Browsing by Author "Chio, Chung-Ching"

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Brain tissue oxygen evaluation by wireless near-infrared spectroscopy
(2016-02-01)
Wang, Che-Chuan
;
Kuo, Jinn-Rung
;
Chen, Yu-Chih
;
Chio, Chung-Ching
;
Wang, Jhi-Joung
Background: Monitoring the partial pressure of oxygen in brain tissue (PbtO(2)) is an important tool for traumatic brain injury (TBI) but is invasive and inconvenient for real time monitoring. Near-infrared spectroscopy (NIRS), which can monitor hemoglobin parameters in the brain tissue, has been used widely as a noninvasive tool for assessing cerebral ischemia and hypoxia. Therefore, it may have the potential as a noninvasive tool for estimating the change of PbtO(2). In this study, a novel wireless NIRS system was designed to monitor hemoglobin parameters of rat brains under different impact strengths and was used to estimate the change of PbtO(2) noninvasively in TBI. Materials and methods: The proposed wireless NIRS system and a PbtO(2) monitoring system were used to monitor the oxygenation of rat brains under different impact strengths. Rats were randomly assigned to four different impact strength groups (sham, 1.6 atm, 2.0 atm, and 2.4 atm; n = 6 per group), and the relationships of concentration changes in oxyhemoglobin (HbO(2)), deoxyhemoglobin (HbR), and total hemoglobin (HbT), and PbtO(2) during and after TBI with different impact strengths were investigated. Triphenyltetrazolium chloride (TTC) staining was also used to evaluate infarction volume. Results: Concentration changes in HbO(2), HbR, and HbT dropped immediately after the impact, increased gradually, and then became stable. Changes in PbtO(2) had a similar tendency with the hemoglobin parameters. There was significant correlation between changes in PbtO(2) and HbO(2) (correlation = 0.76) but not with changes in HbR (correlation = 0.06). In triphenyltetrazolium chloride staining, the infarction volume was highly but negatively associated with oxygen-related parameters like PbtO(2) and HbO(2). Conclusions: Changes in HbO(2) under TBI was highly and positively correlated with changes in PbtO(2). By using the relative changes in HbO(2) as a reference parameter, the proposed
Epigenetic Regulation of the miR142-3p/Interleukin-6 Circuit in Glioblastoma
(2013-12-12)
Chiou, Guang-Yuh
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Chien, Chian-Shiu
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Wang, Mong-Lien
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Chen, Ming-Teh
;
Yang, Yi-Ping
Epigenetic regulation plays a critical role in glioblastoma (GBM) tumorigenesis. However, how microRNAs (miRNAs) and cytokines cooperate to regulate GBM tumor progression is still unclear. Here, we show that interleukin-6 (IL-6) inhibits miR142-3p expression and promotes GBM propagation by inducing DNA methyltransferase 1-mediated hypermethylation of the miR142-3p promoter. Interestingly, miR142-3p also suppresses IL-6 secretion by targeting the 3' UTR of IL-6. In addition, miR142-3p also targets the 3' UTR and suppresses the expression of high-mobility group AT-hook 2 (HMGA2), leading to inhibition of Sox2-related sternness. We further show that HMGA2 enhances Sox2 expression by directly binding to the Sox2 promoter. Clinically, GBM patients whose tumors present upregulated IL-6, HMGA2, and Sox2 protein expressions and hypermethylated miR142-3p promoter also demonstrate poor survival outcome. Orthotopic delivery of miR142-3p blocks IL-6/HMGA2/Sox2 expression and suppresses stem-like properties in GBM-xenotransplanted mice. Collectively, we discovered an IL-6/miR142-3p feed-back-loop-dependent regulation of GBM malignancy that could be a potential therapeutic target.
Evaluation of traumatic brain injury by optical technique
(2015-10-14)
Lin, Bor-Shyh
;
Wang, Che-Chuan
;
Chang, Ming-Hsien
;
Chio, Chung-Ching
;
光電系統研究所
Background: Traumatic brain injury (TBI), usually due to brain shaking or impact, affects the normal brain function and may lead to severe disability or even death. However, there is paucity of information regarding changes in the physiologic state of humans or animals after brain shaking. Methods: In this study, near-infrared spectroscopy (NIRS) was used to continuously monitor the concentration change of oxy-hemoglobin (HbO2) and deoxy-hemoglobin (HbR) to understand changes in the physiological state during and after brain shaking. Laser Doppler flowmetry was also used to monitor changes in cerebral blood flow under TBI to supplement the investigation. Triphenyltetrazolium chloride (TTC) staining was used to monitor changes of infarction volume corresponding to different impact strengths. Result: The experimental results indicated that concentration changes of HbO2 and total-hemoglobin (HbT) were significantly related to the impact strength. The infarction volume was also significantly related to the impact strength. Conclusion: Therefore, the non-invasive monitoring of concentration changes in HbO2, HbR, and HbT using NIRS may have a clinical application for the evaluation of TBI.
Extracellular signal-regulated kinase 1/2 is involved in a tamoxifen neuroprotective effect in a lateral fluid percussion injury rat model
(2014-06-01)
Tsai, Yin-Tzu
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Wang, Che-Chuan
;
Leung, Pak-On
;
Lin, Kao-Chang
;
Chio, Chung-Ching
Background: The aim of the present study was to determine whether tamoxifen (TMX) causes attenuation of traumatic brain injury (TBI) induced by fluid percussion injury. Materials and methods: Immediately after the onset of fluid percussion TBI, anesthetized male Sprague-Dawley rats were divided into three major groups and intraperitoneally administered the vehicle solution (1 mL/kg), TMX (1 mg/kg), or TMX (1 mg/kg) plus the extracellular signal-regulated kinase 1/2 antagonist SL327 (30 mg/kg). Another group of rats were used as sham-operated controls. The functional outcomes, such as motor outcomes, were evaluated using an incline plane. The cellular infarction volume was evaluated by triphenyltetrazolium chloride staining. Neuronal loss, apoptosis, and p-ERK1/2 and Bcl2 expression in neuronal cortex cells were evaluated by immunofluorescence methods. All the parameters were assessed on day 4 after injury. Results: Compared with the sham-operated controls, the TBI-induced motor deficits and cerebral infarction after TBI were significantly attenuated by TMX therapy. The TBI-induced neuronal loss and apoptosis were also significantly reduced by TMX therapy. The numbers of Bcl2- and phospho-ERK1/2-positive neuronal cells in the ischemic cortex after TBI were significantly increased by TMX therapy. These TMX effects were significantly blocked by SL327 administration. Conclusions: Our results suggest that intravenous injection of TMX may ameliorate TBI in rats by increasing neuronal p-ERK1/2 expression, which might lead to an increase in neuronal Bcl2 expression and a decrease in neuronal apoptosis and cell infarction volume, and it might represent one mechanism by which functional recovery occurred. TMX may be a promising TBI treatment strategy. (C) 2014 Elsevier Inc. All rights reserved.
Hypoxic-State Estimation of Brain Cells by Using Wireless Near-Infrared Spectroscopy
(2014-01-01)
Kuo, Jinn-Rung
;
Lin, Bor-Shyh
;
Cheng, Chih-Lun
;
Chio, Chung-Ching
;
影像與生醫光電研究所
Near-infrared spectroscopy (NIRS) is a modern measuring technology in neuroscience. It can be used to noninvasively measure the relative concentrations of oxyhemoglobin (OxyHb) and deoxyhemoglobin (DeoHb), which can reflect information related to cerebral blood volume and cerebral oxygen saturation. Therefore, it has the potential for noninvasive monitoring of cerebral ischemia. However, there is still a lack of reliable physiological information on the relationship between the concentrations of OxyHb and DeoHb in cerebral blood and the exact hypoxic state of brain cells under cerebral ischemia. In this study, we describe a wireless multichannel NIRS system, which we designed to noninvasively monitor the relative concentrations of OxyHb and DeoHb in bilateral cerebral blood before, during, and after middle cerebral artery occlusion. By comparing the results with the lactate/pyruvate ratio measured by microdialysis, we investigated the correlation between the relative concentrations of OxyHb and DeoHb in cerebral blood and the hypoxic state of brain cells. The results showed that the relationship between the concentration changes of DeoHb in cerebral blood and the hypoxic state of brain cells was significant. Therefore, by monitoring the changes in concentrations of DeoHb, the wireless NIRS can be used to estimate the hypoxic state of brain cells indirectly.
Resuscitation from experimental traumatic brain injury by magnolol therapy
(2013-10-01)
Wang, Che-Chuan
;
Lin, Kao-Chang
;
Lin, Bor-Shyh
;
Chio, Chung-Ching
;
Kuo, Jinn-Rung
Background: The purpose of the present study was to determine whether magnolol, a free radical scavenger, mitigates the deleterious effects of traumatic brain injury (TBI). Material and methods: Traumatic brain injuries were induced in anesthetized male Sprague-Dawley rats using fluid percussion, and the rats were divided into groups treated with magnolol (2 mg/kg, intravenously) or vehicle. A group of rats that did not undergo TBI induction was also studied as controls. Biomarkers of TBI, including glycerol and 2,3-dihydroxybenzoic acid, were evaluated by microdialysis. Infraction volume, extent of neuronal apoptosis, and antiapoptosis factor transforming growth factor beta 1 (TGF-beta 1) were also measured. Functional outcomes were assessed by motor assays. Results: Compared with the rats without TBI, the animals with TBI exhibited higher hippocampal glycerol and 2,3-dihydroxybenzoic acid. Relative to the vehicle-treated group, the magnolol-treated group showed decreased hippocampal levels of glycerol and hydroxyl radical levels. The magnolol-treated rats also exhibited decreased cerebral infarction volume and neuronal apoptosis and increased antiapoptosis-associated factor TGF-beta 1 expression. These effects were translated into improved motor function post TBI. Conclusions: Our results suggest that intravenous magnolol injection mitigates the deleterious effects of TBI in rats based on its potent free radical scavenging capability, and the mechanism of anti-neuronal apoptosis is partly due to an increase in TGF-beta 1 expression in the ischemic cortex. (C) 2013 Elsevier Inc. All rights reserved.
The neuronal protective effects of local brain cooling at the craniectomy site after lateral fluid percussion injury in a rat model
(2013-12-01)
Wang, Che-Chuan
;
Chen, Yuan-Shen
;
Lin, Bor-Shyh
;
Chio, Chung-Ching
;
Hu, Chiao-Ya
Background: The aim of the present study is to investigate whether local brain cooling at the craniectomy site causes attenuation of traumatic brain injury (TBI) induced by fluid percussion injury (FPI). Methods: Anesthetized male SpragueeDawley rats were divided into two major treatment groups. Immediately after the onset of fluid percussion TBI, a craniectomy window of 6 x 8 mm was made at the right parietal, and a cold water bag (0 x C-1 x degrees C or 5 x C-6 degrees C) was applied locally for 30 min. Additional groups of rats were used as craniectomy and craniectomy FPI controls. Physiological parameters, such as brain and colonic temperature, mean arterial pressure, and heart rate, were monitored during FPI. Functional motor outcomes were evaluated using the inclined plane test (maximal grasp angle). Cellular infarction volume was calculated using triphenyltetrazolium chloride staining. Apoptosis and neuronal markerepositive cells in the cortex were measured by immunofluorescence staining. All functional and morphologic parameters were assessed 72 h after injury. Results: Compared with the craniectomy + FPI control groups, the groups treated with 5 degrees C-6 degrees C local cold water therapy showed significant attenuation of the FPI-induced motor deficits, weight loss, and cerebral infarction but no effect on colonic temperature. The FPI-induced apoptosis and neuronal loss were also significantly reduced by local cooling. Conclusions: Our results suggest that local cooling with 5 degrees C-6 degrees C cold water therapy may ameliorate TBI in rats by reducing infarction volume, neuronal cell loss, and apoptosis, resulting in improved functional outcome. We propose that the use of local cooling at the craniectomy site after FPI might have clinical benefits in the future. (C) 2013 Elsevier Inc. All rights reserved.
Wireless near-infrared spectroscopy system for determining brain hemoglobin levels in laboratory animals
(2013-04-15)
Kuo, Jinn-Rung
;
Chang, Ming-Hsien
;
Wang, Che-Chuan
;
Chio, Chung-Ching
;
Wang, Jhi-Joung
Traumatic brain injury (TBI) is usually caused by brain shaking or impact. It can affect normal brain function and may even lead to disability or death. However, there are very few studies on the associated physiologic changes in humans or animals. In this study, a non-invasive, wireless multi-channel near-infrared spectroscopy (NIRS) was developed to continuously monitor the concentration change of oxyhemoglobin (HbO(2)), deoxyhemoglobin (HbR), and total hemoglobin (HbT) to elucidate changes in the physiological state of the brain during and after different strength impaction. The triphenyltetrazolium chloride (TTC) staining was also used to monitor changes of infarction volume after different strength impaction. The results indicated that the concentration changes of HbO(2) and HbT, and the changes of infarction volumes were significantly related to the impact strength. In conclusion, the status of TBI can be clinically evaluated by detecting HbO(2) and HbT changes. The system proposed here is stable, accurate, non-invasive, and mostly important wireless which can easily be used for TBI study. (C) 2013 Elsevier B.V. All rights reserved.