Ultrastructural analysis of guided nerve regeneration using progesterone‐ and pregnenolone‐loaded chitosan prostheses

Chávez-Delgado, María Estela; Gómez‐Pinedo, Ulises; Feria‐Velasco, Alfredo; Huerta, Miguel; Castañeda, S. Castro; Toral, Fernando A. López-Dellamary; Párducz, Á.; Anda, Silje; Mora-Galindo, J; García-Estrada, J.

doi:10.1002/jbm.b.30243

Cited by 41 publications

(26 citation statements)

References 44 publications

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“…These include neuroprotection against ischemia and stroke (Cutler, et al, 2005,Djebaili, et al, 2005,Hoffman, et al, 2003,Lapchak, 2004,Meffre, et al, 2007,Shear, et al, 2002,VanLandingham, et al, 2006, recovery of motor function after spinal cord injury (di Michele, et al, 2000,Fiore, et al, 2004,Labombarda, et al, 2006,Patte-Mensah, et al, 2004,Pomata, et al, 2000, regulation of myelination (Chavez-Delgado, et al, 2005,Gago, et al, 2001,Ghoumari, et al, 2005,Ghoumari, et al, 2003,Le Goascogne, et al, 2000,Schumacher, et al, 2000,Schumacher, et al, 2004, proliferation of neuronal stem cells (Suzuki, et al, 2004,Wang, et al, 2005 , neurogenesis in the hippocampus (Keller, et al, 2004,Suzuki, et al, 2004,Wang, et al, 2005, and induction of analgesia (Pathirathna, et al, 2005,Todorovic, et al, 2004. Many of these actions of neurosteroids are discussed in detail in other papers in this issue.…”

Section: Introductionmentioning

confidence: 99%

Endogenous and synthetic neurosteroids in treatment of Niemann–Pick Type C disease

Mellon

Gong

Schonemann

2008

Brain Research Reviews

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The functions for neurosteroids during development and in response to nervous system injury are beginning to be identified. We focused on a mouse model in which we believed neurosteroid production would be altered, and which had a neurodegenerative phenotype. Niemann Pick Type-C (NP-C) is an autosomal recessive neurodegenerative disease caused by mutations in NPC1 (95%) or NPC2 (5%), resulting in lysosomal accumulation of unesterified cholesterol and glycolipids. The NIH mouse model of NP-C has a mutation in the NPC1 gene, and exhibits several pathological features of the most severe NP-C patients. How lysosomal storage and trafficking defects lead to neurodegeneration is unknown. We found that these mice had normal neurosteroidogenic enzyme activity during development, but lost this activity in the early neonatal period, prior to onset of neurological symptoms. Neurons that expressed P450scc, 3ß HSD, as well as those that expressed 3α HSD and 5α reductase were lost in adult NP-C brains, resulting in diminished concentrations of allopregnanolone. We treated NP-C mice with allopregnanolone and found that a single dose in the neonatal period resulted in a doubling of lifespan, substantial delay in onset of neurological symptoms, survival of cerebellar Purkinje and granule cell neurons, and reduction in cholesterol and ganglioside accumulation. The mechanism by which allopregnanolone elicited these effects is unknown. Our in vitro studies showed that Purkinje cell survival promoted by allopregnanolone was lost by treatment with bicuculline, suggesting GABA A receptors may play a role. We treated NP-C mice with a synthetic GABA A neurosteroid, ganaxolone (3α-hydroxy-3β-methyl-5α -pregnan-20-one). Ganaxolone treatment of NP-C mice produced beneficial neurological effects, but these effects were not as robust as those obtained using allopregnanolone. Thus, allopregnanolone may elicit its effects through GABA A receptors and through other mechanisms. Additional studies also suggest that allopregnanolone may elicit its effects through pregnane-X receptors (PXR). Our data suggest that mouse models of neurodegeneration may be beneficial in establishing both physiologic and pharmacologic actions of neurosteroids. These animal models further establish the wide range of functions of these compounds, which may ultimately be useful for treatment of human diseases.

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Section: Introductionmentioning

confidence: 99%

Endogenous and synthetic neurosteroids in treatment of Niemann–Pick Type C disease

Mellon

Gong

Schonemann

2008

Brain Research Reviews

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“…Recent observations have indicated that the best results on guided regeneration of facial nerves of rabbits is obtained with P when used impregnated in biodegradable prostheses, such as chitosan [8]. In particular, the exposure to P induces, in comparison to the vehicle, an increase in the number of Schwann cell nuclei, of nonmyelinated and myelinated nerve fibers (with their respective diameters), as well as in the g ratio of myelinated nerve fibers.…”

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confidence: 99%

Therapeutic approaches to peripheral neuropathy based on neuroactive steroids

Melcangi

Garcia-Segura

2006

Expert Review of Neurotherapeutics

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“…It is difficult to compare the kinematics with other studies due to the different methodologies. 3,4,30,34,36,[53][54][55][56] A previous study 4 demonstrated that when a chitosanplus-progesterone tube is implanted in sectioned peripheral facial nerves of rabbits, progesterone allows the anatomical recovery of the nerve morphology. In contrast, Rosales-Cortes et al 39 found no differences in dog sciatic nerve morphology, even when the nerves were repaired with chitosan alone or chitosan plus progesterone tubes.…”

Section: Discussionmentioning

confidence: 99%

“…14,48 In addition, chitosan has also been used for the delivery of nerve growth factors 13,14,26 and hormones. 3,4,39,40,51 Chitosan tubes impregnated with progesterone have been used for nerve repair, producing partial recovery of muscle function but inducing neuropathic pain and minimal secondary immune adverse reactions. 4,39 However, progesterone has been shown to have anti-nociceptive and neuroprotective effects on the transected trigeminal nerve 23,29 as well as to lead to reduced axonal sprouting in mice.…”

mentioning

confidence: 99%

Aberrant gastrocnemius muscle innervation by tibial nerve afferents after implantation of chitosan tubes impregnated with progesterone favored locomotion recovery in rats with transected sciatic nerve

Sarabia-Estrada

Bañuelos-Pineda

Osuna-Carrasco³

et al. 2015

JNS

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obJect Transection of peripheral nerves produces loss of sensory and/or motor function. After complete nerve cutting, the distal and proximal segment ends retract, but if both ends are bridged with unaltered chitosan, progesteroneimpregnated chitosan, or silicone tubes, an axonal repair process begins. Progesterone promotes nerve repair and has neuroprotective effects thwarting regulation of neuron survival, inflammation, and edema. It also modulates aberrant axonal sprouting and demyelination. The authors compared the efficacy of nerve recovery after implantation of progesterone-loaded chitosan, unaltered chitosan, or silicone tubes after sciatic nerve transection in rats. methods After surgical removal of a 5-mm segment of the proximal sciatic nerve, rats were implanted with progesterone-loaded chitosan, unaltered chitosan, or silicone tubes in the transected nerve for evaluating progesterone and chitosan effects on sciatic nerve repair and ipsilateral hindlimb kinematic function, as well as on gastrocnemius electromyographic responses. In some experiments, tube implantation was performed 90 minutes after nerve transection. results At 90 days after sciatic nerve transection and tube implantation, rats with progesterone-loaded chitosan tubes showed knee angular displacement recovery and better outcomes for step length, velocity of locomotion, and normal hindlimb raising above the ground. In contrast, rats with chitosan-only tubes showed reduced normal raising and pendulum-like hindlimb movements. Aberrant fibers coming from the tibial nerve innervated the gastrocnemius muscle, producing electromyographic responses. Electrical responses in the gastrocnemius muscle produced by sciatic nerve stimulation occurred only when the distal nerve segment was stimulated; they were absent when the proximal or intratubular segment was stimulated. A clear sciatic nerve morphology with some myelinated fiber fascicles appeared in the tube section in rats with progesterone-impregnated chitosan tubes. Some gastrocnemius efferent fibers were partially repaired 90 days after nerve resection. The better outcome in knee angle displacement may be partially attributable to the aberrant neuromuscular synaptic effects, since nerve conduction in the gastrocnemius muscle could be blocked in the progesterone-impregnated chitosan tubes. In addition, in the region of the gap produced by the nerve resection, the number of axons and amount of myelination were reduced in the sciatic nerve implanted with chitosan, progesteroneloaded chitosan, and silicone tubes. At 180 days after sciatic nerve sectioning, the knee kinematic function recovered to a level observed in control rats of a similar age. In rats with progesterone-loaded chitosan tubes, stimulation of the proximal and intratubular sciatic nerve segments produced an electromyographic response. The axon morphology of the proximal and intratubular segments of the sciatic nerve resembled that of the contralateral nontransected nerve. coNclusioNs Progesterone-impregnated chitosan tubes produced...

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Ultrastructural analysis of guided nerve regeneration using progesterone‐ and pregnenolone‐loaded chitosan prostheses

Cited by 41 publications

References 44 publications

Endogenous and synthetic neurosteroids in treatment of Niemann–Pick Type C disease

Endogenous and synthetic neurosteroids in treatment of Niemann–Pick Type C disease

Therapeutic approaches to peripheral neuropathy based on neuroactive steroids

Aberrant gastrocnemius muscle innervation by tibial nerve afferents after implantation of chitosan tubes impregnated with progesterone favored locomotion recovery in rats with transected sciatic nerve

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