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1.
J Neurotrauma ; 2020 May 04.
Artigo em Inglês | MEDLINE | ID: mdl-32233738

RESUMO

Autophagy is the degradation process of dysfunctional intracellular components and has a crucial function in various human diseases. There are three different types of autophagy: macroautophagy, microautophagy, and chaperone-mediated autophagy (CMA). CMA is a major route for the elimination of cellular aberrant proteins and can provide a cytoprotective effect. The present study investigated the expression of lysosome-associated membrane protein type 2A (LAMP2A), which is the hallmark of CMA activity, in damaged neural tissue after spinal cord injury (SCI) in mice. The number of LAMP2A-expressing cells was significantly increased at the lesion following SCI. The increased number of LAMP2A-positive cells was observed from 24 h and peaked at 3 days after injury. A western blot analysis confirmed that the level of LAMP2A protein was significantly increased in the injured spinal cord compared with the uninjured cord. On double staining for LAMP2A and different neural cell type markers, the increased expression of LAMP2A was observed in neurons, astrocytes, oligodendrocytes, and microglia/macrophages following injury. An electron microscopic analysis showed that secondary lysosomes were increased in damaged neurons at the lesion site. Immunoelectron microscopy revealed that the gold particles with anti-LAMP2A antibody were frequently localized at the secondary lysosomes in the injured site. These findings indicated that CMA was clearly activated in damaged neural tissue after SCI. The activation of CMA may contribute to the elimination of intracellular aberrant proteins and exert a neuroprotective effect following SCI.

2.
Cells ; 8(12)2019 Dec 06.
Artigo em Inglês | MEDLINE | ID: mdl-31817643

RESUMO

The receptor-interacting protein kinase 3 (RIPK3) is a key regulator of necroptosis and is involved in various pathologies of human diseases. We previously reported that RIPK3 expression is upregulated in various neural cells at the lesions and necroptosis contributed to secondary neural tissue damage after spinal cord injury (SCI). Interestingly, recent studies have shown that the B-RAFV600E inhibitor dabrafenib has a function to selectively inhibit RIPK3 and prevents necroptosis in various disease models. In the present study, using a mouse model of thoracic spinal cord contusion injury, we demonstrate that dabrafenib administration in the acute phase significantly inhibites RIPK3-mediated necroptosis in the injured spinal cord. The administration of dabrafenib attenuated secondary neural tissue damage, such as demyelination, neuronal loss, and axonal damage, following SCI. Importantly, the neuroprotective effect of dabrafenib dramatically improved the recovery of locomotor and sensory functions after SCI. Furthermore, the electrophysiological assessment of the injured spinal cord objectively confirmed that the functional recovery was enhanced by dabrafenib. These findings suggest that the B-RAFV600E inhibitor dabrafenib attenuates RIPK3-mediated necroptosis to provide a neuroprotective effect and promotes functional recovery after SCI. The administration of dabrafenib may be a novel therapeutic strategy for treating patients with SCI in the future.

3.
Case Rep Orthop ; 2017: 7396564, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29109887

RESUMO

Low transverse sacral fractures are rare, with only two published reports regarding their surgery. The complication associated with surgery for sacral fractures is the prominence of implants. In addition, screw fixation below S3 is impractical. We performed posterior sacral fixation using S2 alar iliac (S2AI) screws and sacral sublaminar wires for low transverse sacral fractures. Case 1 was 65-year-old male with an S2-3 transverse sacral fracture. We performed laminectomy (S2-3) and passed ultrahigh molecular weight polyethylene (UHMWPE) cables from laminectomy area to the third posterior sacral foramina. We inserted S2AI screws and connected rods. We also tightened the UHMWPE cables. The implants did not protrude into skin. One year after surgery, the sacral fracture healed without any displacement. Case 2 was a 42-year-old female with an S2 transverse sacral fracture. We performed laminectomy (S1-3) and passed UHMWPE cables from laminectomy area to the third and fourth posterior sacral foramina. We inserted S1 pedicular screws and S2AI screws and connected rods. We also tightened UHMWPE cables. The implants did not protrude into skin. One year after surgery, the sacral fracture healed without any displacement. We consider sacral sublaminar wires to be useful bone anchors in lower sacrum.

4.
Case Rep Med ; 2016: 9412315, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-28050170

RESUMO

While 22 articles have reported on sacral stress fractures, it is a rare injury and its etiology is not well known. We present the case of a 16-year-old male who presented with low back pain in 2015. He was a high school soccer player with a previous history of a bilateral L5 lumbar spondylolysis in 2014. The patient refrained from soccer and wore a brace for six months. Two months after restarting soccer, he again complained of low back pain. After 1 year, a lumbar spine computed tomography revealed the bone union of the spondylolysis. At his first visit to our hospital, his general and neurological conditions were normal and laboratory data were within the normal range. Sacral coronal magnetic resonance imaging (MRI) of the left sacral ala revealed an oblique lineal signal void surrounding bone marrow edema. Based on his symptoms, sports history, and MRI, he was diagnosed with a sacral stress fracture. He again refrained from soccer; his low back pain soon improved, and, after 1 year, the abnormal signal change had disappeared on sacral MRI. Recurrent low back pain case caused by a sacral stress fracture occurring after the bone union of lumbar spondylolysis is uncommon.

5.
Bioconjug Chem ; 16(6): 1367-74, 2005.
Artigo em Inglês | MEDLINE | ID: mdl-16287232

RESUMO

We prepared block copolymers of (2-ethoxy)ethoxyethyl vinyl ether (EOEOVE) and octadecyl vinyl ether (ODVE) with the number average molecular weights of 6900, 9300, and 16 700 by living cationic polymerization. The poly(EOEOVE) block acts as a temperature-sensitive moiety, and the poly(ODVE) block acts as an anchor moiety. We also investigated the effect of chain length of the copolymer poly(EOEOVE) block on the ability to sensitize liposomes. The copolymers underwent a coil-globule transition at approximately 36 degrees C in the presence of a membrane of egg yolk phosphatidylcholine (EYPC), detected using differential scanning calorimetry (DSC). Liposomes encapsulating calcein, a water-soluble fluorescent dye, were prepared from mixtures of dioleoylphosphatidylethanolamine, EYPC, and the copolymers. While the copolymer-modified liposomes released little calcein below 30 degrees C, release was enhanced above 35 degrees C, indicating that dehydrated copolymer chains destabilized the liposome membrane. In addition, copolymers with a longer poly(EOEOVE) block induced a more drastic enhancement of contents release in a narrow temperature region near the transition temperature of the poly(EOEOVE) block. As a result, the copolymer with an average molecular weight of 16 700 generated highly sensitive liposomes that produced rapid and dramatic release of the contents in response to temperature.


Assuntos
Lipossomos , Polímeros/química , Temperatura , Éteres/química , Fluoresceínas , Transição de Fase , Fosfatidilcolinas , Fosfatidiletanolaminas , Polímeros/síntese química , Relação Estrutura-Atividade , Compostos de Vinila/química
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