Neuroprotective potential of erythropoietin and darbepoetin alfa in an experimental model of sciatic nerve injury

2007 ◽  
Vol 7 (6) ◽  
pp. 645-651 ◽  
Author(s):  
Giovanni Grasso ◽  
Francesco Meli ◽  
Vincenzo Fodale ◽  
Gioacchino Calapai ◽  
Michele Buemi ◽  
...  
Keyword(s):  
Sciatic Nerve ◽  
Peripheral Nerve ◽  
Nerve Injury ◽  
Peripheral Nerve Injury ◽  
Darbepoetin Alfa ◽  
Placebo Treatment ◽  
Sciatic Nerve Injury ◽  
Crush Injury ◽  
Sprague Dawley ◽  
Compound Muscle Action Potentials

Object The objectives of this study were to examine whether the systemic administration of recombinant human erythropoietin (rHuEPO) and its long-lasting derivative darbepoetin alfa expedited functional recovery in a rat model of sciatic nerve injury, and to compare the effects of these agents in the model. Methods Thirty male Sprague–Dawley rats received a crush injury to the left sciatic nerve and subsequently underwent either placebo treatment, daily injections of rHuEPO, or weekly injections of darbepoetin alfa. Results Both rHuEPO and darbepoetin alfa were effective in reducing neurological impairment and improving compound muscle action potentials following nerve injury. Darbepoetin alfa, however, shortened the duration of peripheral nerve recovery and facilitated recovery from the neurological and electrophysiological impairment following crush injury significantly better than rHuEPO. Examination of the footprint length factor data revealed that darbepoetin alfa–treated animals recovered preinjury function by postoperative Day 10, 4 days earlier than animals treated with rHuEPO and 11 days earlier than animals treated with placebo. Conclusions These results suggest that recovery of neurological function in a model of peripheral nerve injury is more rapid with weekly administration of darbepoetin alfa than with daily rHuEPO treatment. Agents that facilitate nerve regeneration have the potential to limit the extent of motor endplate loss and muscle atrophy. The administration of EPO in its long-lasting recombinant forms affords significant neuroprotection in peripheral nerve injury models and may hold promise for future clinical applications.

scholarly journals Reduced Renshaw Recurrent Inhibition after Neonatal Sciatic Nerve Crush in Rats

2014 ◽  
Vol 2014 ◽  
pp. 1-11
Author(s):  
Liang Shu ◽  
Jingjing Su ◽  
Lingyan Jing ◽  
Ying Huang ◽  
Yu Di ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Sciatic Nerve ◽  
Peripheral Nerve ◽  
Nerve Injury ◽  
Peripheral Nerve Injury ◽  
Recurrent Inhibition ◽  
Crush Injury ◽  
Sciatic Nerve Crush ◽  
Nerve Crush ◽  
Nerve Crush Injury

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.

scholarly journals Augmenting Peripheral Nerve Regeneration Using Rat Hair Follicle Stem Cells (rHFSCs) in Rats

2021 ◽  
Author(s):  
Leila Beigom Hejazian ◽  
◽  
Zeinab Akbarnejad ◽  
Fatemeh Moghani Ghoroghi ◽  
Banafshe Esmaeilzade ◽  
...  
Keyword(s):  
Stem Cells ◽  
Sciatic Nerve ◽  
Peripheral Nerve ◽  
Hair Follicle ◽  
Nerve Injury ◽  
Peripheral Nerve Injury ◽  
Sciatic Nerve Injury ◽  
Double Labeling ◽  
Hair Follicle Stem Cells ◽  
Follicle Stem Cells

Introduction: Nowadays, cell therapy is the most advanced treatment of peripheral nerve injury. The aim of this study was to determine the effects of transplantation of hair follicle stem cells on the regeneration of the sciatic nerve injury in rats. Methods: The bulge region of the rat whisker was isolated and cultured. Morphological and biological features of the cultured bulge cells were observed by light microscopy and immunocytochemistry methods. Percentages of CD34, K15 and Nestin cell markers expression were demonstrated by flow cytometry. Rats were randomly divided into 3 groups: Injury group, epineurium group, and epineurium-with-cell group, that rat hair follicular stem cells (rHFSCs) were injected into the site of nerve cut. HFSCs were labeled with BrdU, and double-labeling immunofluorescence was performed to study survival and differentiation of the grafted cells. After 8 weeks, electrophysiological, histological and immunocytochemical analysis assessments were performed. Results: The results of this study show that rat hair follicle stem cells are suitable for cell culture, proliferation and differentiation. The results suggest that transplantation of rat hair follicle stem cells had the potential capability of regenerating sciatic nerve injury; moreover, evidence of electrophysiology and histology show that Epineurium with cell repair was more effective than the other experimental group (p<0.05). Conclusion: The achieved results propose that hair follicle stem cell would improve axonal growth and functional recovery after peripheral nerve injury.

scholarly journals Lack of correlation between spinal microgliosis and long-term development of tactile hypersensitivity in two different sciatic nerve crush injury

2021 ◽  
Vol 17 ◽  
pp. 174480692110113
Author(s):  
Hyoung Woo Kim ◽  
Chan Hee Won ◽  
Seog Bae Oh
Keyword(s):  
Spinal Cord ◽  
Chronic Pain ◽  
Sciatic Nerve ◽  
Peripheral Nerve ◽  
Nerve Injury ◽  
Peripheral Nerve Injury ◽  
Sensory Function ◽  
Crush Injury ◽  
Sciatic Nerve Crush

Microglia activation following peripheral nerve injury has been shown to contribute to central sensitization of the spinal cord for the development of neuropathic pain. In a recent study, we reported that the amount of nerve damage does not necessarily correlate with chronic pain development. Here we compared the response of spinal microglia, using immunohistochemistry as a surrogate of microglial activation, in mice with two different types of crush injury of the sciatic nerve. We confirmed that incomplete crush of the sciatic nerve (partial crush injury, PCI) resulted in tactile hypersensitivity after the recovery of sensory function (15 days after surgery), whereas the hypersensitivity was not observed after the complete crush (full crush injury, FCI). We observed that immunoreactivity for Iba-1, a microglial marker, was greater in the ipsilateral dorsal horn of lumbar (L4) spinal cord of mice 2 days after FCI compared to PCI, positively correlating with the intensity of crush injury. Ipsilateral Iba-1 reactivity was comparable between injuries at 7 days with a significant increase compared to the contralateral side. By day 15 after injury, ipsilateral Iba-1 immunoreactivity was much reduced compared to day 7 and was not different between the groups. Our results suggest that the magnitude of the early microgliosis is dependent on injury severity, but does not necessarily correlate with the long-term development of chronic pain-like hypersensitivity after peripheral nerve injury.

Spontaneous activity of ventral root axons following peripheral nerve injury

1985 ◽  
Vol 62 (3) ◽  
pp. 408-413 ◽  
Author(s):  
Kim J. Burchiel ◽  
Lisa C. Russell
Keyword(s):  
Sciatic Nerve ◽  
Peripheral Nerve ◽  
Spontaneous Activity ◽  
Nerve Injury ◽  
Peripheral Nerve Injury ◽  
Ventral Root ◽  
Root Activity ◽  
Spontaneous Discharge ◽  
Sprague Dawley ◽  
Content Type

✓ In 18 Sprague-Dawley rats, the left sciatic nerve was divided at the mid-femur level. Seven to 9 days later, microfilament recordings were made from the ipsilateral L-5 ventral root. Spontaneous activity in the ventral root, ranging from 0.1 to 6.1 Hz, was recorded in 12 of the 18 animals. Conduction velocity determinations showed this activity to be in A-beta and A-delta fibers. Recordings in 10 normal L-5 ventral roots from five control rats showed no spontaneous activity. In the rats with sciatic nerve division, the ongoing discharge appeared to originate in the cut end of the nerve since mechanical stimulation of the neuroma produced synchronous ventral root activity. Furthermore, cooling of the neuroma inhibited the spontaneous discharge, whereas with rewarming it returned. Spontaneous ventral root activity was also increased by systemic application of epinephrine. This activity was qualitatively similar to spontaneous activity that has been recorded in dorsal root microfilaments after peripheral nerve injury. The observation of an ongoing discharge in potentially nociceptive ventral root axons subsequent to nerve injury may be relevant to the mechanism of chronic pain of peripheral origin.

scholarly journals Bioinformatics analysis of long non-coding RNAs involved in nerve regeneration following sciatic nerve injury

2020 ◽  
Vol 16 ◽  
pp. 174480692097191
Author(s):  
Yuanyuan Jia ◽  
Ming Zhang ◽  
Pei Li ◽  
Wenbo Tang ◽  
Yao Liu ◽  
...  
Keyword(s):  
Sciatic Nerve ◽  
Peripheral Nerve ◽  
Nerve Regeneration ◽  
Nerve Injury ◽  
Peripheral Nerve Injury ◽  
Axon Regeneration ◽  
Sciatic Nerve Injury ◽  
Sciatic Nerve Crush ◽  
Non Coding Rnas

Little is known about the role of epigenetic modification in axon regeneration following peripheral nerve injury. The purpose of the present study was to investigate the role of long non-coding RNAs (lncRNAs) in the regulation of axon regeneration. We used bioinformatics to perform microarray analysis and screened total 476 lncRNAs and 129 microRNAs (miRNAs) of differentially expressed genes after sciatic nerve injury in mice. lncRNA-GM4208 and lncRNA-GM30085 were examined, and the changes in lncRNA expression in the L4–L6 dorsal root ganglia (DRG) following sciatic nerve crush injury were analyzed by reverse transcription-quantitative polymerase chain reaction (RT-qPCR). The expression of lncRNAs in the DRG changed, indicating that they might be related to nerve regeneration in the DRG following peripheral nerve injury.

scholarly journals An Investigation into the Rehabilitative Mechanism of Tuina in the Treatment of Sciatic Nerve Injury

2020 ◽  
Vol 2020 ◽  
pp. 1-11
Author(s):  
Taotao Lv ◽  
Yanjun Mo ◽  
Tianyuan Yu ◽  
Yumo Zhang ◽  
Shuai Shao ◽  
...  
Keyword(s):  
Sciatic Nerve ◽  
Peripheral Nerve ◽  
Nerve Injury ◽  
Myelin Sheath ◽  
Peripheral Nerve Injury ◽  
Sham Group ◽  
Sciatic Nerve Injury ◽  
Ultrastructural Changes ◽  
Rna Seq ◽  
The Right

Objective. To explore the effect of tuina on the gene expression at the point of nerve injury in rats with sciatic nerve injury (SNI) and to elucidate the repair mechanism of tuina promoting the functional recovery of peripheral nerve injury. Methods. In the Sham group, the right sciatic nerve was exposed without clamping. The SNI model was established using the sciatic nerve clamp method on the right leg and then randomly divided into the SNI group and the Tuina group. Seven days after modeling, the Tuina group was treated daily with a “massage and tuina manipulation simulator” (Patent No. ZL 2007 0187403.1), which was used daily to stimulate Yinmen (BL37), Yanglingquan (GB34), and Chengshan (BL57) with point-pressing method, plucking method, and kneading method. The stimulating force was 4N, and the stimulating frequency was 60 times per minute; each method and each point were used for 1 minute, totaling 9 minutes (1 min/acupoint/method × 3 methods × 3 acupoints). Treatment was administered for 21 days, followed by a 1-day rest after the 10th treatment, for a total of 20 times of intervention. The sciatic function index (SFI) was used to evaluate the fine movements of the hind limbs of rats in each group. The ultrastructural changes at the point of nerve injury were observed by transmission electron microscopy, and the gene changes at the point of nerve injury were detected using RNA-sequencing (RNA-seq) technology. Results. Compared with the baseline, the SFI of the SNI group and the Tuina group decreased significantly at the 0th intervention (7 days after molding); compared with the SNI group, the SFI of the Tuina group increased at the 10th intervention (P<0.05) and increased significantly at the 15th and 20th intervention (P<0.01). Compared with the Sham group, the myelin sheath integrity of the sciatic nerve in the SNI group was destroyed and the myelin sheath collapsed seriously, even forming myelin sheath ball, accompanied with severe axonal atrophy and mitochondrial degeneration. The tuina intervention could significantly improve the ultrastructure of the nerve injury point, and the nerve fiber myelin sheath in the Tuina group remained intact, without obvious axonal swelling or atrophy. Atrophic thread granules could be seen in the axon, but there were no vacuolated mitochondria. RNA-seq results showed that there were differences at 221 genes at the point of nerve injury between the Tuina group and the SNI group and the differentially expressed genes (DEGs) are enriched in the biological processes related to the regulation of myocyte. Regulations include the regulation of striated muscle cell differentiation, myoblast differentiation, and myotube differentiation. Conclusion. Tuina can improve the fine motor recovery and protect the myelin integrity in rats with peripheral nerve injury, and this is achieved by changing the gene sequence at the injured point.

Recruitment by SDF-1α of CD34-positive cells involved in sciatic nerve regeneration

2012 ◽  
Vol 116 (2) ◽  
pp. 432-444 ◽  
Author(s):  
Meei-Ling Sheu ◽  
Fu-Chou Cheng ◽  
Hong-Lin Su ◽  
Ying-Ju Chen ◽  
Chun-Jung Chen ◽  
...  
Keyword(s):  
Sciatic Nerve ◽  
Peripheral Nerve ◽  
Nerve Regeneration ◽  
Nerve Injury ◽  
Peripheral Nerve Injury ◽  
Peripheral Nerve Regeneration ◽  
Neurological Function ◽  
Crush Injury ◽  
Local Application ◽  
Angiogenesis Factors

Object Increased integration of CD34+ cells in injured nerve significantly promotes nerve regeneration, but this effect can be counteracted by limited migration and short survival of CD34+ cells. SDF-1α and its receptor mediate the recruitment of CD34+ cells involved in the repair mechanism of several neurological diseases. In this study, the authors investigate the potentiation of CD34+ cell recruitment triggered by SDF-1α and the involvement of CD34+ cells in peripheral nerve regeneration. Methods Peripheral nerve injury was induced in 147 Sprague-Dawley rats by crushing the left sciatic nerve with a vessel clamp. The animals were allocated to 3 groups: Group 1, crush injury (controls); Group 2, crush injury and local application of SDF-1α recombinant proteins; and Group 3, crush injury and local application of SDF-1α antibody. Electrophysiological studies and assessment of regeneration markers were conducted at 4 weeks after injury; neurobehavioral studies were conducted at 1, 2, 3, and 4 weeks after injury. The expression of SDF-1α, accumulation of CD34+ cells, immune cells, and angiogenesis factors in injured nerves were evaluated at 1, 3, 7, 10, 14, 21, and 28 days after injury. Results Application of SDF-1α increased the migration of CD34+ cells in vitro, and this effect was dose dependent. Crush injury induced the expression of SDF-1α, with a peak of 10–14 days postinjury, and this increased expression of SDF-1α paralleled the deposition of CD34+ cells, expression of VEGF, and expression of neurofilament. These effects were further enhanced by the administration of SDF-1α recombinant protein and abolished by administration of SDF-1α antibody. Furthermore, these effects were consistent with improvement in measures of neurological function such as sciatic function index, electrophysiological parameters, muscle weight, and myelination of regenerative nerve. Conclusions Expression of SDF-1α facilitates recruitment of CD34+ cells in peripheral nerve injury. The increased deposition of CD34+ cells paralleled significant expression of angiogenesis factors and was consistent with improvement of neurological function. Utilization of SDF-1α for enhancing the recruitment of CD34+ cells involved in peripheral nerve regeneration may be considered as an alternative treatment strategy in peripheral nerve disorders.

scholarly journals 4-AP-3-MeOH Promotes Structural and Functional Spontaneous Recovery in the Acute Sciatic Nerve Stretch Injury

Dose-Response ◽  
2020 ◽  
Vol 18 (1) ◽  
pp. 155932581989925
Author(s):  
Yan Chen ◽  
Weidong Wang ◽  
Zhimin Zhao ◽  
Dong Ren ◽  
Danmou Xin
Keyword(s):  
Sciatic Nerve ◽  
Peripheral Nerve ◽  
Nerve Injury ◽  
Motor Function ◽  
Peripheral Nerve Injury ◽  
Spontaneous Recovery ◽  
Sciatic Nerve Injury ◽  
Stretch Injury ◽  
Injured Nerve ◽  
Injury Model

Background: 4-AP-3-MeOH, a derivative of 4-aminopyridine, was developed and demonstrated to prevent nerve pulse diffusion due to myelin damage and significantly enhance axonal conduction following nerve injury. Currently, repurposing the existing drug such as 4-AP-3-MeOH to restore motor function is a promising and potential therapy of peripheral nerve injury. However, to evaluate drug effect on sciatic nerve injury is full of challenge. Methods: Sciatic functional index was used to determine and measure the walking track in the stretch injury model. Nerve conductivity was performed by electrical stimulation of a nerve and recording the compound muscle action potential. Myelin thickness and regeneration was imaged and measured with transmission electron microscopy (TEM). Results: In this study, we developed a sciatic nerve injury model to minimize the spontaneous recovery mechanism and found that 4-AP-3-MeOH not only improved walking ability of the animals but also reduced the sensitivity to thermal stimulus. More interesting, 4-AP-3-MeOH enhanced and recovered electric conductivity of injured nerve; our TEM results indicated that the axon sheath thickness was increased and myelin was regenerated, which was an important evidence to support the recovery of injured nerve conductivity with 4-AP-3-MeOH treatment. Conclusions: In summary, our studies suggest that 4-AP-3-MeOH is a viable and promising approach to the therapy of peripheral nerve injury and in support of repurposing the existing drug to restore motor function.

Changes in Crossed Spinal Reflexes After Peripheral Nerve Injury and Repair

2002 ◽  
Vol 87 (4) ◽  
pp. 1763-1771 ◽  
Author(s):  
Antoni Valero-Cabré ◽  
Xavier Navarro
Keyword(s):  
Sciatic Nerve ◽  
Action Potential ◽  
Peripheral Nerve ◽  
Nerve Injury ◽  
Peripheral Nerve Injury ◽  
Tibialis Anterior ◽  
Tibial Nerve ◽  
Spinal Reflexes ◽  
Injury And Repair

We investigated the changes induced in crossed extensor reflex responses after peripheral nerve injury and repair in the rat. Adults rats were submitted to non repaired sciatic nerve crush (CRH, n = 9), section repaired by either aligned epineurial suture (CS, n = 11) or silicone tube (SIL4, n = 13), and 8 mm resection repaired by tubulization (SIL8, n = 12). To assess reinnervation, the sciatic nerve was stimulated proximal to the injury site, and the evoked compound muscle action potential (M and H waves) from tibialis anterior and plantar muscles and nerve action potential (CNAP) from the tibial nerve and the 4th digital nerve were recorded at monthly intervals for 3 mo postoperation. Nociceptive reinnervation to the hindpaw was also assessed by plantar algesimetry. Crossed extensor reflexes were evoked by stimulation of the tibial nerve at the ankle and recorded from the contralateral tibialis anterior muscle. Reinnervation of the hindpaw increased progressively with time during the 3 mo after lesion. The degree of muscle and sensory target reinnervation was dependent on the severity of the injury and the nerve gap created. The crossed extensor reflex consisted of three bursts of activity (C1, C2, and C3) of gradually longer latency, lower amplitude, and higher threshold in control rats. During follow-up after sciatic nerve injury, all animals in the operated groups showed recovery of components C1 and C2 and of the reflex H wave, whereas component C3 was detected in a significantly lower proportion of animals in groups with tube repair. The maximal amplitude of components C1 and C2 recovered to values higher than preoperative values, reaching final levels between 150 and 245% at the end of the follow-up in groups CRH, CS, and SIL4. When reflex amplitude was normalized by the CNAP amplitude of the regenerated tibial nerve, components C1 (300–400%) and C2 (150–350%) showed highly increased responses, while C3 was similar to baseline levels. In conclusion, reflexes mediated by myelinated sensory afferents showed, after nerve injuries, a higher degree of facilitation than those mediated by unmyelinated fibers. These changes tended to decline toward baseline values with progressive reinnervation but still remained significant 3 mo after injury.

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