Neuroprotective Effects of Geopung-Chunghyuldan Based on Its Salvianolic Acid B Content Using an In Vivo Stroke Model.

BACKGROUND: Geopung-Chunghyuldan (GCD) has neuroprotective properties. Salviae miltiorrhizae Radix plays an essential role in GCD's effect. The Salviae miltiorrhizae Radix marker compound is salvianolic acid B; however, its content is not uniform among samples. This study aimed to evaluate the neuroprotective effects of GCD based on salvianolic acid B content. METHODS: The neuroprotective effects of GCD based on the salvianolic acid B content were evaluated by measuring infarct volume 24 h after permanent middle cerebral artery occlusion in an in vivo stroke model. For the experimental group, each GCD was administered immediately before surgery. The control groups were administered distilled water and aspirin (30 mg/kg) in the same way. The salvianolic acid B content in five types of Salviae Miltiorrhizae Radix (two Chinese and three Korean regions) based on different cultivation regions was analyzed by high-performance liquid chromatography. RESULTS: Three samples met the Korean and Chinese Pharmacopeia standards for salvianolic acid B. However, two samples did not. GCDs with high salvianolic acid B showed marked neuroprotective effects compared to the control groups, whereas GCDs with low salvianolic acid B did not. CONCLUSIONS: The salvianolic acid B content of Salviae miltiorrhizae Radix affects the neuroprotection effect of GCD. Stable, raw Salviae miltiorrhizae Radix is essential for GCD homogenization.

Glymphatic system evaluation using diffusion tensor imaging in patients with traumatic brain injury.

PURPOSE: Glymphatic system dysfunction has been reported in animal models of traumatic brain injury (TBI). This study aimed to evaluate the activity of the human glymphatic system using the non-invasive Diffusion Tensor Image-Analysis aLong the Perivascular Space (DTI-ALPS) method in patients with TBI. METHODS: A total of 89 patients with TBI (June 2018 to May 2020) were retrospectively enrolled, and 34 healthy volunteers were included who had no previous medical or neurological disease. Magnetic resonance imaging (MRI) with DTI was performed, and the ALPS index was calculated to evaluate the glymphatic system's activity. Wilcoxon rank-sum test was used to compare the ALPS index between patients with TBI and healthy controls. ANOVA was done to compare the ALPS index among controls and patients with mild/moderate-to-severe TBI. Multivariate logistic regression analyses were used to identify independent clinical and radiological factors associated with the ALPS index. The correlation between Glasgow Coma Scale (GCS) score and the ALPS index was also assessed. RESULTS: The ALPS index was significantly lower in patients with TBI than in healthy controls (median, 1.317 vs. 1.456, P < 0.0001). There were significant differences in the ALPS index between healthy controls and patients with mild/moderate-to-severe TBI (ANOVA, P < 0.001). The presence of subarachnoid hemorrhage (P = 0.004) and diffuse axonal injury (P = 0.001) was correlated with a lower ALPS index in the multivariate analysis. There was a weak positive correlation between the ALPS index and GCS scores (r = 0.242, P = 0.023). CONCLUSIONS: The DTI-ALPS method is useful for evaluating glymphatic system impairment and quantifying its activity in patients with TBI.

Effect of manual aspiration thrombectomy using large-bore aspiration catheter for acute basilar artery occlusion: comparison with a stent retriever system.

BACKGROUND: A large-bore aspiration catheter can be employed for recanalization of acute basilar artery occlusion. Here we compare the results of mechanical thrombectomy using a stent retriever (SR) and manual aspiration thrombectomy (MAT) using a large-bore aspiration catheter system as a first-line recanalization method in acute basilar artery occlusion (BAO). METHODS: The records of 50 patients with acute BAO who underwent mechanical thrombectomy were retrospectively reviewed. Patients were assigned to one of two groups based on the first-line recanalization method. The treatment and clinical outcomes were compared. RESULTS: Sixteen (32%) patients were treated with MAT with a large-bore aspiration catheter and 34 (68%) with a SR as the first-line treatment method. The MAT group had a shorter procedure time (28 vs. 65 min; p = 0.001), higher rate of first-pass recanalization (68.8% vs. 38.2%, p = 0.044), and lower median number of passes (1 vs 2; p = 0.008) when compared with the SR group. There was no significant difference in the incidence of any hemorrhagic complication (6.3% vs. 8.8%; p = 0.754) between the groups. However, there were four cases of procedure-related subarachnoid hemorrhage (SAH) in the SR group and one death occurred due to massive hemorrhage. CONCLUSIONS: Selection of MAT using a large-bore aspiration catheter for acute BAO may be a safe and effective first-line treatment method with higher first-pass recanalization rate and shorter procedure time than SR.

Atrial Fibrillation is Strongly Associated With the Neutrophil to Lymphocyte Ratio in Acute Ischemic Stroke Patients: A Retrospective Study.

BACKGROUND: No study has investigated the relationship between hospital-admission neutrophil and lymphocyte ratio (NLR) and various stroke risk factors. We sought to determine which stroke risk factor could be the most appropriate predictor of NLR in acute ischemic stroke. METHODS: We collected data on various stroke risk factors and National Institutes of Health Stroke Scale (NIHSS) score in 1,053 acute ischemic stroke patients. The regression analysis was adjusted for confounding factors such as stroke risk factors. RESULTS: There was a trend of increased NLR with a rise in alcohol consumption, the prevalence of hypertension, cardioembolism (CE) etiology, the NIHSS scores in men and the prevalence of atrial fibrillation, other heart diseases, CE and small vessel occlusion etiology and the NIHSS scores in women. Multiple linear regression analyses, adjusted for confounding factors, showed that the atrial fibrillation and NIHSS scores in men and atrial fibrillation, diabetes mellitus as well as NIHSS scores in women had a significant positive association with NLR. However, a negative association was showed for body mass index (BMI). CONCLUSION: We confirmed that the atrial fibrillation can be a predictor of high NLR in acute stroke patients, and diabetes mellitus as well as low BMI could be a predictor of high NLR in female acute ischemic stroke patients.

MR imaging features that distinguish spinal cavernous angioma from hemorrhagic ependymoma and serial MRI changes in cavernous angioma.

Cavernous angiomas of the spinal cord exhibit imaging characteristics that may overlap with those of hemorrhagic ependymoma. In the present study, we aimed to identify specific magnetic resonance imaging (MRI) findings that could be used to differentiate cavernous angioma from hemorrhagic ependymoma, and to evaluate serial MRI changes in cases of cavernous angioma. We retrospectively evaluated MR images of spinal cord tumors collected at our hospital from 2007 to 2015. From this cohort of images, 11 pathologically confirmed cavernous angiomas and 14 pathologically confirmed hemorrhagic ependymomas were compared with respect to the size of the tumor, longitudinal location, axial location, enhancement pattern, syrinx, edema, tumor margin, signal intensity of T2WI, signal intensity of T1WI, and longitudinal spreading of the hemorrhage. Serial MR images of seven spinal cavernous angiomas were reviewed. Small size, eccentric axial location, minimal enhancement, and absence of edema were more frequently observed on images of cavernous angioma compared to those of hemorrhagic ependymoma (p < 0.01). Serial MRI changes in cases of cavernous angioma included increased longitudinal spreading of the hemorrhage (6/7, 86 %) and emergence of high signal intensity on T1WI (1/7, 14 %). Small size, eccentric axial location, minimal enhancement, and absence of edema are significant MRI findings that may be used to distinguish Type I and Type II spinal cavernous angiomas from hemorrhagic ependymomas. Furthermore, longitudinal spreading of the hemorrhage may be observed on follow-up MRIs of cavernous angiomas.

Shear wave elastography in evaluation of cervical lymph node metastasis of papillary thyroid carcinoma: elasticity index as a prognostic implication.

PURPOSE: The aim of this study was to evaluate the usefulness of shear wave elastography (SWE) for predicting cervical lymph node (LN) metastasis and the prognostic implication of SWE as histopathologic factors of papillary thyroid carcinoma (PTC). METHODS: Eighty-four LNs of 66 patients with PTC underwent B-mode ultrasonography (BUS) and SWE before ultrasound-guided fine-needle aspiration biopsy or preoperative evaluation. SWE elasticity indices (EI) of mean (Emean), minimum (Emin), maximum (Emax) and the ratio of Emean in LNs and surrounding muscle (Emean-m) were measured at the stiffest portion of LNs (kPa). SWE EI were correlated with the pathologic diagnosis and the histopathologic findings, including number and size of metastatic LNs, the ratio of the number of metastatic LN/dissected LN, and the presence of extranodal extension. Diagnostic performances of SWE EI and BUS for predicting LN metastasis were assessed using receiver operating curve analysis. RESULTS: All SWE EI were significantly higher in metastatic LNs than in benign LNs (p < 0.005). Combined Emean [area under the curve (AUC) 0.811] or Emin (AUC 0.812) with BUS showed significantly higher AUC than BUS (0.738) for predicting metastatic LNs (p = 0.041 and 0.033, respectively). The number of positive LNs/dissected LNs and the largest LN size were significantly correlated with SWE EI (p < 0.05 and p < 0.005, respectively). Metastatic LNs with extranodal extension showed significantly higher SWE EI (p < 0.005) than those without extranodal extension. CONCLUSIONS: Combined use of SWE and BUS was adjunctive to the diagnostic performance of BUS for the prediction of LN metastasis of PTC, and quantitative SWE could predict pathologic prognostic factors of LN metastasis of PTC.

Comparing the effects of kamikihito in Japan and kami-guibi-tang in Korea on memory enhancement: working towards the development of a global study.

Traditional medicine is widely used in East Asia, and studies that demonstrate its usefulness have recently become more common. However, formulation-based studies are not globally understood because these studies are country-specific. There are many types of formulations that have been introduced to Japan and Korea from China. Establishing whether a same-origin formulation has equivalent effects in other countries is important for the development of studies that span multiple countries. The present study compared the effects of same-origin traditional medicine used in Japan and Korea in an in vivo experiment. We prepared drugs that had the same origin and the same components. The drugs are called kamikihito (KKT) in Japan and kami-guibi-tang (KGT) in Korea. KKT (500 mg extract/kg/day) and KGT (500 mg extract/kg/day) were administered to ddY mice, and object recognition and location memory tests were performed. KKT and KGT administration yielded equivalent normal memory enhancement effects. 3D-HPLC showed similar, but not identical, patterns of the detected compounds between KKT and KGT. This comparative research approach enables future global clinical studies of traditional medicine to be conducted through the use of the formulations prescribed in each country.

The safety and efficacy of intra-arterial low-dose tirofiban administration during endovascular therapy in patients with large ischemic core volume.

This study aimed to evaluate the safety and efficacy of intra-arterial (IA) administration of low- dose tirofiban during endovascular therapy in patients with large ischemic core volumes on initial brain CT. Patients were divided into two groups based on the use of IA tirofiban. We identified 87 patients (16 and 71 patients in the tirofiban and no-tirofiban groups, respectively) with acute ischemic stroke due to intracranial artery occlusion who underwent endovascular therapy with a low Alberta Stroke Program Early CT scores (2-5). Multivariate logistic regression analysis revealed no association between IA tirofiban administration and serious postprocedural hemorrhagic complications (adjusted odds ratio (aOR), 0.720; 95% confidence interval (CI) 0.099-5.219; p = 0.960), any radiologic hemorrhage (aOR 0.076; 95% CI 0.003-2.323; p = 0.139), or 3-month mortality (aOR, 0.087; 95% CI 0.005-1.501; p = 0.093). However, IA tirofiban was associated with a lower 90-day mRS score (aOR, 0.197; 95% CI 0.015-1.306; p = 0.017) and change of NIHSS compared with baseline (aOR, 0.698; 95% CI 0.531-0.917; p = 0.010). IA tirofiban administration during endovascular therapy in patients with large ischemic core volumes may be effective and safe.

Behavior of Extracranial-to-Intracranial Extended Arterial Dissections of the Vertebral Artery.

BACKGROUND: Vertebral artery dissections (VADs) may extend from the extracranial to the intracranial vasculature (e+iVAD). We evaluated how the characteristics of e+iVAD differed from those of intracranial VAD (iVAD). METHODS AND RESULTS: From 2002 to 2019, among consecutive patients with cervicocephalic dissection, those with iVAD and e+iVAD were included, and their clinical characteristics were compared. In patients with unruptured dissections, a composite clinical outcome of subsequent ischemic events, subsequent hemorrhagic stroke, or mortality was evaluated. High-resolution magnetic resonance images were analyzed to evaluate intracranial remodeling index. Among 347 patients, 51 (14.7%) had e+iVAD and 296 (85.3%) had iVAD. The hemorrhagic presentation occurred solely in iVAD (0.0% versus 19.3%), whereas e+iVAD exhibited higher ischemic presentation (84.3% versus 27.4%; P<0.001). e+iVAD predominantly presented steno-occlusive morphology (88.2% versus 27.7%) compared with dilatation patterns (11.8% versus 72.3%; P<0.001) of iVAD. The ischemic presentation was significantly associated with e+iVAD (iVAD as a reference; adjusted odds ratio, 3.97 [95% CI, 1.67-9.45]; P=0.002]). Patients with unruptured VAD showed no differences in the rate of composite clinical outcome between the groups (log-rank, P=0.996). e+iVAD had a lower intracranial remodeling index (1.4±0.3 versus 1.6±0.4; P<0.032) and a shorter distance from dural entry to the maximal dissecting segment (6.9±8.4 versus 15.7±7.4; P<0.001). CONCLUSIONS: e+iVAD is associated with lower rates of hemorrhages and higher rates of ischemia than iVAD at the time of admission. This may be explained by a lower intracranial remodeling index and less deep intrusion of the dissecting segment into the intracranial space.

The effectiveness of Kami Guibi-tang for cognitive impairment patients: A retrospective chart review.

Background: and Purpose: The number of patients with cognitive impairment is increasing worldwide. Therapeutic drugs that slow disease progression are being developed; however, further research is required. This study investigated the effects of Kami Guibi-tang on patients with various types of cognitive decline. Methods: This study was a single-center, retrospective chart review of patients who visited KyungHee University Hospital at Gangdong from January 2015 to March 2022. The study included participants who took Kami Guibi-tang for more than 90 days and were assessed on the Korean version Mini-Mental State Examination (MMSE-K) scores before and after treatment. Participants who received other liquid herbal medicines during the treatment were excluded. The outcome of interest was changed scores in MMSE-K and Short form of Geriatric Depression Scale (S-GDS). Results: A total of 31 participants were included. The total MMSE-K score significantly increased with time and showed a significant increase at 3 and 9 months compared with baseline. Among the MMSE-K subscores, the orientation subscore showed a significant increase at three months compared with baseline, and the attention and calculation subscore showed a significant increase with time. In addition, four participants with vascular dementia showed a significant increase in the total MMSE-K score over time and a significant increase after 9 months compared with baseline. The S-GDS score in 31 participants showed a significant decrease with time and at all time points compared with baseline. Conclusions: Kami Guibi-tang may improve cognitive function in patients with cognitive decline.

Prevention of inflammation-mediated neurotoxicity by butylidenephthalide and its role in microglial activation.

Microglial cells are the prime effectors in immune and inflammatory responses of the central nervous system (CNS). During pathological conditions, the activation of these cells helps restore CNS homeostasis. However, chronic microglial activation endangers neuronal survival through the release of various proinflammatory molecules and neurotoxins. Thus, negative regulators of microglial activation have been considered as potential therapeutic candidates to target neurodegeneration, such as that in Alzheimer's and Parkinson's diseases. The rhizome of Ligusticum chuanxiong Hort. (Ligusticum wallichii Franch) has been widely used for the treatment of vascular diseases in traditional oriental medicine. Butylidenephthalide (BP), a major bioactive component from L. chuanxiong, has been reported to have a variety of pharmacological activities, including vasorelaxant, anti-anginal, anti-platelet and anti-cancer effects. The aim of this study was to examine whether BP represses microglial activation. In rat brain microglia, BP significantly inhibited the lipopolysaccharide (LPS)-induced production of nitric oxide (NO), tumour necrosis factor-α and interleukin-1ß. In organotypic hippocampal slice cultures, BP clearly blocked the effect of LPS on hippocampal cell death and inhibited LPS-induced NO production in culture medium. These results newly suggest that BP provide neuroprotection by reducing the release of various proinflammatory molecules from activated microglia.

Angiographic tapering sign as a surrogate marker for large vessel occlusion due to intracranial atherosclerotic stenosis and its clinical implication: a retrospective matched case-control study.

BACKGROUND: The purpose of this study was to investigate whether the initial DSA appearance of the occlusion during mechanical thrombectomy (MT) can help distinguish the nature of the underlying lesion and predict radiological and clinical outcomes. METHODS: We retrospectively reviewed cases of patients with acute ischemic stroke who underwent MT for anterior circulation occlusion between March 2017 and February 2020. Underlying intracranial atherosclerotic stenosis (ICAS) was determined based on the presence of fixed stenosis after endovascular treatment. Patients were categorized based on the appearance of the occlusion observed in the initial DSA as tapering sign (+) or (-) groups. We performed 1:2 propensity score matching to establish a proper control group among the tapering sign (-) group. We analyzed and compared baseline characteristics and clinical outcomes between the two groups. RESULTS: A total of 293 patients (tapering sign (+), n=47; tapering sign (-), n=246) were included in the analysis. The procedure time of MT was significantly longer for the tapering sign (+) group, and the successful recanalization rate after MT was significantly lower in the tapering sign (+) group than in the tapering sign (-) group. Logistic regression showed that ICAS-related occlusion was strongly associated with a positive angiographic tapering sign, and the angiographic tapering sign was a negative factor for the first-pass effect during MT. However, a 3-month good functional outcome was not significantly associated with the angiographic tapering sign. CONCLUSIONS: The tapering sign on the initial DSA could be a surrogate marker for ICAS-related occlusion and procedural difficulty. However, its clinical significance remains unclear.

A Systematic Review of In Vivo Studies of the Efficacy of Herbal Medicines for Anti-Aging in the Last Five Years.

BACKGROUND: The world's population is rapidly aging, and attention to and research on the increase in life expectancy and age-related diseases are needed. This study aimed to review the in vivo studies on the anti-aging effects of herbal medicines. METHODS: In vivo studies of single or complex herbal medicines for anti-aging that were published in the last five years were included in this review. The following databases were used: PubMed, Scopus, ScienceDirect, Web of Science and EMBASE. RESULTS: A total of 41 studies were considered eligible for the review. The articles were classified into body organs and functions, experimental country, herbal medicine, extraction method, administration route, dosage, duration, animal model, aging-induced method, sex, number of animals per group, and outcomes and mechanisms A single herbal extract was used in a total of 21 studies including Alpinia oxyphylla Miq., Acanthopanax senticosus and Lyceum barbarum, and a multi-compound herbal prescription was used in a total of 20 studies, including Modified Qiongyu paste, Wuzi Yanzong recipe, etc. Each herbal medicine had anti-aging effects on learning and memory, cognition, emotion, internal organs, gastrointestinal tracts, sexual functions, musculoskeletal function and so on. The common mechanisms of action were antioxidant and anti-inflammatory, and various effects and mechanisms for each organ and function were identified. CONCLUSIONS: Herbal medicine exhibited beneficial effects on anti-aging in various parts of the body and its function. Further investigation of the appropriate herbal medicine prescriptions and their components is recommended.

Deep learning based automatic detection algorithm for acute intracranial haemorrhage: a pivotal randomized clinical trial.

Acute intracranial haemorrhage (AIH) is a potentially life-threatening emergency that requires prompt and accurate assessment and management. This study aims to develop and validate an artificial intelligence (AI) algorithm for diagnosing AIH using brain-computed tomography (CT) images. A retrospective, multi-reader, pivotal, crossover, randomised study was performed to validate the performance of an AI algorithm was trained using 104,666 slices from 3010 patients. Brain CT images (12,663 slices from 296 patients) were evaluated by nine reviewers belonging to one of the three subgroups (non-radiologist physicians, n = 3; board-certified radiologists, n = 3; and neuroradiologists, n = 3) with and without the aid of our AI algorithm. Sensitivity, specificity, and accuracy were compared between AI-unassisted and AI-assisted interpretations using the chi-square test. Brain CT interpretation with AI assistance results in significantly higher diagnostic accuracy than that without AI assistance (0.9703 vs. 0.9471, p < 0.0001, patient-wise). Among the three subgroups of reviewers, non-radiologist physicians demonstrate the greatest improvement in diagnostic accuracy for brain CT interpretation with AI assistance compared to that without AI assistance. For board-certified radiologists, the diagnostic accuracy for brain CT interpretation is significantly higher with AI assistance than without AI assistance. For neuroradiologists, although brain CT interpretation with AI assistance results in a trend for higher diagnostic accuracy compared to that without AI assistance, the difference does not reach statistical significance. For the detection of AIH, brain CT interpretation with AI assistance results in better diagnostic performance than that without AI assistance, with the most significant improvement observed for non-radiologist physicians.

Significance of headache in intracranial vertebrobasilar artery dissections: an observational study.

Headache may represent acute phase of intracranial vertebrobasilar artery dissection (iVBAD). We aimed to evaluate its clinical significance in iVBAD. Consecutive acute iVBAD patients were grouped into ruptured iVBAD, unruptured iVBAD with no headache, isolated headache, or concurrent headache with neurological symptoms. Composite hemorrhagic/ischemic endpoints, and dynamic arterial changes were graded. Clinical characteristics of the four groups, and association between headache and composite outcomes was evaluated. Headaches were precedent in 79% of the ruptured iVBAD patients (maximal delay, 10D). In unruptured iVBAD, when patients with no headache (N = 69), concurrent headache (N = 111), and isolated headache (N = 126) were compared, concurrent headache was associated with ischemic endpoints (isolated headache as reference, adjusted odds ratio: 6.40, 95% confidence interval [2.03-20.19]). While there were no differences in hemorrhagic endpoints, dynamic arterial changes were higher in the isolated headache group (aOR: 3.98, 95% CI [1.72-9.18]) but not for the concurrent headache group (aOR: 1.59 [0.75-3.38]) compared to no headache group. Headache was more commonly severe (48.4% vs. 17.3%, p < 0.001) and ipsilateral (59.7% vs. 45.5%, p = 0.03) for isolated headache compared to concurrent headache, indicating a higher causal relationship. In iVBAD, isolated headache may be considered an acute-phase biomarker, associated with dynamic arterial changes.

Treatment of nausea and vomiting associated with cerebellar infarction using the traditional herbal medicines banhabaekchulcheonma-tang and oryeong-san: Two case reports (CARE-complaint).

RATIONALE: Metoclopramide is commonly used to treat nausea and vomiting. However, long-term administration of metoclopramide is associated with various adverse effects, and its therapeutic effects are short-lasting. Hence, traditional East Asian medicine has received increasing attention as a short-term strategy for treating these symptoms. PATIENT CONCERNS: The present report discusses the cases of a 71-year-old man and an 80-year-old woman diagnosed with cerebellar infarction. Both patients reported nausea and vomiting, which appeared during hospitalization following cerebellar infarction. DIAGNOSES: One patient was diagnosed with a left cerebellar infarction and hemorrhagic transformation, while the other was diagnosed with a bilateral cerebellar infarction. INTERVENTIONS: Both patients took Banhabaekchulcheonma-tang (BT) and Oryeong-san (OS) extracts. OUTCOMES: The patient in Case 1 experienced a rapid decrease in nausea from day 5 of BT and OS administration, and metoclopramide was discontinued on day 7. The patient in Case 2 experienced a clear decrease in the number of vomiting episodes from day 6 of BT and OS administration and did not take metoclopramide thereafter. LESSONS: Other than drugs used to mitigate symptoms, there are no suitable treatments available for nausea and vomiting caused by cerebellar infarction. In the present cases, nausea and vomiting remained unresolved even after 3 weeks of treatment with conventional therapies; however, these symptoms significantly improved after administration of the traditional East Asian herbal medicines BT and OS, and there were no recurrences. These cases demonstrate that traditional herbal medicine can reduce the side effects associated with long-term administration of metoclopramide and help patients resume their daily lifestyle. In addition, BT and OS treatment can facilitate administration of other drugs, highlighting its potential to aid in the treatment of stroke. Further research including relevant clinical trials is required to obtain more conclusive evidence.

Efficacy of Artemisia annua Linné in improving cognitive impairment in a chronic cerebral hypoperfusion-induced vascular dementia animal model.

BACKGROUND: Vascular dementia (VaD) is the second most common type of dementia after Alzheimer's disease. Currently, no FDA-approved drugs are available for the treatment of VaD. Artemisia annua Linné (AA) is known to have antioxidant properties, but its effects and mechanisms of action on cognitive impairment are still unknown. PURPOSE: In this study, the improvement in cognitive impairment by AA in terms of protection against oxidative stress, neuroinflammation, and preservation of the integrity of the neurovascular unit (NVU) was assessed in an animal model of VaD with bilateral common carotid artery occlusion (BCCAO). METHODS: Eight-week-old male Wistar rats were allowed to adapt for four weeks, and BCCAO was induced at 12 weeks of age. The rats were randomly assigned into four groups, with seven rats in each group: sham group without BCCAO, VaD group that received oral administration of distilled water after BCCAO surgery, and two AA groups that received oral administration of 150 mg/kg or 750 mg/kg AA after BCCAO surgery for 8 weeks. Nine weeks after BCCAO surgery, the cognitive function of the rats was evaluated and accumulated oxidative stress was assessed by immunohistochemistry, immunofluorescence, and western blotting. Damage to the components of the NVU was evaluated, and sirtuin (Sirt) 1 and 2 expression and nuclear factor-erythrocyte 2-associated factor 2 (Nrf2)/Kelch-like ECH-associated protein1 (Keap1) activation were investigated to assess the reduction in cell signaling and antioxidant pathways. RESULTS: BCCAO-induced cerebral perfusion decreased memory function and induced neuroinflammation and oxidative stress. But AA treatment mitigated cognitive impairment and reduced neuroinflammation and oxidative stress caused by chronic cerebral hypoperfusion. AA extracts activated the Nrf2/Keap1/activating antioxidant response elements pathway and maintained Sirt 1 and 2, subsequently leading to the maintenance of neurons, improved construct of microvessels, increased platelet-derived growth factor receptor beta, and platelet-endothelial cell adhesion molecule-1 associated with the blood-brain barrier integrity. CONCLUSION: AA is effective in alleviating BCCAO-induced cognitive decline and its administration may be a useful therapeutic approach for VaD.

Efficacy of Kami Guibi-tang as an Add-On Therapy to Acetylcholinesterase Inhibitor for Cognitive Function in Mild Alzheimer's Disease: A Pilot Study.

Background: Kami Guibi-tang (KGT), a traditional Korean herbal medicine is mainly used to treat insomnia and nervousness. Acetylcholinesterase inhibitors (AChEIs) are the main treatments for mild Alzheimer's disease (AD), a degenerative brain disease. However, currently no drug can fundamentally treat AD or reverse the advanced cognitive decline. This clinical study explored the efficacy and safety of adding KGT to AChEI for cognitive function in mild AD. Methods: This was a pilot study for a larger randomized, double-blind, placebo-controlled trial. Participants between 55-90 years diagnosed with mild AD were recruited from Kyung Hee University Hospital at Gangdong, Seoul, Korea. They were randomized to receive either KGT or placebo for 24 weeks, in addition to their regular AChEI. The primary outcome was treatment efficacy, as assessed by the relative amount of change over the study period in total scores on the Dementia version of the Seoul Neuropsychological Screening Battery (SNSB-D). Changes in SNSB subscores were assessed as secondary outcomes. Safety parameters, including adverse events and abnormalities in blood tests, electrocardiograms, and brain magnetic resonance imaging were also monitored. Results: Between March 2018 and November 2020, seven participants each in the KGT group and the placebo group completed the 24-week trial. There were no significant changes in SNSB-D total or subindex scores for either group (p = 0.69 and 0.63, respectively), and no significant differences were observed between them (p=0.71). No adverse events related to KGT were reported. We also compared and analyzed the results of a previous pilot study conducted on amnestic mild cognitive impairment (aMCI) using protocol of this study. The aMCI group showed a significant improvement in the total SNSB-D score, especially in the memory domain, compared to the mild AD group (p = 0.04 and 0.02, respectively). The Korean Mini-Mental State Exam and Korean Instrumental Activities of Daily Living scores also significantly improved in the aMCI group (p = 0.01 and 0.02, respectively). Conclusions: Compared to placebo, adding KGT to AChEI did not significantly improve cognitive function in SNSB in patients with mild AD. We suggest that KGT would have a positive effect on patients with early stages of cognitive impairment such as aMCI. The findings could assist design larger, longer-term clinical trials of KGT use in elderly patients with mild AD. This study was registered in the Korean Clinical Trial Registry on December 26, 2017, with the CRIS approval number KCT0002904.

Effect of Kami Guibi-tang (KGT) in elderly subjects with insomnia: a study protocol from a single center, randomized, double-blind, placebo-controlled trial.

BACKGROUND: The incidence of insomnia increases with age and is related to cognitive function in older adults; therefore, it is important to manage it actively. In this study, we report a protocol for the evaluation of the efficacy and safety of Kami Guibi-tang (KGT), a herbal prescription that has been widely used in East Asia for insomnia, forgetfulness, and depression, in older adults with insomnia. METHODS: In this single-center, double-blind, randomized controlled trial, 60 older adults with insomnia and subjective cognitive decline will be recruited and randomly assigned to the KGT or placebo group. The KGT group will take KGT granules thrice a day for 12 weeks, whereas the control group will take placebo granules in the same manner. Participants will be assessed for sleep, cognitive function, quality of life, and depression using the Pittsburgh Sleep Quality Index-Korean (PSQI-K), Insomnia Severity Index-Korean (ISI-K), Seoul Neuropsychological Screening Battery-Dement (SNSB-D), 36-item MOS Short Form Survey (SF-36) and Short version of the Geriatric Depression Scale (S-GDS) before and at the end of administration of the investigational product. The PSQI-K, ISI-K, and SF-36 will be further assessed 12 weeks after the end of medication to determine whether the effects on sleep and quality of life are sustained. The PSQI-K total score difference between the two groups at 12 and 24 weeks will be the primary outcome; all other endpoints will be secondary. Safety will be assessed by performing blood tests and electrocardiograms before taking the investigational drug, 6 weeks after taking the drug, and 12 weeks after taking the drug; any adverse events will be observed throughout the study. DISCUSSION: The protocol will provide a detailed process for a clinical trial to evaluate the efficacy and safety of KGT in elderly patients with insomnia. We will also investigate if changes in cognitive function correlated with improvements in insomnia. TRIAL REGISTRATION: This trial was registered at CRIS (Clinical Research Information Service) on April 27, 2023 (KCT0008391, version 2.0).  https://cris.nih.go.kr/cris/search/detailSearch.do?seq=24811&search_page=L .

A Comparative Study on the Neuroprotective Effect of Geopung-Chunghyuldan on In Vitro Oxygen-Glucose Deprivation and In Vivo Permanent Middle Cerebral Artery Occlusion Models.

Geopung-Chunghyuldan (GCD), which is a mixture of Chunghyuldan (CD), Radix Salviae Miltiorrhizae, Radix Notoginseng, and Borneolum Syntheticum, is used to treat ischemic stroke in traditional Korean medicine. This study aimed to investigate the effects of GCD and CD on ischemic brain damage using in vitro and in vivo stroke models, as well as to elucidate the synergistic effects of GCD against ischemic insult. To study the effect of GCD in an in vitro ischemia model, SH-SY5Y cells were exposed to oxygen-glucose deprivation (OGD). Cell death after 16 h of OGD exposure was measured using the MTT assay and live/dead cell counting methods. An in vivo ischemia mice model was established through permanent middle cerebral artery occlusion (pMCAO). To determine the neuroprotective effect of GCD, it was orally administered immediately and 2 h after pMCAO. The infarct volume was measured through 2,3,5-triphenyltetrazolium chloride staining at 24 h after pMCAO. Compared with the control group, GCD treatment significantly reduced OGD-induced cell death in SH-SY5Y cells; however, CD treatment did not show a significant protective effect. In the pMCAO model, compared with the control group, treatment with GCD and CD significantly and mildly reduced the infarct volume, respectively. Our findings indicate that compared with CD, GCD may allow a more enhanced neuroprotective effect in acute ischemic stroke, indicating a potential synergistic neuroprotective effect. The possibility of GCD as a novel alternative choice for the prevention and treatment of ischemic stroke is suggested.