Axonal outgrowth is associated with increased ERK 1/2 activation but decreased caspase 3 linked cell death in Schwann cells after immediate nerve repair in rats

Tsuda, Yoshifumi; Kanje, Martin; Dahlin, Lars B.

doi:10.1186/1471-2202-12-12

Cited by 47 publications

(37 citation statements)

References 25 publications

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“…However, the obstacle for an efficient axonal outgrowth after delayed nerve repair or reconstruction is the events that occur in the distal nerve segment. The impaired axonal outgrowth after a delayed nerve repair or reconstruction after a transection injury seems to be related to factors like a decrease in p-ERK1/2 in Schwann cells in the distal nerve segment (Tsuda, Kanje, & Dahlin, 2011). Furthermore, the numbers of Schwann cells that express the transcription factor ATF3, which is also associated with an efficient axonal outgrowth, decline with time after injury.…”

Section: The Timing Of Nerve Repair and Reconstructionmentioning

confidence: 98%

“…Although it has been suggest that a critical time-point at which outcome of regeneration becomes poor appears to be three months in experimental systems (Jonsson, et al, 2013), even shorter time, 9 like two weeks, is sufficient to observe an impaired axonal outgrowth. This phenomenon is related to both a less activation of Schwann cells and an increased number of apoptotic cells (Tsuda, et al, 2011).…”

Section: If a Nerve Injury Is Not Repaired Within Three Or Six Monthsmentioning

confidence: 99%

“…This is particularly obvious in experimental models if the delay exceeds 30 days with a resulting impaired nerve regeneration (Saito & Dahlin, 2008). Apoptosis, detected by presence of cleaved caspase 3 in Schwann cells, increases substantially in the distal nerve segment if the nerve repair or reconstruction is delayed (Tsuda, et al, 2011). Furthermore, the contact between the outgrowing axons and the Schwann cells seems to be essential for the number of cells that express cleaved caspase 3 only if the nerve repair is immediately performed (Tsuda, et al, 2011).…”

Section: The Timing Of Nerve Repair and Reconstructionmentioning

confidence: 99%

“…Apoptosis, detected by presence of cleaved caspase 3 in Schwann cells, increases substantially in the distal nerve segment if the nerve repair or reconstruction is delayed (Tsuda, et al, 2011). Furthermore, the contact between the outgrowing axons and the Schwann cells seems to be essential for the number of cells that express cleaved caspase 3 only if the nerve repair is immediately performed (Tsuda, et al, 2011). A delayed nerve repair increases the number of Schwann cells that express cleaved caspase 3 from around 10% of the cells in the distal nerve segment up to around 20% after delayed nerve repair irrespective of the length of the delay (Saito, et al, 2009) (Figure 2).…”

Section: The Timing Of Nerve Repair and Reconstructionmentioning

confidence: 99%

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The Role of Timing in Nerve Reconstruction

Dahlin

2013

International Review of Neurobiology

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The surgeon, who treats nerve injuries, should have knowledge about how peripheral nerves react to trauma, particularly an understanding about the extensive pathophysiological alterations that occur both in the peripheral and in the central nervous system. A large number of factors influence the functional outcome, where the surgeon only can affect a few of them.In view of the new knowledge about the delicate intracellular signaling pathways that are rapidly initiated in neurons and in non-neuronal cells with the purpose to induce nerve regeneration, the timing of nerve repair and reconstruction after injury has gained more interest. It is crucial to understand and to utilize the inborn mechanisms for survival and regeneration of neurons and for activation, survival and proliferation of the Schwann cells and other cells that are acting after a nerve injury. Thus, experimental and clinical data clearly point towards the advantage of early nerve repair and reconstruction of injuries. Following an appropriate diagnosis of a nerve injury, the nerve should be promptly repaired or reconstructed, and new rehabilitation strategies should early be initiated. Considering nerve transfers in the treatment arsenal can shorten the time of nerve reinnervation of muscle targets. Timing of nerve repair and reconstruction is crucial after nerve injury.

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Section: The Timing Of Nerve Repair and Reconstructionmentioning

confidence: 98%

Section: If a Nerve Injury Is Not Repaired Within Three Or Six Monthsmentioning

confidence: 99%

Section: The Timing Of Nerve Repair and Reconstructionmentioning

confidence: 99%

Section: The Timing Of Nerve Repair and Reconstructionmentioning

confidence: 99%

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The Role of Timing in Nerve Reconstruction

Dahlin

2013

International Review of Neurobiology

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“…Previous studies, focusing on timing of nerve repair [11,12], have shown that time between trauma and surgery is an important factor for successful recovery. The success rate increases when reconstructive surgery is performed early after trauma [5].…”

Section: Introductionmentioning

confidence: 99%

Axillary nerve injury in young adults—An overlooked diagnosis? Early results of nerve reconstruction and nerve transfers

Dahlin¹,

Coster²,

Björkman³

et al. 2012

Journal of Plastic Surgery and Hand Surgery

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Axillary nerve injury in young adults-An overlooked diagnosis? Early results of nerve reconstruction and nerve transfers.Dahlin, Lars; Cöster, Marcus; Björkman, Anders; Backman, Clas Link to publication Citation for published version (APA): Dahlin, L., Cöster, M., Björkman, A., & Backman, C. (2012). Axillary nerve injury in young adults-An overlooked diagnosis? Early results of nerve reconstruction and nerve transfers. Journal of Plastic Surgery and Hand Surgery, 46(3-4), 257-261. DOI: 10.3109/2000656X.2012.698415 General rights Copyright and moral rights for the publications made accessible in the public portal are retained by the authors and/or other copyright owners and it is a condition of accessing publications that users recognise and abide by the legal requirements associated with these rights.• Users may download and print one copy of any publication from the public portal for the purpose of private study or research.• You may not further distribute the material or use it for any profit-making activity or commercial gain • You may freely distribute the URL identifying the publication in the public portal Ten male young adults (median age at trauma 13 years, range 9-24) with an axillary nerve injury were diagnosed by examination of shoulder function and electromyography (EMG).The patients had either a nerve reconstruction procedure or were treated conservatively and their recovery was monitored.The axillary nerve was explored and reconstructed at a median of eight months (range 1-22 months) after trauma in 8/10 patients. Two patients were treated non-operatively. In 4/8 cases, a reconstruction with sural nerve graft was performed and in 1/8 case only exploration of the nerve was made (minor neuroma). In 3/8 cases a radial nerve branch transfer to the axillary nerve was chosen as the procedure. The shoulder was mobilized after three weeks with physiotherapy and the patients were monitored regularly. Functional recovery was observed in 9/10 cases (median follow up 11 months, range 7-64) with EMG signs of reinnervation in 7patients.Axillary nerve function should not be overlooked in young patients with a minor shoulder trauma. Nerve reconstruction can successfully recreate function.

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Optogenetically Controlled TrkA Activity Improves the Regenerative Capacity of Hair‐Follicle‐Derived Stem Cells to Differentiate into Neurons and Glia

et al. 2020

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one due to prevalent issues such as alloimmune rejection, the availability of cell sources and the potential long-term risk for tumorigenesis. [4][5][6] Hair follicles are an easily accessible structure on the skin and the stem cells harbored within them can consistently undergo self-renewal. [7,8] Hairfollicle-derived stem cells (HSCs) isolated from the bulge region of hair follicles were able to differentiate into neuronal and glial cells in vitro and also regenerate neurons in animal recipients. [8][9][10] HSCs are an ideal cell source for neural regeneration not only due to its differentiation potency to neural cell types, but also its reduced tumorigenicity as somatic stem cells, easy accessibility, as well as its lower rate for immunologic rejection during autologous transplantation.Neurotrophin signaling is a key process that determines neural stem cell function, influencing cell survival, cell division and differentiation. These effects carry on to modulate functions in fatedetermined cells, such as axonal and dendritic growth of neurons, cell death, neurotransmitter secretion, and neuronal activity. [11] Neurotrophin signaling is traditionally mediated through ligand binding to the tropomyosin receptor kinase (Trk) receptor tyrosine kinase family and, with less affinity, to the p75 neurotrophin receptor (p75 NTR ). [11][12][13] Although Trk Hair-follicle-derived stem cells (HSCs) originating from the bulge region of the mouse vibrissa hair follicle are able to differentiate into neuronal and glial lineage cells. The tropomyosin receptor kinase A (TrkA) receptor that is expressed on these cells plays key roles in mediating the survival and differentiation of neural progenitors as well as in the regulation of the growth and regeneration of different neural systems. In this study, the OptoTrkA system is introduced, which is able to stimulate TrkA activity via blue-light illumination in HSCs. This allows to determine whether TrkA signaling is capable of influencing the proliferation, migration, and neural differentiation of these somatic stem cells. It is found that OptoTrkA is able to activate downstream molecules such as ERK and AKT with blue-light illumination, and subsequently able to terminate this kinase activity in the dark. HSCs with OptoTrkA activity show an increased ability for proliferation and migration and also exhibited accelerated neuronal and glial cell differentiation. These findings suggest that the precise control of TrkA activity using optogenetic tools is a viable strategy for the regeneration of neurons from HSCs, and also provides a novel insight into the clinical application of optogenetic tools in cell-transplantation therapy.

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Axonal outgrowth is associated with increased ERK 1/2 activation but decreased caspase 3 linked cell death in Schwann cells after immediate nerve repair in rats

Cited by 47 publications

References 25 publications

The Role of Timing in Nerve Reconstruction

The Role of Timing in Nerve Reconstruction

Axillary nerve injury in young adults—An overlooked diagnosis? Early results of nerve reconstruction and nerve transfers

Optogenetically Controlled TrkA Activity Improves the Regenerative Capacity of Hair‐Follicle‐Derived Stem Cells to Differentiate into Neurons and Glia

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