Vaccine inequity-induced COVID-19 dilemma: Time to sober up.

OBJECTIVE: The aim of the study was to discuss the catastrophic consequences of inequitable vaccine distribution and analyze the main challenges to address it, helping to guide efforts to address inequities in vaccine coverage. METHODS: All published papers written in English were searched through PubMed, Web of Science, and Google Scholar with the combination of relevant terms of COVID-19 vaccine inequity. RESULTS: In this paper, we first outlined the scope of inequitable vaccine distribution and identify its truly catastrophic consequences. Next, from the perspectives of political will, free markets, and profit-driven enterprises based on patent and intellectual property protection, we analyzed in depth the root causes of why this phenomenon is so difficult to combat. In addition, some specific and crucial solutions that should be undertaken in the long term were also put forward in order to provide a useful reference for the authorities, stakeholders, and researchers involved in addressing this worldwide crisis and the next one. CONCLUSIONS: Achieving COVID-19 vaccine equity faces funding gaps, vaccine nationalism, and barriers to access to intellectual property and technology. Thus, the scope of global vaccine inequity is immense, and its repercussions will continue to be felt worldwide, especially among the world's most vulnerable residents, both adults and children. Beyond fundamental issues, the growing vaccine hesitancy and unreliable distribution in low-income countries must be addressed.

Apelin-13 protects against cisplatin-induced ototoxicity by inhibiting apoptosis and regulating STAT1 and STAT3.

The ototoxic side effect of cisplatin is a main cause of sensorineural hearing loss. This side effect limits the clinical application of cisplatin and affects patients' quality of life. This study was designed to investigate the effect of apelin-13 on cisplatin-induced C57BL/6 mice hearing loss model and explore the potential underlying molecular mechanisms. Mice were intraperitoneally injected with 100 µg/kg apelin-13 2 h before 3 mg/kg cisplatin injection for 7 consecutive days. Cochlear explants cultured in vitro were pretreated with 10 nM apelin-13 2 h prior to 30 µM cisplatin treatment for another 24 h. Hearing test and morphology results showed that apelin-13 attenuated cisplatin-induced mice hearing loss and protected cochlear hair cells and spiral ganglion neurons from damage. In vivo and in vitro experimental results showed that apelin-3 reduced cisplatin-induced apoptosis of hair cells and spiral ganglion neurons. In addition, apelin-3 preserved mitochondrial membrane potential and inhibited ROS production in cultured cochlear explants. Mechanistic studies showed that apelin-3 decreased cisplatin-induced cleaved caspase 3 expression but increased Bcl-2; inhibited the expression of pro-inflammatory factors TNF-a and IL-6; and increased STAT1 phosphorylation but decreased STAT3 phosphorylation. In conclusion, our results indicate that apelin-13 could be a potential otoprotective agent to prevent cisplatin-induced ototoxicity by inhibiting apoptosis, ROS production, TNF-α and IL-6 expression, and regulating phosphorylation of STAT1 and STAT3 transcription factors.

Vaccine inequity-induced COVID-19 dilemma: Time to sober up.

UNSTRUCTURED: The ongoing coronavirus disease 2019 pandemic has not only posed a serious threat to public health but has also imposed a heavy burden on medical systems and global economies. To combat this challenge, unprecedented efforts have been made by governments and the scientific community in the development and production of vaccines. As a result, less than a year elapsed between identification of a novel pathogen sequence and large-scale vaccine rollout. However, much of the focus and debate has increasingly shifted to the looming risk of global vaccine inequity and whether we could do more to modify this risk. In this paper, we first outline the scope of inequitable vaccine distribution and identify its truly catastrophic consequences. Then, from the perspectives of political will, free markets and profit-driven enterprises based on patent and intellectual property protection, we analyze in-depth the root causes why this phenomenon is so difficult to combat. Apart from these, some specific and crucial solutions that should be undertaken in the long term were also put forward, in order to provide a useful reference for the authorities, stakeholders and researchers involved in addressing this global crisis and the next one.

Myocarditis or Pericarditis Following the COVID-19 Vaccination in Adolescents: A Systematic Review.

Background: By 16 May 2022, 12,186,798,032 people had been vaccinated with COVID-19 vaccines. Our study found that myocarditis/pericarditis may occur in adolescents after COVID-19 vaccination. Methods: In this regard, we conducted a meta-analysis of seven groups of adolescents aged 12-19 years to compare the incidence of myocarditis/pericarditis after vaccination and compare the relative risk incidence after the first and second doses of a COVID-19 vaccine, and between males and females for risk incidence. Results: We analyzed 22,020,997 subjects from seven studies, including 130 cases of confirmed myocarditis/pericarditis. The overall mean incidence rate was 1.69 cases per 100,000 person-years. Of these, 19 of the 12,122,244 people who received a first dose of a COVID-19 vaccine had myocarditis/pericarditis, an incidence rate of 0.0022% (95% CI 0.0001-0.0034), and 111 of the 1,008,753 people who received a second dose had myocarditis/pericarditis, an incidence rate of 0.0107% (95% CI 0.0059-0.0155). The prevalence relative ratio (RR) after the first and second doses was RR = 5.53 (95% CI: 3.01-10.16), with a higher prevalence after the second dose than after the first dose of a COVID-19 vaccine. After a second dose of a COVID-19 vaccine, the RR for males relative to females was RR = 13.91 (95% CI: 4.30-44.95), with a more pronounced risk of disease in males than in females. Conclusions: Our study showed that myocarditis/pericarditis occurred after vaccination with the BNT162b2 or Comirnaty vaccine, especially after the second vaccination in male adolescents, but the incidence of myocarditis/pericarditis after vaccination with the above vaccines was very rare (0.0022%). Therefore, it is recommended that adolescents should be vaccinated with the COVID-19 universal vaccine as soon as possible and closely monitored for subsequent adverse reactions, which can be treated promptly.

Microglia Polarization in Alzheimer's Disease: Mechanisms and a Potential Therapeutic Target.

Neuroinflammation regulated by microglia is one of the important factors involved in the pathogenesis of Alzheimer's disease (AD). Activated microglia exhibited phenotypes termed as M1 and M2 phenotypes separately. M1 microglia contribute to the development of inflammation via upregulating pro-inflammatory cytokines, while M2 microglia exert anti-inflammation effects through enhancing the expression of anti-inflammation factors. Moreover, M1 and M2 microglia could be mutually transformed under various conditions. Both M1 and M2 microglia are implicated in AD. Amyloid-ß (Aß) and hyperphosphorylated tau are two major components of AD pathological hallmarks, neuritic plaques, and neurofibrillary tangles. Both Aß and hyperphosphorylated tau were involved in microglial activation and subsequent inflammation, which further contribute to neuronal and synaptic loss in AD. In this review, we summarized the roles of M1 and M2 microglia in AD and underlying mechanisms, which will provide an insight into the role of microglia in the pathogenesis of AD and highlight the therapeutic potential of modulating microglia.

A Cross-Sectional Study on Mental Health Problems of Medical and Nonmedical Students in Shandong During the COVID-19 Epidemic Recovery Period.

Background: The coronavirus disease 2019 (COVID-19) pandemic has resulted in a plethora of psychological problems worldwide since its onset in December 2019. In the upheaval period, compared with medical college students, nonmedical students' psychological state deserves additional concern due to their lack of medical knowledge. Although the epidemic in China has been largely controlled for several months, the mental health problems resulting from the COVID-19 epidemic persist to this day. In this study, we assessed the mental health problems and associated risk factors experienced by nonmedical vs. medical college students in universities of Shandong Province during the COVID-19 epidemic recovery period. Methods: An online survey was conducted over the period from 17 to 19 December 2020. A total of 954 Chinese college students (486 nonmedical and 468 medical students) from three universities of Shandong Province participated in the survey. Mental health variables were assessed with use of Patient Health Questionnaire-9 (PHQ-9), Generalized Anxiety Disorder-7 (GAD-7), and Insomnia Severity Index (ISI). Results: Compared with medical students, nonmedical college students had higher prevalence rates of depression (53.9 vs. 46.4%; p = 0.020) and insomnia (28.0 vs. 22.4%, p = 0.049), as well as higher total scores on the PHQ-9 (p = 0.03) and ISI (p < 0.01). Among nonmedical college students, being female and native of non-Shandong were risk factors for anxiety and depression (p < 0.01), while only native of non-Shandong for insomnia (p < 0.01). Among medical students, age (p < 0.01) and living in rural areas (p = 0.04) were risk factors for depression, while only age (p < 0.05) was a risk factor for anxiety and insomnia. Conclusion: Nonmedical college students in the universities of Shandong Province had more mental health problems and more risk factors for developing them during the COVID-19 epidemic recovery period than medical students. These nonmedical students require additional attention and recovery programs to alleviate the increased incidence of psychological problems related to COVID-19.

Latest Effective Measures to Combat COVID-19: A Review.

More and more people realize that implementation of preventive measures is the only option left to counteract the coronavirus disease 2019 (COVID-19) before specific antiviral drugs are developed. Hence, a number of behavioral, clinical and state interventions have been conducted by dozens of countries to stop or slow down the spread of the virus in the early stages of the epidemic. At present, with the evolution of COVID-19 pandemic getting worse, synthesizing and implementing all measures available are of paramount importance. However, some measures are still being controversial. We aimed to assist policymakers in decision making for better pandemic preparedness. We reviewed the literature that reported accumulated scientific experience to date and summarized the epidemic prevention and control measures in three aspects: control the source of infection, cut off the routes of transmission and protect the susceptible population. First of all, some new approaches were introduced to control the source of infection, such as implementing contact-tracing apps, nucleic acid mixed detection, repeated testing and the establishment of some specialized laboratories. Second, we need to take various measures to cut off all possible routes of transmission, especially persistently pay close attention to checking cold chain foods. Third, due to no valid vaccine has yet been developed, some measures that can cut development time of more conventional vaccines should be implemented or considered. By synthesizing the scientific experience in fighting the COVID-19 epidemic, we suggested the latest effective measures should be carried out concurrently from three aspects, so as to avoid making grim situation even worse.

A Comorbid Rat Model of Neuroendocrine-Immune System Alterations Under the Impact of Risk Factors for Stroke.

Hypercholesterolemia and carotid atherosclerosis contribute to the etiology of stroke. However, there has been a lack of appropriate comorbid animal models incorporating some of the ubiquitous characteristics that precede strokes. Curcumin is a natural active polyphenolic compound extracted from the rhizoma of Curcuma longa L. which possesses comprehensive bioactivities. The present study aimed to evaluate whether neurobehavioral deficits, neuroendocrine-immune dysregulations and cerebral microcirculation dysfunction, are part of the initial stages of cerebral ischemia in individuals suffering from carotid atherosclerosis resulting from a high cholesterol diet (HCD) and if they could be tested using a comorbid animal model. Furthermore, the utility of this model will be examined following the administration of curcumin. Adult wild-type SD rats were fed a regular diet or HCD and supplemented with either vehicle or curcumin for 4 weeks. Carotid injury was induced by an air-drying endothelial denudation method at the end of the second week. Plasma cholesterol, carotid pathomorphology, neurobehavioral tests, and neuroendocrine-immune parameters were measured. We found higher plasma levels of total cholesterol (TC), triglyceride (TG), low-density lipoprotein-cholesterol (LDL-C), intima and media (I/M) ratio, but lower high-density lipoprotein-cholesterol (HDL-C), spatial learning and memory capacity impairment, elevated NPY expression in the hypothalamus, increased plasma concentration of leptin, upregulated TNF-α, IL-1ß, and CRP in the circulation as well as TNF-α and IL-1ß in the cerebral cortex, plus enhanced ICAM-1, VCAM-1, and E-selectin in cerebral microvessels in HCD-fed model rats. All these alterations were ameliorated by curcumin. These results suggest that a comorbid rat model was effectively developed by HCD and carotid injury.

Myricitrin ameliorates cognitive deficits in MCAO cerebral stroke rats via histone acetylation-induced alterations of brain-derived neurotrophic factor.

The present study screened the effect of Myricitrin on cognitive deficits post-cerebral ischemic stroke and the involved mechanism. The rats were submitted to middle cerebral artery occlusion (MCAO) and were treated with sodium butyrate or Myricitrin (15 and 30 mg/kg) for 28 days. The spatial memory was studied by Morris water maze (MWM). After 4 weeks, the rats were euthanized and hippocampus region was utilized for neurochemical and biochemical changes. The extent of histone acetylation was studied by ELISA. Protein levels were analyzed by Western blot analysis. The mRNA levels were analyzed by polymerase chain reaction (PCR). In silico bioinformatics docking studies were done for target confirmation of Myricitrin. The treatment of Myricitrin showed improved memory in MWM compared to rats treated with vehicle, and the effects of Myricitrin were similar to sodium butyrate-treated rats. At a dose of 30 mg/kg Myricitrin, the histone deacetylase content was decreased, the expression levels of BDNF were increased, the levels of acetylated H3 and H4 along with Syn-I in the hippocampus region were over-expressed compared to control vehicle-treated rats. However, at low dose, i.e., 15 mg/kg Myricitrin failed to show alterations in biochemical as well as neurochemical markers. Docking studies suggested the BDNF and Sun-I as potential target proteins of Myricitrin. The cognitive ameliorating effect of Myricitrin post-cerebral ischemia stroke can be attributed to increased expression of BDNF and Syn-I and modulation of histone acetylation.

Oleuropein Improved Post Cerebral Stroke Cognitive Function by Promoting Histone Acetylation and Phosphorylation of cAMP Response Element-Binding Protein in MCAO Rats.

BACKGROUND: Post-stroke cognitive impairment (PSCI) is commonest clinical disorder in which peripheral cholinergic activity is important. Oleuropein (OLP) is polyphenol is present in olive oil. Here we evaluated the effect of OLP in cognitive dysfunction rats in post cerebral stroke model. METHODS: The post cerebral stroke cognitive dysfunction PSD rat model was created by occlusion of transient middle cerebral artery. The rats were divided into 6 groups named, Sham + Vehicle, Sham + OLP (50 mg/kg), PSD rats + Vehicle, PSD rats + OLP (20, 50 or 100 mg/kg). The spatial learning was assessed by Morris water maze (MWM). The expression of choline acetyltransferase (ChAT), acetylcholine (ACH), extent of histone acetylation and phosphorylation of cAMP response element-binding protein (CREB) were evaluated by Western blot assay and immunofluorescence staining. RESULTS: Treatment of OLP at various doses showed higher number of spontaneous and rewarded alterations and lesser percentage bias compared to vehicle treated PSD rats. OLP resulted in decreased levels of ChAT and ACH, whereas the degree of histone acetylation and phosphorylation of CREB improved in dose dependent pattern. CONCLUSION: treatment of OLP improved PSCI via increasing the phosphorylation of CREB and histone acetylation, thus attenuating cholinergic activity.

Silencing of NADPH Oxidase 4 Attenuates Hypoxia Resistance in Neuroblastoma Cells SH-SY5Y by Inhibiting PI3K/Akt-Dependent Glycolysis.

Hypoxia-induced chemoresistance is a major obstacle in the development of effective cancer therapy. In our study, the reversal abilities of NADPH oxidase 4 (NOX4) silence on hypoxia resistance and the potential mechanism were investigated. Our data showed that the expression of NOX4 was upregulated in human neuroblastoma cells SH-SY5Y under hypoxia condition time dependently. Knockdown of NOX4 expression by siRNA inhibited glycolysis induced by hypoxia through decreasing the expression of glycolysis-related proteins (HIF-1α, LDHA, and PDK1), decreasing glucose uptake, lactate production, and ROS production, while increasing mitochondria membrane potential. Moreover, NOX4 silence inhibited cell growth under hypoxia condition through suppressing cell proliferation and proliferation-related proteins (Ki-67 and PCNA) compared with the hypoxia 24 h + siRNA NC group. Further, Western blot experiments exhibited that NOX4 siRNA could downregulate the rate of p-Akt/Akt. Treatment with PI3K/Akt signaling activator IGF-1 blocked, while treatment with Akt inhibitor perifosine enhanced the inhibitory effect of si-NOX4 on glycolysis and cell growth. In summary, knockdown of NOX4 had the ability of reversing hypoxia resistance, and the major mechanism is considered to be the inhibition of glycolysis and cell growth via the PI3K/Akt signaling pathway. Therefore, NOX4 could be a novel target against hypoxia resistance in neuroblastoma.

Uric Acid Protects against Focal Cerebral Ischemia/Reperfusion-Induced Oxidative Stress via Activating Nrf2 and Regulating Neurotrophic Factor Expression.

The aim of this study was to investigate whether uric acid (UA) might exert neuroprotection via activating the nuclear factor erythroid 2-related factor 2 (Nrf2) pathway and regulating neurotrophic factors in the cerebral cortices after transient focal cerebral ischemia/reperfusion (FCI/R) in rats. UA was intravenously injected through the tail vein (16 mg/kg) 30 min after the onset of reperfusion in rats subjected to middle cerebral artery occlusion for 2 h. Neurological deficit score was performed to analyze neurological function at 24 h after reperfusion. Terminal deoxynucleotidyl transferase-mediated dNTP nick end labeling (TUNEL) staining and hematoxylin and eosin (HE) staining were used to detect histological injury of the cerebral cortex. Malondialdehyde (MDA), the carbonyl groups, and 8-hydroxyl-2'-deoxyguanosine (8-OHdG) levels were employed to evaluate oxidative stress. Nrf2 and its downstream antioxidant protein, heme oxygenase- (HO-) 1,were detected by western blot. Nrf2 DNA-binding activity was observed using an ELISA-based measurement. Expressions of BDNF and NGF were analyzed by immunohistochemistry. Our results showed that UA treatment significantly suppressed FCI/R-induced oxidative stress, accompanied by attenuating neuronal damage, which subsequently decreased the infarct volume and neurological deficit. Further, the treatment of UA activated Nrf2 signaling pathway and upregulated BDNF and NGF expression levels. Interestingly, the aforementioned effects of UA were markedly inhibited by administration of brusatol, an inhibitor of Nrf2. Taken together, the antioxidant and neuroprotective effects afforded by UA treatment involved the modulation of Nrf2-mediated oxidative stress and regulation of BDNF and NGF expression levels. Thus, UA treatment could be of interest to prevent FCI/R injury.

The melanoma-linked "redhead" MC1R influences dopaminergic neuron survival.

OBJECTIVE: Individuals with Parkinson disease are more likely to develop melanoma, and melanoma patients are reciprocally at higher risk of developing Parkinson disease. Melanoma is strongly tied to red hair/fair skin, a phenotype of loss-of-function polymorphisms in the MC1R (melanocortin 1 receptor) gene. Loss-of-function variants of MC1R have also been linked to increased risk of Parkinson disease. The present study is to investigate the role of MC1R in dopaminergic neurons in vivo. METHODS: Genetic and pharmacological approaches were employed to manipulate MC1R, and nigrostriatal dopaminergic integrity was determined by comprehensive behavioral, neurochemical, and neuropathological measures. RESULTS: MC1Re/e mice, which carry an inactivating mutation of MC1R and mimic the human redhead phenotype, have compromised nigrostriatal dopaminergic neuronal integrity, and they are more susceptible to dopaminergic neuron toxins 6-hydroxydopamine and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Furthermore, a selective MC1R agonist protects against MPTP-induced dopaminergic neurotoxicity. INTERPRETATION: Our findings reveal a protective role of MC1R in the nigrostriatal dopaminergic system, and they provide a rationale for MC1R as a potential therapeutic target for Parkinson disease. Together with its established role in melanoma, MC1R may represent a common pathogenic pathway for melanoma and Parkinson disease. Ann Neurol 2017;81:395-406.

5-HMF attenuates striatum oxidative damage via Nrf2/ARE signaling pathway following transient global cerebral ischemia.

Recent studies have shown 5-hydroxymethyl-2-furfural (5-HMF) has favorable biological effects, and its neuroprotection in a variety of neurological diseases has been noted. Our previous study showed that treatment of 5-HMF led to protection against permanent global cerebral ischemia. However, the underlying mechanisms in cerebral ischemic injury are not fully understood. This study was conducted to investigate the neuroprotective effect of 5-HMF and elucidate the nuclear factor erythroid 2-related factor 2 (Nrf2)/antioxidant response element (ARE) signaling pathway mechanism in the striatum after transient global cerebral ischemia. C57BL/6 mice were subjected to bilateral common carotid artery occlusion for 20 min and sacrificed 24 h after reperfusion. 5-HMF (12 mg/kg) or an equal volume of vehicle was intraperitoneally injected 30 min before ischemia and 5 min after the onset of reperfusion. At 24 h after reperfusion, neurological function was evaluated by neurological disability status scale, locomotor activity test and inclined beam walking test. Histological injury of the striatum was observed by cresyl violet staining and terminal deoxynucleotidyl transferase (TdT)-mediated dNTP nick end labeling (TUNEL) staining. Oxidative stress was evaluated by the carbonyl groups introduced into proteins, and malondialdehyde (MDA) levels. An enzyme-linked immunosorbent assay (ELISA)-based measurement was used to detect Nrf2 DNA binding activity. Nrf2 and its downstream ARE pathway protein expression such as heme oxygenase-1, NAD (P)H:quinone oxidoreductase 1, glutamate-cysteine ligase catalytic subunit and glutamate-cysteine ligase modulatory subunit were detected by western blot. Our results showed that 5-HMF treatment significantly ameliorated neurological deficits, reduced brain water content, attenuated striatum neuronal damage, decreased the carbonyl groups and MDA levels, and activated Nrf2/ARE signaling pathway. Taken together, these results demonstrated that 5-HMF exerted significant antioxidant and neuroprotective effects following transient cerebral ischemia, possibly through the activation of the Nrf2/ARE signaling pathway.

Impact of carotid atherosclerosis combined with hypercholesterolemia on cerebral microvessels and brain parenchyma in a new complex rat model.

Most previous investigations about stroke caused by carotid atherosclerosis have focused on thromboembolism. There is a lack of knowledge about pathophysiology of the brain before ischemic insults. The objective of this study was to develop a new model of hypercholesterolemia plus carotid injury and to investigate the impact of carotid atherosclerosis combined with hypercholesterolemia in the rat brain. The complex rat model was developed by carotid injury induced by an air-drying endothelial denudation method after high cholesterol diet for 2 weeks. Plasma cholesterol, carotid pathomorphology, oxidative stress and inflammation in cerebral microvessels and brain parenchyma were measured at 7, 14 and 28 days after carotid surgery. The results showed that plasma concentrations of total cholesterol and low density lipoprotein-cholesterol were significantly increased, and severe carotid atherosclerosis and stenosis was observed in the complex rat model at 14 and 28 days after carotid surgery. The activity of superoxide dismutase was decreased, while the content of malondialdehyde was increased in cerebral microvessels and brain parenchyma. The levels of tumor necrosis factor-α and interleukin-1ß were elevated in brain tissues of this model. Almost all above changes were more severe than those in either hypercholesterolemia alone group or carotid injury alone group. These results suggest that this complex rat model may more resemble human disease than the classic acute ischemic insult model for assessing the impact of carotid atherosclerosis as a preexisting disease on cerebral microcirculation and brain tissue.

Dietary cholesterol alters memory and synaptic structural plasticity in young rat brain.

Cholesterol plays an important role in synaptic plasticity, learning and memory. To better explore how dietary cholesterol contributes to learning and memory and the related changes in synaptic structural plasticity, rats were categorized into a regular diet (RD) group and a cholesterol-enriched diet (CD) group, and were fed with respective diet for 2 months. Dietary cholesterol impacts on learning and memory, hippocampal synaptic ultrastructure, expression levels of postsynaptic density-95 (PSD-95), synaptophysin (SYP) and cannabinoid receptor type 1 (CB1R) were investigated. We found CD rats had better performances in learning and memory using Morris water maze and object recognition test than RD rats. The memory improvement was accompanied with alterations of synaptic ultrastructure in the CA1 area of the hippocampus evaluated by electron microscopy, enhanced immunoreactivity of SYP, a presynaptic marker in hippocampus detected by immunocytochemistry, as well as increased levels of PSD-95, SYP and decreased level of CB1R in brains of CD rats determined by Western blot. Taken together, the results suggest that the improvement of learning and memory abilities of the young adult rats induced by dietary cholesterol may be linked with changes in synaptic structural plasticity in the brain.

5-hydroxymethyl-2-furfural prolongs survival and inhibits oxidative stress in a mouse model of forebrain ischemia.

In the present study, we hypothesized that 5-hydroxymethyl-2-furfural could attenuate ischemic brain damage by reducing oxidative injury. Thus, mice were subjected to bilateral common carotid artery occlusion to establish a model of permanent forebrain ischemia. The mice were intraperitoneally injected with 5-hydroxymethyl-2-furfural 30 minutes before ischemia or 5 minutes after ischemia. The survival time of mice injected with 5-hydroxymethyl-2-furfural was longer compared with untreated mice. The mice subjected to ischemia for 30 minutes and reperfusion for 5 minutes were intraperitoneally injected with 5-hydroxymethyl-2-furfural 5 minutes prior to reperfusion, which increased superoxide dismutase content and reduced malondialdehyde content, similar to the effects of Edaravone, a hydroxyl radical scavenger used for the treatment of stroke. These findings indicate that intraperitoneal injection of 5-hydroxymethyl-2-furfural can prolong the survival of mice with permanent forebrain ischemia. This outcome may be mediated by its antioxidative effects.

Cornel iridoid glycoside inhibits inflammation and apoptosis in brains of rats with focal cerebral ischemia.

The capacity of cornel iridoid glycoside (CIG) to suppress the manifestations of ischemic stroke was investigated. CIG was administered to rats by the intragastric route once daily for 7 days. Focal cerebral ischemia was induced by 2 h of middle cerebral artery occlusion followed by 24 h of reperfusion. In non-treated rats large infarct areas were observed within 24 h of reperfusion. Examination of the ischemic cerebral cortex revealed microglia and astrocyte activation, increased interleukin-1beta (IL-1 beta) and tumor necrosis factor-alpha (TNF-alpha) concentrations, increased DNA fragmentation in the ischemia penumbra, elevated Bax expression, increased caspase-3 cleavage, and decreased Bcl-2 expression. Pretreatment with CIG decreased the infarct area, DNA fragmentation, IL-1beta and TNF-alpha concentrations, microglia and astrocyte activation, Bax expression, and caspase-3 cleavage while increasing Bcl-2 expression. CIG exerts anti-neuroinflammatory and anti-apoptotic effects which should prove beneficial for prevention or treatment of stroke.

[Effects of epimedium flavonoids on synapse related protein in brains of dementia transgenic mice].

OBJECTIVE: To investigate changes of synapse related protein, such as synaptophysin (SYP) and postsynaptic dense material 95 (PSD-95), in brains of 10 months old transgenic mice, and the effects of Epimedium flavonoids (EF) on expression of SYP and PSD-95 in brain of 10 months old of APP transgenic mice. METHODS: The mice of drug treated group were administered intragastrically by EF (at low doses of 0.03 and high dose of 0.1 g.kg(-1).d(-1)) from 4 to 10 months old. The mice of normal group and negative transgene group were administered of distilled water by the same way. The expression of SYP in CA1, CA3, and dentate gyrus (DG) areas of hippocampus and cortex, and PSD-95 in hippocampus and cortex were detected by immunohistochemistry and Western blot respectively. RESULTS: Compared to negative transgenic mice, the expression of SYP in cortex was decreased by 51.3% (P < 0.01). The IOD value of SYP immuno-reactivity cell in CA1, CA3 and DG areas of hippocampus in 10 months old transgenic mice were significantly decreased (the suppression rates were 59.1%, 57.7% and 56.5% in CA1, CA3 and DG respectively, all P < 0.01). The expression of PSD-95 in cortex decreased by 36.4% (P < 0.01). The count of PSD-95 immuno-reactivity cell in CA1 area of hippocampus decreased with the suppression rate of 18.5% (P < 0.05). After being administered intragastrically by EF for 6 months, the expression of SYP in cortex of EF low doses and high dose group mice increased by 40.0% (P < 0.05) and 106.4% (P < 0.01) respectively in comparison with that of the control group. The IOD value of SYP immuno-reactivity cell in hippocampal CA1, CA3 and DG areas of EF low and high dose group mice were all significantly increased (all P < 0.01). The expression of PSD-95 in cortex of EF low and high dose group mice increased by 57.3% (P < 0.05) and 84.3% (P < 0.01) respectively when compare to the control group. The count of PSD-95 immuno-reactivity cell in CA1 area of hippocampus of mice in EF high dose group increased by 22.5% (P < 0.05). CONCLUSION: Epimedium flavonoids could protect the synaptic structure and function by promoting the expression of synaptophysin and postsynaptic dense material 95, which suggest that Epimedium Flavonoids may have a promising application prospect in improving the synaptic impairment of AD.

[Evaluation of tongue manifestation of blood stasis syndrome and its relationship with blood rheological disorder in a rat model of transient brain ischemia].

OBJECTIVE: To study the tongue tissue blood oxygen saturation measurement for evaluating tongue manifestation of blood stasis syndrome, and to explore its correlation with blood rheological disorder in a rat model of acute transient brain ischemia. METHODS: Twenty-eight SD rats were randomly divided into sham-operated group and ischemia group. Middle cerebral artery occlusion was induced by thread in rats of the ischemia group. Tongue tissue blood oxygen saturation, neurological severity score and the changes of blood viscosity, red blood cell deformity, thrombin time and fibrinogen in the rats were measured after 24-hour reperfusion. RESULTS: Blood viscosity and the content of fibrinogen in the ischemia group were significantly higher than those in the sham-operated group. Red blood cell deformity, thrombin time and tongue tissue blood oxygen saturation in the ischemia group were decreased as compared with the sham-operated group. There was a positive correlation between red blood cell deformity and tongue tissue blood oxygen saturation. CONCLUSION: Tongue tissue blood oxygen saturation is a good measurement for evaluating blood stasis in a rat model of focal cerebral ischemia, and this model can be used as a rat model of stroke with blood stasis syndrome.