Inflammatory Profiling of Schwann Cells in Contact with Growing Axons Distal to Nerve Injury

Activated Schwann cells distal to nerve injury upregulate inflammatory mediators, including cytokines. The goal of the present study was to investigate expression of proinflammatory (IL-1β, TNFα) and anti-inflammatory cytokines (IL-4, IL-10) in activated Schwann cells in relation to growing axons distal to crush injury of rat sciatic nerves. Seven days from sciatic nerve crush, transverse cryostat sections were cut 5 mm distal to lesion and incubated for double immunostaining to indicate Schwann cells (GFAP or S100b) and individual investigated cytokines or to demonstrate growing axons (GAP43). The Schwann cells of naïve sciatic nerves and those removed from sham-operated rats displayed similar weak immunoreactivity for the investigated cytokines. In contrast, increased intensity of cytokine immunofluorescence was found in Schwann cells distal to crush lesion. The cytokine-positive Schwann cells were found in close contact with growing axons detected by immunostaining for GAP43. The results of immunohistochemical analysis distal to nerve crush injury suggest that inflammatory profiling of Schwann cells including upregulation of both pro- and anti-inflammatory cytokines does not prevent growth of axons distal to nerve crush injury.

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Reduced Renshaw Recurrent Inhibition after Neonatal Sciatic Nerve Crush in Rats

Neural Plasticity ◽

10.1155/2014/786985 ◽

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.

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Possible role of antioxidative capacity of (−)-epigallocatechin-3-gallate treatment in morphological and neurobehavioral recovery after sciatic nerve crush injury

Journal of Neurosurgery Spine ◽

10.3171/2016.10.spine16218 ◽

2017 ◽

Vol 27 (5) ◽

pp. 593-613 ◽

Cited By ~ 13

Author(s):

Waleed M. Renno ◽

Ludmil Benov ◽

Khalid M. Khan

Keyword(s):

Spinal Cord ◽

Sciatic Nerve ◽

Nerve Injury ◽

Diameter Ratio ◽

Crush Injury ◽

Sciatic Nerve Crush ◽

Axon Diameter ◽

Nerve Crush ◽

Myelin Thickness ◽

Nerve Crush Injury

OBJECTIVEThis study examined the capacity of the major polyphenolic green tea extract (−)-epigallocatechin-3-gallate (EGCG) to suppress oxidative stress and stimulate the recovery and prompt the regeneration of sciatic nerve after crush injury.METHODSAdult male Wistar rats were randomly assigned to one of 4 groups: 1) Naïve, 2) Sham (sham injury, surgical control group), 3) Crush (sciatic nerve crush injury treated with saline), and 4) Crush+EGCG (sciatic nerve crush injury treated with intraperitoneally administered EGCG, 50 mg/kg). All animals were tested for motor and sensory neurobehavioral parameters throughout the study. Sciatic nerve and spinal cord tissues were harvested and processed for morphometric and stereological analysis. For the biochemical assays, the time points were Day 1, Day 7, Day 14, and Day 28 after nerve injury.RESULTSAfter sciatic nerve crush injury, the EGCG-treated animals (Crush+EGCG group) showed significantly better recovery of foot position and toe spread and 50% greater improvement in motor recovery than the saline-treated animals (Crush group). The Crush+EGCG group displayed an early hopping response at the beginning of the 3rd week postinjury. Animals in the Crush+EGCG group also showed a significant reduction in mechanical allodynia and hyperalgesia latencies and significant improvement in recovery from nociception deficits in both heat withdrawal and tail flick withdrawal latencies compared with the Crush group. In both the Crush+EGCG and Crush groups, quantitative evaluation revealed significant morphological evidence of neuroregeneration according to the following parameters: mean cross-sectional area of axons, myelin thickness in the sciatic nerve (from Week 4 to Week 8), increase of myelin basic protein concentration and gene expression in both the injured sciatic nerve and spinal cord, and fiber diameter to axon diameter ratio and myelin thickness to axon diameter ratio at Week 2 after sciatic nerve injury. However, the axon area remained much smaller in both the Crush+EGCG and Crush groups compared with the Sham and Naïve groups. The number of axons per unit area was significantly decreased in the Crush+EGCG and Crush groups compared with controls. Sciatic nerve injury produced generalized oxidative stress manifested as a significant increase of isoprostanes in the urine and decrease of the total antioxidant capacity (TAC) of the blood from Day 7 until Day 14. EGCG-treated rats showed significantly less increase of isoprostanes than saline-treated animals and also showed full recovery of TAC levels by Day 14 after nerve injury. In spinal cord tissue analysis, EGCG-treated animals showed induced glutathione reductase and suppressed induction of heme oxygenase 1 gene expression compared with nontreated animals.CONCLUSIONSEGCG treatment suppressed the crush-induced production of isoprostanes and stimulated the recovery of the TAC and was associated with remarkable alleviation of motor and sensory impairment and significant histomorphological evidence of neuronal regeneration following sciatic nerve crush injury in rats. The findings of this study suggest that EGCG can be used as an adjunctive therapeutic remedy for nerve injury. However, further investigations are needed to establish the antioxidative mechanism involved in the regenerative process after nerve injury. Only upregulation of glutathione reductase supports the idea that EGCG is acting indirectly via induction of enzymes or transcription factors.

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Catfish Epidermal Preparation Accelerates Healing of Damaged Nerve in a Sciatic Nerve Crush Injury Rat Model

Frontiers in Pharmacology ◽

10.3389/fphar.2021.632028 ◽

2021 ◽

Vol 12 ◽

Author(s):

Waleed M. Renno ◽

Mohammad Afzal ◽

Bincy Paul ◽

Divya Nair ◽

Jijin Kumar ◽

...

Keyword(s):

Sciatic Nerve ◽

Nerve Injury ◽

Axonal Regeneration ◽

Crush Injury ◽

Male Rats ◽

Sciatic Nerve Crush ◽

Spinal Neurons ◽

Nerve Crush ◽

Neurobehavioral Deficits ◽

Nerve Crush Injury

Preliminary investigations showed that preparations from Arabian Gulf catfish (Arius bilineatus, Val) epidermal gel secretion (PCEGS) exhibit potent anti-inflammatory and healing properties as shown in our previous clinical trials for the healing of non-healing diabetic foot ulcers, chronic back pain, and some other neurological disorders. Here, we report for the first time a unique preparation containing only proteins and lipids (soluble protein fraction B, SPF-FB), derived from the PCEGS accelerated the healing and recovery of sensory-motor functions of experimental sciatic nerve crush injury in rats with its unique neuroprotective and neuroregenerative properties on the spinal neurons and peripheral nerve fibers. Male rats were randomly assigned to five groups: (I) NAÏVE, (II) SHAM, (III) CRUSH treated with saline, (IV) CRUSH + SPF-FB treated with 3 mg/kg intraperitoneally (IP) and (V) CRUSH + SPF-FB treated with 6 mg/kg subcutaneously (SC) groups. The crush groups III, IV and V underwent sciatic nerve crush injury, followed by treatment daily for 14 days with saline, SPF-FB IP and SPF-FB SC. All animals were tested for the neurobehavioral parameters throughout the 6 weeks of the study. Sciatic nerve and spinal cord tissues were processed for light and electron histological examinations, stereological analysis, immunohistochemical and biochemical examinations at Week 4 and Week 6 post-injury. Administration of SPF-FB IP or SC significantly enhanced the neurobehavioral sensory and motor performance and histomorphological neuroregeneration of the sciatic nerve-injured rats. The stereological evaluation of the axon area, average axon perimeters, and myelin thickness revealed significant histomorphological evidence of neuroregeneration in the FB-treated sciatic nerve crush injured groups compared to controls at 4 and 6 weeks. SPF-FB treatment significantly prevented the increased in NeuN-immunoreactive neurons, increased GFAP immunoreactive astrocytes, and decreased GAP-43. We conclude that SPF-FB treatment lessens neurobehavioral deficits, enhances axonal regeneration following nerve injury. We conclude that SPF-FB treatment lessens neurobehavioral deficits and enhances axonal regeneration following nerve injury, as well as protects spinal neurons and enhances subcellular recovery by increasing astrocytic activity and decreasing GAP-43 expression.

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Resveratrol regulates the recovery of rat sciatic nerve crush injury by promoting the autophagy of Schwann cells

Life Sciences ◽

10.1016/j.lfs.2020.117959 ◽

2020 ◽

Vol 256 ◽

pp. 117959

Author(s):

Jiayi Zhang ◽

Jingyan Ren ◽

Yang Liu ◽

Dongxu Huang ◽

Laijin Lu

Keyword(s):

Sciatic Nerve ◽

Schwann Cells ◽

Crush Injury ◽

Sciatic Nerve Crush ◽

Nerve Crush ◽

Rat Sciatic Nerve ◽

Nerve Crush Injury

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Muscle-derived GDNF facilitates motor nerve recovery following sciatic nerve crush injury

Journal of the American College of Surgeons ◽

10.1016/j.jamcollsurg.2007.06.230 ◽

2007 ◽

Vol 205 (3) ◽

pp. S92

Author(s):

Terence M. Myckatyn ◽

Christina Kenney ◽

Alice Tong ◽

Jessica Duan ◽

Daniel Hunter ◽

...

Keyword(s):

Sciatic Nerve ◽

Motor Nerve ◽

Crush Injury ◽

Sciatic Nerve Crush ◽

Nerve Crush ◽

Nerve Recovery ◽

Nerve Crush Injury

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Functional Recovery and Vitamin E Level Following Sciatic Nerve Crush Injury in Normal and Diabetic Rats

International Journal of Neuroscience ◽

10.3109/00207459808986472 ◽

1998 ◽

Vol 96 (3-4) ◽

pp. 245-254 ◽

Cited By ~ 10

Author(s):

Khalaf Al Moutaery ◽

Mohammed Arshaduddin ◽

Mohammad Tariq ◽

Saleh Al Deeb

Keyword(s):

Vitamin E ◽

Sciatic Nerve ◽

Functional Recovery ◽

Diabetic Rats ◽

Crush Injury ◽

Sciatic Nerve Crush ◽

Nerve Crush ◽

Nerve Crush Injury

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Canine Adipose-Derived Mesenchymal Stromal Cells Enhance Neuroregeneration in a Rat Model of Sciatic Nerve Crush Injury

Cell Transplantation ◽

10.1177/0963689718809045 ◽

2018 ◽

Vol 28 (1) ◽

pp. 47-54 ◽

Cited By ~ 7

Author(s):

Diego Noé Rodríguez Sánchez ◽

Luiz Antonio de Lima Resende ◽

Giovana Boff Araujo Pinto ◽

Ana Lívia de Carvalho Bovolato ◽

Fábio Sossai Possebon ◽

...

Keyword(s):

Sciatic Nerve ◽

Mesenchymal Stromal Cells ◽

Rat Model ◽

Stromal Cells ◽

Multipotent Mesenchymal Stromal Cells ◽

Crush Injury ◽

Sciatic Nerve Crush ◽

Muscle Weight ◽

Nerve Crush ◽

Nerve Crush Injury

Crush injuries in peripheral nerves are frequent and induce long-term disability with motor and sensory deficits. Due to axonal and myelin sheath disruptions, strategies for optimized axonal regeneration are needed. Multipotent mesenchymal stromal cells (MSC) are promising because of their anti-inflammatory properties and secretion of neurotrophins. The present study investigated the effect of canine adipose tissue MSC (Ad-MSC) transplantation in an experimental sciatic nerve crush injury. Wistar rats were divided into three groups: sham ( n = 8); Crush+PBS ( n = 8); Crush+MSC ( n = 8). Measurements of sciatic nerve functional index (SFI), muscle mass, and electromyography (EMG) were performed. Canine Ad-MSC showed mesodermal characteristics (CD34-, CD45-, CD44+, CD90+ and CD105+) and multipotentiality due to chondrogenic, adipogenic, and osteogenic differentiation. SFI during weeks 3 and 4 was significantly higher in the Crush+MSC group ( p < 0.001). During week 4, the EMG latency in the Crush+MSC groups had better near normality ( p < 0.05). The EMG amplitude showed results close to normality during week 4 in the Crush+MSC group ( p < 0.04). There were no statistical differences in muscle weight between the groups ( p > 0.05), but there was a tendency toward weight gain in the Crush+MSC groups. Better motor functional recovery after crush and perineural canine Ad-MSC transplantation was observed during week 2. This was maintained till week 4. In conclusion, the canine Ad-MSC transplantation showed early pro-regenerative effects between 2–4 weeks in the rat model of sciatic nerve crush injury.

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