Therapeutic Treatment with Pycnogenol® Attenuates Ischemic Brain Injury in Gerbils Focusing on Cognitive Impairment, Neuronal Death, BBB Leakage and Neuroinflammation in the Hippocampus.

BACKGROUND: A gerbil model of ischemia and reperfusion (IR) injury in the forebrain has been developed for studies on mechanisms, prevention and therapeutic strategies of IR injury in the forebrain. Pycnogenol® (PYC), a standardized extract of French maritime pine tree (Pinus pinaster Aiton) has been exploited as an additive for dietary supplement. In the present study, we investigated the neuroprotective effects of post-treatment with PYC and its therapeutic mechanisms in gerbils. METHODS: The gerbils were given sham and IR operation and intraperitoneally injected with vehicle and Pycnogenol® (25, 50 and 100 mg/kg, respectively) immediately, at 24 hours and 48 hours after sham and IR operation. Through 8-arm radial maze test and passive avoidance test, each spatial memory and short-term memory function was assessed. To examine the neuroprotection of Pycnogenol®, we conducted cresyl violet staining, immunohistochemistry for neuronal nuclei, and Fluoro-Jade B histofluorescence. Moreover, we carried out immunohistochemistry for immunoglobulin G (IgG) to investigate blood-brain barrier (BBB) leakage and interleukin-1ß (IL-1ß) to examine change in pro-inflammatory cytokine. RESULTS: We found that IR-induced memory deficits were significantly ameliorated when 100 mg/kg Pycnogenol® was treated. In addition, treatment with 100 mg/kg Pycnogenol®, not 25 mg/kg nor 50 mg/kg, conferred neuroprotective effect against IR injury. For its mechanisms, we found that 100 mg/kg Pycnogenol® significantly reduced BBB leakage and inhibited the expression of IL-1ß. CONCLUSIONS: Therapeutic treatment (post-treatment) with Pycnogenol® after IR effectively attenuated ischemic brain injury in gerbils. Based on these results, we suggest that PYC can be employed as an important material for ischemic drugs.

Risperidone Administration Attenuates Renal Ischemia and Reperfusion Injury following Cardiac Arrest by Antiinflammatory Effects in Rats.

Multi-organ dysfunction following cardiac arrest is associated with poor outcome as well as high mortality. The kidney, one of major organs in the body, is susceptible to ischemia and reperfusion; however, there are few studies on renal ischemia and reperfusion injury (IRI) following the return of spontaneous circulation (ROSC) after cardiac arrest. Risperidone, an atypical antipsychotic drug, has been discovered to have some beneficial effects beyond its original effectiveness. Therefore, the aim of the present study was to investigate possible therapeutic effects of risperidone on renal IRI following cardiac arrest. Rats were subjected to cardiac arrest induced by asphyxia for five minutes followed by ROSC. When serum biochemical analyses were examined, the levels of serum blood urea nitrogen, creatinine, and lactate dehydrogenase were dramatically increased after cardiac arrest, but they were significantly reduced by risperidone administration. Histopathology was examined using hematoxylin and eosin staining. Histopathological injury induced by cardiac arrest was apparently attenuated by risperidone administration. Furthermore, alterations in pro-inflammatory cytokines (interleukin-6 and tumor necrosis factor-α) and anti-inflammatory cytokines (interleukin-4 and interleukin-13) were examined by immunohistochemistry. Pro-inflammatory and anti-inflammatory cytokine immunoreactivities were gradually and markedly increased and decreased, respectively, in the kidneys following cardiac arrest; however, risperidone administration after cardiac arrest significantly attenuated the increased pro-inflammatory cytokine immunoreactivities and the decreased anti-inflammatory cytokine immunoreactivities. Collectively, our current results revealed that, in rats, risperidone administration after cardiac arrest protected kidneys from IRI induced by cardiac arrest and ROSC through anti-inflammatory effects.

Therapeutic Hypothermia after Cardiac Arrest Attenuates Hindlimb Paralysis and Damage of Spinal Motor Neurons and Astrocytes through Modulating Nrf2/HO-1 Signaling Pathway in Rats.

Cardiac arrest (CA) and return of spontaneous circulation (ROSC), a global ischemia and reperfusion event, lead to neuronal damage and/or death in the spinal cord as well as the brain. Hypothermic therapy is reported to protect neurons from damage and improve hindlimb paralysis after resuscitation in a rat model of CA induced by asphyxia. In this study, we investigated roles of nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) in the lumbar spinal cord protected by therapeutic hypothermia in a rat model of asphyxial CA. Male Sprague-Dawley rats were subjected to seven minutes of asphyxial CA (induced by injection of 2 mg/kg vecuronium bromide) and hypothermia (four hours of cooling, 33 ± 0.5 °C). Survival rate, hindlimb motor function, histopathology, western blotting, and immunohistochemistry were examined at 12, 24, and 48 h after CA/ROSC. The rats of the CA/ROSC and hypothermia-treated groups had an increased survival rate and showed an attenuated hindlimb paralysis and a mild damage/death of motor neurons located in the anterior horn of the lumbar spinal cord compared with those of the CA/ROSC and normothermia-treated groups. In the CA/ROSC and hypothermia-treated groups, expressions of cytoplasmic and nuclear Nrf2 and HO-1 were significantly higher in the anterior horn compared with those of the CA/ROSC and normothermia-treated groups, showing that cytoplasmic and nuclear Nrf2 was expressed in both motor neurons and astrocytes. Moreover, in the CA/ROSC and hypothermia-treated group, interleukin-1ß (IL-1ß, a pro-inflammatory cytokine) expressed in the motor neurons was significantly reduced, and astrocyte damage was apparently attenuated compared with those found in the CA/ROSC and normothermia group. Taken together, our results indicate that hypothermic therapy after CA/ROSC attenuates CA-induced hindlimb paralysis by protecting motor neurons in the lumbar spinal cord via activating the Nrf2/HO-1 signaling pathway and attenuating pro-inflammation and astrocyte damage (reactive astrogliosis).

Therapeutic Administration of Oxcarbazepine Saves Cerebellar Purkinje Cells from Ischemia and Reperfusion Injury Induced by Cardiac Arrest through Attenuation of Oxidative Stress.

Research reports using animal models of ischemic insults have demonstrated that oxcarbazepine (a carbamazepine analog: one of the anticonvulsant compounds) extends neuroprotective effects against cerebral or forebrain injury induced by ischemia and reperfusion. However, research on protective effects against ischemia and reperfusion cerebellar injury induced by cardiac arrest (CA) and the return of spontaneous circulation has been poor. Rats were assigned to four groups as follows: (Groups 1 and 2) sham asphyxial CA and vehicle- or oxcarbazepine-treated, and (Groups 3 and 4) CA and vehicle- or oxcarbazepine-treated. Vehicle (0.3% dimethyl sulfoxide/saline) or oxcarbazepine (200 mg/kg) was administered intravenously ten minutes after the return of spontaneous circulation. In this study, CA was induced by asphyxia using vecuronium bromide (2 mg/kg). We conducted immunohistochemistry for calbindin D-28kDa and Fluoro-Jade B histofluorescence to examine Purkinje cell death induced by CA. In addition, immunohistochemistry for 4-hydroxy-2-nonenal (4HNE) was carried out to investigate CA-induced oxidative stress, and immunohistochemistry for Cu, Zn-superoxide dismutase (SOD1) and Mn-superoxide dismutase (SOD2) was performed to examine changes in endogenous antioxidant enzymes. Oxcarbazepine treatment after CA significantly increased the survival rate and improved neurological deficit when compared with vehicle-treated rats with CA (survival rates ≥ 63.6 versus 6.5%), showing that oxcarbazepine treatment dramatically protected cerebellar Purkinje cells from ischemia and reperfusion injury induced by CA. The salvation of the Purkinje cells from ischemic injury by oxcarbazepine treatment paralleled a dramatic reduction in 4HNE (an end-product of lipid peroxidation) and increased or maintained the endogenous antioxidant enzymes (SOD1 and SOD2). In brief, this study shows that therapeutic treatment with oxcarbazepine after CA apparently saved cerebellar neurons (Purkinje cells) from CA-induced neuronal death by attenuating oxidative stress and suggests that oxcarbazepine can be utilized as a therapeutic medicine for ischemia and reperfusion brain (cerebellar) injury induced by CA.

Determination of Optimal Line-Heating Conditions for Flatness Control of Wind Tower Blocks Using Strain as Direct Boundary Method.

The wind tower block is welded with the flange to assemble the wind tower. The inherent strain due to local heating and cooling of the weld affects the flatness of the flange. Therefore, line heating is performed to satisfy the design criteria of the flange flatness, but the work variables depend on the operator's empirical judgment. This study proposed a method to determine the optimum linear heating conditions to control the welded flatness of wind tower blocks and flanges. A proposed method uses the inherent strain method, a simple analysis method, and the optimization is performed based on the deformation superposition method. The changes in flange flatness due to welding and single-point heating were calculated. Then, the flatness change due to single-point heating is superimposed with a scale factor, which represents the magnitude of line heating, and is added to the flatness change due to welding. Using the optimization procedure, the line heating conditions used to derive the flatness that satisfies the design criteria were derived and applied to the analytical model for verification.

Protective Effects of Topical Administration of Laminarin in Oxazolone-Induced Atopic Dermatitis-like Skin Lesions.

Laminarin is a polysaccharide isolated from brown marine algae and has a wide range of bioactivities, including immunoregulatory and anti-inflammatory properties. However, the effects of laminarin on atopic dermatitis have not been demonstrated. This study investigated the potential effects of topical administration of laminarin using a Balb/c mouse model of oxazolone-induced atopic dermatitis-like skin lesions. Our results showed that topical administration of laminarin to the ear of the mice improved the severity of the dermatitis, including swelling. Histological analysis revealed that topical laminarin significantly decreased the thickening of the epidermis and dermis and the infiltration of mast cells in the skin lesion. Serum immunoglobulin E levels were also significantly decreased by topical laminarin. Additionally, topical laminarin significantly suppressed protein levels of oxazolone-induced proinflammatory cytokines, such as interleukin-1ß, tumor necrosis factor-α, monocyte chemoattractant protein-1, and macrophage inflammatory protein-1α in the skin lesion. These results indicate that topical administration of laminarin can alleviate oxazolone-induced atopic dermatitis by inhibiting hyperproduction of IgE, mast cell infiltration, and expressions of proinflammatory cytokines. Based on these findings, we propose that laminarin can be a useful candidate for the treatment of atopic dermatitis.

Effects of Brain Factor­7® against motor deficit and oxidative stress in a mouse model of MPTP­induced Parkinson's disease.

Oxidative stress is strongly implicated in the pathogenesis of Parkinson's disease (PD) through degeneration of dopaminergic neurons. The present study was designed to investigate the underlying mechanisms and therapeutic potential of Brain Factor-7® (BF-7®), a natural compound in silkworm, in a mouse model of PD induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). MPTP (20 mg/kg) was intraperitoneally injected into mice to cause symptoms of PD. Mice were orally administered BF-7® (a mixture of silk peptides) before and after MPTP treatment. Rotarod performance test was used to assess motor performance. Fluoro-Jade B staining for neurons undergoing degeneration and immunohistochemistry of tyrosine hydroxylase for dopaminergic neurons, 4-hydroxy-2-nonenal (4HNE) for lipid peroxidation, 8-hydroxy-2'-deoxyguanosine (8OHdG) for DNA damage and superoxide dismutase (SOD) 1 and SOD2 for antioxidative enzymes in the pars compacta of the substantia nigra were performed. Results showed that BF-7® treatment significantly improved MPTP-induced motor deficit and protected MPTP-induced dopaminergic neurodegeneration. Furthermore, BF-7® treatment significantly ameliorated MPTP-induced oxidative stress. Increased 4HNE and 8OHdG immunoreactivities induced by MPTP were significantly reduced by BF-7®, whereas SOD1 and SOD2 immunoreactivities decreased by MPTP were significantly enhanced by BF-7®. In conclusion, BF-7® exerted protective and/or therapeutic effects in a mouse model of PD by decreasing effects of oxidative stress on dopaminergic neurons in the substantia nigra pars compacta.

Enabling 100C Fast-Charging Bulk Bi Anodes for Na-Ion Batteries.

It is challenging to develop alloying anodes with ultrafast charging and large energy storage using bulk anode materials because of the difficulty of carrier-ion diffusion and fragmentation of the active electrode material. Herein, a rational strategy is reported to design bulk Bi anodes for Na-ion batteries that feature ultrafast charging, long cyclability, and large energy storage without using expensive nanomaterials and surface modifications. It is found that bulk Bi particles gradually transform into a porous nanostructure during cycling in a glyme-based electrolyte, whereas the resultant structure stores Na ions by forming phases with high Na diffusivity. These features allow the anodes to exhibit unprecedented electrochemical properties; the developed Na-Bi half-cell delivers 379 mA h g-1 (97% of that measured at 1C) at 7.7 A g-1 (20C) during 3500 cycles. It also retained 94% and 93% of the capacity measured at 1C even at extremely fast-charging rates of 80C and 100C, respectively. The structural origins of the measured properties are verified by experiments and first-principles calculations. The findings of this study not only broaden understanding of the underlying mechanisms of fast-charging anodes, but also provide basic guidelines for searching battery anodes that simultaneously exhibit high capacities, fast kinetics, and long cycling stabilities.

Relationship between Neuronal Damage/Death and Astrogliosis in the Cerebral Motor Cortex of Gerbil Models of Mild and Severe Ischemia and Reperfusion Injury.

Neuronal loss (death) occurs selectively in vulnerable brain regions after ischemic insults. Astrogliosis is accompanied by neuronal death. It can change the molecular expression and morphology of astrocytes following ischemic insults. However, little is known about cerebral ischemia and reperfusion injury that can variously lead to damage of astrocytes according to the degree of ischemic injury, which is related to neuronal damage/death. Thus, the purpose of this study was to examine the relationship between damage to cortical neurons and astrocytes using gerbil models of mild and severe transient forebrain ischemia induced by blocking the blood supply to the forebrain for five or 15 min. Significant ischemia tFI-induced neuronal death occurred in the deep layers (layers V and VI) of the motor cortex: neuronal death occurred earlier and more severely in gerbils with severe ischemia than in gerbils with mild ischemia. Distinct astrogliosis was detected in layers V and VI. It gradually increased with time after both ischemiae. The astrogliosis was significantly higher in severe ischemia than in mild ischemia. The ischemia-induced increase of glial fibrillary acidic protein (GFAP; a maker of astrocyte) expression in severe ischemia was significantly higher than that in mild ischemia. However, GFAP-immunoreactive astrocytes were apparently damaged two days after both ischemiae. At five days after ischemiae, astrocyte endfeet around capillary endothelial cells were severely ruptured. They were more severely ruptured by severe ischemia than by mild ischemia. However, the number of astrocytes stained with S100 was significantly higher in severe ischemia than in mild ischemia. These results indicate that the degree of astrogliosis, including the disruption (loss) of astrocyte endfeet following ischemia and reperfusion in the forebrain, might depend on the severity of ischemia and that the degree of ischemia-induced neuronal damage may be associated with the degree of astrogliosis.

Astaxanthin Confers a Significant Attenuation of Hippocampal Neuronal Loss Induced by Severe Ischemia-Reperfusion Injury in Gerbils by Reducing Oxidative Stress.

Astaxanthin is a powerful biological antioxidant and is naturally generated in a great variety of living organisms. Some studies have demonstrated the neuroprotective effects of ATX against ischemic brain injury in experimental animals. However, it is still unknown whether astaxanthin displays neuroprotective effects against severe ischemic brain injury induced by longer (severe) transient ischemia in the forebrain. The purpose of this study was to evaluate the neuroprotective effects of astaxanthin and its antioxidant activity in the hippocampus of gerbils subjected to 15-min transient forebrain ischemia, which led to the massive loss (death) of pyramidal cells located in hippocampal cornu Ammonis 1-3 (CA1-3) subfields. Astaxanthin (100 mg/kg) was administered once daily for three days before the induction of transient ischemia. Treatment with astaxanthin significantly attenuated the ischemia-induced loss of pyramidal cells in CA1-3. In addition, treatment with astaxanthin significantly reduced ischemia-induced oxidative DNA damage and lipid peroxidation in CA1-3 pyramidal cells. Moreover, the expression of the antioxidant enzymes superoxide dismutase (SOD1 and SOD2) in CA1-3 pyramidal cells were gradually and significantly reduced after ischemia. However, in astaxanthin-treated gerbils, the expression of SOD1 and SOD2 was significantly high compared to in-vehicle-treated gerbils before and after ischemia induction. Collectively, these findings indicate that pretreatment with astaxanthin could attenuate severe ischemic brain injury induced by 15-min transient forebrain ischemia, which may be closely associated with the decrease in oxidative stress due to astaxanthin pretreatment.

Reversible ammonia uptake at room temperature in a robust and tunable metal-organic framework.

Ammonia is useful for the production of fertilizers and chemicals for modern technology, but its high toxicity and corrosiveness are harmful to the environment and human health. Here, we report the recyclable and tunable ammonia adsorption using a robust imidazolium-based MOF (JCM-1) that uptakes 5.7 mmol g-1 of NH3 at 298 K reversibly without structural deformation. Furthermore, a simple substitution of NO3 - with Cl- in a post-synthetic manner leads to an increase in the NH3 uptake capacity of JCM-1(Cl-) up to 7.2 mmol g-1.

Hyperthermia accelerates neuronal loss differently between the hippocampal CA1 and CA2/3 through different HIF­1α expression after transient ischemia in gerbils.

The hippocampus has a different vulnerability to ischemia according to the subfields CA1 to CA3 (initials of cornu ammonis). It has been reported that body temperature changes during ischemia affect the degree of neuronal death following transient ischemia. Hypoxia­inducible factor 1α (HIF­1α) plays a key role in regulating cellular adaptation to low oxygen conditions. In the present study, we investigated the pattern of neuronal death (loss) in CA1 and CA2/3 following 5 min transient forebrain ischemia (TFI) under hyperthermia (39.5±0.2˚C) and the relationship between neuronal death and changes in HIF­1α expression using western blot analysis and immunohistochemistry in gerbils. Normothermia or hyperthermia was induced for 30 min before and during the TFI, and neuronal death and HIF­1α expression were observed at 0, 3, 6 and 12 h, 1, 2 and 5 days after TFI. Under normothermia, TFI­induced neuronal death of CA1 pyramidal neurons occurred on day 5 after TFI, but CA2/3 pyramidal neurons did not die. In contrast, under hyperthermia, the death of CA1 and CA2/3 pyramidal neurons was observed on day 2 after TFI. Under normothermia, HIF­1α expression was significantly elevated in both CA1 and CA2/3 pyramidal neurons at 12 h and 1 day after TFI, and the increased HIF­1α immunoreactivity in CA1 was dramatically reduced from 2 days after TFI, but not in CA2/3 pyramidal neurons. Under hyperthermia, the basal expression of HIF­1α in the sham group was significantly higher in both CA1 and CA2/3 pyramidal neurons at 0 h after TFI than in the normothermia group. HIF­1 expression was continuously higher, peaked at 12 h after TFI, and then significantly decreased from 1 day after TFI. Overall, the present results indicate that resistance to ischemia in CA2/3 pyramidal neurons is closely associated with the persistence of increased expression of HIF­1α after ischemic insults and that hyperthermia­induced exacerbation of death of pyramidal neurons is closely related to decreased HIF­1α expression after ischemic insults.

Pinus thunbergii bark extract rich in flavonoids promotes hair growth in dorsal skin by regulating inflammatory cytokines and increasing growth factors in mice.

Korean maritime pine bark (Pinus thunbergii) has been used as an alternative medicine due to its beneficial properties, including anti­inflammatory effects. To date, the anti­inflammatory and hair growth­promoting effects of Pinus densiflora bark extract have remained elusive. Therefore, in the present study, Pinus thunbergii bark was extracted with pure water (100˚C) and the extract was examined to determine its polyphenol and flavonoid content. C57BL/6 mice were used to assess the effects of the extract to promote hair growth. The extract (1, 2 and 4%) was topically applied onto shaved dorsal skin and hair growth was observed for 17 days. A significant increase in hair growth was observed with 2 and 4% extract. Based on this finding, the optimal dose of the extract for effective hair growth promotion was determined to be 2%. The mechanisms of hair growth promotion were investigated via immunohistochemical analysis of changes in inflammatory cytokines and growth factors in the hair follicles following treatment with 2% extract. The treatment reduced the levels of TNF­α and IL­1ß, which are pro­inflammatory cytokines, while it enhanced the levels of IL­4 and IL­13, which are anti­inflammatory cytokines, in the hair follicles. In addition, elevated insulin­like growth factor I and vascular epidermal growth factor were detected in hair follicles following treatment. Based on these findings, it was suggested that the extract of Pinus thunbergii bark may be utilized for hair loss prevention and/or hair growth promotion.

Ultrafast Na Transport into Crystalline Sn via Dislocation-Pipe Diffusion.

The charging process of secondary batteries is always associated with a large volume expansion of the alloying anodes, which in many cases, develops high compressive residual stresses near the propagating interface. This phenomenon causes a significant reduction in the rate performance of the anodes and is detrimental to the development of fast-charging batteries. However, for the Na-Sn battery system, the residual stresses that develop near the interface are not stored, but are relieved by the generation of high-density dislocations in crystalline Sn. Direct-contact diffusion experiments show that these dislocations facilitate the preferential transport of Na and accelerate the Na diffusion into crystalline Sn at ultrafast rates via "dislocation-pipe diffusion". Advanced analyses are performed to observe the evolution of atomic-scale structures while measuring the distribution and magnitude of residual stresses near the interface. In addition, multi-scale simulations that combined classical molecular dynamics and first-principles calculations are performed to explain the structural origins of the ultrafast diffusion rates observed in the Na-Sn system. These findings not only address the knowledge gaps regarding the relationship between pipe diffusion and the diffusivity of carrier ions but also provide guidelines for the appropriate selection of anode materials for use in fast-charging batteries.

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.

Brain Factor-7® Improves Cognitive Impairment Following Transient Ischemia and Reperfusion Injury in Gerbil Forebrain through Promoting Remyelination and Restoring Cholinergic and Glutamatergic Neurotransmission in the Hippocampus.

BACKGROUND: Ischemia and reperfusion injury in the brain triggers cognitive impairment which are accompanied by neuronal death, loss of myelin sheath and decline in neurotransmission. In this study, we investigated whether therapeutic administration of Brain Factor-7® (BF-7®; a silk peptide) in ischemic gerbils which were developed by transient (five minutes) ischemia and reperfusion in the forebrain (tFI/R) improved cognitive impairment. METHODS: Short-term memory and spatial memory functions were assessed by passive avoidance test and Barnes maze test, respectively. To examine neuronal change in the hippocampus, cresyl violet staining, immunohistochemistry for neuronal nuclei and fluoro Jade B histofluorescence were performed. We carried out immunohistochemistry for myelin basic protein (a marker for myelin) and receptor interacting protein (a marker for oligodendrocytes). Furthermore, immunohistochemistry for vesicular acetylcholine transporter (as a cholinergic transporter) and vesicular glutamate transporter 1 (as a glutamatergic synapse) was done. RESULTS: Administration of BF-7® significantly improved tFI/R-induced cognitive impairment. tFI/R-induced neuronal death was found in the Cornu Ammonis 1 (CA1) subfield of the hippocampus from five days after tFI/R. Treatment with BF-7® following tFI/R did not restore the death (loss) of CA1 neurons following tFI/R. However, BF-7® treatment to the ischemic gerbils significantly improved remyelination and proliferation of oligodendrocytes in the hippocampus with ischemic injury. Treatment with BF-7® to the ischemic gerbils significantly restored vesicular acetylcholine transporter-immunoreactive and vesicular glutamate transporter 1-immunoreactive structures in the hippocampus with ischemic injury. CONCLUSIONS: Based on these results, we suggest that BF-7® can be utilized for improving cognitive impairments induced by ischemic injury as an additive for health/functional foods and/or medicines.

Ischemia-Induced Cognitive Impairment Is Improved via Remyelination and Restoration of Synaptic Density in the Hippocampus after Treatment with COG-Up® in a Gerbil Model of Ischemic Stroke.

Cerebrovascular disease such as ischemic stroke develops cognitive impairment due to brain tissue damage including neural loss, demyelination and decrease in synaptic density. In the present study, we developed transient ischemia in the forebrain of the gerbil and found cognitive impairment using the Barnes maze test and passive avoidance test for spatial memory and learning memory, respectively. In addition, neuronal loss/death was detected in the Cornu Ammonis 1 (CA1) region of the gerbil hippocampus after the ischemia by cresyl violet histochemistry, immunohistochemistry for neuronal nuclei and histofluorescence with Fluoro-Jade B. Furthermore, in the CA1 region following ischemia, myelin and vesicular synaptic density were significantly decreased using immunohistochemistry for myelin basic protein and vesicular glutamate transporter 1. In the gerbils, treatment with COG-up® (a combined extract of Erigeron annuus (L.) Pers. and Brassica oleracea Var.), which was rich in scutellarin and sinapic acid, after the ischemia, significantly improved ischemia-induced decline in memory function when compared with that shown in gerbils treated with vehicle after the ischemia. In the CA1 region of these gerbils, COG-up® treatment significantly promoted the remyelination visualized using immunohistochemistry myelin basic protein, increased oligodendrocytes visualized using a receptor-interacting protein, and restored the density of glutamatergic synapses visualized using double immunofluorescence for vesicular glutamate transporter 1 and microtubule-associated protein, although COG-up® treatment did not protect pyramidal cells (principal neurons) located in the CA1 region form the ischemic insult. Considering the current findings, a gerbil model of ischemic stroke apparently showed cognitive impairment accompanied by ischemic injury in the hippocampus; also, COG-up® can be employed for improving cognitive decline following ischemia-reperfusion injury in brains.

Therapeutic Effects of Risperidone against Spinal Cord Injury in a Rat Model of Asphyxial Cardiac Arrest: A Focus on Body Temperature, Paraplegia, Motor Neuron Damage, and Neuroinflammation.

Cardiac arrest (CA) causes severe spinal cord injury and evokes spinal cord disorders including paraplegia. It has been reported that risperidone, an antipsychotic drug, effectively protects neuronal cell death from transient ischemia injury in gerbil brains. However, until now, studies on the effects of risperidone on spinal cord injury after asphyxial CA (ACA) and cardiopulmonary resuscitation (CPR) are not sufficient. Therefore, this study investigated the effect of risperidone on hind limb motor deficits and neuronal damage/death in the lumbar part of the spinal cord following ACA in rats. Mortality, severe motor deficits in the hind limbs, and the damage/death (loss) of motor neurons located in the anterior horn were observed two days after ACA/CPR. These symptoms were significantly alleviated by risperidone (an atypical antipsychotic) treatment after ACA. In vehicle-treated rats, the immunoreactivities of tumor necrosis factor-alpha (TNF-α) and interleukin 1-beta (IL-1ß), as pro-inflammatory cytokines, were increased, and the immunoreactivities of IL-4 and IL-13, as anti-inflammatory cytokines, were reduced with time after ACA/CPR. In contrast, in risperidone-treated rats, the immunoreactivity of the pro-inflammatory cytokines was significantly decreased, and the anti-inflammatory cytokines were enhanced compared to vehicle-treated rats. In brief, risperidone treatment after ACA/CPR in rats significantly improved the survival rate and attenuated paralysis, the damage/death (loss) of motor neurons, and inflammation in the lumbar anterior horn. Thus, risperidone might be a therapeutic agent for paraplegia by attenuation of the damage/death (loss) of spinal motor neurons and neuroinflammation after ACA/CPR.

Self-Assembly of Pulverized Nanoparticles: An Approach to Realize Large-Capacity, Long-Lasting, and Ultra-Fast-Chargeable Na-Ion Batteries.

The fabrication of battery anodes simultaneously exhibiting large capacity, fast charging capability, and high cyclic stability is challenging because these properties are mutually contrasting in nature. Here, we report a rational strategy to design anodes outperforming the current anodes by simultaneous provision of the above characteristics without utilizing nanomaterials and surface modifications. This is achieved by promoting spontaneous structural evolution of coarse Sn particles to 3D-networked nanostructures during battery cycling in an appropriate electrolyte. The anode steadily exhibits large capacity (∼480 mAhg-1) and energy retention capability (99.9%) during >1500 cycles even at an ultrafast charging rate of 12 690 mAg-1 (15C). The structural and chemical origins of the measured properties are explained using multiscale simulations combining molecular dynamics and density functional theory calculations. The developed method is simple, scalable, and expandable to other systems and provides an alternative robust route to obtain nanostructured anode materials in large quantities.

Populus tomentiglandulosa Extract Is Rich in Polyphenols and Protects Neurons, Astrocytes, and the Blood-Brain Barrier in Gerbil Striatum Following Ischemia-Reperfusion Injury.

Transient ischemia in brains causes neuronal damage, gliosis, and blood-brain barrier (BBB) breakdown, which is related to ischemia-induced brain dysfunction. Populus species have various pharmacological properties including antioxidant and anti-inflammatory activities. In this study, we found that phenolic compounds were rich in Populus tomentiglandulosa extract and examined the effects of Populus tomentiglandulosa extract on neuronal damage/death, astrogliosis, and BBB breakdown in the striatum, which is related to motor behavior, following 15-min transient ischemia in the forebrain in gerbils. The gerbils were pre-treated with 50, 100, and 200 mg/kg of the extract. The latter showed significant effects against ischemia-reperfusion injury. Ischemia-induced hyperactivity using spontaneous motor activity test was significantly attenuated by the treatment. Striatal cells (neurons) were dead at five days after the ischemia; however, pre-treatment with the extract protected the striatal cells from ischemia/reperfusion injury. Ischemia-induced reactive astrogliosis was significantly alleviated, in particular, astrocyte end feet, which are a component of BBB, were significantly preserved. Immunoglobulin G, which is not found in intact brain parenchyma, was apparently shown (an indicator of extravasation) in striatal parenchyma at five days after the ischemia, but IgG leakage was dramatically attenuated in the parenchyma by the pre-treatment. Based on these findings, we suggest that Populus tomentiglandulosa extract rich in phenolic compounds can be employed as a pharmaceutical composition to develop a preventive material against brain ischemic injury.