• Biomolecules & Therapeutics
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• v.25 no.2
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• pp.149-157
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• 2017

The interleukin-1 receptor antagonist (IL-1RA) is a potential stroke treatment candidate. Intranasal delivery is a novel method thereby a therapeutic protein can be penetrated into the brain parenchyma by bypassing the blood-brain barrier. Thus, this study tested whether intranasal IL-1RA can provide neuroprotection and brain penetration in transient cerebral ischemia. In male Sprague-Dawley rats, focal cerebral ischemia was induced by middle cerebral artery occlusion (MCAO) for 1 h. The rats simultaneously received 50 mg/kg human IL-1RA through the intranasal (IN group) or intraperitoneal route (IP group). The other rats were given 0.5 mL/kg normal saline (EC group). Neurobehavioral function, infarct size, and the concentration of the administered human IL-1RA in the brain tissue were assessed. In addition, the cellular distribution of intranasal IL-1RA in the brain and its effect on proinflammatory cytokines expression were evaluated. Intranasal IL-1RA improved neurological deficit and reduced infarct size until 7 days after MCAO (p<0.05). The concentrations of the human IL-1RA in the brain tissue 24 h after MCAO were significantly greater in the IN group than in the IP group (p<0.05). The human IL-1RA was confirmed to be co-localized with neuron and microglia. Furthermore, the IN group had lower expression of $interleukin-1{\beta}$ and tumor necrosis $factor-{\alpha}$ at 6 h after MCAO than the EC group (p<0.05). These results suggest that intranasal IL-1RA can reach the brain parenchyma more efficiently and provide superior neuroprotection in the transient focal cerebral ischemia.

• Proceedings of the Korean Environmental Health Society Conference
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• 2005.12a
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• pp.87-94
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• 2005

Results from previous studies revealed that metal level in the body is related to certain types of diseases. For example. serum copper level with chronic heart failure, iron and transferrin in the blood serum with acute cerebral vascular diseases, Zn in the CNS, lead with neurotoxicity, hypertension, genetic damage, arsenic with cancer skin lesion, Al with neurobehavioral function (cognitive impairment and memory disorder), and etc. The rate of stroke has increased in recent years and several metals were found to be responsible for causing stroke. This study compared several blood metal concentrations between stroke and non-stroke patients. Patients with stroke (116 samples) and non-stroke (111 samples including lowback pain and others) participated in this study. Total of 227 blood samples were collected and participants completed questionnaires regarding age, gender, occupation, residence, alcohol, smoking, and etc. To be qualified into the stroke group, patients have never experienced stroke previously. Subjects only included ischemic stroke and intracerebral hemorrhage patients diagnosed by brain CT and brain MRI. Patients with high risk of metal exposure such as herbal intake and job related exposure were excluded. 10ml of blood samples were analyzed by ICP-MS method at the Center of Nature and Science at Sangji University. Metal geometric mean (SD) concentrations in blood of study subjects showed higher values, 2.64-36.12%, than WHO reference values in Mn, Ni, Hg, Se, and As. Metal concentration in blood of stroke patients non-adjusted for potential confounders was higher except for Hg and also higher except for Ni in adjusted for potential confounders. Co was significantly higher in stroke patients (p=0.002) than non-stroke patients adjusted for potential confounders. Regression coefficient values of stroke patients was 0.17-8.25 in each metals. Odd ratio of stroke patients had 0.96 (Ni)-2.68 (Co) compared to non-stroke cases. This result means that Co increase of 1 raises the risk ratio of stroke by 2.86 times. Based on the results, metal concentration in blood seems to affect incidence of stroke.

• Journal of Life Science
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• v.29 no.6
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• pp.747-753
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• 2019

Cognitive decline is characterized by reduced long-/short-term memory and attention span, and increased depression and anxiety. Such decline is associated with various degenerative brain disorders, especially Alzheimer's disease (AD) and Parkinson's disease (PD). The increases in elderly populations suffering from cognitive decline create social problems and impose economic burdens, and also pose safety threats; all of these problems have been extensively researched over the past several decades. Possible causes of cognitive decline include metabolic and hormone imbalance, infection, medication abuse, and neuronal changes associated with aging. However, no treatment for cognitive decline is available. In neurodegenerative diseases, changes in the gut microbiota and gut metabolites can alter molecular expression and neurobehavioral symptoms. Changes in the gut microbiota affect memory loss in AD via the downregulation of NMDA receptor expression and increased glutamate levels. Furthermore, the use of probiotics resulted in neurological improvement in an AD model. PD and gut microbiota dysbiosis are linked directly. This interrelationship affected the development of constipation, a secondary symptom in PD. In a PD model, the administration of probiotics prevented neuron death by increasing butyrate levels. Dysfunction of the blood-brain barrier (BBB) has been identified in AD and PD. Increased BBB permeability is also associated with gut microbiota dysbiosis, which led to the destruction of microtubules via systemic inflammation. Notably, metabolites of the gut microbiota may trigger either the development or attenuation of neurodegenerative disease. Here, we discuss the correlation between cognitive decline and the gut microbiota.