The 2022 Annual Report on Toxicology Surveillance and Severe Poisoning Cases at Emergency Departments in Korea

Purpose@#This study investigated the actual incidence of acute poisoning in Korea on a nationwide scale, with the aim of laying the groundwork for future initiatives in prevention, strategic antidote distribution, and the development of effective emergency treatment for acute poisoning. @*Methods@#The study analyzed data from 3,038 patients who presented to emergency departments with poisoning-related conditions from June 1, 2022 to December 31, 2022 at 10 sites in nine cities across the country. We extracted data on general characteristics of the poisoning cases, including demographic characteristics (age and gender), place of exposure, reason for poisoning, route of exposure, and the substance involved in the poisoning incident. Age-related patterns in reasons for poisoning, medical outcomes, frequent and primary poisoning substances, and deaths were also analyzed. @*Results@#The population analyzed in our study was predominantly female, with women constituting 54.74% of all cases. Among infants and children, non-intentional poisoning due to general accidents was the most common cause, accounting for 71.43% of cases. Conversely, suicidal poisoning was more prevalent among teenagers and adults over 20. Fifty-two patients died during the study period, with males comprising approximately two-thirds (67.31%) of these fatalities. Pesticides were the most common poisoning substance among those who died, accounting for 55.77% of such cases. Notably, a significant majority of the victims were elderly individuals aged 60 and above. @*Conclusion@#This study holds substantial significance, since it represents the first comprehensive investigation and analysis of the symptoms, treatment, and causes of death due to poisoning in Korea on a national scale. By substantially expanding the range and types of poisonous substances examined, we were able to more precisely identify the characteristics and clinical patterns of poisoning cases nationwide.

Factors affecting incorrect interpretation of abdominal computed tomography in non-traumatic patients by novice emergency physicians

Objective@#Accurate interpretation of computed tomography (CT) scans is critical for patient care in the emergency department. We aimed to identify factors associated with an incorrect interpretation of abdominal CT by novice emergency residents and to analyze the characteristics of incorrectly interpreted scans. @*Methods@#This retrospective analysis of a prospective observational cohort was conducted at three urban emergency departments. Discrepancies between the interpretations by postgraduate year-1 (PGY-1) emergency residents and the final radiologists’ reports were assessed by independent adjudicators. Potential factors associated with incorrect interpretation included patient age, sex, time of interpretation, and organ category. Adjusted odds ratios (aORs) for incorrect interpretation were calculated using multivariable logistic regression analysis. @*Results@#Among 1,628 eligible cases, 270 (16.6%) were incorrect. The urinary system was the most correctly interpreted organ system (95.8%, 365/381), while the biliary tract was the most incorrectly interpreted (28.4%, 48/169). Normal CT images showed high false-positive rates of incorrect interpretation (28.2%, 96/340). Organ category was found to be a major determinant of incorrect interpretation. Using the urinary system as a reference, the aOR for incorrect interpretation of biliary tract disease was 9.20 (95% confidence interval, 5.0–16.90) and the aOR for incorrectly interpreting normal CT images was 8.47 (95% confidence interval, 4.85–14.78). @*Conclusion@#Biliary tract disease is a major factor associated with incorrect preliminary interpretations of abdominal CT scans by PGY-1 emergency residents. PGY-1 residents also showed high false-positive interpretation rates for normal CT images. Emergency residents’ training should focus on these two areas to improve abdominal CT interpretation accuracy.

Factors affecting incorrect interpretation of abdominal computed tomography in non-traumatic patients by novice emergency physicians

Objective@#Accurate interpretation of computed tomography (CT) scans is critical for patient care in the emergency department. We aimed to identify factors associated with an incorrect interpretation of abdominal CT by novice emergency residents and to analyze the characteristics of incorrectly interpreted scans. @*Methods@#This retrospective analysis of a prospective observational cohort was conducted at three urban emergency departments. Discrepancies between the interpretations by postgraduate year-1 (PGY-1) emergency residents and the final radiologists’ reports were assessed by independent adjudicators. Potential factors associated with incorrect interpretation included patient age, sex, time of interpretation, and organ category. Adjusted odds ratios (aORs) for incorrect interpretation were calculated using multivariable logistic regression analysis. @*Results@#Among 1,628 eligible cases, 270 (16.6%) were incorrect. The urinary system was the most correctly interpreted organ system (95.8%, 365/381), while the biliary tract was the most incorrectly interpreted (28.4%, 48/169). Normal CT images showed high false-positive rates of incorrect interpretation (28.2%, 96/340). Organ category was found to be a major determinant of incorrect interpretation. Using the urinary system as a reference, the aOR for incorrect interpretation of biliary tract disease was 9.20 (95% confidence interval, 5.0–16.90) and the aOR for incorrectly interpreting normal CT images was 8.47 (95% confidence interval, 4.85–14.78). @*Conclusion@#Biliary tract disease is a major factor associated with incorrect preliminary interpretations of abdominal CT scans by PGY-1 emergency residents. PGY-1 residents also showed high false-positive interpretation rates for normal CT images. Emergency residents’ training should focus on these two areas to improve abdominal CT interpretation accuracy.

Association between compliance with Surviving Sepsis Campaign guidelines and outcomes among sepsis and septic shock patient in accordance with Sepsis-3 definitions

Objective@#The Surviving Sepsis Campaign (SSC) guidelines have been associated with reduced mortality in sepsis patients. On the other hand, previous studies were performed using the Sepsis-2 definitions and past guidelines. This study assessed the association between compliance with the 2016 SSC guidelines and the outcomes of patients with sepsis and septic shock in accordance with the latest Sepsis-3 definitions. @*Methods@#Three hundred and fifteen patients with sepsis and septic shock were enrolled in this study. The patients were stratified according to their compliance with the SSC guidelines bundle. The characteristics and outcomes of the compliance and non-compliance groups were compared. In the overall patients, the risk factors for all-cause mortality were assessed using Cox proportional hazards models. @*Results@#Among the patients, 172 and 143 patients were in the compliance group and non-compliance group, respectively. The baseline characteristics and disease severity were similar in the two groups. The all-cause mortality rates were 27.3% and 38.5% in the compliance group and non-compliance group, respectively (P=0.035). The all-cause mortality was significantly lower in the compliance group than in the non-compliance group (log-rank test, P=0.025). The risk factors for the all-cause mortality were age (adjusted hazard ratio [aHR], 1.025; 95% confidence interval [CI], 1.008-1.042; P=0.004), septic shock (aHR, 3.14; 95% CI, 1.98-4.98; P<0.001), and lactate levels (aHR, 1.08; 95% CI, 1.03-1.14; P=0.002). The overall compliance with the guidelines protected against all-cause mortality (aHR, 0.66; 95% CI, 0.45-0.98; P=0.040). @*Conclusion@#Compliance with the SSC guidelines bundle was associated with a lower all-cause mortality among patients with sepsis and septic shock

Discovery and Functional Prediction of Long Non-Coding RNAs Common to Ischemic Stroke and Myocardial Infarction

Objective@#Ischemic stroke and myocardial infarction are 2 of the leading causes of mortality. Both conditions are caused by arterial occlusion, resulting in ischemic necrosis of the cells in the cortex and heart. Long non-coding RNAs (lncRNAs) are a group of non-coding RNAs longer than 200 nucleotides without protein-coding potential. Thousands of lncRNAs have been identified but their involvement in ischemic stroke and myocardial infarction has not been studied extensively. Therefore, this study aimed to identify the role of lncRNAs, particularly those that are commonly altered in these two ischemic injuries. @*Methods@#We combined diverse RNA sequencing data obtained from public databases and performed extensive bioinformatics analyses to determine reliable lncRNAs commonly identified from these datasets. Using sequence analysis, we also detected the lncRNAs that may act as microRNA (miRNA) regulators. @*Results@#We found several altered lncRNAs that were common in ischemic stroke and myocardial infarction models. Some of these lncRNAs, including zinc finger NFX1-type containing 1 antisense RNA 1 and small nucleolar RNA host gene 1, were previously reported to be involved in the pathogenesis of each of these models. Interestingly, several lncRNAs had binding sites for miRNAs that were previously reported to be involved in the hypoxic response, suggesting the possible role of these lncRNAs as regulators in ischemic responses. @*Conclusion@#The lncRNAs identified in this study will be useful in determining the regulatory networks in ischemic stroke and myocardial infarction and in identifying potential specific markers for each of these ischemic diseases.

Intermittent Fasting: a Promising Approach for Preventing Vascular Dementia

Vascular dementia is the most common neuropsychiatric syndrome and is characterized by synaptic dysfunction, neuroinflammation, and cognitive dysfunction. Vascular dementia is associated with various environmental, genetic, and lifestyle risk factors. Recent research has focused on the association between vascular dementia and dietary patterns, suggesting that dietary regulation leads to better control of energy metabolism, improvements in brain insulin resistance, and the suppression of neuroinflammation. Intermittent fasting is a calorie-restriction method known to be more effective in promoting fat loss and regulating the impairment of glucose metabolism as compared with other dietary restriction regimens. Herein, the authors review the effects of intermittent fasting with regard to vascular dementia based on recent evidence and propose that intermittent fasting could be a therapeutic approach for ameliorating vascular dementia pathology and preventing its onset.

Carpinus turczaninowii extract modulates arterial inflammatory response: a potential therapeutic use for atherosclerosis

BACKGROUND/OBJECTIVES: Vascular inflammation is an important feature in the atherosclerotic process. Recent studies report that leaves and branches of Carpinus turczaninowii (C. turczaninowii) have antioxidant capacity and exert anti-inflammatory effects. However, no study has reported the regulatory effect of C. turczaninowii extract on the arterial inflammatory response. This study therefore investigated modulation of the arterial inflammatory response after exposure to C. turczaninowii extract, using human aortic vascular smooth muscle cells (HAoSMCs). MATERIALS/METHODS: Scavenging activity of free radicals, total phenolic content (TPC), cell viability, mRNA expressions, and secreted levels of cytokines were measured in LPS-stimulated (10 ng/mL) HAoSMCs treated with the C. turczaninowii extract. RESULTS: C. turczaninowii extract contains high amounts of TPC (225.6 ± 21.0 mg of gallic acid equivalents/g of the extract), as well as exerts time-and dose-dependent increases in strongly scavenged free radicals (average 14.8 ± 1.97 µg/mL IC50 at 40 min). Cell viabilities after exposure to the extracts (1 and 10 µg/mL) were similar to the viability of non-treated cells. Cytokine mRNA expressions were significantly suppressed by the extracts (1 and 10 µg/mL) at 6 hours (h) after exposure. Interleukin-6 secretion was dose-dependently suppressed 2 h after incubation with the extract, at 1–10 µg/mL in non-stimulated cells, and at 5 and 10 µg/mL in LPS-stimulated cells. Similar patterns were also observed at 24 h after incubation with the extract (at 1–10 µg/mL in non-stimulated cells, and at 10 µg/mL in the LPS-stimulated cells). Soluble intracellular vascular adhesion molecules (sICAM-1) secreted from non-stimulated cells and LPS-stimulated cells were similarly suppressed in a dose-dependent manner after 24 h exposure to the extracts, but not after 2 h. In addition, sICAM-1 concentration after 24 h treatment was positively related to IL-6 levels after 2 h and 24 h exposure (r = 0.418, P = 0.003, and r = 0.524, P < 0.001, respectively). CONCLUSIONS: This study demonstrates that C. turczaninowii modulates the arterial inflammatory response, and indicates the potential to be applied as a therapeutic use for atherosclerosis.

Perspectives in Lipocalin-2: Emerging Biomarker for Medical Diagnosis and Prognosis for Alzheimer's Disease

Lipocalin-2 (LCN2), a secreted glycoprotein belonging to the lipocalin superfamily was reported to participate in various biological processes including cell migration, cell survival, inflammatory responses, and insulin sensitivity. LCN2 is expressed in the multiple tissues such as kidney, liver, uterus, and bone marrow. The receptors for LCN2 were additionally found in microglia, astrocytes, epithelial cells, and neurons, but the role of LCN2 in the central nervous system (CNS) has not been fully understood yet. Recently, in vitro, in vivo, and clinical studies reported the association between LCN2 and the risk of Alzheimer's disease (AD). Here, we reviewed the significant evidences showing that LCN2 contributes to the onset and progression of AD. It may suggest that the manipulation of LCN2 in the CNS would be a crucial target for regulation of the pathogenesis and risk of AD.

The Current Status of Death Certificate Written in an Academic Hospital and the Degree of Agreement in Interpretation: A Single Center Observational Study

PURPOSE: This study aims to review the appropriateness of the issued death certificates and autopsy reports and to evaluate the improvement points of these documents in accordance with the guidelines of the Korean Medical Association and the National Statistical Office. Moreover, this study also examines why the guideline is necessary for the credibility of these documents. METHODS: The death certificates and autopsy reports written by a training hospital were analyzed for a 12-month period, between December 2014 and November 2015. The reference to analysis was the “guidelines to medical certificate 2015” written by the Korean Medical Association, “World Health Organization (WHO) death certificate principle”, and “guideline leaflet,” as provided by the National Statistical Office. Two researchers analyzed the documents that were against the guidelines, and suggested improvement points. The analyzed variables were age, sex, issued date, direct cause of death, manner of death, location of death, and types of accident. The primary goal was to see the rate of issued documents written correctly according to the guidelines and to suggest possible improvement points. The secondary goal was to analyze the reason for accordance and discordance between researchers. RESULTS: There were a total of 603 death certificates and autopsy reports issued during the research period; 562 (93.2%) and 41 (6.8%) cases, respectively. As for the manner of death, 521 cases were “death from disease,” 64 were “external causes,” and 18 were “others or unknown” (86.4%, 10.6%, and 3.0%, respectively). As for the issued department, internal medicine and emergency medicine issued 301 (49.9%) and 126 (20.9%) documents, respectively. Of these, 139 (23.1%) cases were regarded to be in accordance with the guidelines, while 304 (50.4%) were considered to be discordant cases. Among the discordant cases, there were 177 (29.4%) cases that were the mode of death directly written to cause of death. As for the records of “period of occurrence to death” were recorded only 70 (11.7%) cases (including “unknown” 65 cases) and the others were blank. The Kappa number of analysis regarding the evaluation correspondence of the two researchers was 0.44 (95% confidence interval, 0.38 to 0.51). CONCLUSION: The most frequent error was ‘the condition of death to direct cause of death’ with the ratio of 29.4%. This may have been because the rate of concordance between the researchers based on the guidelines was not high enough. There is a need to provide specific guidelines for each case, and also promote and educate regarding significant errors.

The Novel Implication of Androgen in Diabetes-induced Alzheimer's Disease

Alzheimer's disease (AD) is characterized by the accumulation of amyloid beta (Aβ) and the hyperphosphorylation of tau protein in the brain, leading to the increase in inflammation and neuronal loss. Recently, evidences to support the association between type 2 diabetes mellitus (T2DM) and AD have markedly increased by clinical researches and experimental studies. Reduced insulin action and impaired glucose metabolism in the brain leads to diabetes induced AD. Androgen, a male sex hormone, was known to regulate inflammatory response, Aβ deposition in AD, insulin signaling, and synaptic plasticity in brain. Clinical studies demonstrated that androgen deficiency results in the increased risk of AD and its severe progression in male subjects. We reviewed the significant evidences to support that low testosterone levels are linked to diabetes-induced AD based on previous studies. Thus, we highlight the therapeutic potential of androgen in diabetes induced AD.

Agmatine Ameliorates High Glucose-Induced Neuronal Cell Senescence by Regulating the p21 and p53 Signaling

Neuronal senescence caused by diabetic neuropathy is considered a common complication of diabetes mellitus. Neuronal senescence leads to the secretion of pro-inflammatory cytokines, the production of reactive oxygen species, and the alteration of cellular homeostasis. Agmatine, which is biosynthesized by arginine decarboxylation, has been reported in previous in vitro to exert a protective effect against various stresses. In present study, agmatine attenuated the cell death and the expression of pro-inflammatory cytokines such as IL-6, TNF-alpha and CCL2 in high glucose in vitro conditions. Moreover, the senescence associated-beta-galatosidase's activity in high glucose exposed neuronal cells was reduced by agmatine. Increased p21 and reduced p53 in high glucose conditioned cells were changed by agmatine. Ultimately, agmatine inhibits the neuronal cell senescence through the activation of p53 and the inhibition of p21. Here, we propose that agmatine may ameliorate neuronal cell senescence in hyperglycemia.

Involvement of miR-Let7A in inflammatory response and cell survival/apoptosis regulated by resveratrol in THP-1 macrophage

BACKGROUND/OBJECTIVES: Resveratrol, a natural polyphenol, has multiple functions in cellular responses including apoptosis, survival, and differentiation. It also participates in the regulation of inflammatory response and oxidative stress. MicroRNA-Let-7A (miR-Let7A), known as a tumor suppressor miRNA, was recently reported to play a crucial role in both inflammation and apoptosis. Therefore, we examined involvement of miR-Let7A in the modulation of inflammation and cell survival/apoptosis regulated by resveratrol. MATERIALS/METHODS: mRNA expression of pro-/anti-inflammatory cytokines and sirtuin 1 (SIRT1), and protein expression of apoptosis signal-regulating kinase 1 (ASK1), p-ASK1, and caspase-3 and cleaved caspase-3 were measured, and cell viability and Hoechst/PI staining for apoptosis were observed in Lipopolysaccharide (LPS)-stimulated human THP-1 macrophages with the treatment of resveratrol and/or miR-Let7A overexpression. RESULTS: Pre-treatment with resveratrol (25-200 µM) resulted in significant recovery of the reduced cell viabilities under LPS-induced inflammatory condition and in markedly increased expression of miR-Let7A in non-stimulated or LPS-stimulated cells. Increased mRNA levels of tumor necrosis factor-α and interleukin (IL)-6 induced by LPS were significantly attenuated, and decreased levels of IL-10 and brain-derived neurotrophic factor were significantly restored by resveratrol and miR-Let7A overexpression, respectively, or in combination. Decreased expression of IL-4 mRNA by LPS stimulation was also significantly increased by miR-Let7A overexpression co-treated with resveratrol. In addition, decreased SIRT1 mRNA levels, and increased p-ASK1 levels and PI-positive cells by LPS stimulation were significantly restored by resveratrol and miR-Let7A overexpression, respectively, or in combination. CONCLUSIONS: miR-Let7A may be involved in the inflammatory response and cell survival/apoptosis modulated by resveratrol in human THP-1 macrophages.

The association between PGC-1a and Alzheimer's disease / 대한해부학회지

Alzheimer's disease (AD) is a neurodegenerative disorder and its reported pathophysiological features in the brain include the deposition of amyloid beta peptide, chronic inflammation, and cognitive impairment. The incidence of AD is increasing worldwide and researchers have studied various aspects of AD pathophysiology in order to improve our understanding of the disease. Thus far, the onset mechanisms and means of preventing AD are completely unknown. Peroxisome proliferator-activated receptor-γ coactivator (PGC-1α) is a protein related to various cellular mechanisms that lead to the alteration of downstream gene regulation. It has been reported that PGC-1α could protect cells against oxidative stress and reduce mitochondrial dysfunction. Moreover, it has been demonstrated to have a regulatory role in inflammatory signaling and insulin sensitivity related to cognitive function. Here, we present further evidence of the involvement of PGC-1α in AD pathogenesis. Clarifying the relationship between PGC-1α and AD pathology might highlight PGC-1α as a possible target for therapeutic intervention in AD.

Suppression of MicroRNA let-7a Expression by Agmatine Regulates Neural Stem Cell Differentiation

PURPOSE: Neural stem cells (NSCs) effectively reverse some severe central nervous system (CNS) disorders, due to their ability to differentiate into neurons. Agmatine, a biogenic amine, has cellular protective effects and contributes to cellular proliferation and differentiation in the CNS. Recent studies have elucidated the function of microRNA let-7a (let-7a) as a regulator of cell differentiation with roles in regulating genes associated with CNS neurogenesis. MATERIALS AND METHODS: This study aimed to investigate whether agmatine modulates the expression of crucial regulators of NSC differentiation including DCX, TLX, c-Myc, and ERK by controlling let-7a expression. RESULTS: Our data suggest that high levels of let-7a promoted the expression of TLX and c-Myc, as well as repressed DCX and ERK expression. In addition, agmatine attenuated expression of TLX and increased expression of ERK by negatively regulating let-7a. CONCLUSION: Our study therefore enhances the present understanding of the therapeutic potential of NSCs in CNS disorders.

Suppression of MicroRNA let-7a Expression by Agmatine Regulates Neural Stem Cell Differentiation

PURPOSE: Neural stem cells (NSCs) effectively reverse some severe central nervous system (CNS) disorders, due to their ability to differentiate into neurons. Agmatine, a biogenic amine, has cellular protective effects and contributes to cellular proliferation and differentiation in the CNS. Recent studies have elucidated the function of microRNA let-7a (let-7a) as a regulator of cell differentiation with roles in regulating genes associated with CNS neurogenesis. MATERIALS AND METHODS: This study aimed to investigate whether agmatine modulates the expression of crucial regulators of NSC differentiation including DCX, TLX, c-Myc, and ERK by controlling let-7a expression. RESULTS: Our data suggest that high levels of let-7a promoted the expression of TLX and c-Myc, as well as repressed DCX and ERK expression. In addition, agmatine attenuated expression of TLX and increased expression of ERK by negatively regulating let-7a. CONCLUSION: Our study therefore enhances the present understanding of the therapeutic potential of NSCs in CNS disorders.

Current State of Abdominal Computed Tomography Performed in Emergency Department of a Tertiary University Hospital and Development of a Preliminary Interpretation Checklist

PURPOSE: Abdominal computed tomography (CT) is a widely recognized method to diagnose patients with acute abdominal pain in the emergency departments (EDs). We aimed to investigate the current state and interpretations of abdominal CT performed in the ED of a tertiary university hospital. METHODS: This was a retrospective study based on an abdominal CT database and medical records of patients over 15 years of age, who had visited our ED between January 1 and December 31, 2013. The data collected included CT types, final interpretations, characteristics of the patients, and location of pain at the time of CT. RESULTS: A total of 1,978 abdominal CTs were performed among 1,923 patients during the research period. The most frequent organs involved in the major diagnosis were those in the urinary system, followed by the appendix, liver, large intestine, and gallbladder. The most frequently interpreted diagnoses in these organs were in the order of urinary stone, appendicitis, liver cirrhosis, infectious colitis, and acute cholecystitis. The most frequent location of pain was the right lower quadrant (429 cases, 21.7%), and the most frequently performed CT types were contrast-enhanced abdominal and pelvic CT (1,260 cases, 63.7%). CONCLUSION: Various interpretations were derived based on the abdominal CTs, ranging from critical to mild diseases and from common to rare diseases. Based on this study, we have developed a preliminary interpretation checklist for abdominal CTs.

Galanin's implications for post-stroke improvement / 대한해부학회지

Stroke leads to a variety of pathophysiological conditions such as ischemic infarct, cerebral inflammation, neuronal damage, cognitive decline, and depression. Many endeavors have been tried to find the therapeutic solutions to attenuate severe neuropathogenesis after stroke. Several studies have reported that a decrease in the neuropeptide regulator ‘galanin’ is associated with neuronal loss, learning and memory dysfunctions, and depression following a stroke. The present review summarized recent evidences on the function and the therapeutic potential of galanin in post-ischemic stroke to provide a further understanding of galanin's role. Hence, we suggest that galanin needs to be considered as a therapeutic factor in the alleviation of post-stroke pathologies.

miR-Let7A Modulates Autophagy Induction in LPS-Activated Microglia

Microglia regulate the secretion of various immunomediators in central nervous system diseases. Microglial autophagy is the crucial process for cell's survival and cytokine productions. Recent studies have reported that several microRNAs are involved in the autophagy system. miR-Let7A is such a microRNA that plays a role in various inflammation responses, and is magnified as a key modulator particularly in the autophagy system. In present study, we investigated whether miR-Let7A is involved in autophagy in activating microglia. Overexpression of miR-Let7A in LPS-stimulated BV2 microglial cells promoted the induction of the autophagy related factors such as LC3II, Beclin1, and ATG3. Our results suggest a potential role of miR-Let7A in the autophagy process of microglia during CNS inflammation.

Dehydroascorbic Acid Attenuates Ischemic Brain Edema and Neurotoxicity in Cerebral Ischemia: An in vivo Study

Ischemic stroke results in the diverse phathophysiologies including blood brain barrier (BBB) disruption, brain edema, neuronal cell death, and synaptic loss in brain. Vitamin C has known as the potent anti-oxidant having multiple functions in various organs, as well as in brain. Dehydroascorbic acid (DHA) as the oxidized form of ascorbic acid (AA) acts as a cellular protector against oxidative stress and easily enters into the brain compared to AA. To determine the role of DHA on edema formation, neuronal cell death, and synaptic dysfunction following cerebral ischemia, we investigated the infarct size of ischemic brain tissue and measured the expression of aquaporin 1 (AQP-1) as the water channel protein. We also examined the expression of claudin 5 for confirming the BBB breakdown, and the expression of bcl 2 associated X protein (Bax), caspase-3, inducible nitric oxide synthase (iNOS) for checking the effect of DHA on the neurotoxicity. Finally, we examined postsynaptic density protein-95 (PSD-95) expression to confirm the effect of DHA on synaptic dysfunction following ischemic stroke. Based on our findings, we propose that DHA might alleviate the pathogenesis of ischemic brain injury by attenuating edema, neuronal loss, and by improving synaptic connection.

Agmatine Improves Cognitive Dysfunction and Prevents Cell Death in a Streptozotocin-Induced Alzheimer Rat Model

PURPOSE: Alzheimer's disease (AD) results in memory impairment and neuronal cell death in the brain. Previous studies demonstrated that intracerebroventricular administration of streptozotocin (STZ) induces pathological and behavioral alterations similar to those observed in AD. Agmatine (Agm) has been shown to exert neuroprotective effects in central nervous system disorders. In this study, we investigated whether Agm treatment could attenuate apoptosis and improve cognitive decline in a STZ-induced Alzheimer rat model. MATERIALS AND METHODS: We studied the effect of Agm on AD pathology using a STZ-induced Alzheimer rat model. For each experiment, rats were given anesthesia (chloral hydrate 300 mg/kg, ip), followed by a single injection of STZ (1.5 mg/kg) bilaterally into each lateral ventricle (5 microL/ventricle). Rats were injected with Agm (100 mg/kg) daily up to two weeks from the surgery day. RESULTS: Agm suppressed the accumulation of amyloid beta and enhanced insulin signal transduction in STZ-induced Alzheimer rats [experimetal control (EC) group]. Upon evaluation of cognitive function by Morris water maze testing, significant improvement of learning and memory dysfunction in the STZ-Agm group was observed compared with the EC group. Western blot results revealed significant attenuation of the protein expressions of cleaved caspase-3 and Bax, as well as increases in the protein expressions of Bcl2, PI3K, Nrf2, and gamma-glutamyl cysteine synthetase, in the STZ-Agm group. CONCLUSION: Our results showed that Agm is involved in the activation of antioxidant signaling pathways and activation of insulin signal transduction. Accordingly, Agm may be a promising therapeutic agent for improving cognitive decline and attenuating apoptosis in AD.