• Journal of Korean Neurosurgical Society
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• v.65 no.4
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• pp.572-581
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• 2022

Objective : Compared to microscopes, exoscopes have advantages in field-depth, ergonomics, and educational value. Exoscopes are especially well-poised for adaptation into fluorescence-guided surgery (FGS) due to their excitation source, light path, and image processing capabilities. We evaluated the feasibility of near-infrared FGS using a 3-dimensional (3D), 4 K exoscope with near-infrared fluorescence imaging capability. We then compared it to the most sensitive, commercially-available near-infrared exoscope system (3D and 960 p). In-vitro and intraoperative comparisons were performed. Methods : Serial dilutions of indocyanine-green (1-2000 ㎍/mL) were imaged with the 3D, 4 K Olympus Orbeye (system 1) and the 3D, 960 p VisionSense Iridium (system 2). Near-infrared sensitivity was calculated using signal-to-background ratios (SBRs). In addition, three patients with brain tumors were administered indocyanine-green and imaged with system 1, with two also imaged with system 2 for comparison. Results : Systems 1 and 2 detected near-infrared fluorescence from indocyanine green concentrations of >250 ㎍/L and >31.3 ㎍/L, respectively. Intraoperatively, system 1 visualized strong near-infrared fluorescence from two, strongly gadolinium-enhancing meningiomas (SBR=2.4, 1.7). The high-resolution, bright images were sufficient for the surgeon to appreciate the underlying anatomy in the near-infrared mode. However, system 1 was not able to visualize fluorescence from a weakly-enhancing intraparenchymal metastasis. In contrast, system 2 successfully visualized both the meningioma and the metastasis but lacked high resolution stereopsis. Conclusion : Three-dimensional exoscope systems provide an alternative visualization platform for both standard microsurgery and near-infrared fluorescent guided surgery. However, when tumor fluorescence is weak (i.e., low fluorophore uptake, deep tumors), highly sensitive near-infrared visualization systems may be required.

• Journal of Physiology & Pathology in Korean Medicine
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• v.36 no.1
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• pp.11-17
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• 2022

In this study, we investigated the effects of Ginseng Radix (G), Rehmanniae Radix (R), and Fermented red-ginseng extracts (FRG) on cognitive function in scopolamine-induced memory-impaired mice. We measured the effects of G, R, and FRG on the improvement of memory and cognition via behavior analysis. In addition, we measured the acetylcholinesterase (AChE) activity in the hippocampus of each group of mice. The expression of β-amyloid, Tau, and BDNF in the brain tissues were observed through immunohistochemical staining. Ginseng Radix (G) and Fermented red-ginseng (FRG) have effectively improved cognitive function in the water maze test. Ginseng Radix (G), Rehmanniae Radix (R), and Fermented red-ginseng (FRG) have improved the willingness of mice to explore the new environment, as confirmed by Y maze test. In addition, immunohistochemical staining revealed that Ginseng Radix (G) decreased the expression of β-amyloid and Tau in the hippocampus. In addition, fermented red-ginseng (FRG) increased the expression of BDNF. Ginseng Radix (G), Rehmanniae Radix (R), and Fermented red-ginseng (FRG) have decreased the concentration of acetylcholinesterase in the hippocampus as compared with the control group of mice. In conclusion, Ginseng Radix (G), Rehmanniae Radix (R), and Fermented red-ginseng (FRG) are considered to have the potential for development as candidate drugs to control the progression of Alzheimer's disease (AD).

• The Korean Journal of Pain
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• v.35 no.4
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• pp.413-422
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• 2022

Background: The neocortex, including the medial prefrontal cortex (mPFC), contains many neurons expressing nitric oxide synthase (NOS). In addition, increasing evidence shows that the nitric oxide (NO) and opioid systems interact in the brain. However, there have been no studies on the interaction of the opioid and NO systems in the mPFC. The objective of this study was to investigate the effects of administrating L-arginine (L-Arg, a precursor of NO) and N(gamma)-nitro-L-arginine methyl ester (L-NAME, an inhibitor of NOS) into the mPFC for neuropathic pain in rats. Also, we used selective opioid receptor antagonists to clarify the possible participation of the opioid mechanism. Methods: Complete transection of the peroneal and tibial branches of the sciatic nerve was applied to induce neuropathic pain, and seven days later, the mPFC was cannulated bilaterally. The paw withdrawal threshold fifty percent (50% PWT) was recorded on the 14th day. Results: Microinjection of L-Arg (2.87, 11.5 and 45.92 nmol per 0.25 µL) increased 50% PWT. L-NAME (17.15 nmol per 0.25 µL) and naloxonazine (an antagonist of mu opioid receptors, 1.54 nmol per 0.25 µL) inhibited anti-allodynia induced by L-Arg (45.92 nmol per 0.25 µL). Naltrindole (a delta opioid receptor antagonist, 2.45 nmol per 0.25 µL) and nor-binaltorphimine (a kappa opioid receptor antagonist, 1.36 nmol per 0.25 µL) were unable to prevent L-Arg (45.92 nmol per 0.25 µL)-induced antiallodynia. Conclusions: Our results indicate that the NO system in the mPFC regulates neuropathic pain. Mu opioid receptors of this area might participate in pain relief caused by L-Arg.

• Anatomy and Cell Biology
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• v.56 no.2
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• pp.219-227
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• 2023

Adult neurogenesis has been reported in the hypothalamus, subventricular zone and subgranular zone in the hippocamp. Recent studies indicated that new cells in the hypothalamus are affected by diet. We previously showed beneficial effects of safflower seed oil (SSO), a rich source of linoleic acid (LA; 74%), on proliferation and differentiation of neural stem cells (NSCs) in vitro. In this study, the effect of SSO on hypothalamic neurogenesis was investigated in vivo, in comparison to synthetic LA. Adult mice were treated with SSO (400 mg/kg) and pure synthetic LA (300 mg/kg), at similar concentrations of LA, for 8 weeks and then hypothalamic NSCs were cultured and subsequently used for Neurosphere-forming assay. In addition, serum levels of brain-derived neurotrophic factor (BNDF) were measured using enzyme-linked immunosorbent assay. Administration of SSO for 8 weeks in adult mice promoted the proliferation of NSCs isolated from SSO-treated mice. Immunofluorescence staining of the hypothalamus showed that the frequency of astrocytes (glial fibrillary acidic protein⁺ cells) are not affected by LA or SSO. However, the frequency of immature (doublecortin⁺ cells) and mature (neuronal nuclei⁺ cells) neurons significantly increased in LA- and SSO-treated mice, compared to vehicle. Furthermore, both LA and SSO caused a significant increase in the serum levels of BDNF. Importantly, SSO acted more potently than LA in all experiments. The presence of other fatty acids in SSO, such as oleic acid and palmitic acid, suggests that they could be responsible for SSO positive effect on hypothalamic proliferation and neurogenesis, compared to synthetic LA at similar concentrations.

• BMB Reports
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• v.57 no.3
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• pp.149-154
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• 2024

The stomach has emerged as a crucial endocrine organ in the regulation of feeding since the discovery of ghrelin. Gut-derived hormones, such as ghrelin and cholecystokinin, can act through the vagus nerve. We previously reported the satiety effect of hypothalamic clusterin, but the impact of peripheral clusterin remains unknown. In this study, we administered clusterin intraperitoneally to mice and observed its ability to suppress fasting-driven food intake. Interestingly, we found its synergism with cholecystokinin and antagonism with ghrelin. These effects were accompanied by increased c-fos immunoreactivity in nucleus tractus solitarius, area postrema, and hypothalamic paraventricular nucleus. Notably, truncal vagotomy abolished this response. The stomach expressed clusterin at high levels among the organs, and gastric clusterin was detected in specific enteroendocrine cells and the submucosal plexus. Gastric clusterin expression decreased after fasting but recovered after 2 hours of refeeding. Furthermore, we confirmed that stomachspecific overexpression of clusterin reduced food intake after overnight fasting. These results suggest that gastric clusterin may function as a gut-derived peptide involved in the regulation of feeding through the gut-brain axis.

• Journal of Cerebrovascular and Endovascular Neurosurgery
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• v.26 no.2
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• pp.216-222
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• 2024

Dissecting posterior inferior cerebellar artery (PICA) aneurysms are uncommon lesions. Their anatomy and the location of the dissection are variable, however, they usually occurs at the origin of the PICA. Dissecting PICA aneurysms generally have non-vascular morphology involving an entire segment of the artery and cannot be cut. Nevertheless, the detection of these vascular lesions has increased latterly, so it is necessary to recognize it and take the appropriate management modalities for these injuries. In this report, we describe a case of a 73-year-old male patient, who presented a history of severe headache, associated with neck stiffness, nausea, vomiting, dizziness, hypoactivity, mental confusion, and walking difficulty. Radiographic investigation with brain computed tomography (CT) showed mild bleeding in a pre-medullary and pre-pontine cistern, and cerebral angiogram showed a dissecting PICA aneurysm. Despite being a challenging treatment, microsurgery management was the chosen modality. It was performed an end-to-end anastomosis between the p2/p3 segments, showing to be effective with good clinical and radiographic outcomes. We discussed an unusual case, reviewing the current literature on clinical presentations, the angiographic characteristics of the dissecting aneurysms of PICA, and evaluating the clinical and angiographic results of patients undergoing microsurgical treatment.

• Clinical and Experimental Pediatrics
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• v.46 no.11
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• pp.1101-1106
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• 2003

Purpose : In vivo, minocycline appears to be neuroprotective. Thus, the neuroprotective effects of minocycline were studied in a rat brain cortical cell culture induced by hypoxia. Methods : Cultured cells from the brains of Sprague-Dawley rats were divided into two sets of groups : normoxia groups treated with 5% $CO_2$ and hypoxia groups treated with 1% $CO_2$. After several days of incubation, the control groups were not treated with minocycline, while the sample groups were treated with either 1 or $10{\mu}g/mL$ of minocycline. The damaged cells were observed under a microscope, while apoptosis was detected using a TUNEL assay control-stained with DAPI. Results : Among the normoxia groups, the control and sample groups treated with 1 and $10{\mu}g/mL$ of minocycline were all statistically significantly different from each other. Meanwhile, among the hypoxia groups, although the control was significantly different from the sample groups, there was no statistically significant difference between the sample groups. When comparing the normoxia and hypoxia groups, there was a statistically significant difference between the control groups and sample groups treated with $1{\mu}g/mL$ of minocycline, yet no significant difference between the sample groups treated with $10{\mu}g/mL$ of minocycline. Conclusion : Minocycline was found to be neuroprotective in normoxia and hypoxia induced rat brain cortical cell cultures.

• Progress in Medical Physics
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• v.14 no.1
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• pp.34-42
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• 2003

In medical imaging, three-dimensional (3D) display using Virtual Reality Modeling Language (VRML) as a portable file format can give intuitive information more efficiently on the World Wide Web (WWW). The web-based 3D visualization of functional images combined with anatomical images has not studied much in systematic ways. The goal of this study was to achieve a simultaneous observation of 3D anatomic and functional models with planar images on the WWW, providing their locational information in 3D space with a measuring implement using VRML. MRI and ictal-interictal SPECT images were obtained from one epileptic patient. Subtraction ictal SPECT co-registered to MRI (SISCOM) was performed to improve identification of a seizure focus. SISCOM image volumes were held by thresholds above one standard deviation (1-SD) and two standard deviations (2-SD). SISCOM foci and boundaries of gray matter, white matter, and cerebrospinal fluid (CSF) in the MRI volume were segmented and rendered to VRML polygonal surfaces by marching cube algorithm. Line profiles of x and y-axis that represent real lengths on an image were acquired and their maximum lengths were the same as 211.67 mm. The real size vs. the rendered VRML surface size was approximately the ratio of 1 to 605.9. A VRML measuring tool was made and merged with previous VRML surfaces. User interface tools were embedded with Java Script routines to display MRI planar images as cross sections of 3D surface models and to set transparencies of 3D surface models. When transparencies of 3D surface models were properly controlled, a fused display of the brain geometry with 3D distributions of focal activated regions provided intuitively spatial correlations among three 3D surface models. The epileptic seizure focus was in the right temporal lobe of the brain. The real position of the seizure focus could be verified by the VRML measuring tool and the anatomy corresponding to the seizure focus could be confirmed by MRI planar images crossing 3D surface models. The VRML application developed in this study may have several advantages. Firstly, 3D fused display and control of anatomic and functional image were achieved on the m. Secondly, the vector analysis of a 3D surface model was defined by the VRML measuring tool based on the real size. Finally, the anatomy corresponding to the seizure focus was intuitively detected by correlations with MRI images. Our web based visualization of 3-D fusion image and its localization will be a help to online research and education in diagnostic radiology, therapeutic radiology, and surgery applications.

• Applied Microscopy
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• v.35 no.1
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• pp.31-39
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• 2005

Synapses are contact points where one neuron communicates with another. The morphological change of synapses under various physiological or pathological conditions has long been hypothesized to modify their functional properties. 3-dimensional (3-D) reconstruction of synapses with serial ultrathin sections has contributed to the understanding of ultrastructural dimensions and compositions of synapses. The 3-D reconstruction procedures, however, require a great amount of expertise as well as include prohibitively timeconsuming processes. Here, we introduce efficient 3-D reconstruction technique using high-voltage electron microscopy (HVEM). Primarily, we established an optimal section thickness and staining condition to observe synaptic structures in detail under HVEM. The result showed that synaptic profiles were preserved at the section thickness of 250 nm without the overlapping of synaptic ultrastructures. An increase in the reaction time of en bloc staining was most efficient to enhance contrast than the extension of postembedding staining or the addition of uranyl acetate during dehydration. Then, 3-D reconstruction of parallel fiber-Purkinje cell synapses in the rat cerebellum was carried out with serial HVEM images and reconstruction software. The images were aligned and the contours of synapses were outlined on each section. 3-D synapses were finally extracted from the section files by grouping all the synaptic contours. The reconstructed synapse model clearly demonstrated the configuration of pre and postsynaptic components. These results suggest that 3-D reconstruction of synapses using HVEM is much efficient and suitable for massive quantitative studies on synaptic connectivity than conventional TEM approach using numerous ultrathin sections.

• Journal of Life Science
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• v.25 no.6
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• pp.703-708
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• 2015

Hox genes encode a highly conserved family of homeodomain-containing transcription factors controlling vertebrate pattern formation along the anteroposterior body axis during embryogenesis. Retinoic acid (RA) is a key morphogen in embryogenesis and a critical regulator of both adult and embryonic cellular activity. Specifically, RA regulates Hox gene expression in mouse- or human-derived embryonic carcinoma (EC) cells. Histone modification has been reported to play a pivotal role in the process of RA-induced gene expression and cell differentiation. As histone modification is thought to play an essential role in RA-induced Hox gene expression, we examined RA-induced initiation of collinear expression of Hox genes and the corresponding histone modifications in F9 murine embryonic teratocarcinoma (EC) cells. Hox expression patterns and histone modifications were analyzed by semiquantitative RT-PCR, RNA-sequencing, and chromatin immuno-precipitation (ChIP)-PCR analyses. The Hoxc4 gene (D0) was initiated earlier than the Hoxc5 to –c10 genes (D3) upon RA treatment (day 0 [D0], day 1 [D1], and day 3 [D3]). The Hox nonexpressing D0 sample had a strong repressive marker, H3K27me3, than the D1 and D3 samples. In the D1 and D3 samples, reduced enrichment of the H3K27me3 marker was observed in the whole cluster. The active H3K4me3 marker was closely associated with the collinear expression of Hoxc genes. Thus, the Hoxc4 gene (D1) and all Hoxc genes (D3) expressed H3K4me3 upon transcription activation. In conclusion, these data indicated that removing H3K27me3 and acquiring H3K4me3 regulated RA-induced Hoxc gene collinearity in F9 cells.