• Animal cells and systems
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• v.13 no.4
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• pp.411-418
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• 2009

We are reporting the identification, expression patterns, and possible biological functions of zebrafish kif3b (kif3bz) encoding 475 amino acids. Kif3Bz contains the kinesin motor domain, catalytic domain, KISc domain, and one single coiled coil domain. Phylogenetic analysis indicates that kif3bz is a highly conserved gene among the tested vertebrates. First of all, both maternal and zygotic messages of kif3bz were evenly distributed in the blastomeres at 2-cell stage. Its ubiquitous expression throughout the blastomeres continued till 40% epiboly. However, kif3bz transcripts became restricted in Kupffer's vesicle at tailbud and 6-somite stages. At 13-somite stage, kif3bz expression pattern became specific to the telencephalon, diencephalon, trigeminal placode, and somites. Such expression patterns were further intensified in the telencephalon, diencephalons, hind brain, pronephric ducts, optic vesicles, and spinal cord neurons in the 23-somite stage embryos, and last till 24 hpf. We discussed possible functions of Kif3Bz related to the vertebrate embryonic development.

• Molecules and Cells
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• v.44 no.8
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• pp.549-556
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• 2021

Decoding the molecular mechanisms underlying axon guidance is key to precise understanding of how complex neural circuits form during neural development. Although substantial progress has been made over the last three decades in identifying numerous axon guidance molecules and their functional roles, little is known about how these guidance molecules collaborate to steer growth cones to their correct targets. Recent studies in Drosophila point to the importance of the combinatorial action of guidance molecules, and further show that selective fasciculation and defasciculation at specific choice points serve as a fundamental strategy for motor axon guidance. Here, I discuss how attractive and repulsive guidance cues cooperate to ensure the recognition of specific choice points that are inextricably linked to selective fasciculation and defasciculation, and correct pathfinding decision-making.

• Journal of Korean Neurosurgical Society
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• v.49 no.2
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• pp.83-91
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• 2011

Objective : Minocycline, a second-generation tetracycline-class antibiotic, has been well established to exert a neuroprotective effect in animal models and neurodegenerative disease through the inhibition of microglia. Here, we investigated the effects of minocycline on motor recovery and neuropathic pain in a rat model of spinal cord injury. Methods : To simulate spinal cord injury, the rats' spinal cords were hemisected at the 10th thoracic level (T10). Minocycline was injected intraperitoneally, and was administered 30 minutes prior surgery and every second postoperative day until sacrifice 28 days after surgery. Motor recovery was assessed via the Basso-Beattie-Bresnahan test Mechanical hyperalgesia was measured throughout the 28-day post -operative course via the von Frey test Microglial and astrocyte activation was assessed by immunohistochemical staining for ionized calcium binding adaptor molecule 1 (lba1) and glial fibrillary acidic protein (GFAP) at two sites: at the level of hemisection and at the 5th lumbar level (L5). Results : In rats, spinal cord hemisection reduced locomotor function and induced a mechanical hyperalgesia of the ipsilateral hind limb. The expression of lba1 and GFAP was also increased in the dorsal and ventral horns of the spinal cord at the site of hemisection and at the L5 level. Intraperitoneal injection of minocycline facilitated overall motor recovery and attenuated mechanical hyperalgesia. The expression of lba1 and GFAP in the spinal cord was also reduced in rats treated with minocycline. Conclusion : By inhibiting microglia and astrocyte activation, minocycline may facilitate motor recovery and attenuate mechanical hyperalgesia in individuals with spinal cord injuries.

• Animal cells and systems
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• v.12 no.4
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• pp.219-230
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• 2008

We are reporting the expression patterns and possible biological functions of a novel Kinesin-like protein, Surhe, in the zebrafish. Homology studies of derived amino acid sequences suggest that Surhe has an amino-terminal kinesin motor domain that is similar to that of the emerging MKLP-1 subfamily [Kim and Endow, 2000] and two coiledcoil domains in a central region. Cellular localization studies in mammalian cells revealed that Surhe protein is located in cytoplasm, suggesting that Surhe may be involved in the intracellular transport. During the developmental process, surhe transcripts are highly expressed in early embryonic stages. Overexpression of the dominant negative form of Surhe significantly down-regulates the dorsalization markers, such as goosecoid, bozozok, and chordin. Taken together, we postulate that Surhe may be involved in dorsalization process as a motor molecule.

• Journal of Ginseng Research
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• v.45 no.3
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• pp.390-400
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• 2021

Background: We recently showed that gintonin, an active ginseng ingredient, exhibits antibrain neurodegenerative disease effects including multiple target mechanisms such as antioxidative stress and antiinflammation via the lysophosphatidic acid (LPA) receptors. Amyotrophic lateral sclerosis (ALS) is a spinal disease characterized by neurodegenerative changes in motor neurons with subsequent skeletal muscle paralysis and death. However, pathophysiological mechanisms of ALS are still elusive, and therapeutic drugs have not yet been developed. We investigate the putative alleviating effects of gintonin in ALS. Methods: The G93A-SOD1 transgenic mouse ALS model was used. Gintonin (50 or 100 mg/kg/day, p.o.) administration started from week seven. We performed histological analyses, immunoblot assays, and behavioral tests. Results: Gintonin extended mouse survival and relieved motor dysfunctions. Histological analyses of spinal cords revealed that gintonin increased the survival of motor neurons, expression of brain-derived neurotrophic factors, choline acetyltransferase, NeuN, and Nissl bodies compared with the vehicle control. Gintonin attenuated elevated spinal NAD(P) quinone oxidoreductase 1 expression and decreased oxidative stress-related ferritin, ionized calcium-binding adapter molecule 1-immunoreactive microglia, S100β-immunoreactive astrocyte, and Olig2-immunoreactive oligodendrocytes compared with the control vehicle. Interestingly, we found that the spinal LPA1 receptor level was decreased, whereas gintonin treatment restored decreased LPA1 receptor expression levels in the G93A-SOD1 transgenic mouse, thereby attenuating neurological symptoms and histological deficits. Conclusion: Gintonin-mediated symptomatic improvements of ALS might be associated with the attenuations of neuronal loss and oxidative stress via the spinal LPA1 receptor regulations. The present results suggest that the spinal LPA1 receptor is engaged in ALS, and gintonin may be useful for relieving ALS symptoms.

• Journal of Life Science
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• v.29 no.11
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• pp.1258-1266
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• 2019

Yangkyuksanhwa-Tang (YKSH), consisting of nine different herbs, is commonly used in Soyangin-type individuals with stroke, based on the Sasang Constitution Theory in Korea. However, no evidence has yet confirmed a beneficial effect of YKSH in ischemic stroke treatment. In this study, we investigated the effects of YKSH on ischemic brain injury in a mouse model of cerebral ischemia. Focal cerebral ischemia in mice was induced by photothrombosis, and behavioral recovery was evaluated. Infarct volume, inflammation, and newly generated cells were evaluated by histology and immunochemistry. YKSH treatment resulted in a significant recovery from the motor impairments induced by focal cerebral ischemia, as determined with wire grip and rotarod tests. YKSH treatment also decreased the infarct volume and the number of cells positive for tumor necrosis factor-${\alpha}$ and myeloperoxidase when compared with a vehicle-treated control group. By contrast, YKSH treatment considerably increased the number of cells positive for glial fibrillary acidic protein and ionized calcium-binding adapter molecule 1, as well as the number of cells doubly positive for Ki67/doublecortin when compared with the vehicle-treated group. These results suggest that YKSH treatment attenuated the infarct size by anti-inflammatory action, astrocyte and microglia activation, and neuronal proliferation, thereby facilitating neurofunctional recovery from a cerebral ischemic assault. YKSH could therefore be a potential treatment for neurofunctional restoration of the injured brains of patients with stroke.

• Journal of Korean Neurosurgical Society
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• v.60 no.4
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• pp.417-423
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• 2017

Objective : Repair of sensorial nerve defect is an important issue on peripheric nerve surgery. The aim of the present study was to determine the effects of sensory-motor nerve bridging on the denervated dermatomal area, in rats with sensory nerve defects, using a neural cell adhesion molecule (NCAM). Methods : We compared the efficacy of end-to-side (ETS) coaptation of the tibial nerve for sural nerve defect repair, in 32 Sprague-Dawley rats. Rats were assigned to 1 of 4 groups : group A was the sham operated group, group B rats had sural nerves sectioned and buried in neighboring muscles, group C experienced nerve sectioning and end-to-end (ETE) anastomosis, and group D had sural nerves sectioned and ETS anastomosis was performed using atibial nerve bridge. Neurological evaluation included the skin pinch test and histological evaluation was performed by assessing NCAM expression in nerve terminals. Results : Rats in the denervated group yielded negative results for the skin pinch tests, while animals in the surgical intervention groups (group C and D) demonstrated positive results. As predicted, there were no positively stained skin specimens in the denervated group (group B); however, the surgery groups demonstrated significant staining. NCAM expression was also significantly higher in the surgery groups. However, the mean NCAM values were not significantly different between group C and group D. Conclusion : Previous research indicates that ETE nerve repair is the gold standard for peripheral nerve defect repair. However, ETS repair is an effective alternative method in cases of sensorial nerve defect when ETE repair is not possible.

• Biomolecules & Therapeutics
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• v.29 no.5
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• pp.483-491
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• 2021

Parkinson's disease (PD) is a neurodegenerative disorder that involves the loss of dopaminergic neurons in the substantia nigra (SN). Matrix metalloproteinases-8 (MMP-8), neutrophil collagenase, is a functional player in the progressive pathology of various inflammatory disorders. In this study, we administered an MMP-8 inhibitor (MMP-8i) in Leucine-rich repeat kinase 2 (LRRK2) G2019S transgenic mice, to determine the effects of MMP-8i on PD pathology. We observed a significant increase of ionized calcium-binding adapter molecule 1 (Iba1)-positive activated microglia in the striatum of LRRK2 G2019S mice compared to normal control mice, indicating enhanced neuro-inflammatory responses. The increased number of Iba1-positive activated microglia in LRRK2 G2019S PD mice was down-regulated by systemic administration of MMP-8i. Interestingly, this LRRK2 G2019S PD mice showed significantly reduced size of cell body area of tyrosine hydroxylase (TH) positive neurons in SN region and MMP-8i significantly recovered cellular atrophy shown in PD model indicating distinct neuro-protective effects of MMP-8i. Furthermore, MMP-8i administration markedly improved behavioral abnormalities of motor balancing coordination in rota-rod test in LRRK2 G2019S mice. These data suggest that MMP-8i attenuates the pathological symptoms of PD through anti-inflammatory processes.

• Journal of Korean Medicine Rehabilitation
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• v.20 no.2
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• pp.1-15
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• 2010

Objectives : This study was performed to evaluate the effects of root of Cibotii rhizoma(CR) ethanol extract on the tissue and neuronal damage of the spinal cord injury(SCI). Methods : SCI was induced by mechanical contusion following laminectomy of 10th thoracic vertebra in Sprague-Dawley rats. CR was orally given once a day for 7 days after SCI. Tissue damage and nerve fiber degeneration were examined with cresyl violet and luxol fast blue(LFS) histochemistry. HSP72(as neuronal damage marker), MAP2(as nerve fiber degeneration marker), c-Fos(immediate early gene), and Bax(pro-apoptotic molecule) expressions were examined using immuno-histochemistry. Individual immuno-positive cells expressing HSP72, MAP2, c-Fos and Bax were observed on the damaged level and the upper thoracic and lower lumbar spinal segments. Results : 1. CR reduced degeneration of nerve fibers and motor neuron shrinkage in the ventral horn of the lower lumbar spinal segment, but generally it did not seem to ameliorate the tissue injury following SCI. 2. CR reduced demyelination in the ventral and lateral funiculus of the lower lumbar spinal segment. 3. CR reduced HSP72 expression on the neurons in the peri-central canal gray matter adjacent to the damaged region. 4. CR strengthened MAP2 expression on the motor neurons in the ventral horn and on nerve fibers in the lateral funiculus of the lower lumbar spinal segment. 5. CR reduced c-Fos positive cells in the peri-lesion and the dorsal horn of the damaged level and in the ventral horn of the lower lumbar spinal segment. 6. CR reduced Bax positive cells in the peri-lesion and the dorsal horn of the damaged level and in the ventral horn of the lower lumbar spinal segment. Conclusions : These results suggest that CR plays an inhibitory role against secondary neuronal damage and nerve fiber degeneration. following SCI.

• The Journal of Korean Physical Therapy
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• v.19 no.2
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• pp.41-55
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• 2007

Purpose: This study aimed to compare the effect on nerve regeneration of ultrasound irradiation in rats with peripheral nerve injury. Methods: To investigate alterations of the NCAM immunoreactivity in non-crushed part and crushed part of the spinal cord, the unilateral sciatic nerve of the rats were crushed. The expression of NCAM was used as the marked of peripheral nerve regeneration, and also plays an important role in developing nerve system. Experimental animals were sacrificed by perfusion fixation at post-injury 1, 3, 7, 14 days after ultrasound irradiation. The pulsed US was applied at a frequency of 1MHz and a spatial average-temporal average Intensity of 0.5W/of (20% pulse ratio) for 1 mins. The Luxol fast blue-cresyl violet stain were also done to observe the morphological changes. Results: Alteration of NCAM immunoreactivity in the crushed part and the non-crushed part of lower lumbar spinal cord were observed. NCAM-immunoreactivity cells were some increased in the dorsal horn lamina I, III and cell ventral horn at 1 day after unilateral sciatic nerve injury. However, there was not significant difference in the relationship between crushed part and non-crushed part. NCAM-inmmunoreactivity was remarkably increased at 3 days after unilateral sciatic nerve injuryin the gray matter and white matter. NCAM-immunoreactivity was increased in the ventral horn and post horn of experimental crushed part. Also, NCAM-immunoreactivity in large motor neurons in ventral horns lamina VIII, IX were increased at 7 days after unilateral sciatic nerve injury. At 14 days after sciatic nerve crushed injury, there was no significant difference. All group were decreased for 14 days. In the time course of NCAM expression, all groups showed a significant difference at 3day groups(p<0.05). Whereas, CC group was noted a significant difference between 3day and 7 day group respectively. In NCAM expression, there were significantly increased in all group. In the relationship between CNC group and ENC group, significant difference was detected among 3, 7, 14 day group(p<0.05). The difference between CC group and ENC group were noted in all groups(p<0.05). Conclusion: It is consequently suggested that the effects of the ultrasound irradiation may increase the NCAM immunoreactive neurons and glial cell in the spinal cord after unilateral sciatic nerve crushed injury. Therefore, the increased NCAM immunoreactivity in the spinal cord may reflect the neuronal damage and healing process induced by a ultrasound irradiation after peripheral nerve injury in rat.