Influence of chronic inflammation in peripheral target tissue on recovery of crushed nerve injury

Kato, Naoki; Nemoto, Koichi; Kawaguchi, Masahisa; Amako, Masatoshi; Arino, Hiroshi; Fujikawa, Kyosuke

doi:10.1007/s007760170008

Cited by 9 publications

(6 citation statements)

References 14 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Expression of MCP1 is reported for denervated Schwann cells, to recruit macrophages to the injury site (Deshmane et al, 2009; Tofaris et al, 2002), then assist Schwann cells in cellular debris clearing, and stimulation of axonal regrowth (Dubovy, Jancalek, & Kubek, 2013; Jessen et al, 2015). But persistent MCP1 expression produces a chronic inflammatory state, hindering nerve regeneration (Kato et al, 2001). We suggest that the elevated MCP1 detected in old nerves is likely derived from undifferentiated Schwann cells and is causal for the observed increase in macrophage infiltration.…”

Section: Discussionmentioning

confidence: 99%

Inflammaging impairs peripheral nerve maintenance and regeneration

et al. 2018

View full text Add to dashboard Cite

The regenerative capacity of peripheral nerves declines during aging, contributing to the development of neuropathies, limiting organism function. Changes in Schwann cells prompt failures in instructing maintenance and regeneration of aging nerves; molecular mechanisms of which have yet to be delineated. Here, we identified an altered inflammatory environment leading to a defective Schwann cell response, as an underlying mechanism of impaired nerve regeneration during aging. Chronic inflammation was detected in intact uninjured old nerves, characterized by increased macrophage infiltration and raised levels of monocyte chemoattractant protein 1 (MCP1) and CC chemokine ligand 11 (CCL11). Schwann cells in the old nerves appeared partially dedifferentiated, accompanied by an activated repair program independent of injury. Upon sciatic nerve injury, an initial delayed immune response was followed by a persistent hyperinflammatory state accompanied by a diminished repair process. As a contributing factor to nerve aging, we showed that CCL11 interfered with Schwann cell differentiation in vitro and in vivo. Our results indicate that increased infiltration of macrophages and inflammatory signals diminish regenerative capacity of aging nerves by altering Schwann cell behavior. The study identifies CCL11 as a promising target for anti‐inflammatory therapies aiming to improve nerve regeneration in old age.

show abstract

Section: Discussionmentioning

confidence: 99%

Inflammaging impairs peripheral nerve maintenance and regeneration

et al. 2018

View full text Add to dashboard Cite

show abstract

“…It is possible that a 7-day interval is too short for immunological responses to develop systemically. However, it is likely that the immune system would have been primed locally in some way by the first gene transfer, if this vector is immunogenic, even after as short a time as 7 days, as an adjuvant arthritis model in the rat, induced by injection of complete Freund's adjuvant, shows marked inflammatory swelling at 7 days after the injection (Kato et al 2001(Kato et al , 2002. Therefore, the absence of a decline in transfection efficiency following a second gene transfer in the present study seems to indicate the feasibility of further repeated gene transfer.…”

Section: Discussionmentioning

confidence: 99%

Efficient gene transfer from innervated muscle into rat peripheral and central nervous systems using a non‐viral haemagglutinating virus of Japan (HVJ)‐liposome method

Kato¹,

Nakanishi

Nemoto³

et al. 2003

Journal of Neurochemistry

Self Cite

View full text Add to dashboard Cite

We evaluated the feasibility of gene delivery into the peripheral and central nervous systems via retrograde axonal transport following injection of a haemagglutinating virus of Japan (HVJ)-liposome-DNA complex vector into an innervated muscle. Transfection efficiency was assessed by measuring luciferase activity, and was compared statistically with that achieved using a liposome-DNA control vector. High luciferase activity was observed in the injected muscle, the ipsilateral sciatic nerve, and the ipsilateral dorsal root ganglia on day 1 after gene transfer. The spinal cord also showed luciferase activity, although this was lower than in the other tissues. However, no activity was observed in the contralateral sciatic nerve or the contralateral dorsal root ganglia. In addition, we performed gene transfer twice, with a 1-week interval, to evaluate the feasibility of repeated therapeutic gene delivery. Again, a high transfection efficiency was observed immediately, even after the second gene transfer, and transfection efficiency was significantly higher at each defined time-point using the HVJ-liposome complex vector than using a control vector. These results indicate that this method could be used for repeated therapeutic gene delivery into muscle, nerve, dorsal root ganglia, and possibly spinal cord, without the need for a surgical approach, making it well suited to clinical applications.

show abstract

“…Different cuff materials should be explored in future experiments using a similar neurotrophic factor delivery paradigm. On the other hand, others have postulated that an inflammatory reaction around a peripheral nerve may be considered as a conditioning lesion, stimulating nerve regeneration (Dahlin, 1992;Kato et al, 2001). …”

Section: Discussionmentioning

confidence: 99%

Functional Reinnervation of the Canine Bladder after Spinal Root Transection and Immediate End-on-End Repair

Ruggieri

Braverman

D’Andrea

et al. 2006

Journal of Neurotrauma

View full text Add to dashboard Cite

The goal of this study was to transect and immediately repair ventral roots, selected by their ability to stimulate bladder contraction, to assess the feasibility of bladder reinnervation in a canine model. Brain-derived neurotrophic factor (BDNF) was delivered via an osmotic pump (0.5 or 5 mg/mL) to a cuff surrounding the reanastomosis site to the two root bundles on one side. Electrodes were implanted bilaterally immediately proximal to the site of surgical reanastomosis. Results were compared to four root-intact, control animals that also received bilateral electrode implantation. At 6-12 months post-surgery, five of eight nerve transected and repaired animals showed increased pressure and bladder emptying during electrical stimulation of the repaired ventral roots contralateral to the BDNF delivery side. Nerve tracing studies one year postoperatively determined the repaired roots to be S1 and S2 and showed regrowth of axons from the spinal cord to nerve sites proximal to the repair site and to the bladder, and the presence of neurofilament-labeled axons growing across the ventral root repair site. In conclusion, transected ventral and dorsal roots in the sacral spine can be repaired and are capable of functionally reinnervating the urinary bladder. This feasibility study paves the way for future studies utilizing other more proximal motor nerves to bypass the transection site for bladder reinnervation.

show abstract

Influence of chronic inflammation in peripheral target tissue on recovery of crushed nerve injury

Cited by 9 publications

References 14 publications

Inflammaging impairs peripheral nerve maintenance and regeneration

Inflammaging impairs peripheral nerve maintenance and regeneration

Efficient gene transfer from innervated muscle into rat peripheral and central nervous systems using a non‐viral haemagglutinating virus of Japan (HVJ)‐liposome method

Functional Reinnervation of the Canine Bladder after Spinal Root Transection and Immediate End-on-End Repair

Contact Info

Product

Resources

About