14, 21, or 28. Thermal withdrawal latencies returned to near baseline by 7 days postsurgery when the injuries were at PN14, and lasted up to 14 days when the injury was imposed at PN28. There was mechanical allodynia following injury at 1 day postinjury and at 14 days after injury at PN14. Measurements of mRNA from spinal cord at 1, 7, and 14 days postinjury at PN14, 21, and 28 showed that both the magnitude and duration of elevated immune markers and chemokines/cytokines were greater in the older animals, corresponding to the development of hyperalgesia. Thus, we confirm the late onset of neuropathic pain but found no evidence of emergent hyperalgesia if the injury was before PN21. This may be due to the use of a

  17. Transplantation of tissue engineering neural network and formation of neuronal relay into the transected rat spinal cord.

    Science.gov (United States)

    Lai, Bi-Qin; Che, Ming-Tian; Du, Bao-Ling; Zeng, Xiang; Ma, Yuan-Huan; Feng, Bo; Qiu, Xue-Chen; Zhang, Ke; Liu, Shu; Shen, Hui-Yong; Wu, Jin-Lang; Ling, Eng-Ang; Zeng, Yuan-Shan

    2016-12-01

    Severe spinal cord injury (SCI) causes loss of neural connectivity and permanent functional deficits. Re-establishment of new neuronal relay circuits after SCI is therefore of paramount importance. The present study tested our hypothesis if co-culture of neurotrophin-3 (NT-3) gene-modified Schwann cells (SCs, NT-3-SCs) and TrkC (NT-3 receptor) gene-modified neural stem cells (NSCs, TrkC-NSCs) in a gelatin sponge scaffold could construct a tissue engineering neural network for re-establishing an anatomical neuronal relay after rat spinal cord transection. Eight weeks after transplantation, the neural network created a favorable microenvironment for axonal regeneration and for survival and synaptogenesis of NSC-derived neurons. Biotin conjugates of cholera toxin B subunit (b-CTB, a transneuronal tracer) was injected into the crushed sciatic nerve to label spinal cord neurons. Remarkably, not only ascending and descending nerve fibers, but also propriospinal neurons, made contacts with b-CTB positive NSC-derived neurons. Moreover, b-CTB positive NSC-derived neurons extended their axons making contacts with the motor neurons located in areas caudal to the injury/graft site of spinal cord. Further study showed that NT-3/TrkC interactions activated the PI3K/AKT/mTOR pathway and PI3K/AKT/CREB pathway affecting synaptogenesis of NSC-derived neurons. Together, our findings suggest that NT-3-mediated TrkC signaling plays an essential role in constructing a tissue engineering neural network thus representing a promising avenue for effective exogenous neuronal relay-based treatment for SCI.

  18. Activation of Growth-associated Protein by Intragastric Brazilein in Motor Neuron of Spinal Cord Connected with Injured Sciatic Nerve in Mice

    Institute of Scientific and Technical Information of China (English)

    CAO Jian; LI Li-sen; LIU Biao; LIU Hao-yu; ZHANG Hui; ZHAO Ming-ming; YIN Wei-tian

    2011-01-01

    The purpose of this study is to explore the expression of growth-associated protein(GAP-43) in spinal cord segments connected with injured sciatic nerve by the treatment with brazilein in mice. Unilateral sciatic nerve interruption and anastomosis were performed. Physiological saline(blank group), high dose, middle dose and low dose of brazilein were administrated intragastrically to healthy adult BALB/c mice in separate groups. L4-6 spinal segments connected with the sciatic nerve were harvested. Real-time PCR(Polymerase chain reaction) and Western blot analysis were performed to detect the expression of GAP-43 in spinal segments. Histological staining on myelin and the electrophysiology were performed to examine the sciatic nerve recovery. GAP-43 was activated in spinal cord L4-6 connected with injured sciatic nerve. In the survival time of 12 h, 24 h, 3 d, 5 d, 7 d and 14 d, GAP-43 expression in the motor neurons of spinal cord of the high dose group and that in the middle dose group were significantly higher than those on the low dose and blank groups. Myelin in the high dose group and that in the middle dose group were more mature and the potential amplitude and MNCV(motor nerve conduction velocity) in the high and middle dose groups were obviously higher than those in the low dose group and blank group. Brazilein facilitates the expression of GAP-43 in neurons in spinal cord L4-6 segments connected with injured sciatic nerve, which promotes nerve regeneration.

  19. Nerve growth factor receptor molecules in rat brain

    Energy Technology Data Exchange (ETDEWEB)

    Taniuchi, M.; Schweitzer, J.B.; Johnson, E.M. Jr.

    1986-03-01

    The authors have developed a method to immunoprecipitate rat nerve growth factor (NGF) receptor proteins and have applied the method to detect NGF receptor molecules in the rat brain. Crosslinking /sup 125/I-labeled NGF to either PC12 cells or cultured rat sympathetic neurons yielded two radiolabeled molecules (90 kDa and 220 kDa) that were immunoprecipitated by monoclonal antibody 192-IgG. Further, 192-IgG precipitated two radiolabeled proteins, with the expected sizes (80 kDa and 210 kDa) of noncrosslinked NGF receptor components, from among numerous surface-iodinated PC12 cell proteins. These results demonstrate the specific immunoprecipitation of NGF receptor molecules by 192-IgG. They applied the /sup 125/I-NGF crosslinking and 192-IgG-mediated immunoprecipitation procedures to plasma membrane preparations of rat brain: NGF receptor molecules of the same molecular masses as the peripheral receptor components were consistently detected in all regions and in preparations from whole brains. Removal of the peripheral sympathetic innervation of the brain did not eliminate these NGF receptor proteins, indicating that the receptor is endogenous to central nervous system tissues. They also observed retrograde transport of /sup 125/I-labeled 192-IgG from the parietal cortex to the nucleus basalis and from the hippocampus to the nucleus of the diagonal band of Broca and the medial septal nucleus. These findings demonstrate the presence in brain of NGF receptor molecules indistinguishable from those of the peripheral nervous system.

  20. SPINAL ANTINOCICEPTION BY MORPHINE IN RATS IS ANTAGONIZED BY GALANIN RECEPTOR ANTAGONISTS

    NARCIS (Netherlands)

    REIMANN, W; ENGLBERGER, W; FRIDERICHS, E; SELVE, N; WILFFERT, B

    1994-01-01

    Galanin, a 29 amino acid peptide, has been reported to possess antinociceptive properties at the spinal site and to potentiate opioid-induced antinociception. Our aim was to investigate whether also endogenous galanin interacts with an exogenously administered opioid, morphine, in the rat spinal cor

  1. Expression of PirB in normal and injured spinal cord of rats.

    Science.gov (United States)

    Zhou, Yingchun; Qian, Rongjun; Rao, Jing; Weng, Mixia; Yi, Xuxia

    2010-08-01

    The expression of paired immunoglobulin-like receptor B (PirB) in normal and injured spinal cord of rats was investigated. The SD rat hemi-sectioned spinal cord injury (SCI) model was established. Before and 1, 3, 7, 10 days after SCI, the spinal cord tissues were harvested, and Western blot and immunohistochemistry were used to examine the expression and location of PirB. The results showed that the expression level of PirB in the normal spinal cord of SD rats was low. At the first day after SCI, the expression of PirB was obviously increased, and that in the injured spinal cord from the first day to the 10th day was significantly higher than in the normal spinal cord. The positive expression of PirB in neurons from different regions of gray matter of the injured spinal cord was seen. It was concluded that the expression of PirB in the normal spinal cord of rats was low. The expression of PirB in SCI was significantly increased till at least the 10th day.

  2. Positron emission tomography for serial imaging of the contused adult rat spinal cord.

    NARCIS (Netherlands)

    Nandoe, R.D.S.; Yu, J.; Seidel, J.; Rahiem, S.T.; Hurtado, A.; Tsui, B.M.; Grotenhuis, J.A.; Pomper, M.G.; Oudega, M.

    2010-01-01

    We investigated whether small-animal positron emission tomography (PET) could be used in combination with computed tomography (CT) imaging techniques for longitudinal monitoring of the injured spinal cord. In adult female Sprague-Dawley rats (n = 6), the ninth thoracic (T9) spinal cord segment was e

  3. Evaluation of the excopula ejaculatory potentials of Bersama engleriana in spinal male rats

    Institute of Scientific and Technical Information of China (English)

    Pierre Watcho; Miguel Carro-Juarez

    2009-01-01

    tive ejaculation in spinal male rat is mediated through dopaminergic and oxytocinergic pathways. This prolonged ejaculatory latency caused by B. Engleriana could support its potential use in patients with rapid ejaculation.

  4. Angiogenic microspheres promote neural regeneration and motor function recovery after spinal cord injury in rats

    National Research Council Canada - National Science Library

    Yu, Shukui; Yao, Shenglian; Wen, Yujun; Wang, Ying; Wang, Hao; Xu, Qunyuan

    2016-01-01

    ... (bFGF) encapsulated in angiogenic microspheres. These spheres were delivered to sites of spinal cord contusion injury in rats, and their ability to induce vessel formation, neural regeneration and improve hindlimb motor function was assessed...

  5. Effect of bleeding on nerve regeneration and epineural scar formation in rat sciatic nerves: an experimental study.

    Science.gov (United States)

    Servet, Erkan; Bekler, Halil; Kılınçoğlu, Volkan; Özler, Turhan; Özkut, Afşar

    2016-01-01

    Epineural scar formation is one of the most significant negative factors affecting surgical repair after peripheral nerve injury. The scar tissue mechanically hinders axonal regeneration and causes adhesions between nerves and surrounding tissues. A hemostatic agent Ankaferd Blood Stopper (ABS; İmmun Gıda İlaç Kozmetik San. ve Tic. Ltd. Şti., Istanbul, Turkey) has not been previously used. Decreasing the postoperative bleeding and adhesions between nerve and surrounding tissues will prevent the formation of scar tissue, as well as corresponding compressive neuropathy and/or deceleration of axonal regeneration. The purpose of this experimental study was to investigate the effects of bleeding on nerve healing and scar tissue after repair of peripheral nerve injuries. The right sciatic nerve of 30 Sprague-Dawley male rats (weighing 260-330 g) was cut 1.5 cm proximal to the trifurcation and repaired primarily with 8/0 sutures using epineural technique. The rats were then divided into 3 groups. Saline was applied in Group 1 (n=10), ABS in Group 2 (n=10), and heparin in Group 3 (n=10) for 5 minutes to the repair site and surrounding tissues. In each group, electrophysiological measurements were performed with electromyography (EMG) at postoperative week 12. Magnetic resonance diffusion tensor imaging was used at week 12. Macroscopical and histopathological evaluations were conducted after sacrificing the rats at week 24 with total excision of the repaired sciatic nerves and surrounding tissues. The ABS and saline groups showed better healing than the heparin group. The ABS and saline groups were better in the histopathologic evaluations, but there was no statistically significant difference between the 2 groups. Statistically significant differences were not found between the 3 groups. Significant results may be obtained with larger studies.

  6. Lack of Analgesic Synergy of the Cholecystokinin Receptor Antagonist Proglumide and Spinal Cord Stimulation for the Treatment of Neuropathic Pain in Rats.

    Science.gov (United States)

    Inoue, Shinsuke; Johanek, Lisa M; Sluka, Kathleen A

    2017-08-01

    Neuropathic pain is difficult to manage and treat. Spinal cord stimulation (SCS) has become an established procedure for treating chronic neuropathic pain that is refractory to pharmacological therapy. In order to achieve better analgesia, a number of studies have evaluated the effectiveness of combining drug therapy with SCS. Cholecystokinin antagonists, such as proglumide, enhance the analgesic efficacy of endogenous opioids in animal models of pain. We previously reported that both systemic and spinal administration of proglumide enhances analgesia produced by both low- and high-frequency transcutaneous electrical nerve stimulation (TENS). Since SCS produces analgesia through endogenous opioids, we hypothesized that the analgesic effect of SCS would be enhanced through co-administration with proglumide in animals with neuropathic pain. Male Sprague-Dawley rats (n = 40) with spared nerve injury were given proglumide (20 mg/kg, i.p.) or saline prior to treatment with SCS (sham, 4 Hz, and 60 Hz). Mechanical withdrawal thresholds of the paw were measured before and after induction of nerve injury, and after SCS. Physical activity levels were measured after SCS. Both proglumide and SCS when given independently significantly increased withdrawal thresholds two weeks after nerve injury. However, there was no additional effect of combining proglumide and SCS on mechanical withdrawal thresholds or activity levels in animals with nerve injury. Proglumide may be a candidate for achieving analgesia for patients with refractory neuropathic pain conditions, but does not enhance analgesia produced by SCS. © 2017 International Neuromodulation Society.

  7. Rat models of spinal cord injury: from pathology to potential therapies

    Science.gov (United States)

    2016-01-01

    ABSTRACT A long-standing goal of spinal cord injury research is to develop effective spinal cord repair strategies for the clinic. Rat models of spinal cord injury provide an important mammalian model in which to evaluate treatment strategies and to understand the pathological basis of spinal cord injuries. These models have facilitated the development of robust tests for assessing the recovery of locomotor and sensory functions. Rat models have also allowed us to understand how neuronal circuitry changes following spinal cord injury and how recovery could be promoted by enhancing spontaneous regenerative mechanisms and by counteracting intrinsic inhibitory factors. Rat studies have also revealed possible routes to rescuing circuitry and cells in the acute stage of injury. Spatiotemporal and functional studies in these models highlight the therapeutic potential of manipulating inflammation, scarring and myelination. In addition, potential replacement therapies for spinal cord injury, including grafts and bridges, stem primarily from rat studies. Here, we discuss advantages and disadvantages of rat experimental spinal cord injury models and summarize knowledge gained from these models. We also discuss how an emerging understanding of different forms of injury, their pathology and degree of recovery has inspired numerous treatment strategies, some of which have led to clinical trials. PMID:27736748

  8. Immune system augmentation by glatiramer acetate of peripheral nerve regeneration-crush versus transection models of rat sciatic nerve.

    Science.gov (United States)

    Luria, Shai; Cohen, Avraham; Safran, Ori; Firman, Shimon; Liebergall, Meir

    2013-10-01

    Immune system augmentation, using the antigen glatiramer acetate (GA), which is known to affect cellular immunity, has been shown to have a positive effect on peripheral nerve regeneration. We aimed to compare the effect of GA on the regeneration of crushed versus transected nerves. Wild-type rats underwent crush or transection and repair of the sciatic nerve. They were examined 3 weeks postinjury histologically (axon count) and functionally (tibialis anterior muscle weight and footprint analysis). GA was found to augment regeneration both histologically and functionally. In the transected nerve, a significant increase in axon count distal to the injury site was seen in the GA group versus control. A similar yet statistically insignificant trend was found in the crushed nerve. Improvement was found in the footprint analysis between the GA and control groups in both crush and transected nerve groups. We found improvement in the footprint analysis in the crush versus transection group. GA was found to improve the regeneration of the peripheral nerve. Histologically, this was more pronounced in the transection injury. The discrepancy between the different functional measures examined may be explained by the distance of the reinnervated muscles evaluated from the injury site. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

  9. Effects of intraneural and perineural injection and concentration of Ropivacaine on nerve injury during peripheral nerve block in Wistar rats

    Directory of Open Access Journals (Sweden)

    Ilvana Hasanbegovic

    2013-12-01

    Full Text Available Introduction: Injury during peripheral nerve blocks is relatively uncommon, but potentially devastating complication. Recent studies emphasized that location of needle insertion in relationship to the fascicles may be the predominant factor that determines the risk for neurologic complications. However, it is wellestablished that concentration of local anesthetic is also associated with the risk for injury. In this study, we examined the effect of location of injection and concentration of Ropivacaine on risk for neurologic complications. Our hypothesis is that location of the injection is more prognostic for occurrence of nerve injury than the concentration of Ropivacaine.Methods: In experimental design of the study fi fty Wistar rats were used and sciatic nerves were randomized to receive: Ropivacaine or 0.9% NaCl, either intraneurally or perineurally. Pressure data during application was acquired by using a manometer and was analyzed using software package BioBench. Neurologic examination was performed thought the following seven days, there after the rats were sacrificed while sciatic nerves were extracted for histological examination.Results: Independently of tested solution intraneural injections in most of cases resulted with high injection pressure, followed by obvious neurologic defi cit and microscopic destruction of peripheral nerves. Also, low injection pressure, applied either in perineural or intraneural extrafascicular area, resulted with transitory neurologic defi cit and without destruction of the nerve normal histological structure.Conclusions: The main mechanism which leads to neurologic injury combined with peripheral nerve blockade is intrafascicular injection. Higher concentrations of Ropivacaine during intrafascicular applications magnify nerve injury.

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

    Science.gov (United States)

    Chou, An-Kuo; Yang, Ming-Chang; Tsai, Hung-Pei; Chai, Chee-Yin; Tai, Ming-Hong; Kwan, Aij-Li; Hong, Yi-Ren

    2014-01-01

    Neuropathic pain due to peripheral nerve injury may be associated with abnormal central nerve activity. Glial cell-line-derived neurotrophic factor (GDNF) can help attenuate neuropathic pain in different animal models of nerve injury. However, whether GDNF can ameliorate neuropathic pain in the spinal cord dorsal horn (SCDH) in constriction-induced peripheral nerve injury remains unknown. We investigated the therapeutic effects of adenoviral-mediated GDNF on neuropathic pain behaviors, microglial activation, pro-inflammatory cytokine expression and programmed cell death in a chronic constriction injury (CCI) nerve injury animal model. In this study, neuropathic pain was produced by CCI on the ipsilateral SCDH. Mechanical allodynia was examined with von Frey filaments and thermal sensitivity was tested using a plantar test apparatus post-operatively. Target proteins GDNF-1, GDNFRa-1, MMP2, MMP9, p38, phospho-p38, ED1, IL6, IL1β, AIF, caspase-9, cleaved caspase-9, caspase-3, cleaved caspase-3, PARP, cleaved PARP, SPECTRIN, cleaved SPECTRIN, Beclin-1, PKCσ, PKCγ, iNOS, eNOS and nNOS were detected. Microglial activity was measured by observing changes in immunoreactivity with OX-42. NeuN and TUNEL staining were used to reveal whether apoptosis was attenuated by GDNF. Results showed that administrating GDNF began to attenuate both allodynia and thermal hyperalgesia at day 7. CCI-rats were found to have lower GDNF and GDNFRa-1 expression compared to controls, and GDNF re-activated their expression. Also, GDNF significantly down-regulated CCI-induced protein expression except for MMP2, eNOS and nNOS, indicating that the protective action of GDNF might be associated with anti-inflammation and prohibition of microglia activation. Immunocytochemistry staining showed that GDNF reduced CCI-induced neuronal apoptosis. In sum, GDNF enhanced the neurotrophic effect by inhibiting microglia activation and cytokine production via p38 and PKC signaling. GDNF could be a good

  11. Photostimulation of sensory neurons of the rat vagus nerve

    Science.gov (United States)

    Rhee, Albert Y.; Li, Gong; Wells, Jonathon; Kao, Joseph P. Y.

    2008-02-01

    We studied the effect of infrared (IR) stimulation on rat sensory neurons. Primary sensory neurons were prepared by enzymatic dissociation of the inferior (or "nodose") ganglia from the vagus nerves of rats. The 1.85-μm output of a diode laser, delivered through a 200-μm silica fiber, was used for photostimulation. Nodose neurons express the vanilloid receptor, TRPV1, which is a non-selective cation channel that opens in response to significant temperature jumps above 37 C. Opening TRPV1 channels allows entry of cations, including calcium (Ca 2+), into the cell to cause membrane depolarization. Therefore, to monitor TRPV1 activation consequent to photostimulation, we used fura-2, a fluorescent Ca 2+ indicator, to monitor the rise in intracellular Ca 2+ concentration ([Ca 2+]i). Brief trains of 2-msec IR pulses activated TRPV1 rapidly and reversibly, as evidenced by transient rises in [Ca 2+]i (referred to as Ca 2+ transients). Consistent with the Ca 2+ transients arising from influx of Ca 2+, identical photostimulation failed to evoke Ca 2+ responses in the absence of extracellular Ca 2+. Furthermore, the photo-induced Ca 2+ signals were abolished by capsazepine, a specific blocker of TRPV1, indicating that the responses were indeed mediated by TRPV1. We discuss the feasibility of using focal IR stimulation to probe neuronal circuit properties in intact neural tissue, and compare IR stimulation with another photostimulation technique-focal photolytic release of "caged" molecules.

  12. Plasticity of urinary bladder reflexes evoked by stimulation of pudendal afferent nerves after chronic spinal cord injury in cats.

    Science.gov (United States)

    Tai, Changfeng; Chen, Mang; Shen, Bing; Wang, Jicheng; Liu, Hailong; Roppolo, James R; de Groat, William C

    2011-03-01

    Bladder reflexes evoked by stimulation of pudendal afferent nerves (PudA-to-Bladder reflex) were studied in normal and chronic spinal cord injured (SCI) adult cats to examine the reflex plasticity. Physiological activation of pudendal afferent nerves by tactile stimulation of the perigenital skin elicits an inhibitory PudA-to-Bladder reflex in normal cats, but activates an excitatory reflex in chronic SCI cats. However, in both normal and chronic SCI cats electrical stimulation applied to the perigenital skin or directly to the pudendal nerve induces either inhibitory or excitatory PudA-to-Bladder reflexes depending on stimulation frequency. An inhibitory response occurs at 3-10 Hz stimulation, but becomes excitatory at 20-30 Hz. The inhibitory reflex activated by electrical stimulation significantly (Preflex significantly (Preflex in normal cats; however, in chronic SCI cats a volume less than 20% of bladder capacity was sufficient to unmask an excitatory response. This study revealed the co-existence of both inhibitory and excitatory PudA-to-Bladder reflex pathways in cats before and after chronic SCI. However our data combined with published electrophysiological data strongly indicates that the spinal circuitry for both the excitatory and inhibitory PudA-to-Bladder reflexes undergoes a marked reorganization after SCI. Copyright © 2010 Elsevier Inc. All rights reserved.

  13. Percutaneous nerve stimulation in chronic neuropathic pain patients due to spinal cord injury: a pilot study.

    Science.gov (United States)

    Kopsky, David Jos; Ettema, Frank Willem Leo; van der Leeden, Marike; Dekker, Joost; Stolwijk-Swüste, Janneke Marjan

    2014-03-01

    The long-term prognosis for neuropathic pain resolution following spinal cord injury (SCI) is often poor. In many SCI patients, neuropathic pain continues or even worsens over time. Thus, new treatment approaches are needed. We conducted a pilot study to evaluate the feasibility and effect of percutaneous (electrical) nerve stimulation (P(E)NS) in SCI patients with chronic neuropathic pain. In 18 weeks, 12 P(E)NS treatments were scheduled. Assessment with questionnaires was performed at baseline (T0), after 8 weeks (T8), 18 weeks (T18), and 12 weeks post-treatment (T30). From 26 screened patients, 17 were included. In total, 91.2% questionnaires were returned, 2 patients dropped out, and 4.2% of the patients reported minor side effects. Pain scores on the week pain diary measured with the numerical rating scale improved significantly at T8, from 6.5 at baseline to 5.4, and were still significantly improved at T18. Pain reduction of ≥ 30% directly after a session was reported in 64.6% sessions. In total, 6 patients experienced reduction in size of the pain areas at T18 and T30, with a mean reduction of 45.8% at T18 and 45.3% at T30. P(E)NS is feasible as an intervention in SCI patients and might have a positive effect on pain reduction in a part of this patient group. © 2013 The Authors Pain Practice © 2013 World Institute of Pain.

  14. Effect of nerve growth factor on changes of myelin basic protein and functional repair of peripheral nerve following sciatic nerve injury in rats

    Institute of Scientific and Technical Information of China (English)

    邵阳; 马海涵; 伍亚民; 陈恒胜; 曾琳; 李民; 龙在云; 李应玉; 杨恒文

    2002-01-01

    To investigate the therapeutic effect of nerve growth factor ( NGF ) on changes of myelin basic protein (MBP) and functional repair of sensory and motor nerve following sciatic nerve injury. Methods: The sciatic nerves of rats were injured by sectioning with shaver, and divided into 3 groups: NGF group ( Group A ), group of normal saline solution ( Group B), untreated group (Group C). The time point of observation was at the 4th week after operation. Sensory evoked potential (SEP) and motor evoked potential (MEP) were detected by Model WD-4000 nerve potential working diagnosis system. Immunohistochemical analysis was used for identification of MBP. Results: The latency of SEP in the Group A at the 4th week after operation was shorter than that in the Group B ( P < 0.05). The MEP was elicited in 76 % of the Group A and was higher than that in the Group B. Results of immunohistochemistry showed that there were less MBP-positive cells in the Group A than in the Group B in one and four weeks respectively. Conclusions: NGF can improve the conductive function of injured peripheral nerve and facilitate regeneration of nerve.

  15. FUNCTIONAL MAGNETIC RESONANCE IMAGING OF THE SPINAL CORD DURING SENSORY STIMULATION IN DIABETIC RATS

    Science.gov (United States)

    Malisza, Krisztina L.; Jones, Cheryl; Gruwel, Marco L.H.; Foreman, Derek; Fernyhough, Paul; Calcutt, Nigel A.

    2009-01-01

    Purpose To determine if differences exist between control and diabetic rats in functional MRI activity of the spinal cord and if fMRI can provide a means of early detection of diabetic neuropathy. Materials and Methods fMRI of the spinal cord, using noxious electrical stimulation (15 V (~8 mA), 0.3 ms, 3 Hz) of the hind paw, was performed in groups of control and streptozotocin (STZ)-induced type 1 diabetic rats. Results Diabetic rats were lighter, hyperglycemic and had lower blood pH than controls. FMRI activity at the lumbar enlargement of the spinal cord was identified in the dorsal horn ipsilateral to stimulus of all animals. Signal intensity changes across the lumbar spinal cord during periods of activity were not significantly different between control and diabetic rats, with a trend towards greater signal changes in controls. When specific regions of the spinal cord were analyzed, control rats exhibited significantly increased BOLD fMRI activity in both ipsilateral and contralateral dorsal horn compared to diabetic rats. Conclusion The results of this study are consistent with reports that primary afferent input to the spinal cord is diminished by diabetes, and suggest that BOLD fMRI may be useful in early detection of diabetic neuropathy. PMID:19629995

  16. Toe out angle : a functional index for the evaluation of sciatic nerve recovery in the rat model

    NARCIS (Netherlands)

    Varejao, ASP; Cabrita, AM; Geuna, S; Melo-Pinto, P; Filipe, VM; Gramsbergen, A; Meek, MF

    2003-01-01

    In experimental peripheral nerve studies, the rat sciatic nerve model is widely used to examine functional outcome following nerve injury and repair. A variety of evaluation methods exist in the literature, but an adequate selection continues to be a critical point for the researcher. Rats with scia

  17. Methods to evaluate functional nerve recovery in adult rats : walking track analysis, video analysis and the withdrawal reflex

    NARCIS (Netherlands)

    Dijkstra, [No Value; Meek, MF; Robinson, PH; Gramsbergen, A

    2000-01-01

    The aim of this study was to compare different methods for the evaluation of functional nerve recovery. Three groups of adult male Wistar rats were studied. In group A, a 12-mm gap between nerve ends was bridged by an autologous nerve graft; in rats of group B we performed a crush lesion of the scia

  18. Effects of Nogo-neutralizing antibody and neurotrophin-3 on axonal regeneration following spinal cord injury in rats

    Institute of Scientific and Technical Information of China (English)

    Ruisen Zhan; Shijie Chen; Weiguo Wang; Haibin Long

    2008-01-01

    BACKGROUND: Recent studies have suggested that regeneration of the central nerve fiber following spinal cord injury occurs under specific conditions.OBJECTIVE: To study the effects of Nogo-neutralizing antibody (IN-l), in combination with neurotrophin-3 (NT-3), on axonal regeneration and motor function following spinal cord injury in the rat.DESIGN, TIME AND SETTING: A randomized, controlled, animal study combining immunohistochemistry was performed at the Laboratory of Neuroanatomy of Xiangya Medical College, and Central Laboratory of Xiangya the Third Hospital, Central South University from January 2006 to December 2007.MATERIALS: Eighteen healthy, Sprague Dawley rats were randomly divided into three groups, with six rats per group: control, IN-1, and IN-1/NT-3. Hemisectioned spinal cord injury models were established by cutting the posterior 2/3 of spinal cord, which is equivalent to the T8 level.METHODS: A polyethylene tubing was inserted through into subarachnoid cavity, equivalent to the superior margin at the Ts level. Saline, IN-1, and IN-1/NT-3 were respectively injected into control, IN-1, and IN-1/NT-3 groups, three times/day for seven consecutive days.MAIN OUTCOME MEASURES: At 2 weeks post-surgery, biotin dextran amine (10%) was injected into the fight sensorimotor cortex area. At day 28 post-surgery, spinal cord tissue was prepared for frozen sections.Positive astrocytic expression was observed with glial fibrillary acidic protein (GFAP) immunohistochemical staining whose proliferation level was represented by gray value, i.e. the higher the gray value was, the less the positive cells were, and growth of positive fibers was observed with a biotin dextran amine histological reaction. Motor function was measured according to BBB scores pre-operatively, as well as at days 1, 7, 14,21. and 28 post-operatively.RESULTS: Three rats died during experimentation. By random supplement, a total of 18 rats were included.GFAP-positive astrocytes were observed in all

  19. Spinal Anesthesia in Infant Rats: Development of a Model and Assessment of Neurological Outcomes

    Science.gov (United States)

    Yahalom, Barak; Athiraman, Umeshkumar; Soriano, Sulpicio G.; Zurakowski, David; Carpino, Elizabeth; Corfas, Gabriel; Berde, Charles B.

    2012-01-01

    Background Previous studies in infant rats and case-control studies of human infants undergoing surgery have raised concerns about potential neurodevelopmental toxicities of general anesthesia. Spinal anesthesia is an alternative to general anesthesia for some infant surgeries. To test for potential toxicity, we developed a spinal anesthesia model in infant rats. Methods Rats of postnatal ages 7, 14, and 21 days were assigned to: no treatment; 1% isoflurane for either 1 h or 6 h, or lumbar spinal injection of saline or bupivacaine, at doses of 3.75 mg/kg (low dose) or 7.5 mg/kg (high dose). Subgroups of animals underwent neurobehavioral testing and blood gas analysis. Brain and lumbar spinal cord sections were examined for apoptosis using cleaved caspase-3 immunostaining. Lumbar spinal cord was examined histologically. Rats exposed to spinal or general anesthesia as infants underwent Rotarod testing of motor performance as adults. Data were analyzed using analysis of variance (ANOVA) using general linear models, Friedman Tests, and Mann–Whitney U tests, as appropriate. Results Bupivacaine 3.75 mg/kg was effective for spinal anesthesia in all age groups, and produced sensory and motor function recovered in 40 to 60 min. Blood gases were similar among groups. Brain and spinal cord apoptosis increased in rats receiving 6 h of 1% isoflurane, but not among the other treatments. All groups showed intact motor performance at adulthood. Conclusions Spinal anesthesia is technically feasible in infant rats, and appears benign in terms of neuroapoptotic and neuromotor sequelae. PMID:21555934

  20. A PARYLENE-BASED MICROELECTRODE ARRAY IMPLANT FOR SPINAL CORD STIMULATION IN RATS.

    Science.gov (United States)

    Nandra, Mandheerej S; Lavrov, Igor A; Edgerton, V Reggie; Tai, Yu-Chong

    2011-01-23

    The design and fabrication of an epidural spinal cord implant using a parylene-based microelectrode array is presented. Rats with hindlimb paralysis from a complete spinal cord transection were implanted with the device and studied for up to eight weeks, where we have demonstrated recovery of hindlimb stepping functionality through pulsed stimulation. The microelectrode array allows for a high degree of freedom and specificity in selecting the site of stimulation compared to wire-based implants, and triggers varied biological responses that can lead to an increased understanding of the spinal cord and locomotion recovery for victims of spinal cord injury.

  1. Optimal Vagus Nerve Stimulation Frequency for Suppression of Spike-and-Wave Seizures in Rats.

    Science.gov (United States)

    Jiao, Jianhang; Harreby, Kristian R; Sevcencu, Cristian; Jensen, Winnie

    2016-06-01

    Vagus nerve stimulation (VNS) is used as an adjunctive therapy for drug-resistant epilepsy and results in a 50% seizure reduction in up to 50% of treated patients. The VNS frequency used in the clinic today is in the range of 10-30 Hz. The evidence for choosing the stimulation frequency is limited, and little knowledge is available on the effect of other VNS frequencies. Deep brain, trigeminal nerve, or spinal cord stimulation studies have suggested the use of stimulation frequencies above 80 Hz for seizure control. Therefore, our objective for the present study was to investigate if VNS using frequencies higher than those currently used in the clinic could be more effective in attenuating seizures. Spike-and-wave (SW) discharges were induced in 11 rats, which then were subjected to VNS sessions applied at the frequencies of 10, 30, 80, 130, and 180 Hz combined with control intervals without stimulation. The anticonvulsive effect of VNS was evaluated by comparing the normalized mean power (nMP) and frequency (nMSF) of the SW discharges derived from intracortical recordings collected during the stimulation and control intervals. Compared with the control intervals, all the tested VNS frequencies significantly reduced the nMP (in the range of 9-21%). However, we found that 130 and 180 Hz VNS induced a 50% larger attenuation of seizures than that achieved by 30 Hz VNS. In addition, we found that 80, 130, and 180 Hz VNS induced a significant reduction of the nMSF, that is by 5, 7, and 8%, respectively. These results suggest that a VNS stimulation frequency in the range of 130-180 Hz may be more effective in inhibiting seizures than the 30 Hz VNS applied in the clinic today.

  2. Nerve growth factor facilitates redistribution of adrenergic and non-adrenergic non-cholinergic perivascular nerves injured by phenol in rat mesenteric resistance arteries.

    Science.gov (United States)

    Yokomizo, Ayako; Takatori, Shingo; Hashikawa-Hobara, Narumi; Goda, Mitsuhiro; Kawasaki, Hiromu

    2016-01-05

    We previously reported that nerve growth factor (NGF) facilitated perivascular sympathetic neuropeptide Y (NPY)- and calcitonin gene-related peptide (CGRP)-containing nerves injured by the topical application of phenol in the rat mesenteric artery. We also demonstrated that mesenteric arterial nerves were distributed into tyrosine hydroxylase (TH)-, substance P (SP)-, and neuronal nitric oxide synthase (nNOS)-containing nerves, which had axo-axonal interactions. In the present study, we examined the effects of NGF on phenol-injured perivascular nerves, including TH-, NPY-, nNOS-, CGRP-, and SP-containing nerves, in rat mesenteric arteries in more detail. Wistar rats underwent the in vivo topical application of 10% phenol to the superior mesenteric artery, proximal to the abdominal aorta, under pentobarbital-Na anesthesia. The distribution of perivascular nerves in the mesenteric arteries of the 2nd to 3rd-order branches isolated from 8-week-old Wistar rats was investigated immunohistochemically using antibodies against TH-, NPY-, nNOS-, CGRP-, and SP-containing nerves. The topical phenol treatment markedly reduced the density of all nerves in these arteries. The administration of NGF at a dose of 20µg/kg/day with an osmotic pump for 7 days significantly increased the density of all perivascular nerves over that of sham control levels. These results suggest that NGF facilitates the reinnervation of all perivascular nerves injured by phenol in small resistance arteries.

  3. The Dilator Naris Muscle as a Reporter of Facial Nerve Regeneration in a Rat Model

    NARCIS (Netherlands)

    Weinberg, J.S.; Kleiss, I.J.; Knox, C.J.; Heaton, J.T.; Hadlock, T.A.

    2016-01-01

    OBJECTIVE: Many investigators study facial nerve regeneration using the rat whisker pad model, although widely standardized outcomes measures of facial nerve regeneration in the rodent have not yet been developed. The intrinsic whisker pad "sling" muscles producing whisker protraction, situated at t

  4. Development of a Model for Nerve Agent Inhalation in Conscious Rats

    Science.gov (United States)

    2013-05-23

    Toxicol Mech Meth 14:183–94. Bajgar J. (2004). Organophosphates /nerve agent poisoning : mechanism of action, diagnosis, prophylaxis, and treatment. Adv...See reprint. 15. SUBJECT TERMS Chemical warfare, cholinesterases, inhalation exposure, nerve agents, organophosphates , vapor 16. SECURITY...exposure system for assessing respiratory toxicity of vaporized chemical agents in untreated, non-anesthetized rats. The organophosphate diisopropyl

  5. Nerve function and oxidative stress in diabetic and vitamin E deficient rats

    NARCIS (Netherlands)

    Gispen, W.H.; Dam, P.S. van; Asbeck, B.S. van; Bravenboer, B.; Oirschot, J.F.L.M. van; Marx, J.J.

    1997-01-01

    Nerve dysfunction in diabetes is associated with increased oxidative stress. Vitamin E depletion also leads to enhanced presence of reactive oxygen species (ROS). We compared systemic and endoneurial ROS activity and nerve conduction in vitamin E-depleted control and streptozotocin-diabetic rats (CE

  6. Muscle differentiation after sciatic nerve transection and reinnervation in adult rats

    NARCIS (Netherlands)

    Ijkema-Paassen, J; Meek, MF; Gramsbergen, A

    Reinnervation after peripheral nerve transections generally leads to poor functional recovery. In order to study whether changes in muscles might be a contributing factor in this phenomenon we studied muscle morphology and fibre type distributions after sciatic nerve transection in the rat hind

  7. Transformation of the output of spinal lamina I neurons after nerve injury and microglia stimulation underlying neuropathic pain

    Directory of Open Access Journals (Sweden)

    Salter Michael W

    2007-09-01

    Full Text Available Abstract Background Disinhibition of neurons in the superficial spinal dorsal horn, via microglia – neuron signaling leading to disruption of chloride homeostasis, is a potential cellular substrate for neuropathic pain. But, a central unresolved question is whether this disinhibition can transform the activity and responses of spinal nociceptive output neurons to account for the symptoms of neuropathic pain. Results Here we show that peripheral nerve injury, local spinal administration of ATP-stimulated microglia or pharmacological disruption of chloride transport change the phenotype of spinal lamina I output neurons, causing them to 1 increase the gain of nociceptive responsiveness, 2 relay innocuous mechanical input and 3 generate spontaneous bursts of activity. The changes in the electrophysiological phenotype of lamina I neurons may account for three principal components of neuropathic pain: hyperalgesia, mechanical allodynia and spontaneous pain, respectively. Conclusion The transformation of discharge activity and sensory specificity provides an aberrant signal in a primarily nociceptive ascending pathway that may serve as a basis for the symptoms of neuropathic pain.

  8. Continuous intrathecal fluid infusions elevate nerve growth factor levels and prevent functional deficits after spinal cord ischemia.

    Science.gov (United States)

    Bowes, M; Tuszynski, M H; Conner, J; Zivin, J A

    2000-11-17

    Continuous intracerebroventricular or intrathecal infusions of neurotrophic factors have been reported to prevent neuronal degeneration, stimulate axonal sprouting and ameliorate behavioral deficits in various models of CNS injury and aging. In the present study, the ability of intrathecal infusions of recombinant human nerve growth factor (NGF) to reduce functional deficits following spinal cord ischemia was investigated. Adult rabbits underwent intrathecal cannulation and continuous infusions of either 300 microg/ml recombinant human NGF or artificial CSF (vehicle) at a rate of 143 microl/day for 7 days prior to induction of spinal cord ischemia. Continuous infusions were maintained after induction of ischemia. Four days later, both NGF-treated and vehicle-infused subjects showed a significant amelioration of functional motor deficits compared to lesioned, non-infused subjects (PNGF-infused subjects (mean+/-S.E.M.). Significantly elevated NGF protein levels were attained within the spinal cords of both NGF-treated subjects and artificial CSF-infused subjects, although levels were substantially higher in NGF-treated subjects (9.8+/-3.8 ng/g in NGF-infused vs. 2.0+/-0.4 ng/g in vehicle-infused and only 0.4+/-0.2 ng/g in lesioned, non-infused animals). These findings indicate that the process of intrathecal cannulation and fluid infusion elicits alterations in the spinal cord environment that are neuroprotective, including spontaneous elevations in NGF levels.

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

    Science.gov (United States)

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

    2016-06-02

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

  10. The Neuroprotective Effect of Kefir on Spinal Cord Ischemia/Reperfusion Injury in Rats.

    Science.gov (United States)

    Guven, Mustafa; Akman, Tarik; Yener, Ali Umit; Sehitoglu, Muserref Hilal; Yuksel, Yasemin; Cosar, Murat

    2015-05-01

    The main causes of spinal cord ischemia are a variety of vascular pathologies causing acute arterial occlusions. We investigated neuroprotective effects of kefir on spinal cord ischemia injury in rats. Rats were divided into three groups : 1) sham operated control rats; 2) spinal cord ischemia group fed on a standard diet without kefir pretreatment; and 3) spinal cord ischemia group fed on a standard diet plus kefir. Spinal cord ischemia was performed by the infrarenal aorta cross-clamping model. The spinal cord was removed after the procedure. The biochemical and histopathological changes were observed within the samples. Functional assessment was performed for neurological deficit scores. The kefir group was compared with the ischemia group, a significant decrease in malondialdehyde levels was observed (pkefir group were significantly higher than ischemia group (pkefir group is compared with ischemia group, there was a significant decrease in numbers of dead and degenerated neurons (pkefir group compared with ischemia group (pkefir group were significantly higher than ischemia group at 24 h (pkefir pretreatment in spinal cord ischemia/reperfusion reduced oxidative stress and neuronal degeneration as a neuroprotective agent. Ultrastructural studies are required in order for kefir to be developed as a promising therapeutic agent to be utilized for human spinal cord ischemia in the future.

  11. Expression of adrenomedullin in rats after spinal cord injury and intervention effect of recombinant human erythropoietin

    Science.gov (United States)

    Zhao, Liang; Jing, Yu; Qu, Lin; Meng, Xiangwei; Cao, Yang; Tan, Huibing

    2016-01-01

    The expression of adrenomedullin (ADM) in injured tissue of rat spinal cord was observed and the effect of recombinant human erythropoietin was analyzed. A total of 45 Sprague-Dawley rats were selected and divided into 3 equal groups including, a sham-operation group in which rats received an excision of vertebral plate; a spinal cord injury model group and a recombinant human erythropoietin group in which rats with spinal cord injury received a caudal vein injection of 300 units recombinant human erythropoietin after injury. Hematoxylin and eosin staining was performed to observe the spinal cord injury conditions. Immunohistochemical staining was performed to observe the expression of ADM. Pathologic changes in the group of recombinant human erythropoietin at various times were significantly less severe than those in the group of spinal cord injury model. The expression of ADM was increased particularly in the group of recombinant human erythropoietin (P<0.01). The improved Tarlov scores of the group of spinal cord injury model and the group of recombinant human erythropoietin were lower than those of the sham-operation group at 3, 6 and 9 days (P<0.01). Thus, the recombinant human erythropoietin is capable of alleviating the secondary injury of spinal cord. One of the mechanisms may be achieved by promoting the increase of ADM expression. PMID:28101163

  12. Full inhibition of spinal FAAH leads to TRPV1-mediated analgesic effects in neuropathic rats and possible lipoxygenase-mediated remodeling of anandamide metabolism.

    Science.gov (United States)

    Starowicz, Katarzyna; Makuch, Wioletta; Korostynski, Michal; Malek, Natalia; Slezak, Michal; Zychowska, Magdalena; Petrosino, Stefania; De Petrocellis, Luciano; Cristino, Luigia; Przewlocka, Barbara; Di Marzo, Vincenzo

    2013-01-01

    Neuropathic pain elevates spinal anandamide (AEA) levels in a way further increased when URB597, an inhibitor of AEA hydrolysis by fatty acid amide hydrolase (FAAH), is injected intrathecally. Spinal AEA reduces neuropathic pain by acting at both cannabinoid CB1 receptors and transient receptor potential vanilloid-1 (TRPV1) channels. Yet, intrathecal URB597 is only partially effective at counteracting neuropathic pain. We investigated the effect of high doses of intrathecal URB597 on allodynia and hyperalgesia in rats with chronic constriction injury (CCI) of the sciatic nerve. Among those tested, the 200 µg/rat dose of URB597 was the only one that elevated the levels of the FAAH non-endocannabinoid and anti-inflammatory substrates, oleoylethanolamide (OEA) and palmitoylethanolamide (PEA), and of the endocannabinoid FAAH substrate, 2-arachidonoylglycerol, and fully inhibited thermal and tactile nociception, although in a manner blocked almost uniquely by TRPV1 antagonism. Surprisingly, this dose of URB597 decreased spinal AEA levels. RT-qPCR and western blot analyses demonstrated altered spinal expression of lipoxygenases (LOX), and baicalein, an inhibitor of 12/15-LOX, significantly reduced URB597 analgesic effects, suggesting the occurrence of alternative pathways of AEA metabolism. Using immunofluorescence techniques, FAAH, 15-LOX and TRPV1 were found to co-localize in dorsal spinal horn neurons of CCI rats. Finally, 15-hydroxy-AEA, a 15-LOX derivative of AEA, potently and efficaciously activated the rat recombinant TRPV1 channel. We suggest that intrathecally injected URB597 at full analgesic efficacy unmasks a secondary route of AEA metabolism via 15-LOX with possible formation of 15-hydroxy-AEA, which, together with OEA and PEA, may contribute at producing TRPV1-mediated analgesia in CCI rats.

  13. Full inhibition of spinal FAAH leads to TRPV1-mediated analgesic effects in neuropathic rats and possible lipoxygenase-mediated remodeling of anandamide metabolism.

    Directory of Open Access Journals (Sweden)

    Katarzyna Starowicz

    Full Text Available Neuropathic pain elevates spinal anandamide (AEA levels in a way further increased when URB597, an inhibitor of AEA hydrolysis by fatty acid amide hydrolase (FAAH, is injected intrathecally. Spinal AEA reduces neuropathic pain by acting at both cannabinoid CB1 receptors and transient receptor potential vanilloid-1 (TRPV1 channels. Yet, intrathecal URB597 is only partially effective at counteracting neuropathic pain. We investigated the effect of high doses of intrathecal URB597 on allodynia and hyperalgesia in rats with chronic constriction injury (CCI of the sciatic nerve. Among those tested, the 200 µg/rat dose of URB597 was the only one that elevated the levels of the FAAH non-endocannabinoid and anti-inflammatory substrates, oleoylethanolamide (OEA and palmitoylethanolamide (PEA, and of the endocannabinoid FAAH substrate, 2-arachidonoylglycerol, and fully inhibited thermal and tactile nociception, although in a manner blocked almost uniquely by TRPV1 antagonism. Surprisingly, this dose of URB597 decreased spinal AEA levels. RT-qPCR and western blot analyses demonstrated altered spinal expression of lipoxygenases (LOX, and baicalein, an inhibitor of 12/15-LOX, significantly reduced URB597 analgesic effects, suggesting the occurrence of alternative pathways of AEA metabolism. Using immunofluorescence techniques, FAAH, 15-LOX and TRPV1 were found to co-localize in dorsal spinal horn neurons of CCI rats. Finally, 15-hydroxy-AEA, a 15-LOX derivative of AEA, potently and efficaciously activated the rat recombinant TRPV1 channel. We suggest that intrathecally injected URB597 at full analgesic efficacy unmasks a secondary route of AEA metabolism via 15-LOX with possible formation of 15-hydroxy-AEA, which, together with OEA and PEA, may contribute at producing TRPV1-mediated analgesia in CCI rats.

  14. Full Inhibition of Spinal FAAH Leads to TRPV1-Mediated Analgesic Effects in Neuropathic Rats and Possible Lipoxygenase-Mediated Remodeling of Anandamide Metabolism

    Science.gov (United States)

    Starowicz, Katarzyna; Makuch, Wioletta; Korostynski, Michal; Malek, Natalia; Slezak, Michal; Zychowska, Magdalena; Petrosino, Stefania; De Petrocellis, Luciano; Cristino, Luigia; Przewlocka, Barbara; Di Marzo, Vincenzo

    2013-01-01

    Neuropathic pain elevates spinal anandamide (AEA) levels in a way further increased when URB597, an inhibitor of AEA hydrolysis by fatty acid amide hydrolase (FAAH), is injected intrathecally. Spinal AEA reduces neuropathic pain by acting at both cannabinoid CB1 receptors and transient receptor potential vanilloid-1 (TRPV1) channels. Yet, intrathecal URB597 is only partially effective at counteracting neuropathic pain. We investigated the effect of high doses of intrathecal URB597 on allodynia and hyperalgesia in rats with chronic constriction injury (CCI) of the sciatic nerve. Among those tested, the 200 µg/rat dose of URB597 was the only one that elevated the levels of the FAAH non-endocannabinoid and anti-inflammatory substrates, oleoylethanolamide (OEA) and palmitoylethanolamide (PEA), and of the endocannabinoid FAAH substrate, 2-arachidonoylglycerol, and fully inhibited thermal and tactile nociception, although in a manner blocked almost uniquely by TRPV1 antagonism. Surprisingly, this dose of URB597 decreased spinal AEA levels. RT-qPCR and western blot analyses demonstrated altered spinal expression of lipoxygenases (LOX), and baicalein, an inhibitor of 12/15-LOX, significantly reduced URB597 analgesic effects, suggesting the occurrence of alternative pathways of AEA metabolism. Using immunofluorescence techniques, FAAH, 15-LOX and TRPV1 were found to co-localize in dorsal spinal horn neurons of CCI rats. Finally, 15-hydroxy-AEA, a 15-LOX derivative of AEA, potently and efficaciously activated the rat recombinant TRPV1 channel. We suggest that intrathecally injected URB597 at full analgesic efficacy unmasks a secondary route of AEA metabolism via 15-LOX with possible formation of 15-hydroxy-AEA, which, together with OEA and PEA, may contribute at producing TRPV1-mediated analgesia in CCI rats. PMID:23573230

  15. The Survival Effects of Electeromagnetic Fields on Dorsal Root Ganglia Neurons of the Crushed Sciatic Nerve in the Rat

    Directory of Open Access Journals (Sweden)

    M.R. Nikravesh

    2003-07-01

    Full Text Available Previous studies have been shown that electromagnetic fields (EMF result in increasing the rate of nerve regeneration. Therefore it could be assumed following axotomy the signal induction of these fields may protect neural cells from death. For this study 24 male wistar rats (2 month age divided to 4 groups (experimental 1, 2, control and sham. For axotomy, the animals were anesthetized and their right Sciatic Nerve (SN were exposed and crushed in the mid portion of the thigh in experimental and control groups. In the sham group the SN just exposed (no compression. In the next phase experimental groups were exposed to the 50 HZ electeromagnetic field (EMF, 1.1mTl 2-4 hr/day (for 10 days. After 8 weeks, Dorsal Root Ganglions (DRGs in the lumbar segments (L4-L6 of spinal cord were sampled, processed sectioned serially and stained with toluidine blue (pH=4.5. By using stereological quantitative technique (physical disector, the neurons in the crushed side (DRGs were counted and compared in the all of groups. Statistical analyses of results have been shown a remarkable reduction in neuronal density in (DRGs of control. On the other hand we observed a cell death DRG significant among experimental groups (p<0/05. In addition we compared DRG volume in all groups but they didn’t show any significant difference. These findings indicate that the EMF may play a survival role against neuronal death during nerve injuries.

  16. Repair of spinal cord injury by implantation of bFGF-incorporated HEMA-MOETACL hydrogel in rats

    Science.gov (United States)

    Chen, Bo; He, Jianyu; Yang, Hao; Zhang, Qian; Zhang, Lingling; Zhang, Xian; Xie, En; Liu, Cuicui; Zhang, Rui; Wang, Yi; Huang, Linhong; Hao, Dingjun

    2015-03-01

    There is no effective strategy for the treatment of spinal cord injury (SCI). An appropriate combination of hydrogel materials and neurotrophic factor therapy is currently thought to be a promising approach. In this study, we performed experiments to evaluate the synergic effect of implanting hydroxyl ethyl methacrylate [2-(methacryloyloxy)ethyl] trimethylammonium chloride (HEMA-MOETACL) hydrogel incorporated with basic fibroblast growth factor (bFGF) into the site of surgically induced SCI. Prior to implantation, the combined hydrogel was surrounded by an acellular vascular matrix. Sprague-Dawley rats underwent complete spinal cord transection at the T-9 level, followed by implantation of bFGF/HEMA-MOETACL 5 days after transection surgery. Our results showed that the bFGF/HEMA-MOETACL transplant provided a scaffold for the ingrowth of regenerating tissue eight weeks after implantation. Furthermore, this newly designed implant promoted both nerve tissue regeneration and functional recovery following SCI. These results indicate that HEMA-MOETACL hydrogel is a promising scaffold for intrathecal, localized and sustained delivery of bFGF to the injured spinal cord and provide evidence for the possibility that this approach may have clinical applications in the treatment of SCI.

  17. Somatotopic organization of lumbar muscle-innervating neurons in the ventral horn of the rat spinal cord.

    Science.gov (United States)

    Takahashi, Yuzuru; Ohtori, Seiji; Takahashi, Kazuhisa

    2010-04-01

    The ventral horn of the rat spinal cord was investigated with respect to the somatotopic organization of the motor neurons that innervate the lumbar muscles. Neurotracer 1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine perchlorate (DiI) was applied to specific sites in lumbar muscles. Spinal cord segments at L1 through L4 levels were cut into 40-mum serial transverse sections. Labeled neurons were located in the ventromedial nucleus (VM) and lateromedial nucleus (LM) nuclei of Rexed's lamina IX. Motor neurons innervating the m. interspinales lumborum and m. multifidus were without exception present in the VM, whereas all motor neurons innervating the m. rectus abdominis were present in the LM. Forty percent of motor neurons innervating the m. quadratus lumborum were present in the VM and the other 60% were in the LM. Although most of the motor neurons innervating the m. psoas major were present in the LM, a few labeled neurons existed in the VM. These results suggest that the border zone demarcating the areas of innervation of the dorsal and ventral rami of spinal nerves crosses the m. quadratus lumborum.

  18. NGF message and protein distribution in the injured rat spinal cord.

    Science.gov (United States)

    Brown, Arthur; Ricci, Mary-Jo; Weaver, Lynne C

    2004-07-01

    Nerve growth factor (NGF) content of the spinal cord is increased after cord injury. NGF can cause central sprouting of sensory fibers after spinal cord injury (SCI), leading to autonomic dysfunction and pain. NGF also can promote the death of oligodendroglia after SCI. Knowing the source of intraspinal NGF would benefit strategies for minimizing abnormal plasticity and cell death after SCI. We identified these sources, using RNA in situ hybridization to detect NGF mRNA and double-labeling immunocytochemistry for NGF and cell-marking antigens. In uninjured and sham-injured rats, we identified NGF mRNA in leptomeningeal cells and in neurons in the intermediate grey matter, whereas NGF protein was observed only in leptomeningeal cells. At 3-7 days after transection or clip-compression SCI, NGF mRNA and protein were expressed in the lesion and throughout the intermediate grey matter and white matter rostral and caudal to the injury site. Transection-SCI was used to permit comparisons to previous studies; clip-compression injury was used as a more clinically relevant model. mRNA and protein in adjacent sections were expressed in ramified microglia, astrocytes, intermediate grey neurons, pial cells, and leptomeningeal and Schwann cells in the lateral white matter and the lesion site. Rounded macrophages in the lesion were immunoreactive (Ir) for NGF, but the cells expressing NGF mRNA were not in the same areas of the lesion and were not stained by a macrophage marker. Our data demonstrate that glia, neurons, meningeal cells and Schwann cells but not macrophages contribute to the increased intraspinal NGF after SCI.

  19. Nerve Tissue Prefabrication Inside the Rat Femoral Bone: Does It Work?

    Science.gov (United States)

    Ozbek, Zuhtu; Kocman, Atacan Emre; Ozatik, Orhan; Soztutar, Erdem; Ozkara, Emre; Kose, Aydan; Arslantas, Ali; Cetin, Cengiz

    2017-01-01

    To investigate whether nerve regeneration can be induced in the tubular bone between distal and proximal cut nerve ends. Twenty adult Wistar rats were used for the study. Rats were divided into three groups; femoral bone conduit group, nerve transection group, sham group. The sciatic nerve was surgically cut and from both ends inserted into the adjacent femoral bone tunnel in the femoral bone conduit group. The sciatic nerve was cut transversely in the nerve transection group. In the Sham group, only sciatic nerve exploration was performed, without a nerve cut. The groups were evaluated functionally and morphologically. All results showed that axonal growth existed through the osseous canal. To the best of our knowledge, this is the first study to evaluate neural regeneration inside the bone. We can speculate that the bone marrow provides a convenient microenvironment for peripheral nerve regeneration. In addition to prefabricating peripheral nerves, this novel model may help to establish further strategies for engineering of other tissues in the bone marrow.

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

    Institute of Scientific and Technical Information of China (English)

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

    2014-01-01

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

  1. Aliskiren ameliorates sympathetic nerve sprouting and suppresses the inducibility of ventricular tachyarrhythmia in postinfarcted rat heart

    Institute of Scientific and Technical Information of China (English)

    JIA Yin-yu; BAO Zhi-wei; WEI Mei-fang; ZHU Jian-hua; GUI Le

    2013-01-01

    Background Aliskiren is an oral renin inhibitor,which inhibits the first rate limiting step in the renin angiotensin aldosterone system.In this study,sympathetic nerve sprouting and the inducibility of ventricular fibrillation after aliskiren treatment in myocardial infarction were investigated.Methods Male Sprague Dawley rats after coronary artery ligation were randomly allocated to four groups:angiotensin converting enzyme inhibitor enalapril,angiotensin receptor blocker valsartan,β adrenergic receptor