Dimethyl sulfoxide (DMSO) produces widespread apoptosis in the developing central nervous system

Hanslick, Jennifer L.; Lau, Karen; Noguchi, Kevin K.; Olney, John W.; Zorumski, Charles F.; Mennerick, Steven; Farber, Nuri B.

doi:10.1016/j.nbd.2008.11.006

Cited by 187 publications

(168 citation statements)

References 48 publications

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“…This delay in axonal regeneration could be due to the effect of DMSO that was used as solvent. Studies have shown that DMSO affects the structure and functions of sciatic nerve in rats [96], and induces apoptosis in the mouse brain [97]. My findings support the results of previous studies, which have shown that nerve injury upregulates LC3 [98,99].…”

Section: Resultssupporting

confidence: 88%

Autophagy in Peripheral Neuropathy

Osman¹

2017

Linköping University Medical Dissertations

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Peripheral neuropathy includes a wide range of diseases affecting millions around the world, and many of these diseases have unknown etiology. Peripheral neuropathy in diabetes represents a large proportion of peripheral neuropathies. Nerve damage can also be caused by trauma. Peripheral neuropathies are a significant clinical problem and efficient treatments are largely lacking. In the case of a transected nerve, different methods have been used to repair or reconstruct the nerve, including the use of nerve conduits, but functional recovery is usually poor. Autophagy, a cellular mechanism that recycles damaged proteins, is impaired in the brain in many neurodegenerative diseases affecting animals and humans. No research, however, has investigated the presence of autophagy in the human peripheral nervous system. In this study, I present the first structural evidence of autophagy in human peripheral nerves. I also show that the density of autophagy structures is higher in peripheral nerves of patients with chronic idiopathic axonal polyneuropathy (CIAP) and inflammatory neuropathy than in controls. The density of these structures increases with the severity of the neuropathy. In animal model, using Goto-Kakizaki (GK) rats with diabetes resembling human type 2 diabetes, activation of autophagy by local administration of rapamycin incorporated in collagen conduits that were used for reconnection of the transected sciatic nerve led to an increase in autophagy proteins LC3 and a decrease in p62 suggesting that the autophagic flux was activated. In addition, immunoreactivity of neurofilaments, which are parts of the cytoskeleton of axons, was increased indicating increased axonal regeneration. I also show that many proteins involved in axonal regeneration and cell survival were up-regulated by rapamycin in the injured sciatic nerve of GK rats four weeks after injury. Taken together, these findings provide new knowledge about the involvement of autophagy in neuropathy and after peripheral nerve injury and reconstruction using collagen conduits. 6 Populärvetenskaplig sammanfattningNervskador (neuropati) orsakade av sjukdomar eller olycksfall påverkar miljontals individer runt om i världen. Nervskador som orsakas av diabetes kallas diabetesneuropati och drabbar varannan patient med diabetes. Neuropati kan också orsakas av kronisk inflammation i nerven eller uppstå utan känd orsak, så kallad kronisk idiopatisk axonal polyneuropati. Patienterna som drabbas av neuropati uppvisar varierande symptom beroende på vilka nerver som drabbas men domningar, stickningar, smärta, känselbortfall och muskelsvaghet finns ofta i symptombilden. Nervskador efter trauma kräver oftast kirurgisk rekonstruktion. För närvarande finns det ingen behandling för diabetesneuropati. Allt fler människor i fysiskt aktiv ålder drabbas av åldersdiabetes (typ 2 diabetes). Detta leder till att fler patienter med diabetes drabbas av traumatiska nervskador som kräver nervreparation. Det är därför viktigt att utveckla reparationsmetoder som fungerar br...

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Section: Resultssupporting

confidence: 88%

Autophagy in Peripheral Neuropathy

Osman¹

2017

Linköping University Medical Dissertations

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“…solution in sterile saline) twice at 0 h and 2 h. DMSO (SigmaAldrich, St. Louis, MO) (5 ml/kg or 10 ml/kg) was injected intraperitoneally into P7 C57BL/6By mice according to a method that induces neurodegeneration in P7 mice ( 39 ). Two microliters of saline or LPS (Sigma-Aldrich; serotype, 0127:B8) (1 mg/kg) in saline were injected intracerebrally into P7 C57BL/6By mice according to a method that induces brain injury, including astrogliosis, in P5 rats ( 40 ).…”

Section: Gm2 Elevation In Activated Gliamentioning

confidence: 99%

“…We then tested the possibility that treatments other than ethanol, which are known to induce neurodegeneration and/or glial activation, increase GM2 levels in the developing brain. It has been shown that DMSO, like ethanol, induces neurodegeneration in P7 mice ( 39 ). Therefore, lipid profi les of the brain harvested 24 h after the intraperitoneal injection of DMSO into P7 C57BL/6By mice were analyzed as described in the Materials and Methods.…”

Section: Gm2 Elevation Occurs In Microglia And/or Astrocytes Of P7 MImentioning

confidence: 99%

Ganglioside accumulation in activated glia in the developing brain: comparison between WT and GalNAcT KO mice

Saito

Hui

et al. 2015

Journal of Lipid Research

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“…Even at a concentration as low as 0.5%, DMSO could lead to apoptosis in the central nervous system, and at the postnatal age of 7 and 30 which are equivalent to human childhood ages, severe damage was observed after DMSO exposure. 46 Therefore, as the peak incidence of osteosarcoma in adolescents is in 10-14-year-olds, when pubertal growth starts, 4 DMSO might cause damage in the central nervous system when used as a solvent for hydrophobic anticancer drugs. In this study, APNPs did not show significant toxicity, so the curcumin-loaded APNPs could accelerate the internalization of curcumin with low toxicity induced by short polypeptides, although further in vivo studies are required to investigate this.…”

Section: Discussionmentioning

confidence: 99%

Selective inhibition of MG-63 osteosarcoma cell proliferation induced by curcumin-loaded self-assembled arginine-rich-RGD nanospheres

Chang¹,

Sun²,

Webster³

2015

IJN

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Osteosarcoma is the most frequent primary malignant form of bone cancer, comprising 30% of all bone cancer cases. The objective of this in vitro study was to develop a treatment against osteosarcoma with higher selectivity toward osteosarcoma cells and lower cytotoxicity toward normal healthy osteoblast cells. Curcumin (or diferuloylmethane) has been found to have antioxidant and anticancer effects by multiple cellular pathways. However, it has lower water solubility and a higher degradation rate in alkaline conditions. In this study, the amphiphilic peptide C18GR7RGDS was used as a curcumin carrier in aqueous solution. This peptide contains a hydrophobic aliphatic tail group leading to their self-assembly by hydrophobic interactions, as well as a hydrophilic head group composed of an arginine-rich and an arginine-glycine-aspartic acid structure. Through characterization by transmission electron microscopy, self-assembled structures of spherical amphiphilic nanoparticles (APNPs) with diameters of 10–20 nm in water and phosphate-buffered saline were observed, but this structure dissociated when the pH value was reduced to 4. Using a method of codissolution with acetic acid and dialysis tubing, the solubility of curcumin was enhanced and a homogeneous solution was formed in the presence of APNPs. Successful encapsulation of curcumin in APNPs was then confirmed by Fourier transform infrared and X-ray diffraction analyses. The cytotoxicity and cellular uptake of the APNP/curcumin complexes on both osteosarcoma and normal osteoblast cell lines were also evaluated by methyl-thiazolyl-tetrazolium assays and confocal fluorescence microscopy. The results showed that the curcumin-loaded APNPs had significant selective cytotoxicity against MG-63 osteosarcoma cells when compared with normal osteoblasts. We have demonstrated for the first time that APNPs can encapsulate hydrophobic curcumin in their hydrophobic cores, and curcumin-loaded APNPs could be an innovative treatment for the selective inhibition of osteosarcoma cells.

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Dimethyl sulfoxide (DMSO) produces widespread apoptosis in the developing central nervous system

Cited by 187 publications

References 48 publications

Autophagy in Peripheral Neuropathy

Autophagy in Peripheral Neuropathy

Ganglioside accumulation in activated glia in the developing brain: comparison between WT and GalNAcT KO mice

Selective inhibition of MG-63 osteosarcoma cell proliferation induced by curcumin-loaded self-assembled arginine-rich-RGD nanospheres

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Dimethyl sulfoxide (DMSO) produces widespread apoptosis in the developing central nervous system

Cited by 187 publications

References 48 publications

Autophagy in Peripheral Neuropathy

Autophagy in Peripheral Neuropathy

Ganglioside accumulation in activated glia in the developing brain: comparison between WT and GalNAcT KO mice

Selective inhibition of MG-63 osteosarcoma cell&nbsp;proliferation induced by curcumin-loaded self-assembled arginine-rich-RGD nanospheres

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Selective inhibition of MG-63 osteosarcoma cell proliferation induced by curcumin-loaded self-assembled arginine-rich-RGD nanospheres