Supraclavicular cephalic vein draining into the internal jugular vein via the external jugular vein.

PURPOSE: The aim of this study is to report rare anatomical variations of the cephalic vein (CV) in a 77-year-old Korean male cadaver. CASE REPORT: On the right upper arm, the CV located lateral to the deltopectoral groove passed anterior to the clavicle at the lateral one-fourth of the clavicle without anastomosis to the axillary vein. It was connected to the transverse cervical and suprascapular veins by two communicating branches in the middle of its course at the neck, and opened into the external jugular vein at its junction with the internal jugular veins. The suprascapular and anterior jugular veins were flowed into the subclavian vein at the jugulo-subclavian venous confluence, and were connected by a short communicating branch. CONCLUSION: Detailed knowledge of the variations in the CV is expected to be helpful in decreasing unpredicted injuries and possible postoperative complications when invasive venous access is performed through the CV.

Physical Stress Induced Reduction of Proliferating Cells and Differentiated Neuroblasts Is Ameliorated by Fermented Laminaria japonica Extract Treatment.

Laminaria japonica is widely cultivated in East Asia, including South Korea. Fucoidan, a main component of L. japonica, protects neurons from neurological disorders such as ischemia and traumatic brain injury. In the present study, we examined the effects of extract from fermented L. japonica on the reduction of proliferating cells and neuroblasts in mice that were physically (with electric food shock) or psychologically (with visual, auditory and olfactory sensation) stressed with the help of a communication box. Vehicle (distilled water) or fermented L. japonica extract (50 mg/kg) were orally administered to the mice once a day for 21 days. On the 19th day of the treatment, physical and psychological stress was induced by foot shock using a communication box and thereafter for three days. Plasma corticosterone levels were significantly increased after exposure to physical stress and decreased Ki67 positive proliferating cells and doublecortin immunoreactive neuroblasts. In addition, western blot analysis demonstrated that physical stress as well as psychological stress decreased the expression levels of brain-derived neurotrophic factor (BDNF) and the number of phosphorylated cAMP response element binding protein (pCREB) positive nuclei in the dentate gyrus. Fermentation of L. japonica extract significantly increased the contents of reduced sugar and phenolic compounds. Supplementation with fermented L. japonica extract significantly ameliorated the increases of plasma corticosterone revels and decline in the proliferating cells, neuroblasts, and expression of BDNF and pCREB in the physically stressed mice. These results indicate that fermented L. japonica extract has positive effects in ameliorating the physical stress induced reduction in neurogenesis by modulating BDNF and pCREB expression in the dentate gyrus.

Pyridoxine Deficiency Exacerbates Neuronal Damage after Ischemia by Increasing Oxidative Stress and Reduces Proliferating Cells and Neuroblasts in the Gerbil Hippocampus.

We investigated the effects of pyridoxine deficiency on ischemic neuronal death in the hippocampus of gerbil (n = 5 per group). Serum pyridoxal 5'-phosphate levels were significantly decreased in Pyridoxine-deficient diet (PDD)-fed gerbils, while homocysteine levels were significantly increased in sham- and ischemia-operated gerbils. PDD-fed gerbil showed a reduction in neuronal nuclei (NeuN)-immunoreactive neurons in the medial part of the hippocampal CA1 region three days after. Reactive astrocytosis and microgliosis were found in PDD-fed gerbils, and transient ischemia caused the aggregation of activated microglia in the stratum pyramidale three days after ischemia. Lipid peroxidation was prominently increased in the hippocampus and was significantly higher in PDD-fed gerbils than in Control diet (CD)-fed gerbils after ischemia. In contrast, pyridoxine deficiency decreased the proliferating cells and neuroblasts in the dentate gyrus in sham- and ischemia-operated gerbils. Nuclear factor erythroid-2-related factor 2 (Nrf2) and brain-derived neurotrophic factor (BDNF) levels also significantly decreased in PDD-fed gerbils sham 24 h after ischemia. These results suggest that pyridoxine deficiency accelerates neuronal death by increasing serum homocysteine levels and lipid peroxidation, and by decreasing Nrf2 levels in the hippocampus. Additionally, it reduces the regenerated potentials in hippocampus by decreasing BDNF levels. Collectively, pyridoxine is an essential element in modulating cell death and hippocampal neurogenesis after ischemia.

Phosphoglycerate Mutase 1 Promotes Cell Proliferation and Neuroblast Differentiation in the Dentate Gyrus by Facilitating the Phosphorylation of cAMP Response Element-Binding Protein.

In a previous study, we observed a significant increase in phosphoglycerate mutase 1 (PGAM1) levels after pyridoxine treatment. In the present study, we investigated the effects of PGAM1 on novel object recognition, cell proliferation, and neuroblast differentiation in the dentate gyrus. We generated a Tat-PGAM1 fusion protein to cross the blood-brain barrier and neuronal plasma membrane. We administered the Tat peptide, control-PGAM1, or Tat-PGAM1 fusion protein to 8-week-old mice once a day for 3 weeks and tested novel object recognition memory. The mice were then euthanized to conduct western blot analysis for polyhistidine expression and immunohistochemical analysis for Ki67, doublecortin, and phosphorylated cAMP response element-binding protein. Mice treated with Tat peptide showed similar exploration times for familiar and new objects and the discrimination index was significantly lower in this group than in the control group. Tat-PGAM1 moderately increased the exploration time of new objects when compared to familiar objects, while the discrimination index was significantly higher in the Tat-PGAM1-treated group, but not in the control-PGAM1-treated group, when compared with the control group. Higher PGAM1 protein expression was observed in the hippocampus of Tat-PGAM1-treated mice when compared with the hippocampi of control, Tat peptide-, and control-PGAM1-treated mice, using western blot analysis. In addition, the numbers of proliferating cells and differentiated neuroblasts were significantly lower in the Tat peptide-treated group than in the control group. In contrast, the numbers of proliferating cells and differentiated neuroblasts in the dentate gyrus were higher in the Tat-PGAM1-treated group than in the control group. Administration of Tat-PGAM1 significantly facilitated the phosphorylation of cAMP response element-binding protein in the dentate gyrus. Administration of control-PGAM1 did not show any significant effects on novel object recognition, cell proliferation, and neuroblast differentiation in the dentate gyrus. These results suggest that PGAM1 plays a role in cell proliferation and neuroblast differentiation in the dentate gyrus via the phosphorylation of cAMP response element-binding protein in the hippocampus.

Leaf extracts from Dendropanax morbifera Léveille mitigate mercury-induced reduction of spatial memory, as well as cell proliferation, and neuroblast differentiation in rat dentate gyrus.

BACKGROUND: The brain is susceptible to methylmercury toxicity, which causes irreversible damage to neurons and glia and the leaf extract Dendropanax morbifera Léveille (DML) has various biological functions in the nervous system. In this study, we examined the effects of DML on mercury-induced proliferating cells and differentiated neuroblasts. METHODS: Dimethylmercury (5 µg/kg) and galantamine (5 mg/kg) was administered intraperitoneally and/or DML (100 mg/kg) was orally to 7-week-old rats every day for 36 days. One hour after the treatment, novel object recognition test was examined. In addition, spatial probe tests were conducted on the 6th day after 5 days of continuous training in the Morris swim maze. Thereafter, the rats were euthanized for immunohistochemical staining analysis with Ki67 and doublecortin and measurement for acetylcholinesterase (AChE) activity. RESULTS: Dimethylmercury-treated rats showed reduced discrimination index in novel object recognition test and took longer to find the platform than did control group. Compared with dimethylmercury treatment alone, supplementation with DML or galatamine significantly ameliorated the reduction of discrimination index and reduced the time spent to find the platform. In addition, the number of platform crossings was lower in the dimethylmercury-treated group than in controls, while the administration of DML or galantamine significantly increased the number of crossings than did dimethylmercury treatment alone. Proliferating cells and differentiated neuroblasts, assessed by Ki67 and doublecortin immunohistochemical staining was significantly decreased in the dimethylmercury treated group versus controls. Supplementation with DML or galantamine significantly increased the number of proliferating cells and differentiated neuroblasts in the dentate gyrus. In addition, treatment with dimethylmercury significantly increased AChE activity in hippocampal homogenates, while treatment with dimethylmercury+DML or dimethylmercury+galantamine significantly ameliorated this increase. CONCLUSIONS: These results suggest that DML may be a functional food that improves dimethylmercury-induced memory impairment and ameliorates dimethylmercury-induced reduction in proliferating cells and differentiated neuroblasts, and demonstrates corresponding activation of AChE activity in the dentate gyrus.

Active Control of Inertial Focusing Positions and Particle Separations Enabled by Velocity Profile Tuning with Coflow Systems.

Inertial microfluidics has drawn much attention not only for its diverse applications but also for counterintuitive new fluid dynamic behaviors. Inertial focusing positions are determined by two lift forces, that is, shear gradient and wall-induced lift forces, that are generally known to be opposite in direction in the flow through a channel. However, the direction of shear gradient lift force can be reversed if velocity profiles are shaped properly. We used coflows of two liquids with different viscosities to produce complex velocity profiles that lead to inflection point focusing and alteration of inertial focusing positions; the number and the locations of focusing positions could be actively controlled by tuning flow rates and viscosities of the liquids. Interestingly, 3-inlet coflow systems showed focusing mode switching between inflection point focusing and channel face focusing depending on Reynolds number and particle size. The focusing mode switching occurred at a specific size threshold, which was easily adjustable with the viscosity ratio of the coflows. This property led to different-sized particles focusing at completely different focusing positions and resulted in highly efficient particle separation of which the separation threshold was tunable. Passive separation techniques, including inertial microfluidics, generally have a limitation in the control of separation parameters. Coflow systems can provide a simple and versatile platform for active tuning of velocity profiles and subsequent inertial focusing characteristics, which was demonstrated by active control of the focusing mode using viscosity ratio tuning and temperature changes of the coflows.

Ultrastructural Changes and Expression of PCNA and RPE65 in Sodium Iodate-Induced Acute Retinal Pigment Epithelium Degeneration Model.

Alteration in retinal pigment epithelium (RPE) results in the visual dysfunction and blindness of retinal degenerative diseases. Injection of sodium iodate (NaIO3) generates degeneration of RPE. We analyzed the sequential ultrastructure and expression of proliferating cell nuclear antigen (PCNA) and retina-specific RPE65 in NaIO3-induced retinal degeneration model. Adult male rats were injected 1% NaIO3 (50 mg/kg) and eyes were enucleated at 1, 3, 5, 7 and 14 days post-injection (DPI), fixed, and processed for histological analysis. NaIO3-induced retinal degeneration was successfully established. At 1 DPI, most RPE cells were degenerated and replaced by a few proliferating RPE cells in the peripheral area. At 3 DPI, the RPE and photoreceptor out segments (POS) underwent a marked morphological change, including POS disruption, accumulation of residual bodies in RPE and POS, and hyperplasia of the RPE cell. At 5 DPI, POS showed a maximum increase in the outer segment debris and the retina showed partial detachment. These abnormal morphological changes gradually decreased by day 7. At 14 DPI, the damaged RPE and POS were partially regenerated from the peripheral to the central region. Expression of PCNA and RPE65 increased from day 3 onward. The damaged RPE showed earlier expression of PCNA and RPE65 than POS. The RPE damaged by NaIO3 rapidly proliferated to put down roots on Bruch's membrane from the peripheral retina and proliferation and hyperplasia of the RPE had a regular direction of progress. Therefore, NaIO3-induced acute changes in retina mimic the patho-morphologic features of RPE-related diseases.

Gintonin Attenuates D-Galactose-Induced Hippocampal Senescence by Improving Long-Term Hippocampal Potentiation, Neurogenesis, and Cognitive Functions.

BACKGROUND: Ginseng has been used to improve brain function and increase longevity. However, little is known about the ingredients of ginseng and molecular mechanisms of its anti-brain aging effects. Gintonin is a novel exogenous ginseng-derived lysophosphatidic acid (LPA) receptor ligand; LPA and LPA1 receptors are involved in adult hippocampal neurogenesis. D-galactose (D-gal) is used to induce brain -aging in animal models because long-term treatment with D-gal facilitates hippocampal aging in experimental adult animals by decreasing hippocampal neurogenesis and inducing learning and memory dysfunction. OBJECTIVE: To investigate the protective effects of gintonin on D-gal-induced hippocampal senescence, impairment of long-term potentiation (LTP), and memory dysfunction. METHODS: Brain hippocampal aging was induced by D-gal administration (150 mg/kg/day, s.c.; 10 weeks). From the 7th week, gintonin (50 or 100 mg/kg/day, per os) was co-administered with D-gal for 4 weeks. We performed histological analyses, LTP measurements, and object location test. RESULTS: Co-administration of gintonin ameliorated D-gal-induced reductions in hippocampal Ki67-immunoreactive proliferating cells, doublecortin-immunoreactive neuroblasts, 5-bromo-2'-deoxyuridine-incorporating NeuN-immunoreactive mature neurons, and LPA1 receptor expression. Co-administration of gintonin in D-gal-treated mice increased the expression of phosphorylated cyclic adenosine monophosphate response element binding protein in the hippocampal dentate gyrus. In addition, co-administration of gintonin in D-gal-treated mice enhanced LTP and restored the cognitive functions compared with those in mice treated with D-gal only. CONCLUSION: These results show that gintonin administration restores D-gal-induced memory deficits by enhancing hippocampal LPA1 receptor expression, LTP, and neurogenesis. Finally, the present study shows that gintonin exerts anti-brain aging effects that are responsible for alleviating brain aging-related dysfunction.

Differential Effects of Low- and High-dose Zinc Supplementation on Synaptic Plasticity and Neurogenesis in the Hippocampus of Control and High-fat Diet-fed Mice.

In the present study, we investigated the concentration-dependent effect of zinc (Zn) supplementation on the adult hippocampus in a high-fat diet (HFD)-fed obese mouse model. Four-weeks after HFD- and control diet (CD)-feeding, mice were provided with low (15 ppm) or high (60 ppm) doses of Zn in their drinking water for additional 4 more weeks along with their respective diets. Compared to the CD-fed mice, HFD-feeding elicited the reduction of neurogenic markers such as nestin, Ki67, doublecortin (DCX), and 5-bromo-2'-deoxyuridine (BrdU) in the dentate gyrus. Additionally, HFD-feeding reduced the levels of synaptic markers (synaptophysin and N-methyl-D-aspartate receptor) and brain-derived neurotrophic factor (BDNF), while lipid peroxidation was significantly increased in the hippocampus of HFD-fed mice. Against detrimental effects of high-dose Zn, low-dose Zn supplementation in CD-fed mice did not yield any remarkable changes in these parameters. Interestingly, administration of low doses of Zn to HFD-induced obese mice prominently ameliorated HFD-induced changes in neurogenic, synaptic plasticity markers and BDNF levels as well as lipid peroxidation in the hippocampus. In contrast, high-dose Zn supplementation in HFD-fed mice exacerbated the reduction of markers for neurogenesis and synaptic plasticity as well as BDNF levels, but not 4-HNE levels, in the hippocampus. These results suggest that low-dose Zn supplementation in obese mice could reverse the HFD-induced reduction in neurogenic and synaptic marker proteins in the hippocampus by reducing lipid peroxidation and improving BDNF expression, while high-dose Zn supplementation exacerbates the reduction of neurogenesis by affecting synaptic markers and BDNF levels in the hippocampus.

Pyridoxine improves hippocampal cognitive function via increases of serotonin turnover and tyrosine hydroxylase, and its association with CB1 cannabinoid receptor-interacting protein and the CB1 cannabinoid receptor pathway.

BACKGROUND: In the present study, we investigated the effects of pyridoxine on hippocampal functions and changes in protein profiles based on the proteomic approach. METHODS: Eight-week-old mice received intraperitoneal injections of physiological saline (vehicle) or 350mg/kg pyridoxine twice a day for 21days. RESULTS: Phosphoglycerate mutase 1 was up-regulated, while CB1 cannabinoid receptor-interacting protein 1 (CRIP1) was down-regulated, in the pyridoxine-treated group. Additionally, the serotonin and tyrosine hydroxylase was increased in the hippocampus of the pyridoxine-treated group than in that of the vehicle-treated group. Furthermore, discrimination indices based on the novel object recognition test were significantly higher in the pyridoxine-treated group than in the vehicle-treated group. Administration of CRIP1a siRNA significantly increases the discrimination index as well as cell proliferation and neuroblast differentiation in the dentate gyrus. In addition, the administration of rimonabant, a CB1 cannabinoid receptor antagonist, for 3weeks significantly decreased the novel object recognition memory, the tyrosine hydroxylase level, the amount of cell proliferation, and neuroblast differentiation in the dentate gyrus. Treatment with pyridoxine significantly increased novel object recognition memory, but slightly ameliorated rimonabant-induced reduction in serotonin, the tyrosine hydroxylase level, the amount of cell proliferation, and neuroblast differentiation in the dentate gyrus. CONCLUSION: These results suggest that pyridoxine promotes hippocampal functions by increasing serotonin and tyrosine hydroylase immunoreactivity in the hippocampus. This positive effect may be associated with CRIP1a and CB1 cannabinoid receptor function. GENERAL SIGNIFICANCE: Vitamin-B6 enhances hippocampal functions and this is closely associated with CRIP1a and CB1 cannabinoid receptors.

Comparison of Adult Hippocampal Neurogenesis and Susceptibility to Treadmill Exercise in Nine Mouse Strains.

The genetic background of mice has various influences on the efficacy of physical exercise, as well as adult neurogenesis in the hippocampus. In this study, we investigated the basal level of hippocampal neurogenesis, as well as the effects of treadmill exercise on adult hippocampal neurogenesis in 9 mouse strains: 8 very commonly used laboratory inbred mouse strains (C57BL/6, BALB/c, A/J, C3H/HeJ, DBA/1, DBA/2, 129/SvJ, and FVB) and 1 outbred mouse strain (ICR). All 9 strains showed diverse basal levels of cell proliferation, neuroblast differentiation, and integration into granule cells in the sedentary group. C57BL/6 mice showed the highest levels of cell proliferation, neuroblast differentiation, and integration into granule cells at basal levels, and the DBA/2 mice showed the lowest levels. The efficacy of integration into granule cells was maximal in ICR mice. Treadmill exercise increased adult hippocampal neurogenesis in all 9 mouse strains. These results suggest that the genetic background of mice affects hippocampal neurogenesis and C57BL/6 mice are the most useful strain to assess basal levels of cell proliferation and neuroblast differentiation, but not maturation into granule cells. In addition, the DBA/2 strain is not suitable for studying hippocampal neurogenesis.

Hairy and Enhancer of Split 6 (Hes6) Deficiency in Mouse Impairs Neuroblast Differentiation in Dentate Gyrus Without Affecting Cell Proliferation and Integration into Mature Neurons.

Hes6 is a member of the hairy-enhancer of split homolog (Hes) family of transcription factors and interacts with other Hes family genes. During development, Hes genes are expressed in neural stem cells and progenitor cells. However, the role of Hes6 in adult hippocampal neurogenesis remains unclear. We therefore investigated the effects of Hes6 on adult hippocampal neurogenesis, by comparing Hes6 knockout and wild-type mice. To this end, we immunostained for markers of neural stem cells and progenitor cells (nestin), proliferating cells (Ki67), post-mitotic neuroblasts and immature neurons (doublecortin, DCX), mature neuronal cells (NeuN), and astrocyte (S100ß). We also injected 5-bromo-2'-deoxyuridine (BrdU) to trace the fate of mitotic cells. Nestin- and Ki67-positive proliferating cells did now show any significant differences between wild and knockout groups. Hes6 knockout negatively affects neuroblast differentiation based on DCX immunohistochemistry. On the contrary, the ratio of the BrdU and NeuN double-positive cells did not show any significance, even though it was slightly higher in the knockout group. These results suggest that Hes6 is involved in the regulation of neuroblast differentiation during adult neurogenesis, but does not influence integration into mature neurons.

Physical exercise ameliorates the reduction of neural stem cell, cell proliferation and neuroblast differentiation in senescent mice induced by D-galactose.

BACKGROUND: Aging negatively affects adult hippocampal neurogenesis, and exercise attenuates the age-related reduction in adult hippocampal neurogenesis. In the present study, we used senescent mice induced by D-galactose to examine neural stem cells, cell proliferation, and neuronal differentiation with or without exercise treatment. D-galactose (100 mg/kg) was injected to six-week-old C57BL/6 J mice for 6 weeks to induce the senescent model. During these periods, the animals were placed on a treadmill and acclimated to exercise for 1 week. Then treadmill running was conducted for 1 h/day for 5 consecutive days at 10-12 m/min for 5 weeks. RESULTS: Body weight and food intake did not change significantly after D-galactose administration with/without treadmill exercise, although body weight and food intake was highest after treadmill exercise in adult animals and lowest after treadmill exercise in D-galactose-induced senescent model animals. D-galactose treatment significantly decreased the number of nestin (a neural stem cell marker), Ki67 (a cell proliferation marker), and doublecortin (DCX, a differentiating neuroblast marker) positive cells compared to those in the control group. In contrast, treadmill exercise significantly increased Ki67- and DCX-positive cell numbers in both the vehicle- and D-galactose treated groups. In addition, phosphorylated cAMP-response element binding protein (pCREB) and brain derived neurotrophic factor (BDNF) was significantly decreased in the D-galactose treated group, whereas exercise increased their expression in the subgranular zone of the dentate gyrus in both the vehicle- and D-galactose-treated groups. CONCLUSION: These results suggest that treadmill exercise attenuates the D-galactose-induced reduction in neural stem cells, cell proliferation, and neuronal differentiation by enhancing the expression of pCREB and BDNF in the dentate gyrus of the hippocampus.

Comparison of N-methyl-D-aspartate receptor subunit 1 and 4-hydroxynonenal in the hippocampus of natural and chemical-induced aging accelerated mice.

In this study, we compared N-methyl-D-aspartate receptor type 1 (NMDAR1) and 4-hydroxynonenal (4-HNE) in the hippocampus of D-galactose (D-gal)-induced and naturally aging models of mice. These markers represent general phenotypes in aging, and they allowed us to examine the possibility of D-gal as a chemical model agent for aging. We observed an age-dependent reduction of NMDAR1 and an increase in 4-HNE in the dentate gyrus, CA1, and CA3 regions of the hippocampus via immunohistochemistry and western blot analyses. In the D-gal-induced chemical aging model, we observed similar changes in NMDAR1 and 4-HNE although the degree of reduction/increase in NMDAR1/4-HNE was not as severe as that in the naturally aged mice. These results suggest that the D-gal-induced aging model is comparable to naturally aged mice and may be useful for studies of the aging hippocampus.

Tat-DJ-1 protects neurons from ischemic damage in the ventral horn of rabbit spinal cord via increasing antioxidant levels.

The DJ-1 gene is highly conserved in diverse species and DJ-1 is known as an anti-oxidative stress factor. In this study, we investigated the neuroprotective effects of DJ-1 against ischemic damage in the rabbit spinal cord. Tat-DJ-1 fusion proteins were constructed to facilitate the penetration of DJ-1 protein into the neurons. Tat-1-DJ-1 fusion protein was administered to the rabbit 30 min after ischemia/reperfusion, and transient spinal cord ischemia was induced by occlusion of the aorta at the subrenal region for 15 min. The administration of Tat-DJ-1 significantly improved the Tarlov score compared to that in the Tat (vehicle)-treated group at 24, 48 and 72 h after ischemia/reperfusion. At 72 h after ischemia/reperfusion, the number of cresyl violet-positive neurons was significantly increased in the Tat-DJ-1-treated group compared to that in the vehicle-treated group. Lipid peroxidation as judged from the malondialdehyde levels was significantly decreased in the Tat-DJ-1-treated group compared to that in the vehicle-treated group. In contrast, superoxide dismutase and catalase levels were significantly increased in the Tat-DJ-1-treated group compared to that in the vehicle-treated group. This result suggests that DJ-1 protects neurons from ischemic damage in the ventral horn of the spinal cord via its antioxidant effects.

Dendropanax morbifera Léveille extract facilitates cadmium excretion and prevents oxidative damage in the hippocampus by increasing antioxidant levels in cadmium-exposed rats.

BACKGROUND: Dendropanax morbifera Léveille is used in herbal medicine as a cancer treatment. In this study, we investigated the effects of Dendropanax morbifera stem extract (DMS) on cadmium (Cd) excretion from the blood and kidney and brain tissues of rats exposed to cadmium, as well as the effects of DMS on oxidative stress and antioxidant levels in the hippocampus after Cd exposure. METHODS: Seven-week-old Sprague-Dawley rats were exposed to 2 mg/kg of cadmium by intragastric gavage and were orally administered 100 mg/kg of DMS for 4 weeks. Animals were sacrificed and Cd determination was performed using inductively coupled plasma mass spectrometry. In addition, the effects of Cd and/or DMS on oxidative stress were assayed by measuring reactive oxygen species production, protein carbonyl modification, lipid peroxidation levels, and antioxidant levels in hippocampal homogenates. RESULTS: Exposure to Cd significantly increased Cd content in the blood, kidneys, and hippocampi. DMS treatment significantly reduced Cd content in the blood and kidneys, but not in the hippocampi. Exposure to Cd significantly increased reactive oxygen species production, protein carbonyl modification, lipid peroxidation, total sulfhydryl content, reduced glutathione content, and glutathione reductase activity. In contrast, Cu, Zn-superoxide dismutase (SOD1), catalase (CAT), glutathione peroxidase (GPx), and glutathione-S-transferase (GST) activity in the hippocampus were significantly decreased after exposure to Cd, and administration of DMS significantly inhibited these Cd-induced changes. CONCLUSION: These results indicate that DMS facilitates cadmium excretion from the kidneys, reduces cadmium-induced oxidative stress in the hippocampus, and modulates SOD1, CAT, GPx, and glutathione-S-transferase activities.

Valeriana officinalis root extract suppresses physical stress by electric shock and psychological stress by nociceptive stimulation-evoked responses by decreasing the ratio of monoamine neurotransmitters to their metabolites.

BACKGROUND: In this study, we investigate the effects of valerian root extracts (VE) on physical and psychological stress responses by utilizing a communication box. METHODS: Eight-week-old ICR mice received oral administration of VE (100 mg/kg/0.5 ml) or equal volume of distilled water in every day for 3 weeks prior to being subjected to physical or psychological stress for 3 days, which are induced by communication box developed for physical electric shock and psychological stress by nociceptive stimulation-evoked responses. The stress condition was assessed by forced swimming test and serum corticosterone levels. In addition, norepinephrine (NE), serotonin (5-HT), and their metabolites such as 3-methoxy-4-hydroxyphenylethyleneglycol sulfate (MHPG-SO4) and 5-hydroxyindoleacetic acid (5-HIAA) were measured in the hippocampus and amygdala at 1 h after final stress condition, respectively. RESULTS: Immobility time and corticosterone levels were significantly increased in both the physical and psychological stress groups compared to the control group. The administration of VE significantly reduced these parameters in both the physical and psychological stress groups. In addition, compared to the control group, physical and psychological stress groups showed significantly increased levels of MHPG-SO4 and 5-HIAA in the hippocampus and amygdala, respectively. The administration of VE significantly suppressed the increase of MHPG-SO4 and 5-HIAA in the two stress groups. CONCLUSION: These results suggest that VE can suppress physical and psychological stress responses by modulating the changes in 5-HT and NE turnover in the hippocampus and amygdala.

Cynomorium songaricum extract enhances novel object recognition, cell proliferation and neuroblast differentiation in the mice via improving hippocampal environment.

BACKGROUND: Cynomorium songaricum Rupr. (CS) has been used as a medicine to treat many diseases as well as to alleviate age-related issues, such as memory impairment, dementia, and stress. In this study, we assessed the effects of Cynomorium songaricum extract (CSE) on the novel object recognition, cell proliferation and neuroblast differentiation in the dentate gyrus of mice by using 5-bromodeoxyuridine (BrdU) and polysialylated neural cell adhesion molecule (PSA-NCAM). We also measured serum corticosterone levels to assess its correlation with neurogenesis and stress. METHODS: Male C57BL/6 J mice were divided into 3 groups: vehicle-treated, 40 mg/kg CSE-treated, and 100 mg/kg CSE-treated. The vehicle and CSE were given to mice once a day for 3 weeks. BrdU was injected twice a day for 3 days to label newly generated cells. RESULTS: Administration of CSE significantly increased the preferential exploration of new objects in these mice. In addition, administration of CSE decreased serum levels of corticosterone. BrdU-positive cells as well as brain-derived neurotrophic factor (BDNF) mRNA expression in the dentate gyrus were higher in the CSE-treated groups than in the vehicle-treated group. PSA-NCAM-positive neuroblasts and their well-developed tertiary dendrites were also significantly increased by the treatment of CSE. These effects were prominent at the higher dosage than at the lower dosage. CONCLUSION: These results suggest that administration of CSE increases cell proliferation and neuroblast differentiation in the dentate gyrus of mice by reducing serum corticosterone levels and increasing BDNF levels in this area.

New insight into the vasto-adductor membrane for safer adductor canal blockade.

Background: : This study aimed to identify exact anatomical landmarks and ideal injection volumes for safe adductor canal blocks (ACB). Methods: : Fifty thighs from 25 embalmed adult Korean cadavers were used. The measurement baseline was the line connecting the anterior superior iliac spine (ASIS) to the midpoint of the patellar base. All target points were measured perpendicular to the baseline. The relevant cadaveric structures were observed using ultrasound (US) and confirmed in living individuals. US-guided dye injection was performed to determine the ideal volume. Results: : The apex of the femoral triangle was 25.3 ± 2.2 cm distal to the ASIS on the baseline and 5.3 ± 1.0 cm perpendicular to that point. The midpoint of the superior border of the vasto-adductor membrane (VAM) was 27.4 ± 2.0 cm distal to the ASIS on the baseline and 5.0 ± 1.1 cm perpendicular to that point. The VAM had a trapezoidal shape and was connected as an aponeurosis between the medial edge of the vastus medialis muscle and lateral edge of the adductor magnus muscle. The nerve to the vastus medialis penetrated the muscle proximal to the superior border of the VAM in 70% of specimens. The VAM appeared on US as a hyperechoic area connecting the vastus medialis and adductor magnus muscles between the sartorius muscle and femoral artery. Conclusions: : Confirming the crucial landmark, the VAM, is beneficial when performing ACB. It is advisable to insert the needle obliquely below the superior VAM border, and a 5 mL injection is considered sufficient.

Effects of treadmill exercise on neural stem cells, cell proliferation, and neuroblast differentiation in the subgranular zone of the dentate gyrus in cyclooxygenase-2 knockout mice.

Cyclooxygenase-2 (COX-2) function has been implicated in a number of physiological processes, including inflammatory responses, synaptic transmission, and synaptic plasticity in the brain. However, the specific role of COX-2 in exercise-induced neurogenesis is still debatable. Here, we assessed the role of COX-2 in exercise-induced plasticity by comparing COX-2 knockout mice to wild-type control littermates. We investigated the number of neural stem cells, and the degree of cell proliferation and neuronal differentiation in COX-2 knockout and its wild-type mice that either exercised or remained inactive. Wild-type and COX-2 knockout mice were put on a treadmill and were either sedentary or were forced to run 1 h/day for five consecutive days at a pace of 10-12 m/min for 5 weeks. Loss of COX-2 expression in the knockout mice was confirmed with two measures: (1) COX immunolabeling in the hippocampus, and (2) the identification of abnormal kidney development using hematoxylin and eosin staining, including subcapsular glomerular hypoplasia and hypertrophy of the deeper cortical glomeruli. Compared to wild-type mice, COX-2 knockout mice exhibited a significant reduction in the neural stem cells (nestin-positive cells), cell proliferation (Ki67-positive cells), and neuroblast differentiation (doublecortin-positive cells). In contrast, exercise significantly increased the neural stem cells, cell proliferation, and neuroblast differentiation in both the wild-type and COX-2 knockout mice although the NeuN-immunoreactive neurons were similar in all groups. Expression of phosphorylated cAMP-response element binding protein was decreased in knockout mice. Exercise increased its expression in the subgranular zone of the dentate gyrus in both wild-type and knockout mice. These results suggest that the COX-2 pathway is one of important factors on neural stem cells, cell proliferation and neuroblast differentiation in sedentary mice. The ability of exercise to increase these types of neural plasticity, regardless of COX-2 signaling, suggests that the effects of exercise on neural stem cells, cell proliferation, and neuroblast differentiation are induced via a pathway that is independent of COX-2.