The Effect of FK1706 on Erectile Function Following Bilateral Cavernous Nerve Crush Injury in a Rat Model

Hayashi, Narihiko; Minor, Thomas X.; Carrión, Rafael; Price, Raymond D.; Nunes, Lora; Lue, Tom F.

doi:10.1016/j.juro.2006.03.071

Cited by 42 publications

(40 citation statements)

References 19 publications

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“…10,57 Recently, a crush injury model has been used to mimic nerve-sparing radical prostatectomy. 7,9 In this study, we combined nerve crush with cryo-injury because we aimed to create a severe nerve injury model, which preserves the neural sheath, but takes a considerable time to achieve nerve regeneration, similar to the clinical outcomes observed in patients receiving nerve-sparing radical prostatectomy, and confirmed that nerve regeneration hardly occur for at least 4 weeks after the nerve injury using our methods.…”

Section: Discussionsupporting

confidence: 59%

Herpes simplex virus vector-mediated delivery of glial cell line-derived neurotrophic factor rescues erectile dysfunction following cavernous nerve injury

Kato

Wolfe²,

Coyle

et al. 2007

Gene Ther

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Erectile dysfunction (ED) is frequently associated with injury to the cavernous nerve sustained during pelvic surgery. Functional recovery from cavernous nerve injury is generally incomplete and occurs over an extended time frame. We employed a therapeutic gene transfer approach with herpes simplex virus (HSV) vector expressing glial cell line-derived neurotrophic factor (GDNF). Rat cavernous nerve was injured bilaterally using a clamp and dry ice. For HSV-treated groups, 20 ml of purified vector stock was administered directly to and around the damaged nerve. Delivery of an HSV vector expressing both green fluorescent protein (GFP) and lacZ (HSV-LacZ) was used as a control. Intracavernous pressure along with systemic arterial pressure (ICP/AP) was measured 2 and 4 weeks after the nerve injury. Fluorogold (FG) was injected into the penile crus 7 days before killing to assess nerve survival. Approximately 60% of major pelvic ganglion (MPG) cells were GFP positive after viral administration. At 4 weeks after nerve injury, rats treated with HSV-GDNF exhibited significant recovery of ICP/AP compared with control vector or untreated groups. The HSV-GDNF group also yielded more FG-positive MPG cells than the control vector group. HSV vector-mediated delivery of GDNF presents a viable approach for the treatment of ED following cavernous nerve injury.

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Section: Discussionsupporting

confidence: 59%

Herpes simplex virus vector-mediated delivery of glial cell line-derived neurotrophic factor rescues erectile dysfunction following cavernous nerve injury

Kato

Wolfe²,

Coyle

et al. 2007

Gene Ther

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“…1) became available as tool compounds and were extensively tested in a variety of animal models such as sciatic [6,7,9,10], cavernous [11,12] or optic nerve crush [13], spinal cord injury [14][15][16], streptozotocin-induced diabetic neuropathy [17,18], or MPTP-or 6-OHDA-induced degeneration of dopaminergic neurons (Table 1) [19][20][21]. These studies provided enticing indications that non-immunosuppressive FK506 analogs might be useful for the treatment of various forms of physical nerve injury, painful diabetic neuropathy or Parkinson's disease.…”

Section: The Rise and Fall Of The Neuroimmunophilin Conceptmentioning

confidence: 99%

FKBPs and their role in neuronal signaling

Hausch

2015

Biochimica et Biophysica Acta (BBA) - General Subjects

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“…Alternative evidences suggest the neuromodulatory actions might course through an anti-apoptotic effect, protecting neurons by the upregulation of glutathione (antioxidant) and production of neurotrophic factors. Interestingly, the fact that IPLs mainly target injured nerves and molecular signaling for FK1706 and GPI1046 likely involves immunophilin type-specific binding proteins, damaged neurons should expressed those specific binding proteins, as reported for FK506 [29,96,97].…”

Section: Role Of Immunophilins In the Treatment Of Neurogenic Erectilmentioning

confidence: 75%

“…It is believed that FK1706 have a FKBP12-independent action, thus subsequently causing calcineurin inhibition and the disruption of the cytokine synthesis cascade [96,97]. Alternative evidences suggest the neuromodulatory actions might course through an anti-apoptotic effect, protecting neurons by the upregulation of glutathione (antioxidant) and production of neurotrophic factors.…”

Section: Role Of Immunophilins In the Treatment Of Neurogenic Erectilmentioning

confidence: 99%

Immunophilin Dysfunction and Neuropathology

Park

Rosado²,

Redondo³

et al. 2011

CMC

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In case of nervous damages, like nervous system trauma or various neurodegenerative diseases such as dementia or Parkinson, several treatments are available to restore neurological function. In spite of these treatments, results are often insufficient or not satisfactory in many neurologic diseases, especially for central nervous system (CNS) lesions. To minimize neurological dysfunction, it is critical to reduce neuronal death, avoiding loss of the synaptic connections, and securing viable neurons to extend axons. Unfortunately, there are no effective strategies to fulfill these basic needs except for some cases of peripheral neural damage up to now. Rescue of damaged neurons, stimulation of neurogenesis and transplantation of nervous tissue are strategies proposed to prevent neurodegenerative disorders. A number of studies have recently reported successful axon regeneration and neurological recovery by using immunosuppressants, such as FK506. Immunosuppressants act as excellent agents for enhancing the rate and extent of axon regeneration and neurological recovery. FK506 and other neuroimmunophilin ligands (NILs) might reverse neuronal degeneration. In several animal models mimicking Parkinson's disease, dementia and surgical damage, NILs induces resprouting, by acting as neurotrophic agents and preventing nerve damage, although more studies are necessary to identify new NILs with neuroprotective action, but lacking the side immunological effects observed in the ligands analyzed to date. This review explores the new clinical role of immunosuppressants in the treatment of nerve surgery of autologous, allografts or xenografts. Results of studies regarding immunosuppressant treatment of nervous system trauma and neurodegenerative diseases, like neurogenic erectile dysfunction, will be here considered.

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The Effect of FK1706 on Erectile Function Following Bilateral Cavernous Nerve Crush Injury in a Rat Model

Abstract: Bilateral cavernous nerve crush causes reproducible erectile dysfunction, consistent with prior experiments. High dose subcutaneous FK1706 therapy promotes significant neuroregeneration and erectile function recovery.

Cited by 42 publications

References 19 publications

Herpes simplex virus vector-mediated delivery of glial cell line-derived neurotrophic factor rescues erectile dysfunction following cavernous nerve injury

Herpes simplex virus vector-mediated delivery of glial cell line-derived neurotrophic factor rescues erectile dysfunction following cavernous nerve injury

FKBPs and their role in neuronal signaling

Immunophilin Dysfunction and Neuropathology

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