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1.  A Prosaposin-Derived Peptide Alleviates Kainic Acid-Induced Brain Injury 
PLoS ONE  2015;10(5):e0126856.
Four sphingolipid activator proteins (i.e., saposins A–D) are synthesized from a single precursor protein, prosaposin (PS), which exerts exogenous neurotrophic effects in vivo and in vitro. Kainic acid (KA) injection in rodents is a good model in which to study neurotrophic factor elevation; PS and its mRNA are increased in neurons and the choroid plexus in this animal model. An 18-mer peptide (LSELIINNATEELLIKGL; PS18) derived from the PS neurotrophic region prevents neuronal damage after ischemia, and PS18 is a potent candidate molecule for use in alleviating ischemia-induced learning disabilities and neuronal loss. KA is a glutamate analog that stimulates excitatory neurotransmitter release and induces ischemia-like neuronal degeneration; it has been used to define mechanisms involved in neurodegeneration and neuroprotection. In the present study, we demonstrate that a subcutaneous injection of 0.2 and 2.0 mg/kg PS18 significantly improved behavioral deficits of Wistar rats (n = 6 per group), and enhanced the survival of hippocampal and cortical neurons against neurotoxicity induced by 12 mg/kg KA compared with control animals. PS18 significantly protected hippocampal synapses against KA-induced destruction. To evaluate the extent of PS18- and KA-induced effects in these hippocampal regions, we performed histological evaluations using semithin sections stained with toluidine blue, as well as ordinal sections stained with hematoxylin and eosin. We revealed a distinctive feature of KA-induced brain injury, which reportedly mimics ischemia, but affects a much wider area than ischemia-induced injury: KA induced neuronal degeneration not only in the CA1 region, where neurons degenerate following ischemia, but also in the CA2, CA3, and CA4 hippocampal regions.
PMCID: PMC4436272  PMID: 25993033
2.  Clinical Outcomes of Surgical Treatments for Traumatic Spinal Injuries due to Snowboarding 
Asian Spine Journal  2015;9(1):90-98.
Study Design
Retrospective study.
To assess treatment outcomes of snowboarding-related spinal and spinal cord injuries.
Overview of Literature
Snowboarding-related spinal or spinal cord injury have a great impact on social and sporting activities.
A retrospective review of 19 cases of surgically treated snowboard-related injury was done. Analyzed parameters included site of injury, type of fracture, peri- and postoperative complications, pre- and postoperative neurological status, activities of daily living, and participation in sports activities at the final follow-up.
The major site of injury was the thoracolumbar junction caused by fracture-dislocation (13/19 cases). The remaining 6 cases had cervical spine injuries. Over 60% of the patients had Frankel A and B paralysis. All patients were surgically treated by posterior fusion with instrumentation. Five underwent additional anterior fusion. Surgical outcome was restoration of ambulatory capacity in 12 patients (63.2%). Ultimately, 15 patients (78.9%) could return to work. Patients with complete paralysis upon admission showed reduced ambulatory capacity compared to those with incomplete paralysis. None of the patients again participated in any sports activities, including snowboarding.
Snowboarding-related spinal or spinal cord injury has a great impact on social as well as sports activities. It is necessary to enhance promotion of injury prevention emphasizing the snowboarders' responsibility code.
PMCID: PMC4330225  PMID: 25705340
Snowboarding; Spinal injury; Surgical treatment; Clinical outcomes
3.  Stochastic Process Underlying Emergent Recognition of Visual Objects Hidden in Degraded Images 
PLoS ONE  2014;9(12):e115658.
When a degraded two-tone image such as a “Mooney” image is seen for the first time, it is unrecognizable in the initial seconds. The recognition of such an image is facilitated by giving prior information on the object, which is known as top-down facilitation and has been intensively studied. Even in the absence of any prior information, however, we experience sudden perception of the emergence of a salient object after continued observation of the image, whose processes remain poorly understood. This emergent recognition is characterized by a comparatively long reaction time ranging from seconds to tens of seconds. In this study, to explore this time-consuming process of emergent recognition, we investigated the properties of the reaction times for recognition of degraded images of various objects. The results show that the time-consuming component of the reaction times follows a specific exponential function related to levels of image degradation and subject's capability. Because generally an exponential time is required for multiple stochastic events to co-occur, we constructed a descriptive mathematical model inspired by the neurophysiological idea of combination coding of visual objects. Our model assumed that the coincidence of stochastic events complement the information loss of a degraded image leading to the recognition of its hidden object, which could successfully explain the experimental results. Furthermore, to see whether the present results are specific to the task of emergent recognition, we also conducted a comparison experiment with the task of perceptual decision making of degraded images, which is well known to be modeled by the stochastic diffusion process. The results indicate that the exponential dependence on the level of image degradation is specific to emergent recognition. The present study suggests that emergent recognition is caused by the underlying stochastic process which is based on the coincidence of multiple stochastic events.
PMCID: PMC4277371  PMID: 25542034
4.  Prosaposin Overexpression following Kainic Acid-Induced Neurotoxicity 
PLoS ONE  2014;9(12):e110534.
Because excessive glutamate release is believed to play a pivotal role in numerous neuropathological disorders, such as ischemia or seizure, we aimed to investigate whether intrinsic prosaposin (PS), a neuroprotective factor when supplied exogenously in vivo or in vitro, is up-regulated after the excitotoxicity induced by kainic acid (KA), a glutamate analog. In the present study, PS immunoreactivity and its mRNA expression in the hippocampal and cortical neurons showed significant increases on day 3 after KA injection, and high PS levels were maintained even after 3 weeks. The increase in PS, but not saposins, detected by immunoblot analysis suggests that the increase in PS-like immunoreactivity after KA injection was not due to an increase in saposins as lysosomal enzymes after neuronal damage, but rather to an increase in PS as a neurotrophic factor to improve neuronal survival. Furthermore, several neurons with slender nuclei inside/outside of the pyramidal layer showed more intense PS mRNA expression than other pyramidal neurons. Based on the results from double immunostaining using anti-PS and anti-GABA antibodies, these neurons were shown to be GABAergic interneurons in the extra- and intra-pyramidal layers. In the cerebral cortex, several large neurons in the V layer showed very intense PS mRNA expression 3 days after KA injection. The choroid plexus showed intense PS mRNA expression even in the normal rat, and the intensity increased significantly after KA injection. The present study indicates that inhibitory interneurons as well as stimulated hippocampal pyramidal and cortical neurons synthesize PS for neuronal survival, and the choroid plexus is highly activated to synthesize PS, which may prevent neurons from excitotoxic neuronal damage. To the best of our knowledge, this is the first study that demonstrates axonal transport and increased production of neurotrophic factor PS after KA injection.
PMCID: PMC4251898  PMID: 25461957
5.  Temporal Changes in Prosaposin Expression in the Rat Dentate Gyrus after Birth 
PLoS ONE  2014;9(5):e95883.
Neurogenesis in the hippocampal dentate gyrus occurs constitutively throughout postnatal life. Adult neurogenesis includes a multistep process that ends with the formation of a postmitotic and functionally integrated new neuron. During adult neurogenesis, various markers are expressed, including GFAP, nestin, Pax6, polysialic acid-neural cell adhesion molecule (PSA-NCAM), neuronal nuclei (NeuN), doublecortin, TUC-4, Tuj-1, and calretinin. Prosaposin is the precursor of saposins A–D; it is found in various organs and can be excreted. Strong prosaposin expression has been demonstrated in the developing brain including the hippocampus, and its neurotrophic activity has been proposed. This study investigated changes in prosaposin in the dentate gyrus of young and adult rats using double immunohistochemistry with antibodies to prosaposin, PSA-NCAM, and NeuN. Prosaposin immunoreactivity was intense in the dentate gyrus at postnatal day 3 (P3) and P7, but decreased gradually after P14. In the dentate gyrus at P28, immature PSA-NCAM-positive neurons localized exclusively in the subgranular zone were prosaposin-negative, whereas mature Neu-N-positive neurons were positive for prosaposin. Furthermore, these prosaposin-negative immature neurons were saposin B-positive, suggesting that the neurons take up and degrade prosaposin. In situ hybridization assays showed that prosaposin in the adult dentate gyrus is dominantly the Pro+9 type, a secreted type of prosaposin. These results imply that prosaposin secreted from mature neurons stimulates proliferation and maturation of immature neurons in the dentate gyrus.
PMCID: PMC4037173  PMID: 24871372
6.  Decrease in Prosaposin in the Dystrophic mdx Mouse Brain 
PLoS ONE  2013;8(11):e80032.
Duchenne muscular dystrophy caused by a mutation in the X-linked dystrophin gene induces metabolic and structural disorders in the brain. A lack of dystrophin in brain structures is involved in impaired cognitive function. Prosaposin (PS), a neurotrophic factor, is abundant in the choroid plexus and various brain regions. We investigated whether PS serves as a link between dystrophin loss and gross and/or ultrastructural brain abnormalities.
Methodology/Principal Findings
The distribution of PS in the brains of juvenile and adult mdx mice was investigated by immunochemistry, Western blotting, and in situ hybridization. Immunochemistry revealed lower levels of PS in the cytoplasm of neurons of the cerebral cortex, hippocampus, cerebellum, and choroid plexus in mdx mice. Western blotting confirmed that PS levels were lower in these brain regions in both juveniles and adults. Even with low PS production in the choroids plexus, there was no significant PS decrease in cerebrospinal fluid (CSF). In situ hybridization revealed that the primary form of PS mRNA in both normal and mdx mice was Pro+9, a secretory-type PS, and the hybridization signals for Pro+9 in the above-mentioned brain regions were weaker in mdx mice than in normal mice. We also investigated mitogen-activated protein kinase signalling. Stronger activation of ERK1/2 was observed in mdx mice, ERK1/2 activity was positively correlated with PS activity, and exogenous PS18 stimulated both p-ERK1/2 and PS in SH-SY5Y cells.
Low levels of PS and its receptors suggest the participation of PS in some pathological changes in the brains of mdx mice.
PMCID: PMC3828254  PMID: 24244600
7.  Motion Induced Artifact Mimicking Cervical Dens Fracture on the CT Scan: A Case Report 
Asian Spine Journal  2012;6(3):216-218.
The diagnostic performance of helical computed tomography (CT) is excellent. However, some artifacts have been reported, such as motion, beam hardening and scatter artifacts. We herein report a case of motion-induced artifact mimicking cervical dens fracture. A 60-year-old man was involved in a motorcycle accident that resulted in cervical spinal cord injury and quadri plegia. Reconstructed CT images of the cervical spine showed a dens fracture. We assessed axial CT in detail, and motion artifact was detected.
PMCID: PMC3429615  PMID: 22977704
Reconstruction; Motion artifact; Mimicking; Cervical fracture

Results 1-7 (7)