Motor function impairment is a common outcome of stroke.Constraint-induced movement therapy（CIMT）involving intensive use of the impaired limb while restraining the unaffected limb is widely used to overcome the effe...Motor function impairment is a common outcome of stroke.Constraint-induced movement therapy（CIMT）involving intensive use of the impaired limb while restraining the unaffected limb is widely used to overcome the effects of＇learned non-use＇and improve limb function after stroke.However,the underlying mechanism of CIMT remains unclear.In the present study,rats were randomly divided into a middle cerebral artery occlusion（model）group,a CIMT＋model（CIMT）group,or a sham group.Restriction of the affected limb by plaster cast was performed in the CIMT and sham groups.Compared with the model group,CIMT significantly improved the forelimb functional performance in rats.By western blot assay,the expression of phosphorylated extracellular regulated protein kinase in the bilateral cortex and hippocampi of cerebral ischemic rats in the CIMT group was significantly lower than that in the model group,and was similar to sham group levels.These data suggest that functional recovery after CIMT may be related to decreased expression of phosphorylated extracellular regulated protein kinase in the bilateral cortex and hippocampi.展开更多
Here,we discuss an important problem in medicine as development of efctive strategies for brain drug delivery.This problem is related to the blood-brain barrier(BBB),which is a“customs”controlling the entrance of di...Here,we discuss an important problem in medicine as development of efctive strategies for brain drug delivery.This problem is related to the blood-brain barrier(BBB),which is a“customs”controlling the entrance of different molecules from blood into the brain protecting the normal function of central nervous system(CNS).We show three interfaces of anatomical side of BBB and two functional types of BBB一physical and transporter barriers.Although this protective mechanism is essential for health of CNS,it also creates a hindrance to the entry of drugs into the brain.The BBB was discovered over 100 years ago but till now,there is no efective methods for brain drug delivery.There ane more than 70 approaches for overcoming BBB incuding physical,chenical and biological techniques but all of these tools have limitation to be widely used in clinical practice due to invasi venes,challenge in performing,very costly or lim-itation of drug concentration.Photodynamic therapy(PDT)is usual clinical method of surgical navigation for the resection of brain tumor and anti-cancer therapy.Nowadays,the application of PDT is considered as a potential promising tool for brain drug delivery via opening of BBB.Here,we show the first sucoessful experimental results in this field discussing the adventures and disadv antages of PDT-related BBB disruption as well as altematives to overcome these limitations and possi ble mechanisms with new pathways for brain clearance via gly mphatic and lymphatic systems.展开更多
In this manuscript a comprehensive coverage of recent developments in the drug therapy of vasospasm while providing the background information that neuroscientists need to understand its rationale. The range of new ag...In this manuscript a comprehensive coverage of recent developments in the drug therapy of vasospasm while providing the background information that neuroscientists need to understand its rationale. The range of new agents available for treatment of cerebral vasospasm is expanding rapidly along with rapid advances in pharmacology and physiology that are uncovering the mechanisms of this disease. Although there are many publications for treatment of cerebral vaso-spasm, most are focusing on different aspects of vasospasm treatment and many have limited value due to insufficient quality. Moreover, the complexity of this, in many cases deleterious condition, is enormous and the information needed to understand drug effects is accordingly often not readily available in a single source. A number of pharmacological and medical therapies are currently in use or being investigated in an attempt to reverse cerebral vasospasm, but only a few have proven to be useful. Current research efforts promise the eventual production of new medical therapies. At last, recommendations for the use of different treatment stages based on currently available clinical data are provided.展开更多
Lipogenesis is often highly upregulated in breast cancer brain metastases to adapt to intracranial low lipid microenvironments.Lipase inhibitors hold therapeutic potential but their intra-tumoral distribution is often...Lipogenesis is often highly upregulated in breast cancer brain metastases to adapt to intracranial low lipid microenvironments.Lipase inhibitors hold therapeutic potential but their intra-tumoral distribution is often blocked by the blood-tumor barrier(BTB).BTB activates its Wnt signaling to maintain barrier properties,e.g.,Mfsd2a-mediated BTB low transcytosis.Here,we reported VCAM-1-targeting nano-wogonin(W@V-NPs)as an adjuvant of nano-orlistat(O@V-NPs)to intensify drug delivery and inhibit lipogenesis of brain metastases.W@V-NPs were proven to be able to inactivate BTB Wnt signaling,downregulate BTB Mfsd2a,accelerate BTB vesicular transport,and enhance tumor accumulation of O@V-NPs.With the ability to specifically kill cancer cells in a lipid-deprived environment with IC_(50) at 48 ng/mL,W@V-NPs plus O@V-NPs inhibited the progression of brain metastases with prolonged survival of model mice.The combination did not induce brain edema,cognitive impairment,and systemic toxicity in healthy mice.Targeting Wnt signaling could safely modulate the BTB to improve drug delivery and metabolic therapy against brain metastases.展开更多
Aneurysm rupture can result in subarachnoid hemorrhage,a condition with potentially severe consequences,such as disability and death.In the acute stage,early brain injury manifests as intracranial pressure elevation,g...Aneurysm rupture can result in subarachnoid hemorrhage,a condition with potentially severe consequences,such as disability and death.In the acute stage,early brain injury manifests as intracranial pressure elevation,global cerebral ischemia,acute hydrocephalus,and direct blood–brain contact due to aneurysm rupture.This may subsequently cause delayed cerebral infarction,often with cerebral vasospasm,significantly affecting patient outcomes.Chronic complications such as brain volume loss and chronic hydrocephalus can further impact outcomes.Investigating the mechanisms of subarachnoid hemorrhage-induced brain injury is paramount for identifying effective treatments.Stem cell therapy,with its multipotent differentiation capacity and anti-inflammatory effects,has emerged as a promising approach for treating previously deemed incurable conditions.This review focuses on the potential application of stem cells in subarachnoid hemorrhage pathology and explores their role in neurogenesis and as a therapeutic intervention in preclinical and clinical subarachnoid hemorrhage studies.展开更多
Houshiheisan is composed of wind-dispelling （chrysanthemun fower, divaricate saposhnikovia root, Manchurian wild ginger, cassia twig, Szechwan lovage rhizome, and platycodon root） and deficiency-nourishing （ginseng...Houshiheisan is composed of wind-dispelling （chrysanthemun fower, divaricate saposhnikovia root, Manchurian wild ginger, cassia twig, Szechwan lovage rhizome, and platycodon root） and deficiency-nourishing （ginseng, Chinese angelica, large-head atractylodes rhizome, Indian bread, and zingiber） drugs. In this study, we assumed these drugs have protective effects against cerebral ischemia, on neurovascular units. Houshiheisan was intragastrically administered in a rat model of focal cerebral ischemia. Hematoxylin-eosin staining, transmission electron microscopy, immu- nofluorescence staining, and western blot assays showed that Houshiheisan reduced pathological injury to the ischemic penumbra, protected neurovascular units, visibly up-regtflated neuronal nuclear antigen expression, and down-regulated amyloid precursor protein and amyloid-[3 42 expression. Wind-dispelling and deficiency-nourishing drugs maintained NeuN expression to varying degrees, but did not affect amyloid precursor protein or amyloid-~ 42 expression in the ischemic penumbra. Our results suggest that the compound prescription Houshiheisan effectively suppresses abnormal amyloid precursor protein accumulation, reduces amyloid substance depo- sition, maintains stabilization of the internal environment of neurovascular units, and minimizes injury to neurovascular units in the ischemic penumbra.展开更多
One hundred patients with focal epilepsy were recruited for the present study and their seizures controlled with antiepileptic drugs. The patients then orally received a capsule of tall gastrodis tuber powder, a tradi...One hundred patients with focal epilepsy were recruited for the present study and their seizures controlled with antiepileptic drugs. The patients then orally received a capsule of tall gastrodis tuber powder, a traditional Chinese drug, and underwent single photon emission computed tomography, long-term electroencephalogram, and CT/MRI. Blood drug levels were monitored throughout the study. Before treatment with tall gastrodis tuber, 35 of the 100 cases had abnormal CT/MRI scans; 79 cases had abnormal single photon emission computed tomography images; 86 cases had abnormal electroencephalogram; and a total of 146 abnormal perfusion foci were observed across the 100 subjects. After treatment, the number of patients with normal single photon emission computed tomography images increased by 12; normal electroencephalogram was observed in an additional 27 cases and the number of patients with epileptiform discharge decreased by 29 （34% of 86）; the total number of abnormal perfusion foci decreased by 52 （36%） and changes in abnormal loci were visible in 65 patients. These changes indicate that the administration of tall gastrodis tuber in combination with antiepileptic drugs repairs abnormal perfusion foci in patients with focal epilepsy Our results demonstrate that traditional Chinese drugs can repair abnormal perfusion foci and, as such, are a promising new pathway in the treatment of focal epilepsy.展开更多
AIM:To investigate whether cocktail theraphy combined with of neuroprotectants may have more advantages over single agents in treating focal cerebral ischemic cascade.METHODS:With the use of suture occlusin techique,t...AIM:To investigate whether cocktail theraphy combined with of neuroprotectants may have more advantages over single agents in treating focal cerebral ischemic cascade.METHODS:With the use of suture occlusin techique,the right middle cerebral artery in rats was occluded.Tirty minutes later,Frutose 1,6 diphosphate(FDP) (50 mg/kg,n=20), MK 801(1 mg/kg,n=20) and N acetylcystein (NAC)(150 mg/kg,n=20) were singly or combinantly infused intraperitoneally.At the same time the cocktail treated group(n=20)were infused the above agents combinationly and the control group(n=20)were infused normal saline intraperitoneally.6 hours and 24 hours after focal cerebral ischemia the animals were weighted and neurologically assessed on 5 point scale.The animals were killed,brains were stained 2,3,5 triphenyltetrazolium chloride for assessment of the infarct volume and then embedden onto slides with paraffin for morphological assessment and terminal transferase dUTP nick ending labeling(TUNEL )were carried out for apoptosis and immunohistochemistry were carried out to investigate the changes in bcl 2.RESULTS:All Neuroprotectants decreased volume of infarction (P< 0.05,F test).While cocktail treated group showed more distinct decrease than other groups(P< 0.05,F test).FDP treated group did not decrease the apoptosis of the neurons and did not increase the bcl 2 expression as well.MK 801 treated group,NAC treated group and cocktail treated group significantly decreased the apoptosis of the neurons and increased the bcl 2 expression (P< 0.05,F test).With cocktail treated group showing more distinct effect (P< 0.05,F test).CONCLUSION:Cocktail may be more effective than single neuroprotectant in this modle.展开更多
Aside from the important role of brain natriuretic peptide (BNP) in diagnosis, and differential diagnosis of heart failure, this biological peptide has proved to be an independent surrogate marker of rehospitalization...Aside from the important role of brain natriuretic peptide (BNP) in diagnosis, and differential diagnosis of heart failure, this biological peptide has proved to be an independent surrogate marker of rehospitalization and death of the fatal disease. Several randomized clinical trials demonstrated that drugs such as beta blocker, angiotensin converting enzyme inhibitor, spiro- nolactone and amiodarone have beneficial effects in decreasing circulating BNP level during the management of chronic heart failure. The optimization of clinical decision-making appeals for a representative surrogate marker for heart failure prognosis. The serial point-of-care assessments of BNP concentration provide a therapeutic goal of clinical multi-therapy and an objective guid- ance for optimal treatment of heart failure. Nevertheless new questions and problems in this area remain to be clarified. On the basis of current research advances, this article gives an overview of BNP peptide and its property and role in the management of heart failure.展开更多
Apoptosis,a key mechanism of programmed cell death,is triggered by caspase-3 protein and lowering its levels with gene therapy may rescue cell death after central nervous system damage.We developed a novel,non-viral g...Apoptosis,a key mechanism of programmed cell death,is triggered by caspase-3 protein and lowering its levels with gene therapy may rescue cell death after central nervous system damage.We developed a novel,non-viral gene therapy to block caspase-3 gene expression using small interfering RNA(siRNA)delivered by polybutylcyanoacrylate nanoparticles(CaspNPs).In vitro CaspNPs significantly blocked caspase-3 protein expression in C6 cells,and when injected intraocularly in vivo,CaspNPs lowered retinal capsase-3 immunofluorescence by 57.9%in rats with optic nerve crush.Longitudinal,repeated retinal ganglion cell counts using confocal neuroimaging showed that post-traumatic cell loss after intraocular CaspNPs injection was only 36.1%versus 63.4%in lesioned controls.Because non-viral gene therapy with siRNA-nanoparticles can selectively silence caspace-3 gene expression and block apoptosis in post-mitotic neurons,siRNA delivery with nanoparticles may be promising for neuroprotection or restoration of central visual system damage and other neurological disorders.The animal study procedures were approved by the German National Act on the use of experimental animals(Ethic Committee Referat Verbraucherschutz,Veterinärangelegenheiten;Landesverwaltungsamt Sachsen-Anhalt,Halle,Germany,#IMP/G/01-1150/12 and#IMP/G/01-1469/17).展开更多
BACKGROUNDIntracranial Listeria infections are common in newborns and immunocompromisedindividuals, but brainstem abscesses are rare.CASE SUMMARYWe report a rare case of brainstem abscesses caused by Listeria monocyto...BACKGROUNDIntracranial Listeria infections are common in newborns and immunocompromisedindividuals, but brainstem abscesses are rare.CASE SUMMARYWe report a rare case of brainstem abscesses caused by Listeria monocytogenes in apreviously healthy adult patient. The patient’s magnetic resonance imagingexamination showed multiple brain abscesses, and his second cerebrospinal fluidculture test indicated the presence of Listeria monocytogenes. Despite earlyempirical therapy, the patient’s condition progressively deteriorated. Because thepatient's abscesses were located in the brainstem and multiple lobes, surgery wasnot possible. The patient died 40 d after admission.CONCLUSIONThis case highlights the importance of rational clinical use of drugs to avoidpotentially serious infectious complications.展开更多
The effect of Radix Salviae Miltiorrhizae (RSM) on the gene expression of nitric oxide synthase (NOS) in rat brains daring ischemia was studied with in situ hybridization and the results were analyzed with IBAS 2000 I...The effect of Radix Salviae Miltiorrhizae (RSM) on the gene expression of nitric oxide synthase (NOS) in rat brains daring ischemia was studied with in situ hybridization and the results were analyzed with IBAS 2000 Image Analysis System. It was found that NOS gene expression of cerebral cortex and caudate-putamen was markedly increased in 24 hours in ischemia group (P【 0.01). In RSM-treated rats, although the NOS gene expression of ischemic side was also increased as compared with contralateral cortex and caudate-putamen, it was significantly lower in RSM-treated rats than those of the controls (P【 0.05, P【 0.01). The present study indicates that RSM can partly inhibit NOS gene ex pression of cerebral cortex and caudate-putamen during ischemia. This may be one of the protective mechanisms of RSM on cerebral ischemia.展开更多
基金supported by grants from the National Natural Science Foundation of China,No.81372119a grant from the Science and Technology Commission of Shanghai Municipality,No.12ZR1404000
文摘Motor function impairment is a common outcome of stroke.Constraint-induced movement therapy（CIMT）involving intensive use of the impaired limb while restraining the unaffected limb is widely used to overcome the effects of＇learned non-use＇and improve limb function after stroke.However,the underlying mechanism of CIMT remains unclear.In the present study,rats were randomly divided into a middle cerebral artery occlusion（model）group,a CIMT＋model（CIMT）group,or a sham group.Restriction of the affected limb by plaster cast was performed in the CIMT and sham groups.Compared with the model group,CIMT significantly improved the forelimb functional performance in rats.By western blot assay,the expression of phosphorylated extracellular regulated protein kinase in the bilateral cortex and hippocampi of cerebral ischemic rats in the CIMT group was significantly lower than that in the model group,and was similar to sham group levels.These data suggest that functional recovery after CIMT may be related to decreased expression of phosphorylated extracellular regulated protein kinase in the bilateral cortex and hippocampi.
基金supported by Grant of Russian Science Foundation No.17-15-01263.
文摘Here,we discuss an important problem in medicine as development of efctive strategies for brain drug delivery.This problem is related to the blood-brain barrier(BBB),which is a“customs”controlling the entrance of different molecules from blood into the brain protecting the normal function of central nervous system(CNS).We show three interfaces of anatomical side of BBB and two functional types of BBB一physical and transporter barriers.Although this protective mechanism is essential for health of CNS,it also creates a hindrance to the entry of drugs into the brain.The BBB was discovered over 100 years ago but till now,there is no efective methods for brain drug delivery.There ane more than 70 approaches for overcoming BBB incuding physical,chenical and biological techniques but all of these tools have limitation to be widely used in clinical practice due to invasi venes,challenge in performing,very costly or lim-itation of drug concentration.Photodynamic therapy(PDT)is usual clinical method of surgical navigation for the resection of brain tumor and anti-cancer therapy.Nowadays,the application of PDT is considered as a potential promising tool for brain drug delivery via opening of BBB.Here,we show the first sucoessful experimental results in this field discussing the adventures and disadv antages of PDT-related BBB disruption as well as altematives to overcome these limitations and possi ble mechanisms with new pathways for brain clearance via gly mphatic and lymphatic systems.
文摘In this manuscript a comprehensive coverage of recent developments in the drug therapy of vasospasm while providing the background information that neuroscientists need to understand its rationale. The range of new agents available for treatment of cerebral vasospasm is expanding rapidly along with rapid advances in pharmacology and physiology that are uncovering the mechanisms of this disease. Although there are many publications for treatment of cerebral vaso-spasm, most are focusing on different aspects of vasospasm treatment and many have limited value due to insufficient quality. Moreover, the complexity of this, in many cases deleterious condition, is enormous and the information needed to understand drug effects is accordingly often not readily available in a single source. A number of pharmacological and medical therapies are currently in use or being investigated in an attempt to reverse cerebral vasospasm, but only a few have proven to be useful. Current research efforts promise the eventual production of new medical therapies. At last, recommendations for the use of different treatment stages based on currently available clinical data are provided.
基金supported by the National Natural Science Foundation of China(32171381 and 81973254)the National Innovation of Science and Technology-2030(Program of Brain Science and Brain-Inspired Intelligence Technology)grant(2021ZD0204004,China)+1 种基金Jiangsu Key Laboratory of Neuropsychiatric Diseases Research Major Program(No.ZZ2101,China)the Priority Academic Program Development of the Jiangsu Higher Education Institutes(PAPD),Suzhou International Joint Laboratory for Diagnosis and Treatment of Brain Diseases,and the Suzhou Science and Technology Development Project(No.SJC2022021,China).
文摘Lipogenesis is often highly upregulated in breast cancer brain metastases to adapt to intracranial low lipid microenvironments.Lipase inhibitors hold therapeutic potential but their intra-tumoral distribution is often blocked by the blood-tumor barrier(BTB).BTB activates its Wnt signaling to maintain barrier properties,e.g.,Mfsd2a-mediated BTB low transcytosis.Here,we reported VCAM-1-targeting nano-wogonin(W@V-NPs)as an adjuvant of nano-orlistat(O@V-NPs)to intensify drug delivery and inhibit lipogenesis of brain metastases.W@V-NPs were proven to be able to inactivate BTB Wnt signaling,downregulate BTB Mfsd2a,accelerate BTB vesicular transport,and enhance tumor accumulation of O@V-NPs.With the ability to specifically kill cancer cells in a lipid-deprived environment with IC_(50) at 48 ng/mL,W@V-NPs plus O@V-NPs inhibited the progression of brain metastases with prolonged survival of model mice.The combination did not induce brain edema,cognitive impairment,and systemic toxicity in healthy mice.Targeting Wnt signaling could safely modulate the BTB to improve drug delivery and metabolic therapy against brain metastases.
基金funded by Taiju Life Social Welfare Foundation(to HS).
文摘Aneurysm rupture can result in subarachnoid hemorrhage,a condition with potentially severe consequences,such as disability and death.In the acute stage,early brain injury manifests as intracranial pressure elevation,global cerebral ischemia,acute hydrocephalus,and direct blood–brain contact due to aneurysm rupture.This may subsequently cause delayed cerebral infarction,often with cerebral vasospasm,significantly affecting patient outcomes.Chronic complications such as brain volume loss and chronic hydrocephalus can further impact outcomes.Investigating the mechanisms of subarachnoid hemorrhage-induced brain injury is paramount for identifying effective treatments.Stem cell therapy,with its multipotent differentiation capacity and anti-inflammatory effects,has emerged as a promising approach for treating previously deemed incurable conditions.This review focuses on the potential application of stem cells in subarachnoid hemorrhage pathology and explores their role in neurogenesis and as a therapeutic intervention in preclinical and clinical subarachnoid hemorrhage studies.
基金supported by the National Natural Science Foundation of China,No.30973782,81373526the Natural Science Foundation of Beijing,No.7102014,7122018the Beijing Municipal Higher Learning Institution Talent Teaching Plan"Young and Middle-aged Talented People Training"Project,No.PXM2011014226
文摘Houshiheisan is composed of wind-dispelling （chrysanthemun fower, divaricate saposhnikovia root, Manchurian wild ginger, cassia twig, Szechwan lovage rhizome, and platycodon root） and deficiency-nourishing （ginseng, Chinese angelica, large-head atractylodes rhizome, Indian bread, and zingiber） drugs. In this study, we assumed these drugs have protective effects against cerebral ischemia, on neurovascular units. Houshiheisan was intragastrically administered in a rat model of focal cerebral ischemia. Hematoxylin-eosin staining, transmission electron microscopy, immu- nofluorescence staining, and western blot assays showed that Houshiheisan reduced pathological injury to the ischemic penumbra, protected neurovascular units, visibly up-regtflated neuronal nuclear antigen expression, and down-regulated amyloid precursor protein and amyloid-[3 42 expression. Wind-dispelling and deficiency-nourishing drugs maintained NeuN expression to varying degrees, but did not affect amyloid precursor protein or amyloid-~ 42 expression in the ischemic penumbra. Our results suggest that the compound prescription Houshiheisan effectively suppresses abnormal amyloid precursor protein accumulation, reduces amyloid substance depo- sition, maintains stabilization of the internal environment of neurovascular units, and minimizes injury to neurovascular units in the ischemic penumbra.
基金funded by the Key Project of Gansu Province, No.2GS054-A43-014-19
文摘One hundred patients with focal epilepsy were recruited for the present study and their seizures controlled with antiepileptic drugs. The patients then orally received a capsule of tall gastrodis tuber powder, a traditional Chinese drug, and underwent single photon emission computed tomography, long-term electroencephalogram, and CT/MRI. Blood drug levels were monitored throughout the study. Before treatment with tall gastrodis tuber, 35 of the 100 cases had abnormal CT/MRI scans; 79 cases had abnormal single photon emission computed tomography images; 86 cases had abnormal electroencephalogram; and a total of 146 abnormal perfusion foci were observed across the 100 subjects. After treatment, the number of patients with normal single photon emission computed tomography images increased by 12; normal electroencephalogram was observed in an additional 27 cases and the number of patients with epileptiform discharge decreased by 29 （34% of 86）; the total number of abnormal perfusion foci decreased by 52 （36%） and changes in abnormal loci were visible in 65 patients. These changes indicate that the administration of tall gastrodis tuber in combination with antiepileptic drugs repairs abnormal perfusion foci in patients with focal epilepsy Our results demonstrate that traditional Chinese drugs can repair abnormal perfusion foci and, as such, are a promising new pathway in the treatment of focal epilepsy.
文摘AIM:To investigate whether cocktail theraphy combined with of neuroprotectants may have more advantages over single agents in treating focal cerebral ischemic cascade.METHODS:With the use of suture occlusin techique,the right middle cerebral artery in rats was occluded.Tirty minutes later,Frutose 1,6 diphosphate(FDP) (50 mg/kg,n=20), MK 801(1 mg/kg,n=20) and N acetylcystein (NAC)(150 mg/kg,n=20) were singly or combinantly infused intraperitoneally.At the same time the cocktail treated group(n=20)were infused the above agents combinationly and the control group(n=20)were infused normal saline intraperitoneally.6 hours and 24 hours after focal cerebral ischemia the animals were weighted and neurologically assessed on 5 point scale.The animals were killed,brains were stained 2,3,5 triphenyltetrazolium chloride for assessment of the infarct volume and then embedden onto slides with paraffin for morphological assessment and terminal transferase dUTP nick ending labeling(TUNEL )were carried out for apoptosis and immunohistochemistry were carried out to investigate the changes in bcl 2.RESULTS:All Neuroprotectants decreased volume of infarction (P< 0.05,F test).While cocktail treated group showed more distinct decrease than other groups(P< 0.05,F test).FDP treated group did not decrease the apoptosis of the neurons and did not increase the bcl 2 expression as well.MK 801 treated group,NAC treated group and cocktail treated group significantly decreased the apoptosis of the neurons and increased the bcl 2 expression (P< 0.05,F test).With cocktail treated group showing more distinct effect (P< 0.05,F test).CONCLUSION:Cocktail may be more effective than single neuroprotectant in this modle.
文摘Aside from the important role of brain natriuretic peptide (BNP) in diagnosis, and differential diagnosis of heart failure, this biological peptide has proved to be an independent surrogate marker of rehospitalization and death of the fatal disease. Several randomized clinical trials demonstrated that drugs such as beta blocker, angiotensin converting enzyme inhibitor, spiro- nolactone and amiodarone have beneficial effects in decreasing circulating BNP level during the management of chronic heart failure. The optimization of clinical decision-making appeals for a representative surrogate marker for heart failure prognosis. The serial point-of-care assessments of BNP concentration provide a therapeutic goal of clinical multi-therapy and an objective guid- ance for optimal treatment of heart failure. Nevertheless new questions and problems in this area remain to be clarified. On the basis of current research advances, this article gives an overview of BNP peptide and its property and role in the management of heart failure.
基金MT was funded by the Leistungsorientierte Mittelvergabe(LOM)scholarship offered by the medical faculty of Magdeburg and the Deutscher Akademischer Austauschdienst(DAAD).
文摘Apoptosis,a key mechanism of programmed cell death,is triggered by caspase-3 protein and lowering its levels with gene therapy may rescue cell death after central nervous system damage.We developed a novel,non-viral gene therapy to block caspase-3 gene expression using small interfering RNA(siRNA)delivered by polybutylcyanoacrylate nanoparticles(CaspNPs).In vitro CaspNPs significantly blocked caspase-3 protein expression in C6 cells,and when injected intraocularly in vivo,CaspNPs lowered retinal capsase-3 immunofluorescence by 57.9%in rats with optic nerve crush.Longitudinal,repeated retinal ganglion cell counts using confocal neuroimaging showed that post-traumatic cell loss after intraocular CaspNPs injection was only 36.1%versus 63.4%in lesioned controls.Because non-viral gene therapy with siRNA-nanoparticles can selectively silence caspace-3 gene expression and block apoptosis in post-mitotic neurons,siRNA delivery with nanoparticles may be promising for neuroprotection or restoration of central visual system damage and other neurological disorders.The animal study procedures were approved by the German National Act on the use of experimental animals(Ethic Committee Referat Verbraucherschutz,Veterinärangelegenheiten;Landesverwaltungsamt Sachsen-Anhalt,Halle,Germany,#IMP/G/01-1150/12 and#IMP/G/01-1469/17).
文摘BACKGROUNDIntracranial Listeria infections are common in newborns and immunocompromisedindividuals, but brainstem abscesses are rare.CASE SUMMARYWe report a rare case of brainstem abscesses caused by Listeria monocytogenes in apreviously healthy adult patient. The patient’s magnetic resonance imagingexamination showed multiple brain abscesses, and his second cerebrospinal fluidculture test indicated the presence of Listeria monocytogenes. Despite earlyempirical therapy, the patient’s condition progressively deteriorated. Because thepatient's abscesses were located in the brainstem and multiple lobes, surgery wasnot possible. The patient died 40 d after admission.CONCLUSIONThis case highlights the importance of rational clinical use of drugs to avoidpotentially serious infectious complications.
文摘The effect of Radix Salviae Miltiorrhizae (RSM) on the gene expression of nitric oxide synthase (NOS) in rat brains daring ischemia was studied with in situ hybridization and the results were analyzed with IBAS 2000 Image Analysis System. It was found that NOS gene expression of cerebral cortex and caudate-putamen was markedly increased in 24 hours in ischemia group (P【 0.01). In RSM-treated rats, although the NOS gene expression of ischemic side was also increased as compared with contralateral cortex and caudate-putamen, it was significantly lower in RSM-treated rats than those of the controls (P【 0.05, P【 0.01). The present study indicates that RSM can partly inhibit NOS gene ex pression of cerebral cortex and caudate-putamen during ischemia. This may be one of the protective mechanisms of RSM on cerebral ischemia.
