5-lipoxygenase expression in a brain damage model induced by chronic oral administration of aluminum

A preliminary study has found that the 5-lipoxygenase inhibitor, caffeic acid, has a marked protective effect on acute brain injury induced by intracerebroventricular microinjection of aluminum. In this experiment, chronic brain injury and neuronal degeneration model was established in rats by chronic oral administration of aluminum, and then intervened using caffeic acid. Results showed that caffeic acid can downregulate chronic aluminum overload-induced 5-1ipoxygenase mRNA and protein expression, and repair the aluminum overload-induced hippocampal neuronal damage and spatial orientation impairment. It is suggested that direct intervention of 5-lipoxygenase expression has a neuroprotective role in the degeneration induced by chronic aluminum overload brain injury model.

Neuropsychological Profile of a Patient with Acquired Brain Damage Following Vascular Lesion of the Left Anterior Cingulate Cortex

Stroke is a physiological alteration associated with changes in blood flow that can result in sudden-onset cognitive impairment. It has a heterogenous clinical presentation with varying degrees of severity correlated with specific central nervous system zones or areas, and its prognosis is uncertain. This case study describes a 62-year-old male patient with acquired brain damage of the anterior cingulate cortex as a result of an ischemic event in the territory of the left anterior cerebral artery. Cognitive function was assessed using the neuropsychological executive function and frontal lobe test battery (BANFE-2) as well as other neuropsychological tests. The results show a profile of higher mental functions characterized by the presence of dysexecutive syndrome with marked behavioral alteration and diencephalic amnesia. .

Lyophilized recombinant human brain natriuretic peptide for chronic heart failure:Effects on cardiac function and inflammation

BACKGROUND Chronic heart failure(CHF)is a serious and prevalent condition characterized by impaired cardiac function and inflammation.Standard therapy for CHF has limitations,prompting the exploration of alternative treatments.Recombinant human brain natriuretic peptide(BNP)has emerged as a potential therapy,with evidence suggesting that it can improve cardiac function and reduce inflammation in patients with CHF.However,further research is required to determine the efficacy and safety of lyophilized recombinant human BNP in CHF patients and its impact on microinflammatory status.This study aimed to investigate the effects of lyophilized recombinant human BNP therapy on CHF patients’cardiac function and microinflammatory status.AIM To investigate the effects of freeze-dried recombinant human BNP therapy on cardiac function and microinflammatory status in patients with CHF.METHODS In total,102 CHF patients admitted to our hospital from January 2021 to January 2022 were randomly assigned to control and observation groups(n=51 patients/group).The control patients were treated with standard HF therapy for 3 d,whereas the observational patients were injected with the recombinant human BNP for 3 d.Clinical efficacy,inflammatory factor levels,myocardial damage,cardiac function before and after the treatment,and adverse reactions during treatment were compared between the two groups.RESULTS The overall clinical efficacy was higher in the observation group than in the control group.Compared with baseline,serum hypersensitive C-reactive protein,N-terminal proBNP,and troponin I level,and physical,emotional,social,and economic scores were lower in both groups after treatment,with greater reductions in levels and scores noted in the observation group than in the control group.The overall incidence of adverse reactions in the observation group was not significantly different compared with that in the control group(P>0.05).CONCLUSION Freeze-dried recombinant human BNP therapy can improve heart function and enhance microinflammatory status,thereby improving overall quality of life without any obvious side effects.This therapy is safe and reliable.

Resatorvid protects against hypoxic-ischemic brain damage in neonatal rats

Secondary brain damage caused by hyperactivation of autophagy and inflammatory responses in neurons plays an important role in hypoxic-ischemic brain damage(HIBD).Although previous studies have implicated Toll-like receptor 4(TLR4)and nuclear factor kappa-B(NF-κB)in the neuroinflammatory response elicited by brain injury,the role and mechanisms of the TLR4-mediated autophagy signaling pathway in neonatal HIBD are still unclear.We hypothesized that this pathway can regulate brain damage by modulating neuron autophagy and neuroinflammation in neonatal rats with HIBD.Hence,we established a neonatal HIBD rat model using the Rice-Vannucci method,and injected 0.75,1.5,or 3 mg/kg of the TLR4 inhibitor resatorvid(TAK-242)30 minutes after hypoxic ischemia.Our results indicate that administering TAK-242 to neonatal rats after HIBD could significantly reduce the infarct volume and the extent of cerebral edema,alleviate neuronal damage and neurobehavioral impairment,and decrease the expression levels of TLR4,phospho-NF-κB p65,Beclin-1,microtubule-associated protein l light chain 3,tumor necrosis factor-α,and interleukin-1βin the hippocampus.Thus,TAK-242 appears to exert a neuroprotective effect after HIBD by inhibiting activation of autophagy and the release of inflammatory cytokines via inhibition of the TLR4/NF-κB signaling pathway.This study was approved by the Laboratory Animal Ethics Committee of Affiliated Hospital of Yangzhou University,China(approval No.20180114-15)on January 14,2018.

Hyperbaric oxygen treatment promotes neural stem cell proliferation in the subventricular zone of neonatal rats with hypoxic-ischemic brain damage

Hyperbaric oxygen therapy for the treatment of neonatal hypoxic-ischemic brain damage has been used clinically for many years, but its effectiveness remains controversial. In addition, the mechanism of this potential neuroprotective effect remains unclear. This study aimed to investigate the influence of hyperbaric oxygen on the proliferation of neural stem cells in the subventricular zone of neonatal Sprague-Dawley rats （7 days old） subjected to hypoxic-ischemic brain damage. Six hours after modeling, rats were treated with hyperbaric oxygen once daily for 7 days. Immunohistochemistry revealed that the number of 5-bromo-2＇-deoxyuridine positive and nestin positive cells in the subventricular zone of neonatal rats increased at day 3 after hypoxic-ischemic brain damage and peaked at day 5. After hyperbaric oxygen treatment, the number of 5-bromo-2＇- deoxyuddine positive and nestin positive cells began to increase at day 1, and was significantly higher than that in normal rats and model rats until day 21. Hematoxylin-eosin staining showed that hyperbaric oxygen treatment could attenuate pathological changes to brain tissue in neonatal rats, and reduce the number of degenerating and necrotic nerve cells. Our experimental findings indicate that hyperbaric oxygen treatment enhances the proliferation of neural stem cells in the subventricular zone of neonatal rats with hypoxic-ischemic brain damage, and has therapeutic potential for promoting neurological recovery following brain injury.

Negative regulation of miRNA-9 on oligodendrocyte lineage gene 1 during hypoxic-ischemic brain damage

Oligodendrocyte lineage gene 1 plays a key role in hypoxic-ischemic brain damage and myelin repair, miRNA-9 is involved in the occurrence of many related neurological disorders. Bioin- formatics analysis demonstrated that miRNA-9 complementarily, but incompletely, bound oligodendrocyte lineage gene 1, but whether miRNA-9 regulates oligodendrocyte lineage gene 1 remains poorly understood. Whole brain slices of 3-day-old Sprague-Dawley rats were cultured and divided into four groups： control group; oxygen-glucose deprivation group （treatment with 8% O2 ＋ 92% N2 and sugar-free medium for 60 minutes）; transfection control group （after oxygen and glucose deprivation for 60 minutes, transfected with control plasmid） and miRNA-9 transfection group （after oxygen and glucose deprivation for 60 minutes, transfected with miRNA-9 plasmid）. From the third day of transfection, and with increasing culture days, oligodendrocyte lineage gene 1 expression increased in each group, peaked at 14 days, and then decreased at 21 days. Real-time quantitative PCR results, however, demonstrated that oligoden- drocyte lineage gene 1 expression was lower in the miRNA-9 transfection group than that in the transfection control group at 1, 3, 7, 14, 21 and 28 days after transfection. Results suggested that miRNA-9 possibly negatively regulated oligodendrocyte lineage gene 1 in brain tissues during hypoxic-ischemic brain damage.

Neuroprotective effects of autophagy inhibition on hippocampal glutamate receptor subunits after hypoxia-ischemia-induced brain damage in newborn rats

Autophagy has been suggested to participate in the pathology of hypoxic-ischemic brain damage（HIBD）.However,its regulatory role in HIBD remains unclear and was thus examined here using a rat model.To induce HIBD,the left common carotid artery was ligated in neonatal rats,and the rats were subjected to hypoxia for 2 hours.Some of these rats were intraperitoneally pretreated with the autophagy inhibitor 3-methyladenine（10 m M in 10 μL） or the autophagy stimulator rapamycin（1 g/kg） 1 hour before artery ligation.Our findings demonstrated that hypoxia-ischemia-induced hippocampal injury in neonatal rats was accompanied by increased expression levels of the autophagy-related proteins light chain 3 and Beclin-1 as well as of the AMPA receptor subunit GluR 1,but by reduced expression of GluR 2.Pretreatment with the autophagy inhibitor 3-methyladenine blocked hypoxia-ischemia-induced hippocampal injury,whereas pretreatment with the autophagy stimulator rapamycin significantly augmented hippocampal injury.Additionally,3-methyladenine pretreatment blocked the hypoxia-ischemia-induced upregulation of Glu R1 and downregulation of GluR2 in the hippocampus.By contrast,rapamycin further elevated hippocampal Glu R1 levels and exacerbated decreased GluR2 expression levels in neonates with HIBD.Our results indicate that autophagy inhibition favors the prevention of HIBD in neonatal rats,at least in part,through normalizing Glu R1 and GluR2 expression.

TP53-induced glycolysis and apoptosis regulator alleviates hypoxia/ischemia-induced microglial pyroptosis and ischemic brain damage

Our previous studies have demonstrated that TP53-induced glycolysis and apoptosis regulator(TIGAR)can protect neurons after cerebral ischemia/reperfusion.However,the role of TIGAR in neonatal hypoxic-ischemic brain damage(HIBD)remains unknown.In the present study,7-day-old Sprague-Dawley rat models of HIBD were established by permanent occlusion of the left common carotid artery followed by 2-hour hypoxia.At 6 days before induction of HIBD,a lentiviral vector containing short hairpin RNA of either TIGAR or gasdermin D(LV-sh_TIGAR or LV-sh_GSDMD)was injected into the left lateral ventricle and striatum.Highly aggressively proliferating immortalized(HAPI)microglial cell models of in vitro HIBD were established by 2-hour oxygen/glucose deprivation followed by 24-hour reoxygenation.Three days before in vitro HIBD induction,HAPI microglial cells were transfected with LV-sh_TIGAR or LV-sh_GSDMD.Our results showed that TIGAR expression was increased in the neonatal rat cortex after HIBD and in HAPI microglial cells after oxygen/glucose deprivation/reoxygenation.Lentivirusmediated TIGAR knockdown in rats markedly worsened pyroptosis and brain damage after hypoxia/ischemia in vivo and in vitro.Application of exogenous nicotinamide adenine dinucleotide phosphate(NADPH)increased the NADPH level and the glutathione/oxidized glutathione ratio and decreased reactive oxygen species levels in HAPI microglial cells after oxygen/glucose deprivation/reoxygenation.Additionally,exogenous NADPH blocked the effects of TIGAR knockdown in neonatal HIBD in vivo and in vitro.These findings show that TIGAR can inhibit microglial pyroptosis and play a protective role in neonatal HIBD.The study was approved by the Animal Ethics Committee of Soochow University of China(approval No.2017LW003)in 2017.

Effects of ephedrine on expression of Nogo-A and synaptophysin in neonatal rats following hypoxic-ischemic brain damage

BACKGROUND： Central nervous system axons regenerate poorly following neonatal hypoxic-ischemic brain damage （HIBD）, partly due to inhibitors, such as Nogo-A. Very few studies have addressed the regulation of Nogo-A in neonatal rats following HIBD. However, numerous studies have shown that ephedrine accelerates neuronal remodeling and promotes recovery of neural function in neonatal rats following HIBD. OBJECTIVE： To investigate the effects of ephedrine on expression of Nogo-A and synaptophysin in brain tissues of neonatal rats following HIBD. DESIGN, TIME AND SETTING： A completely randomized, controlled study was performed at the Immunohistochemistry Laboratory of the Research Institute of Pediatrics, Children＇s Hospital of Chongqing Medical University from August 2008 to March 2009. MATERIALS： Ephedrine hydrochloride （Chifeng Pharmaceutical Group, China）, rabbit anti-Nogo-A polyclonal antibody （Abcam, UK）, and rabbit anti-synaptophysin polyclonal antibody （Lab Vision, USA） were used in this study. METHODS： A total of 96 healthy, neonatal, Sprague Dawley rats were randomly assigned to three groups （n = 32）： sham operation, HIBD, and ephedrine. The HIBD model was established by permanent occlusion of the left common carotid artery, followed by 2 hours of hypoxia （8% oxygen and 92% nitrogen）. In the sham operation group, the left common carotid artery was exposed, but was not ligated or subjected to hypoxia. Rats in the ephedrine group were intraperitoneally injected with ephedrine immediately following HIBD, with 1.5 mg/kg each time. Rats in the sham operation and HIBD groups were injected with an equal volume of saline. All neonatal rats were treated once daily for 7 days. MAIN OUTCOME MEASURES： Histopathological damage to the cortex and hippocampus was determined by hematoxylin-eosin staining. Expression of Nogo-A and synaptophysin was detected using immunohistochemical staining. RESULTS： Neuronal degeneration and edema were observed in the hypoxJc-Jschemic cortex and hippocampus by hematoxylin-eosin staining. Compared with the sham operation group, the levels of Nogo-A significantly increased in the HIBD group at various time points （P 〈 0.01）. Nogo-A expression was significantly reduced in the ephedrine group compared with the HIBD group （P 〈 0.01）. Synaptophysin expression was significantly decreased in the hypoxic-ischemJc cortex, compared with the sham operation group （P 〈 0.01）. Synaptophysin levels were significantly increased in the ephedrine group, compared with the HIBD group （P 〈 0.01）. CONCLUSION： Altered Nogo-A expression was associated with inversely altered synaptophysin expression. The use of ephedrine normalized expression levels of Nogo-A and synaptophysin following HIBD.

The role of pineal microRNA-325 in regulating circadian rhythms after neonatal hypoxic-ischemic brain damage

Circadian rhythm disorder is a common,but often neglected,consequence of neonatal hypoxic-ischemic brain damage(HIBD).However,the underlying molecular mechanisms remain largely unknown.We previously showed that,in a rat model of HIBD,up-regulation of microRNA-325(miR-325)in the pineal gland is responsible for the suppression of Aanat,a key enzyme involved in melatonin synthesis and circadian rhythm regulation.To better understand the mechanism by which miR-325 affects circadian rhythms in neonates with HIBD,we compared clinical samples from neonates with HIBD and samples from healthy neonates recruited from the First Affiliated Hospital of Soochow University(Dushuhu Branch)in 2019.We found that circulating miR-325 levels correlated positively with the severity of sleep and circadian rhythm disorders in neonates with HIBD.Furthermore,a luciferase reporter gene assay revealed that LIM homeobox 3(LHX3)is a novel downstream target of miR-325.In addition,in miR-325 knock-down mice,the transcription factor LHX3 exhibited an miR-325-dependent circadian pattern of expression in the pineal gland.We established a neonatal mouse model of HIBD by performing doublelayer ligation of the left common carotid artery and exposing the pups to a low-oxygen environment for 2 hours.Lhx3 mRNA expression was significantly down-regulated in these mice and partially rescued in miR-325 knockout mice subjected to the same conditions.Finally,we showed that improvement in circadian rhythm-related behaviors in animals with HIBD was dependent on both miR-325 and LHX3.Taken together,our findings suggest that the miR-325-LHX3 axis is responsible for regulating circadian rhythms and provide novel insights into the identification of potential therapeutic targets for circadian rhythm disorders in patients with neonatal HIBD.The clinical trial was approved by Institutional Review Board of Children’s Hospital of Soochow University(approval No.2015028)on July 20,2015.Animal experiments were approved by Animal Care and Use Committee,School of Medicine,Soochow University,China(approval No.XD-2016-1)on January 15,2016.

Role of Toll-like receptor 4 and Janus kinase and signal transducer and activator of transcription signal transduction pathway in sepsis-induced brain damage

The Janus kinase and signal transducer and activator of transcription （JAK/STAT） signal transduction pathway is involved in sepsis-induced functional damage to the heart, liver, kidney, and other organs. However, the cellular and molecular mechanisms underlying sepsis-induced brain damage remain elusive. In the present study, we found severe loss of neurons in the hippocampal CA1 region in rats with sepsis-induced brain damage following intraperitoneal injection of endotoxin, The expression of toll-like receptor 4, tumor necrosis factor a, and interleukin-6 was significantly increased in brain tissues following lipopolysaccharide exposure. AG490 （JAK2 antagonist） and rapamycin （STAT3 antagonist） significantly reduced neuronal loss and suppressed the increased expression of toll-like receptor 4, tumor necrosis factor a, and interleukin-6 in the hippocampal CA1 region in sepsis-induced brain damaged rats. Overall, these data suggest that blockade of the JAK/STAT signal transduction pathway is neuroprotective in sepsis-induced brain damage via the inhibition of toll-like receptor 4, tumor necrosis factor a, and interleukin-6 exoression.

Estrogen inhibits lipid peroxidation after hypoxic-ischemic brain damage in neonatal rats

Sprague-Dawley neonatal rats within 7 days after birth were used in this study. The left common carotid artery was occluded and rats were housed in an 8% O2 environment for 2 hours to establish a hypoxic-ischemic brain damage model. 17β-estradiol （1 × 10-5 M） was injected into the rat abdominal cavity after the model was successfully established. The left hemisphere was obtained at 12, 24, 48, 72 hours after operation. Results showed that malondialdehyde content in the left brain of neonatal rats gradually increased as modeling time prolonged, while malondialdehyde content of 17β-estrodial-treated rats significantly declined by 24 hours, reached lowest levels at 48 hours, and then peaked at 72 hours after injury. Nicotinamide-adenine dinucleotide phosphate histochemical staining showed the nitric oxide synthase-positive cells and fibers dyed blue/violet and were mainly distributed in the cortex, hippocampus and medial septal nuclei. The number of nitric oxide synthase-positive cells peaked at 48 hours and significantly decreased after 17β-estrodial treatment. Our experimental findings indicate that estrogen plays a protective role following hypoxic-ischemic brain damage by alleviating lipid peroxidation through reducing the expression of nitric oxide synthase and the content of malondialdehyde.

Flunarizine and lamotrigine prophylaxis effects on neuron-specific enolase, S-100, and brain-specific creatine kinase in a fetal rat model of hypoxic-ischemic brain damage

BACKGROUND： Calcium antagonists may act as neuroprotectants, diminishing the influx of calcium ions through voltage-sensitive calcium channels. When administered prophylactically, they display neuroprotective effects against hypoxic-ischemic brain damage in newborn rats. OBJECTIVE： To investigate the neuroprotective effects of flunarizine （FNZ）, lamotrigine （LTG） and the combination of both drugs, on hypoxic-ischemic brain damage in fetal rats. DESIGN AND SETTING： This randomized, complete block design was performed at the Department of Pediatrics, Shenzhen Fourth People＇s Hospital, Guangdong Medical College. MATERIALS： Forty pregnant Wistar rats, at gestational day 20, were selected for the experiment and were randomly divided into FNZ, LTG, FNZ ＋ LTG, and model groups, with 10 rats in each group. METHODS： Rats in the FNZ, LTG, and FNZ ＋ LTG groups received intragastric injections of FNZ （0.5 mg/kg/d）, LTG （10 mg/kg/d）, and FNZ （0.5 mg/kg/d） ＋ LTG （10 mg/kg/d）, respectively. Drugs were administered once a day for 3 days prior to induction of hypoxia-ischemia. Rats in the model group were not administered any drugs. Three hours after the final administration, eight pregnant rats from each group underwent model establishment hypoxia-ischemia brain damage to the fetal rats. Cesareans were performed at 6, 12, 24, and 48 hours later; and 5 fetal rats were removed from each mother and kept warm. Two fetuses without model establishment were removed by planned cesarean at the same time and served as controls. A total of 0.3 mL serum was collected from fetal rats at 6, 12, 24, and 48 hours, respectively, following birth. MAIN OUTCOME MEASURES： Serum protein concentrations of neuron-specific enolase and S-100 were measured by ELISA. Serum concentrations of brain-specific creatine kinase were measured using an electrogenerated chemiluminescence method. RESULTS： Serum concentrations of neuron-specific enolase, S-100, and brain-specific creatine kinase were significantly higher in the hypoxic-ischemic fetal rats, compared with the non-hypoxic-ischemic group. Serum concentrations of neuron-specific enolase, S-100, and brain-specific creatine kinase were significantly less in the FNZ, LTG, and FNZ ＋ LTG groups following ischemia, compared with the model group （P 〈 0.01）. However, these values were significantly greater in the FNZ and LTG groups, compared with the FNZ ＋ LTG group, following ischemia （P 〈 0.01）. CONCLUSION： Preventive antenatal use of oral FNZ and LTG has positive neuroprotective effects on intrauterine hypoxic-ischemic brain damage. The combined effect of these two drugs is superior.

Environmental enrichment promotes neural remodeling in newborn rats with hypoxic-ischemic brain damage

We evaluated the effect of hypoxic-ischemic brain damage and treatment with early environmental enrichment intervention on development of newborn rats, as evaluated by light and electron microscopy and morphometry. Early intervention with environmental enrichment intelligence training attenuated brain edema and neuronal injury, promoted neuronal repair, and increased neuronal plasticity in the frontal lobe cortex of the newborn rats with hypoxic-ischemic brain damage.

Thrombolytic activity of cheonggukjang kinase in recovery from brain damage in a rat cerebral embolic stroke model

Cheonggukjang is a soybean paste made by fermenting whole cooked soybeans with Bacillus subtilis. Cheonggukjang contains a fibrinolytic enzyme that could provide clinical applications for removing blood clots. In the present study, the term ＂cheonggukjang kinase＂ （CGK） was used to refer to this fibrinolytic enzyme. The thrombolytic effects of CGK were analyzed in a rat model of cerebral embolic stroke produced by middle cerebral artery occlusion （MCAO）. Results from fibrin and platelet-rich clot lysis assays demonstrated that thrombolytic activity was greatest in CGKs, which were cultured for 40 hours. In addition, T50, the time needed to decompose 50% of the clot, did not change with plasminogen treatment, indicating that CGK was not a plasminogen activator, but was rather presumed to act as a plasmin-like protein. An intravenous infusion of CGK （1 U plasmin-like activity/100 μg CGK/kg） at 1 hour after MCAO resulted in removal of clots in a rat model of cerebral embolic stroke. CGK-treated groups exhibited a significant dose-dependent reduction in infarct volume. CGK treatment also improved functional recovery, as assessed by neurological deficit scores. Decreased infarct volume and improved functional recovery following CGK treatment was greater compared with recombinant tissue plasminogen activator （10 mg/kg）. These results suggested that CGK effectively reduced infarct volume and improved functional recovery following ischemic brain injury. CGK exhibits a number of potential clinical applications ir the treatment of cerebral embolic stroke.

660 nm red light-enhanced bone marrow mesenchymal stem cell transplantation for hypoxic-ischemic brain damage treatment

Bone marrow mesenchymal stem cell transplantation is an effective treatment for neonatal hy- poxic-ischemic brain damage. However, the in vivo transplantation effects are poor and their survival, colonization and differentiation efficiencies are relatively low. Red or near-infrared light from 600-1,000 nm promotes cellular migration and prevents apoptosis. Thus, we hypothesized that the combination of red light with bone marrow mesenchymal stem cell transplantation would be effective for the treatment of hypoxic-ischemic brain damage. In this study, the migra- tion and colonization of cultured bone marrow mesenchymal stem cells on primary neurons after oxygen-glucose deprivation were detected using Transwell assay. The results showed that, after a 40-hour irradiation under red light-emitting diodes at 660 nm and 60 mW/cmz, an increasing number of green fluorescence-labeled bone marrow mesenchymal stem cells migrated towards hypoxic-ischemic damaged primary neurons. Meanwhile, neonatal rats with hypoxic-ischemic brain damage were given an intraperitoneal injection of 1 x 106 bone marrow mesenchymal stem cells, followed by irradiation under red light-emitting diodes at 660 nm and 60 mW/cm2 for 7 successive days. Shuttle box test results showed that, after phototherapy and bone marrow mesenchymal stem cell transplantation, the active avoidance response rate of hypoxic-ischemic brain damage rats was significantly increased, which was higher than that after bone marrow mesenchymal stem cell transplantation alone. Experimental findings indicate that 660 nm red light emitting diode irradiation promotes cells, thereby enhancing the contribution ic-ischemic brain damage. the migration of bone marrow mesenchymal stem of cell transplantation in the treatment of hypox-

Evidence for a therapeutic effect of Braintone on ischemic brain damage

This study used a novel combination of in vivo and in vitro experiments to show that Braintone had neuroprotective effects and clarified the molecular mechanisms underlying its efficacy. The Chinese herbal extract Braintone is composed of Radix Rhodiolase Essence, Radix Notoginseng Essence, Fofium Ginkgo Essence and Rhizoma Chuanxiong. In vivo experiments showed that cerebral infarction volume was reduced, hemispheric water content decreased, and neurological deficits were alleviated in a rat model of permanent middle cerebral artery occlusion after administration of 87.5, 175 or 350 mg/kg Braintone for 7 consecutive days. Western blot analysis showed that Braintone enhanced the expression of hypoxia-inducible factor la, heme oxygenase-1 and vascular endothe- lial growth factor in the ischemic cortex of these rats. The 350 mg/kg dose of Braintone produced the most dramatic effects. For the in vitro experiments, prior to oxygen-glucose deprivation, rats were intragastrically injected with 440, 880 or 1 760 mg/kg Braintone to prepare a Braintone-co ntaining serum, which was used to pre-treat human umbilical vein endothelial cells for 24 hours. Human umbilical vein endothelial cell injury was alleviated with this pre-treatment. Western blot and real-time PCR analysis showed that the Braintone-containing serum increased the levels of hy- poxia-inducible factor la mRNA and protein, heine oxygenase-1 protein and vascular endothelial growth factor mRNA in oxygen-glucose deprived human umbilical vein endothelial cells. The 1 760 mg/kg dose produced the greatest increases in expression. Collectively, these experimental findings suggest that Braintone has neuroprotective effects on ischemia-induced brain damage via the up-regulation of hypoxia-inducible factor la, heme oxygenase-1 and vascular endothelial growth factor expression in vascular endothelial cells.

Protective effects on acute hypoxic-ischemic brain damage in mfat-1 transgenic mice by alleviating neuroinflammation

Acute hypoxic-ischemic brain damage(HIBD)mainly occurs in adults as a result of perioperative cardiac arrest and asphyxia.The benefits of n-3 polyunsaturated fatty acids(n-3 PUFAs)in maintaining brain growth and development are well documented.However,possible protective targets and underlying mechanisms of mfat-1 mice on HIBD require further investigation.The mfat-1 transgenic mice exhibited protective effects on HIBD,as indicated by reduced infarct range and improved neurobehavioral defects.RNA-seq analysis showed that multiple pathways and targets were involved in this process,with the anti-inflammatory pathway as the most significant.This study has shown for the first time that mfat-1 has protective effects on HIBD in mice.Activation of a G protein-coupled receptor 120(GPR120)-related anti-inflammatory pathway may be associated with perioperative and postoperative complications,thus innovating clinical intervention strategy may potentially benefit patients with HIBD.

EFFECT OF MILD HYPOTHERMIA ON ACTIVITY NITRIC OXIDE SYNTHASE IN CORTICAL NEURONS AND GLYCEMIA LEVELS OF NEONATAL RATS WITH HYPOXIC ISCHEMIC BRAIN DAMAGE

Through investigating the effect of mild hypothermia on activity of nitric oxide snythase (NOS) in cortical neurons and glycemia levels of neonatal rats with hypoxic ischemic brain damage (HIBD). We studied the mechanism of protecting hypoxic ischemic neurons of mild hypothermia. We established neonatal rat HIBD models, used NOS immunohistochemistry and glycemia determination by micromethod. The number of cortical NOS positive neurons after hypoxic ischemia was significantly decreased as compared with controls. The glycemia levels was significantly increased than that controls. No significant difference was found in number of cortical NOS positive neurons and glycemia levels between 31℃ and 34℃ mild hypothemia. The results imply that hypothermia can decrease overproduction of NO through inhibiting the increase of the activity of NOS, and increase the glycemia levels, thus protect the hypoxic ischemic neurons.

Animal model of repetitive mild traumatic brain injury for human traumatic axonal injury and chronic traumatic encephalopathy

Chronic traumatic encephalopathy（CTE）is a chronic neurodegenerative disease featured with tauopathy.CTE is tightly related with repetitive mild traumatic brain injury（m TBI）,which is interchangeably known as concussion（Mc Kee et al.,2009,2013）.This disease is differentiated by neuropathological features from other neurological diseases that involve tau protein aggregation and tangle formation abnormalities like Alzheimer＇s disease （AD）, frontotemporal dementia, and Parkinson- ism linked to chromosome 17 （FTDP-17）.