Delayed fatal rupture of vertebral artery after treated with flow-diverter in fibromuscular dysplasia patient: A case report and review of the literature

Fibromuscular dysplasia (FMD) is a noninflammatory arterial diseases that affects predominantly women. Multiple studies have demonstrated an increased prevalence of FMD in patients who experience carotid or vertebral artery dissection (VAD). This case report presents a 57-year-old female who presented with a headache and was diagnosed with partially thrombosed giant aneurysm of vertebral artery. This aneurysm was successfully treated with flow-diverter and coil, but new onset rupture of vertebral artery was detected two weeks later, leading to internal trapping. This case report underscores the need for awareness and understanding of treatment of dissection and aneurysm in patient who is suspected FMD

Reducing Microbial Contamination in Hematopoietic Stem Cell Products and Quality Improvement Strategy: Retrospective Analysis of 1996-2021 Data

Background@#Sterility and safety assurance of hematopoietic stem cell (HSC) products is critical in transplantation. Microbial contamination can lead to product disposal and increases the risk of unsuccessful clinical outcomes. Therefore, it is important to implement and maintain good practice guidelines and regulations for the HSC collection and processing unit in each hospital. We aimed to share our experiences and suggest strategies to improve the quality assurance of HSC processing. @*Methods@#We retrospectively analyzed microbial culture results of 11,743 HSC products processed over a 25-year period (January 1996 to May 2021). Because of reorganization of the HSC management system in 2008, the 25-year period was divided into periods 1 (January 1996 to December 2007) and 2 (January 2008 to May 2021). We reviewed all culture results of the HSC products and stored aliquot samples and collected culture results for peripheral blood and catheter samples. @*Results@#Of the 11,743 products in total, 35 (0.3%) were contaminated by microorganisms, including 19 (0.5%) of 3,861 products during period 1 and 16 (0.2%) of 7,882 products during period 2. Penicillium was the most commonly identified microorganism (15.8%) during period 1 and coagulase-negative Staphylococcus was the most commonly identified (31.3%) during period 2. HSC product contamination occurred most often during HSC collection and processing. @*Conclusions@#The contamination rate decreased significantly during period 2, when the HSC management system was reorganized. Our results imply that handling HSC products by trained personnel and adopting established protocols, including quality assurance programs, aid in decreasing the contamination risk.

Safe and time-saving treatment method for acute cerebellar infarction: Navigation-guided burr-hole aspiration – 6-years single center experience

Objective@#While patients with medically intractable acute cerebellar infarction typically undergo suboccipital craniectomy and removal of the infarcted tissue, this procedure is associated with long operating times and postoperative complications. This study aimed to investigate the effectiveness of minimally invasive navigationguided burr hole aspiration surgery for the treatment of acute cerebellar infarction. @*Methods@#Between January 2015 and December 2021, 14 patients with acute cerebellar infarction, who underwent navigation-guided burr hole aspiration surgery, were enrolled in this study. @*Results@#The preoperative mean Glasgow Coma Scale (GCS) score was 12.7, and the postoperative mean GCS score was 14.3. The mean infarction volume was 34.3 cc at admission and 23.5 cc immediately following surgery. Seven days after surgery, the mean infarction volume was 15.6 cc. There were no surgery-related complications during the 6-month follow-up period and no evidence of clinical deterioration. The mean operation time from skin incision to catheter insertion was 28 min, with approximately an additional 13 min for extra-ventricular drainage. The mean Glasgow Outcome Scale score after 6 months was 4.8. @*Conclusions@#Navigation-guided burr hole aspiration surgery is less time-consuming and invasive than conventional craniectomy, and is a safe and effective treatment option for acute cerebellar infarction in selected cases, with no surgery-related complication.

Therapeutic effects of stiripentol against ischemia-reperfusion injury in gerbils focusing on cognitive deficit, neuronal death, astrocyte damage and blood brain barrier leakage in the hippocampus

Stiripentol is an anti-epileptic drug for the treating of refractory status epilepticus. It has been reported that stiripentol can attenuate seizure severity and reduce seizure-induced neuronal damage in animal models of epilepsy. The objective of the present study was to investigate effects of post-treatment with stiripentol on cognitive deficit and neuronal damage in the cornu ammonis 1 (CA1) region of the hippocampus proper following transient ischemia in the forebrain of gerbils. To evaluate ischemia-induced cognitive impairments, passive avoidance test and 8-arm radial maze test were performed. It was found that post-treatment with stiripentol at 20 mg/kg, but not 10 or 15 mg/kg, reduced ischemia-induced memory impairment. Transient ischemia-induced neuronal death in the CA1 region was also significantly attenuated only by 20 mg/kg stiripentol treatment after transient ischemia. In addition, 20 mg/kg stiripentol treatment significantly decreased ischemia-induced astrocyte damage and immunoglobulin G leakage. In brief, stiripentol treatment after transient ischemia ameliorated transient ischemia-induced cognitive impairment in gerbils, showing that pyramidal neurons were protected and astrocyte damage and blood brain barrier leakage were significantly attenuated in the hippocampus. Results of this study suggest stiripentol can be developed as a candidate of therapeutic drug for ischemic stroke.

Protective Role of Transduced Tat-Thioredoxin1 (Trx1) against Oxidative Stress-Induced Neuronal Cell Death via ASK1-MAPK Signal Pathway

Oxidative stress plays a crucial role in the development of neuronal disorders including brain ischemic injury. Thioredoxin 1 (Trx1), a 12 kDa oxidoreductase, has anti-oxidant and anti-apoptotic functions in various cells. It has been highly implicated in brain ischemic injury. However, the protective mechanism of Trx1 against hippocampal neuronal cell death is not identified yet. Using a cell permeable Tat-Trx1 protein, protective mechanism of Trx1 against hydrogen peroxide-induced cell death was examined using HT-22 cells and an ischemic animal model. Transduced Tat-Trx1 markedly inhibited intracellular ROS levels, DNA fragmentation, and cell death in H 2O 2-treatment HT-22 cells. Tat-Trx1 also significantly inhibited phosphorylation of ASK1 and MAPKs in signaling pathways of HT-22 cells. In addition, Tat-Trx1 regulated expression levels of Akt, NF-κB, and apoptosis related proteins. In an ischemia animal model, Tat-Trx1 markedly protected hippocampal neuronal cell death and reduced astrocytes and microglia activation. These findings indicate that transduced Tat-Trx1 might be a potential therapeutic agent for treating ischemic injury.

Safety and Efficacy of Selective Intra-arterial Thrombolysis for Central Retinal Artery Occlusion

Purpose@#The purpose of this study was to determine the efficacy and safety of selective intra-arterial thrombolysis in patients with central retinal artery occlusion (CRAO). @*Methods@#Medical records for 44 eyes of 44 patients diagnosed with acute non-arteritic CRAO and thrombolysis between October 2010 and February 2019 were analyzed retrospectively. Based on visual acuity, fundoscopic findings, and fluorescein angiography, the patients were classified into three stages: incomplete, subtotal, and total. The perfusion state using the best-corrected visual acuity (BCVA), arm to retina time, and arteriovenous passage times, after 1 month, 6 months, and at the final visit after the procedure, were compared with baseline readings. @*Results@#Improvement of visual acuity was confirmed in 31 out of 44 patients (70.45%). The mean BCVA of 44 patients changed from 1.65 ± 0.78 logarithmic minimum angle of resolution (logMAR) at the first visit to 1.18 ± 0.91 logMAR at the last visit (p = 0.114). The BCVA according to CRAO stage was 0.08 ± 0.11 logMAR for the incomplete stage at the first visit, 0.06 ± 0.05 logMAR (p = 0.933) 1 month after the procedure, and 0.05 ± 0.07 logMAR (p = 0.933) at the last visit. In the subtotal stage, the results were 1.81 ± 0.54 logMAR at the first visit, 1.63 ± 0.76 logMAR (p = 0.035) 1 month after the procedure, and 1.36 ± 0.85 logMAR (p = 0.014) at the last visit. For the total stage of BCVA, the result at the first visit was 2.36 ± 0.25 logMAR, and it was 2.30 ± 0.30 logMAR (p = 0.510) 1 month after the procedure, and 2.42 ± 0.30 logMAR (p = 0.642) at the last visit. Reperfusion was observed in 40 patients out of the 44 (90.91%). @*Conclusions@#Selective intra-arterial thrombolysis can be helpful in patients with subtotal CRAO in terms of visual improvement and retinal arterial reperfusion.

Comparison of age‐dependent alterations in thioredoxin 2 and thioredoxin reductase 2 expressions in hippocampi between mice and rats / 한국실험동물학회지

Background@#Aging is one of major causes triggering neurophysiological changes in many brain substructures, including the hippocampus, which has a major role in learning and memory. Thioredoxin (Trx) is a class of small redox proteins. Among the Trx family, Trx2 plays an important role in the regulation of mitochondrial membrane potential and is controlled by TrxR2. Hitherto, age-dependent alterations in Trx2 and TrxR2 in aged hippocampi have been poorly investigated. Therefore, the aim of this study was to examine changes in Trx2 and TrxR2 in mouse and rat hippocampi by age and to compare their differences between mice and rats. @*Results@#Trx2 and TrxR2 levels using Western blots in mice were the highest at young age and gradually reduced with time, showing that no significant differences in the levels were found between the two subfields. In rats, however, their expression levels were the lowest at young age and gradually increased with time. Nevertheless, there were no differences in cellular distribution and morphology in their hippocampi when it was observed by cresyl violet staining. In addition, both Trx2 and TrxR2 immunoreactivities in the CA1-3 fields were mainly shown in pyramidal cells (principal cells), showing that their immunoreactivities were altered like changes in their protein levels. @*Conclusions@#Our current findings suggest that Trx2 and TrxR2 expressions in the brain may be different according to brain regions, age and species. Therefore, further studies are needed to examine the reasons of the differences of Trx2 and TrxR2 expressions in the hippocampus between mice and rats.

Protective Role of Transduced Tat-Thioredoxin1 (Trx1) against Oxidative Stress-Induced Neuronal Cell Death via ASK1-MAPK Signal Pathway

Oxidative stress plays a crucial role in the development of neuronal disorders including brain ischemic injury. Thioredoxin 1 (Trx1), a 12 kDa oxidoreductase, has anti-oxidant and anti-apoptotic functions in various cells. It has been highly implicated in brain ischemic injury. However, the protective mechanism of Trx1 against hippocampal neuronal cell death is not identified yet. Using a cell permeable Tat-Trx1 protein, protective mechanism of Trx1 against hydrogen peroxide-induced cell death was examined using HT-22 cells and an ischemic animal model. Transduced Tat-Trx1 markedly inhibited intracellular ROS levels, DNA fragmentation, and cell death in H 2O 2-treatment HT-22 cells. Tat-Trx1 also significantly inhibited phosphorylation of ASK1 and MAPKs in signaling pathways of HT-22 cells. In addition, Tat-Trx1 regulated expression levels of Akt, NF-κB, and apoptosis related proteins. In an ischemia animal model, Tat-Trx1 markedly protected hippocampal neuronal cell death and reduced astrocytes and microglia activation. These findings indicate that transduced Tat-Trx1 might be a potential therapeutic agent for treating ischemic injury.

Safety and Efficacy of Selective Intra-arterial Thrombolysis for Central Retinal Artery Occlusion

Purpose@#The purpose of this study was to determine the efficacy and safety of selective intra-arterial thrombolysis in patients with central retinal artery occlusion (CRAO). @*Methods@#Medical records for 44 eyes of 44 patients diagnosed with acute non-arteritic CRAO and thrombolysis between October 2010 and February 2019 were analyzed retrospectively. Based on visual acuity, fundoscopic findings, and fluorescein angiography, the patients were classified into three stages: incomplete, subtotal, and total. The perfusion state using the best-corrected visual acuity (BCVA), arm to retina time, and arteriovenous passage times, after 1 month, 6 months, and at the final visit after the procedure, were compared with baseline readings. @*Results@#Improvement of visual acuity was confirmed in 31 out of 44 patients (70.45%). The mean BCVA of 44 patients changed from 1.65 ± 0.78 logarithmic minimum angle of resolution (logMAR) at the first visit to 1.18 ± 0.91 logMAR at the last visit (p = 0.114). The BCVA according to CRAO stage was 0.08 ± 0.11 logMAR for the incomplete stage at the first visit, 0.06 ± 0.05 logMAR (p = 0.933) 1 month after the procedure, and 0.05 ± 0.07 logMAR (p = 0.933) at the last visit. In the subtotal stage, the results were 1.81 ± 0.54 logMAR at the first visit, 1.63 ± 0.76 logMAR (p = 0.035) 1 month after the procedure, and 1.36 ± 0.85 logMAR (p = 0.014) at the last visit. For the total stage of BCVA, the result at the first visit was 2.36 ± 0.25 logMAR, and it was 2.30 ± 0.30 logMAR (p = 0.510) 1 month after the procedure, and 2.42 ± 0.30 logMAR (p = 0.642) at the last visit. Reperfusion was observed in 40 patients out of the 44 (90.91%). @*Conclusions@#Selective intra-arterial thrombolysis can be helpful in patients with subtotal CRAO in terms of visual improvement and retinal arterial reperfusion.

Comparison of age‐dependent alterations in thioredoxin 2 and thioredoxin reductase 2 expressions in hippocampi between mice and rats / 한국실험동물학회지

Background@#Aging is one of major causes triggering neurophysiological changes in many brain substructures, including the hippocampus, which has a major role in learning and memory. Thioredoxin (Trx) is a class of small redox proteins. Among the Trx family, Trx2 plays an important role in the regulation of mitochondrial membrane potential and is controlled by TrxR2. Hitherto, age-dependent alterations in Trx2 and TrxR2 in aged hippocampi have been poorly investigated. Therefore, the aim of this study was to examine changes in Trx2 and TrxR2 in mouse and rat hippocampi by age and to compare their differences between mice and rats. @*Results@#Trx2 and TrxR2 levels using Western blots in mice were the highest at young age and gradually reduced with time, showing that no significant differences in the levels were found between the two subfields. In rats, however, their expression levels were the lowest at young age and gradually increased with time. Nevertheless, there were no differences in cellular distribution and morphology in their hippocampi when it was observed by cresyl violet staining. In addition, both Trx2 and TrxR2 immunoreactivities in the CA1-3 fields were mainly shown in pyramidal cells (principal cells), showing that their immunoreactivities were altered like changes in their protein levels. @*Conclusions@#Our current findings suggest that Trx2 and TrxR2 expressions in the brain may be different according to brain regions, age and species. Therefore, further studies are needed to examine the reasons of the differences of Trx2 and TrxR2 expressions in the hippocampus between mice and rats.

The effect of 4-hexylresorinol administration on NAD+ level and SIRT activity in Saos-2 cells / 대한악안면성형재건외과학회지

Background@#4-hexylresorcinol (4HR) has been shown to have anti-oxidant activity similar to that of resveratrol. As resveratrol increases sirtuin (SIRT) activity, 4HR might behave similarly to resveratrol.Method: In this study, the expression levels of SIRT1, SIRT3, and SIRT6 were evaluated after 4HR administration (1–100 μM). As NAD+ is a substrate for SIRTs, its levels with SIRT activity were also studied. @*Results@#In the results, SIRT3 (100 μM at 24 h) and SIRT6 (1–100 μM at 24 h and 10 μM at 8 h) were shown to have significantly higher expression levels compared to untreated control (p < 0.05). Pan-SIRT activity and the NAD+ level was significantly increased compared to that of the untreated control (p < 0.05; 10 and 100 μM at 24 h). @*Conclusion@#4HR administration increased SIRT activity and the NAD+ level in Saos-2 cells.

Hematopoietic Stem Cell Registry Report: 2018 / 대한수혈학회지

Background@#Hematopoietic stem cell (HSC) transplantation is an important therapeutic option for many malignant and non-malignant diseases. The whole transplant process involves multiple areas and complex steps. The laboratory procedures include the collection, processing, and storage of HSC. The HSC registry aims to identify the current situation and draw improvement points by voluntarily registering the information of an HSC graft collected by each institute sharing the analyzed data. This study analyzed and shared the data for 2018. @*Methods@#Data for 2018 registered at the HSC registry website (www.ksfa-registry.org) was downloaded and analyzed. The data were to enter the information of each collection and include the demography of the donors, transplant type, instrument, vascular access, mobilization modality, and the number of CD34＋ cells. @*Results@#Two thousand eight hundred eighty-eight collection datasets from 1,373 donors were registered from 19 institutes, which was slightly higher than that reported in 2017. The number of collections in one patient was in the range of 1∼17 times, and the average was two times. In allogeneic HSCT, the number of related donors was higher than that of unrelated donors. The frequency of collecting more than four times per donor was 25.2% for autologous donors, compared to 95.4% for allogeneic donors less than twice. @*Conclusion@#The HSC registry is not limited to identifying the current situation and sharing the analyzed data, but is expected to contribute to the development of guidelines, education of human resources, and the standardization of laboratory procedures involved in hematopoietic stem cell transplantation.

Changes of fat-mass and obesity-associated protein expression in the hippocampus in animal models of high-fat diet-induced obesity and D-galactose-induced aging / 한국실험동물학회지

Fat-mass and obesity-associated protein (Fto) is highly expressed in the brain including, the hippocampus, and its expression is significantly decreased in the brain of Alzheimer’s disease patients. In the present study, we measured Fto immunoreactivity and protein levels in the hippocampus of obese and aged mice, which were induced by high-fat diet for 12 weeks and D-galactose treatment for 10 weeks, respectively. The obesity and aging phenotypes were assessed by physiological parameters and Morris water maze test, respectively. High fat diet fed mice showed significant increases in body weight and blood glucose levels compared to that in the control or D-galactose-induced aged mice. In addition, treatment with D-galactose significantly decreased the spatial memory. Fto immunoreactivity in the control group was mainly detected in the pyramidal cells of the CA1 and CA3 regions and in the granule cells of the dentate gyrus. In the hippocampus of high-fat diet-fed mice, Fto immunoreactive structures were similarly found in the hippocampus compared to that in the control group, but Fto immunoreactivity in high-fat diet-fed mice was also found in the stratum oriens and radiatum of the CA1 and CA3 regions and the polymorphic layer of the dentate gyrus. In the hippocampus of D-galactose-induced aged mice, fewer Fto immunoreactive structures were detected in the granule cell layer of the dentate gyrus compared to the control group. Fto mRNA and protein levels based on quantitative real-time polymerase chain reaction and western blot assays were slightly increased in the hippocampus of high-fat diet-fed mice compared to that in control mice. In addition, Fto mRNA and protein levels were significantly decreased in the aged hippocampus compared to that in the control group. Fto protein levels are susceptible to the aging process, but not in the hippocampus of high-fat diet-induced obesity. The reduction of Fto in aged mice may be associated with reduced memory impairment in mice.

Dual antiplatelet treatment associated with reduced risk of symptomatic vasospasm and delayed cerebral ischemia in aneurysmal subarachnoid hemorrhage

Objective@#Cerebral vasospasm and delayed cerebral ischemia (DCI) are considered complications after aneurysmal subarachnoid hemorrhage (aSAH). Several hypotheses involving platelet activation have been asserted in the pathophysiology of cerebral vasospasm and DCI. This study aimed to investigate the effect of dual antiplatelet treatment (DAPT) on symptomatic vasospasm and DCI in patients with aSAH. @*Methods@#A retrospective study was conducted on patients with aSAH from 2009 to 2018. The patients are divided into 2 groups according to the treatment method such as simple or balloon-assisted coil embolization group (SB coiling), and stent-assisted coil embolization group. Patients treated by SB coiling without DAPT were classified as the control group. Patients who required dual antiplatelet treatment due to stent-assisted coil embolization were classified as DAPT group. The incidence of symptomatic vasospasm and DCI was compared between the two groups. @*Results@#Of 743 patients with aSAH, 563 patients were treated with clipping, 115 patients treated with SB coiling, and 65 patients receive stent-assisted coiling. Among 115 patients underwent SB coiling, 14 patients were excluded by the exclusion criteria. Total number of control group (SB coiling) was 101, DAPT group (stent-assisted coiling) was 65. Depending on whether or not taking DAPT, the incidence of symptomatic vasospasm was lower in the DAPT group (p=0.010). DCI incidence was also lower in the DAPT group, which was statistically significant (p=0.029). @*Conclusions@#DAPT reduces the frequency of symptomatic vasospasm and DCI in patients with aSAH in our single-center study. To warranting this topic, further, larger prospective and randomized studies should be needed.

Heat shock protein 70 increases cell proliferation, neuroblast differentiation, and the phosphorylation of CREB in the hippocampus / 한국실험동물학회지

In the present study, we investigated the effects of heat shock protein 70 (HSP70) on novel object recognition, cell proliferation, and neuroblast differentiation in the hippocampus. To facilitate penetration into the blood–brain barrier and neuronal plasma membrane, we created a Tat-HSP70 fusion protein. Eight-week-old mice received intraperitoneal injections of vehicle (10% glycerol), control-HSP70, or Tat-HSP70 protein once a day for 21 days. To elucidate the delivery efficiency of HSP70 into the hippocampus, western blot analysis for polyhistidine was conducted. Polyhistidine protein levels were significantly increased in control-HSP70- and Tat-HSP70-treated groups compared to the control or vehicle-treated group. However, polyhistidine protein levels were significantly higher in the Tat-HSP70-treated group compared to that in the control-HSP70-treated group. In addition, immunohistochemical study for HSP70 showed direct evidences for induction of HSP70 immunoreactivity in the control-HSP70- and Tat-HSP70-treated groups. Administration of Tat-HSP70 increased the novel object recognition memory compared to untreated mice or mice treated with the vehicle. In addition, the administration of Tat-HSP70 significantly increased the populations of proliferating cells and differentiated neuroblasts in the dentate gyrus compared to those in the control or vehicle-treated group based on the Ki67 and doublecortin (DCX) immunostaining. Furthermore, the phosphorylation of cAMP response element-binding protein (pCREB) was significantly enhanced in the dentate gyrus of the Tat-HSP70-treated group compared to that in the control or vehicle-treated group. Western blot study also demonstrated the increases of DCX and pCREB protein levels in the Tat-HSP70-treated group compared to that in the control or vehicle-treated group. In contrast, administration of control-HSP70 moderately increased the novel object recognition memory, cell proliferation, and neuroblast differentiation in the dentate gyrus compared to that in the control or vehicle-treated group. These results suggest that Tat-HSP70 promoted hippocampal functions by increasing the pCREB in the hippocampus.

RbAp48 expression and neuronal damage in the gerbil hippocampus following 5 min of transient ischemia / 한국실험동물학회지

Histone-binding protein RbAp48 has been known to be involved in histone acetylation, and epigenetic alterations of histone modifications are closely associated with the pathogenesis of ischemic reperfusion injury. In the current study, we investigated chronological change of RbAp48 expression in the hippocampus following 5 min of transient ischemia in gerbils. RbAp48 expression was examined 1, 2, 5, and 10 days after transient ischemia using immunohistochemistry. In sham operated gerbils, RbAp48 immunoreactivity was strong in pyramidal and non-pyramidal cells in the hippocampus. After transient ischemia, RbAp48 immunoreactivity was changed in the cornu ammonis 1 subfield (CA1), not in CA2/3. RbAp48 immunoreactivity in CA1 pyramidal neurons was gradually decreased and not detected at 5 and 10 days after ischemia. RbAp48 immunoreactivity in non-pyramidal cells was maintained until 2 days post-ischemia and significantly increased from 5 days post-ischemia. Double immunohistofluorescence staining revealed that RbAp48 immunoreactive non-pyramidal cells were astrocytes. At 5 days post-ischemia, death of pyramidal neurons occurred only in the CA1. These results showed that RbAp48 immunoreactivity was distinctively altered in pyramidal neurons and astrocytes in the hippocampal CA1 following 5 mins of transient ischemia. Ischemia-induced change in RbAp48 expression may be closely associated with neuronal death and astrocyte activation following 5 min of transient ischemia.

Transduced Tat-aldose Reductase Protects Hippocampal Neuronal Cells against Oxidative Stress-induced Damage

Aldose reductase (AR) protein, a member of the NADPH-dependent aldo-keto reductase family, reduces a wide range of aldehydes and enhances cell survival by inhibition of oxidative stress. Oxidative stress is known as one of the major pathological factor in ischemia. Since the precise function of AR protein in ischemic injury is fully unclear, we examined the function of AR protein in hippocampal neuronal (HT-22) cells and in an animal model of ischemia in this study. Cell permeable Tat-AR protein was produced by fusion of protein transduction domain in Tat for delivery into the cells. Tat-AR protein transduced into HT-22 cells and significantly inhibited cell death and regulated the mitogen-activate protein kinases (MAPKs), Bcl-2, Bax, and Caspase-3 under oxidative stress condition. In an ischemic animal model, Tat-AR protein transduced into the brain tissues through the blood-brain barrier (BBB) and drastically decreased neuronal cell death in hippocampal CA1 region. These results indicate that transduced Tat-AR protein has protective effects against oxidative stress-induced neuronal cell death in vitro and in vivo, suggesting that Tat-AR protein could be used as potential therapeutic agent in ischemic injury.

Bacopa monnieri extract improves novel object recognition, cell proliferation, neuroblast differentiation, brain-derived neurotrophic factor, and phosphorylation of cAMP response element-binding protein in the dentate gyrus / 한국실험동물학회지

Bacopa monnieri is a medicinal plant with a long history of use in Ayurveda, especially in the treatment of poor memory and cognitive deficits. In the present study, we hypothesized that Bacopa monnieri extract (BME) can improve memory via increased cell proliferation and neuroblast differentiation in the dentate gyrus. BME was administered to 7-week-old mice once a day for 4 weeks and a novel object recognition memory test was performed. Thereafter, the mice were euthanized followed by immunohistochemistry analysis for Ki67, doublecortin (DCX), and phosphorylated cAMP response element-binding protein (CREB), and western blot analysis of brain-derived neurotrophic factor (BDNF). BME-treated mice showed moderate increases in the exploration of new objects when compared with that of familiar objects, leading to a significant higher discrimination index compared with vehicle-treated mice. Ki67 and DCX immunohistochemistry showed a facilitation of cell proliferation and neuroblast differentiation following the administration of BME in the dentate gyrus. In addition, administration of BME significantly elevated the BDNF protein expression in the hippocampal dentate gyrus, and increased CREB phosphorylation in the dentate gyrus. These data suggest that BME improves novel object recognition by increasing the cell proliferation and neuroblast differentiation in the dentate gyrus, and this may be closely related to elevated levels of BDNF and CREB phosphorylation in the dentate gyrus.

Changes of myelin basic protein in the hippocampus of an animal model of type 2 diabetes / 한국실험동물학회지

In this study, we observed chronological changes in the immunoreactivity and expression level of myelin basic protein (MBP), one of the most abundant proteins in the central nervous system, in the hippocampus of Zucker diabetic fatty (ZDF) rats and their control littermates (Zucker lean control; ZLC). In the ZLC group, body weight steadily increased with age; the body weight of the ZDF group, however, peaked at 30 weeks of age, and subsequently decreased. Based on the changes of body weight, animals were divided into the following six groups: early (12-week), middle (30-week), and chronic (52-week) diabetic groups and their controls. MBP immunoreactivity was found in the alveus, strata pyramidale, and lacunosum-moleculare of the CA1 region, strata pyramidale and radiatum of the CA3 region, and subgranular zone, polymorphic layer, and molecular layer of the dentate gyrus. MBP immunoreactivity was lowest in the hippocampus of 12-week-old rats in the ZLC group, and highest in 12-week-old rats in the ZDF group. Diabetes increased MBP levels in the 12-week-old group, while MBP immunoreactivity decreased in the 30-week-old group. In the 52-week-old ZLC and ZDF groups, MBP immunoreactivity was detected in the hippocampus, similar to the 30-week-old ZDF group. Western blot results corroborated with immunohistochemical results. These results suggested that changes in the immunoreactivity and expression of MBP in the hippocampus might be a compensatory response to aging, while the sustained levels of MBP in diabetic animals could be attributed to a loss of compensatory responses in oligodendrocytes.

Decrease in glucose transporter 1 levels and translocation of glucose transporter 3 in the dentate gyrus of C57BL/6 mice and gerbils with aging / 한국실험동물학회지

In the present study, we compared the cell-specific expression and changes protein levels in the glucose transporters (GLUTs) 1 and 3, the major GLUTs in the mouse and gerbil brains using immunohistochemistry and Western blot analysis. In both mouse and gerbils, GLUT1 immunoreactivity was mainly found in the blood vessels in the dentate gyrus, while GLUT3 immunoreactivity was detected in the subgranular zone and the molecular layer of the dentate gyrus. GLUT1-immunoreactivity in blood vessels and GLUT1 protein levels were significantly decreased with age in the mice and gerbils, respectively. In addition, few GLUT3-immunoreactive cells were found in the subgranular zone in aged mice and gerbils, but GLUT3-immunoreactivity was abundantly found in the polymorphic layer of dentate gyrus in mice and gerbils with a dot-like pattern. Based on the double immunofluorescence study, GLUT3-immunoreactive structures in gerbils were localized in the glial fibrillary acidic protein-immunoreactive astrocytes in the dentate gyrus. Western blot analysis showed that GLUT3 expression in the hippocampal homogenates was slightly, although not significantly, decreased with age in mice and gerbils, respectively. These results indicate that the reduction in GLUT1 in the blood vessels of dentate gyrus and GLUT3 in the subgranular zone of dentate gyrus may be associated with the decrease in uptake of glucose into brain and neuroblasts in the dentate gyrus. In addition, the expression of GLUT3 in the astrocytes in polymorphic layer of dentate gyrus may be associated with metabolic changes in glucose in aged hippocampus.