Polyethylene Glycol Rapidly Restores Axonal Integrity and Improves the Rate of Motor Behavior Recovery After Sciatic Nerve Crush Injury

The inability to rapidly (within minutes to hours) improve behavioral function after severance of peripheral nervous system axons is an ongoing clinical problem. We have previously reported that polyethylene glycol (PEG) can rapidly restore axonal integrity (PEG-fusion) between proximal and distal segments of cut- and crush-severed rat axons in vitro and in vivo. We now report that PEG-fusion not only reestablishes the integrity of crush-severed rat sciatic axons as measured by the restored conduction of compound action potentials (CAPs) and the intraaxonal diffusion of fluorescent dye across the lesion site, but also produces more rapid recovery of appropriate hindlimb motor behaviors. Improvement in recovery occurred during the first few postoperative weeks for the foot fault (FF) asymmetry test and between week 2 and week 3 for the Sciatic Functional Index (SFI) based on analysis of footprints. That is, the FF test was the more sensitive indicator of early behavioral recovery, showing significant postoperative improvement of motor behavior in PEG-treated animals at 24–48 h. In contrast, the SFI more sensitively measured longer-term postoperative behavioral recovery and deficits at 4–8 wk, perhaps reflecting the development of fine (distal) motor control. These and other data show that PEG-fusion not only rapidly restores physiological and morphological axonal continuity, but also more quickly improves behavioral recovery.

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LncRNA BC083743 Promotes the Proliferation of Schwann Cells and Axon Regeneration Through miR-103-3p/BDNF After Sciatic Nerve Crush

Journal of Neuropathology & Experimental Neurology ◽

10.1093/jnen/nlaa069 ◽

2020 ◽

Vol 79 (10) ◽

pp. 1100-1114

Author(s):

Lin Gao ◽

Aiqin Feng ◽

Peijian Yue ◽

Yue Liu ◽

Qiaoyu Zhou ◽

...

Keyword(s):

Sciatic Nerve ◽

Schwann Cells ◽

Axon Regeneration ◽

Underlying Mechanism ◽

Regulation Mechanism ◽

Sciatic Nerve Crush ◽

Bdnf Expression ◽

Nerve Crush

Abstract To investigate the underlying mechanism of lncRNA BC083743 in regulating the proliferation of Schwann cells (SCs) and axon regeneration after sciatic nerve crush (SNC), we used a rat model. Sciatic function index and the atrophy ratio of gastrocnemius muscle were evaluated. The relationship among BC083743, miR-103-3p, and brain-derived neurotrophic factor (BDNF) and their regulation mechanism in the repair of SNC were investigated using in vivo and in vitro experiments. The expression changes of BC083743 were positively associated with that of BDNF following SNC, but the expression changes of miR-103-3p were inversely associated with that of BDNF. The SC proliferation and BDNF expression could be promoted by overexpression of BC083743, while they were inhibited by a miR-103-3p mimic. In addition, BC083743 interacted with and regulated miR-103-3p, thereby promoting BDNF expression and SC proliferation. BC083743 overexpression also promoted axon regeneration through miR-103-3p. In vivo experiments also indicated that BC083743 overexpression promoted the repair of SNC. In conclusion, LncRNA BC083743 promotes SC proliferation and the axon regeneration through miR-103-3p/BDNF after SNC.

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Organosilane and Polyethylene Glycol Functionalized Magnetic Mesoporous Silica Nanoparticles as Carriers for CpG Immunotherapy In Vitro and In Vivo

PLoS ONE ◽

10.1371/journal.pone.0140265 ◽

2015 ◽

Vol 10 (10) ◽

pp. e0140265 ◽

Cited By ~ 10

Author(s):

Hengrui Zheng ◽

Songsong Wen ◽

Yang Zhang ◽

Zhenliang Sun

Keyword(s):

Polyethylene Glycol ◽

Mesoporous Silica ◽

Silica Nanoparticles ◽

Mesoporous Silica Nanoparticles ◽

Magnetic Mesoporous Silica

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In vitro and in vivo effects of polyethylene glycol (PEG)-modified lipid in DOTAP/cholesterol-mediated gene transfection

International Journal of Nanomedicine ◽

10.2147/ijn.s10462 ◽

2010 ◽

pp. 371 ◽

Cited By ~ 5

Author(s):

Hans Skovgaard Poulsen ◽

Arildsen ◽

Jack Roth ◽

Hans Skovgaard Poulsen ◽

Tuxen Poulsen ◽

...

Keyword(s):

Polyethylene Glycol ◽

Gene Transfection ◽

In Vivo Effects

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Biocompatibility Assessment of Polyethylene Glycol-Poly L-Lysine-Poly Lactic-Co-Glycolic Acid Nanoparticles In Vitro and In Vivo

Journal of Nanoscience and Nanotechnology ◽

10.1166/jnn.2015.9509 ◽

2015 ◽

Vol 15 (5) ◽

pp. 3710-3719 ◽

Cited By ~ 13

Author(s):

Liting Guo ◽

Baoan Chen ◽

Ran Liu ◽

Ping Liu ◽

Guohua Xia ◽

...

Keyword(s):

Polyethylene Glycol ◽

Glycolic Acid

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Exogenous L-lactate promotes astrocyte plasticity but is not sufficient for enhancing striatal synaptogenesis or motor behavior in mice

10.1101/2020.04.13.039446 ◽

2020 ◽

Author(s):

Adam J. Lundquist ◽

Tyler J. Gallagher ◽

Giselle M. Petzinger ◽

Michael W. Jakowec

Keyword(s):

Motor Behavior ◽

Early Gene ◽

Specific Gene ◽

Motor Circuits ◽

Specific Manner ◽

Primary Astrocytes ◽

Exercise Induced ◽

The Brain

AbstractL-lactate is an energetic and signaling molecule that is key to the metabolic and neuroplastic connection between astrocytes and neurons and may be involved in exercise-induced neuroplasticity. This study sought to explore the role of L-lactate in astrocyte reactivity and neuroplasticity. Using in vitro cultures of primary astrocytes, we show L-lactate increased expression of plasticity-related genes, including neurotrophic factors, Bdnf, Gdnf, Cntf and the immediate early gene cFos. L-lactate’s promotion of neurotrophic factor expression may be mediated in part by the lactate receptor HCAR1 since application of the HCAR1 agonist 3,5-DHBA also increased expression of Bdnf in primary astrocytes. In vivo L-lactate administration to healthy mice caused a similar increase in the expression of plasticity-related genes as well as increased astrocyte morphological complexity in a region-specific manner, with increased astrocytic response found in the striatum but not the ectorhinal cortex, regions of the brain where increases in regional cerebral blood flow are increased or unaltered, respectively, with motor behavior. Additionally, L-lactate administration did not cause synaptogenesis or improve motor behavior based on the latency to fall on the accelerating rotarod, suggesting that L-lactate administration can initiate astrocyte-specific gene expression, but the activation of motor circuits is necessary to initiate striatal neuroplasticity. These results suggest that peripheral L-lactate is likely an important molecular component of exercise-induced neuroplasticity by acting in an astrocyte-specific manner to prime the brain for neuroplasticity.

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Inhibition of the autophagic protein ULK1 attenuates axonal degeneration in vitro and in vivo, enhances translation, and modulates splicing

Cell Death and Differentiation ◽

10.1038/s41418-020-0543-y ◽

2020 ◽

Vol 27 (10) ◽

pp. 2810-2827 ◽

Cited By ~ 1

Author(s):

Björn Friedhelm Vahsen ◽

Vinicius Toledo Ribas ◽

Jonas Sundermeyer ◽

Alexander Boecker ◽

Vivian Dambeck ◽

...

Keyword(s):

Cortical Neurons ◽

Axonal Degeneration ◽

Dominant Negative ◽

Focal Lesion ◽

Pathological Feature ◽

Nerve Crush ◽

Cord Injury ◽

Rat Cortical Neurons

Abstract Axonal degeneration is a key and early pathological feature in traumatic and neurodegenerative disorders of the CNS. Following a focal lesion to axons, extended axonal disintegration by acute axonal degeneration (AAD) occurs within several hours. During AAD, the accumulation of autophagic proteins including Unc-51 like autophagy activating kinase 1 (ULK1) has been demonstrated, but its role is incompletely understood. Here, we study the effect of ULK1 inhibition in different models of lesion-induced axonal degeneration in vitro and in vivo. Overexpression of a dominant negative of ULK1 (ULK1.DN) in primary rat cortical neurons attenuates axotomy-induced AAD in vitro. Both ULK1.DN and the ULK1 inhibitor SBI-0206965 protect against AAD after rat optic nerve crush in vivo. ULK1.DN additionally attenuates long-term axonal degeneration after rat spinal cord injury in vivo. Mechanistically, ULK1.DN decreases autophagy and leads to an mTOR-mediated increase in translational proteins. Consistently, treatment with SBI-0206965 results in enhanced mTOR activation. ULK1.DN additionally modulates the differential splicing of the degeneration-associated genes Kif1b and Ddit3. These findings uncover ULK1 as an important mediator of axonal degeneration in vitro and in vivo, and elucidate its function in splicing, defining it as a putative therapeutic target.

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Photoacoustic effect invokes auditory response in infrared neuron stimulation

Journal of Innovative Optical Health Sciences ◽

10.1142/s1793545818500402 ◽

2019 ◽

Vol 12 (01) ◽

pp. 1850040

Author(s):

Muqun Yang ◽

Tian Guan ◽

Yonghong He

Keyword(s):

Fluorescence Microscopy ◽

Guinea Pig ◽

Action Potentials ◽

Photoacoustic Effect ◽

In Vivo Experiments ◽

Compound Action Potentials ◽

Auditory Response ◽

Compound Action

Infrared neuron stimulation is regarded as an innovative approach for stimulating cochleae in animals while the exact mechanism still remains unknown. In this paper, we studied compound action potentials of guinea pig cochleae with chronic or acute deafness. We recorded optical compound action potentials and analyzed stretched cochlear preparations by fluorescence microscopy. Photoacoustic signals were measured by hydrophone and microphone, respectively. In our experiment, we observed a switch response effect in vitro and in vivo experiments. Therefore, we proposed photoacoustic effect could invoke auditory response in infrared neuron stimulation.

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The fibroblast-derived protein PI16 controls neuropathic pain

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.1913444117 ◽

2020 ◽

Vol 117 (10) ◽

pp. 5463-5471 ◽

Cited By ~ 1

Author(s):

Pooja Singhmar ◽

Ronnie The Phong Trinh ◽

Jiacheng Ma ◽

XiaoJiao Huo ◽

Bo Peng ◽

...

Keyword(s):

Neuropathic Pain ◽

Dorsal Root ◽

Clinical Problem ◽

Endothelial Barrier ◽

Leukocyte Infiltration ◽

Spared Nerve Injury ◽

Protein Levels ◽

Major Clinical Problem

Chronic pain is a major clinical problem of which the mechanisms are incompletely understood. Here, we describe the concept that PI16, a protein of unknown function mainly produced by fibroblasts, controls neuropathic pain. The spared nerve injury (SNI) model of neuropathic pain increases PI16 protein levels in fibroblasts in dorsal root ganglia (DRG) meninges and in the epi/perineurium of the sciatic nerve. We did not detect PI16 expression in neurons or glia in spinal cord, DRG, and nerve. Mice deficient in PI16 are protected against neuropathic pain. In vitro, PI16 promotes transendothelial leukocyte migration. In vivo, Pi16−/− mice show reduced endothelial barrier permeability, lower leukocyte infiltration and reduced activation of the endothelial barrier regulator MLCK, and reduced phosphorylation of its substrate MLC2 in response to SNI. In summary, our findings support a model in which PI16 promotes neuropathic pain by mediating a cross-talk between fibroblasts and the endothelial barrier leading to barrier opening, cellular influx, and increased pain. Its key role in neuropathic pain and its limited cellular and tissue distribution makes PI16 an attractive target for pain management.

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