Histologic Assessment of Nerve Regeneration in the Rat

Mackinnon, Susan E.; Hudson, Alan R.; Hunter, Daniel A.

doi:10.1097/00006534-198503000-00014

Cited by 171 publications

(100 citation statements)

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“…Because of its peripheral nerve size, the rat sciatic nerve has been the most commonly experimental model used in studies concerning the peripheral nerve regeneration and possible thera-peutic approaches . Although sciatic nerve injuries are rare in humans, this experimental model provides a very realistic testing bench for lesions involving plurifascicular mixed nerves with axons of different size and type competing to reach and reinnervate distal targets ( Amado et al, 2008;Mackinnon et al, 1985). Focal crush causes axonal interruption but preserves the connective sheaths (axonotmesis).…”

Section: Introductionmentioning

confidence: 99%

Use of poly(DL-lactide-ε-caprolactone) membranes and mesenchymal stem cells from the Wharton's jelly of the umbilical cord for promoting nerve regeneration in axonotmesis: In vitro and in vivo analysis

et al. 2012

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Cellular systems implanted into an injured nerve may produce growth factors or extracellular matrix molecules, modulate the inflammatory process and eventually improve nerve regeneration. In the present study, we evaluated the therapeutic value of human umbilical cord matrix MSCs (HMSCs) on rat sciatic nerve after axonotmesis injury associated to Vivosorbs membrane. During HMSCs expansion and differentiation in neuroglial-like cells, the culture medium was collected at 48, 72 and 96 h for nuclear magnetic resonance (NMR) analysis in order to evaluate the metabolic profile. To correlate the HMSCs ability to differentiate and survival capacity in the presence of the Vivosorbs membrane, the [Ca 2þ ]i of undifferentiated HMSCs or neuroglial-differentiated HMSCs was determined by the epifluorescence technique using the Fura-2AM probe. The Vivosorbs membrane proved to be adequate and used as scaffold associated with undiffer-entiated HMSCs or neuroglial-differentiated HMSCs. In vivo testing was carried out in adult rats where a sciatic nerve axonotmesis injury was treated with undifferentiated HMSCs or neuroglial differentiated HMSCs with or without the Vivosorbs membrane. Motor and sensory functional recovery was evaluated throughout a healing period of 12 weeks using sciatic functional index (SFI), extensor postural thrust (EPT), and withdrawal reflex latency (WRL).Stereological analysis was carried out on regenerated nerve fibers. In vitro investigation showed the formation of typical neuroglial cells after differentiation, which were positively stained for the typical specific neuroglial markers such as the GFAP, the GAP-43 and NeuN.NMR showed clear evidence that HMSCs expansion is glycolysis-dependent but their differentiation requires the switch of the metabolic profile to oxidative metabolism. In vivo studies showed enhanced recovery of motor and sensory function in animals treated with transplanted undifferentiated and differentiated HMSCs that was accompanied by an increase in myelin sheath. Taken together, HMSC from the umbilical cord Wharton jelly might be useful for improving the clinical outcome after peripheral nerve lesion.

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Section: Introductionmentioning

confidence: 99%

Use of poly(DL-lactide-ε-caprolactone) membranes and mesenchymal stem cells from the Wharton's jelly of the umbilical cord for promoting nerve regeneration in axonotmesis: In vitro and in vivo analysis

et al. 2012

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“…In the peripheral nervous system, nerves after axonotmesis injuries can regenerate, without any treatment but in most clinical cases a muscle regional neurogenic atrophy occurs. When neurotmesis injuries occur, the nerves must be surgically treated by direct end-to-end suture [33,47,48] , using appropriate microsurgery techniques and suturing material. Nowadays most tissue engineered nerve grafts are composed of a neural scaffold prepared with a variety of biomaterials, and surgically applied in neurotmesis injuries with loss of nervous tissue where the direct end-to-end suture is not possible creating tension in the suture line and compromising the nerve regeneration [9] .…”

Section: Discussionmentioning

confidence: 99%

“…The morphological evaluation together with functional data has been used to assess neural regeneration after induced neurotmesis injuries, but some subjective evaluation, depending on the operator/research analysis is observed [9] . Some methods for evaluation of nerve recovery, like peroxidase and retrograde fluorescent labeling, histomorphometry, and retrograde transport of horseradish [47,56] fail in assessing the functional recovery, which is essential to evaluate the success of a scaffold application [57,58] . The present experimental work includes a variety of independent evaluation tools considering the morphologic and functional recovery, in order to understand and estimate the potential therapeutic benefit of a nerve repair strategy [9] .…”

Section: Discussionmentioning

confidence: 99%

Evaluation of biodegradable electric conductive tube-guides and mesenchymal stem cells

Ribeiro¹,

Pereira²,

Caseiro³

et al. 2015

WJSC

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“…Classical and newly developed methods of assessing nerve recovery, including histomorphometry, retrograde transport of horseradish peroxidase and retrograde fluorescent labeling do not necessarily predict the reestablishment of motor and sensory functions (Shen and Zhu 1995;Almquist and Eeg-Olofssn 1970;De Medinaceli et al, 1989;Mackinnon 1985;Varej˜ao et al, 2004). Although such techniques are useful in studying the nerve regeneration process, they generally fail in assessing functional recovery (Shen and Zhu 1995).…”

Section: Discussionmentioning

confidence: 99%

Local Administration of Nimodipine and Improvement of Functional Recovery of the Transected Sciatic Nerve after Bridging with Inside-out Artery Graft

Mohammadi¹,

Alijanpour²,

Alijanpour³

et al. 2015

IJN

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Nimodipine is a US Food and Drug Administration approved drug that has been shown to act as a possible pharmacologic treatment for facial nerve injury. The objective was to assess the effect of locally administered nimodipine on transected peripheral nerve regeneration and functional recovery. Sixty male healthy white Wistar rats were divided into four experimental groups (n = 15), randomly: In transected group (TC), left sciatic nerve was transected and stumps were fixed in the adjacent muscle. In treatment group defect was bridged using an inside-out artery graft (IOAG/Nimodipine) filled with 10 μL nimodipine (100 ng/mL). In artery graft group (IOAG), the graft was filled with phosphate-buffered saline alone. In sham-operated group (SHAM), sciatic nerve was exposed and manipulated. Each group was subdivided into three subgroups of five animals each and regenerated nerve fibers were studied 4, 8 and 12 weeks after surgery. Behavioral testing, biomechanical studies, sciatic nerve functional study, gastrocnemius muscle mass and morphometric indices confirmed faster recovery of regenerated axons in IOAG/Nimodipine than IOAG group (p < 0.05). In immunohistochemistry, location of reactions to S-100 in IOAG/Nimodipine was clearly more positive than that in IOAG group.When loaded in an artery graft nimodipine accelerated and improved functional recovery and morphometric indices of sciatic nerve. This may have clinical implications for the surgical management of patients after facial nerve transection.

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Histologic Assessment of Nerve Regeneration in the Rat

Cited by 171 publications

References 0 publications

Use of poly(DL-lactide-ε-caprolactone) membranes and mesenchymal stem cells from the Wharton's jelly of the umbilical cord for promoting nerve regeneration in axonotmesis: In vitro and in vivo analysis

Use of poly(DL-lactide-ε-caprolactone) membranes and mesenchymal stem cells from the Wharton's jelly of the umbilical cord for promoting nerve regeneration in axonotmesis: In vitro and in vivo analysis

Evaluation of biodegradable electric conductive tube-guides and mesenchymal stem cells

Local Administration of Nimodipine and Improvement of Functional Recovery of the Transected Sciatic Nerve after Bridging with Inside-out Artery Graft

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