Constraint-induced movement therapy promotes motor function recovery and downregulates phosphorylated extracellular regulated protein kinase expression in ischemic brain tissue of rats

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.

Blood–brain barrier and laser technology for drug brain delivery

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.

New Developments in Drug Therapy and Research of Cerebral Vasospasm

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.

Therapeutic potential of stem cells in subarachnoid hemorrhage

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.

抗氧化纳米药物介导心肌缺血再灌注损伤的靶向治疗

背景:心肌缺血再灌注时过量活性氧会加速心肌损伤,抗氧化疗法虽有效但存在低生物利用度和靶向特异性差等局限性。纳米药物以精准靶向与延长药效的优势在心肌保护中展现出广阔应用前景。目的:总结心肌再灌注损伤过程中活性氧产生的途径以及纳米医学治疗心肌缺血性损伤的最新进展。方法:检索中国知网和PubMed数据库中关于抗氧化纳米药物介导心肌缺血再灌注损伤靶向治疗的相关文献,以“纳米,纳米药物,纳米材料,纳米技术,心肌缺血再灌注损伤,氧化应激,活性氧”为中文检索词,以“nanostructures,nanomedicine,nanomaterials,nanotechnology,myocardial ischemia reperfusion injury,oxidative stress,reactive oxygen species”为英文检索词,检索时限为2019年8月至2024年8月,通过阅读文献题目和摘要进行初步筛选,然后剔除与文章主题相关性不高的文献,最终纳入65篇文献进行分析。结果与结论:高浓度活性氧的累积是心肌缺血再灌注损伤的核心机制之一。不同来源途径的活性氧能够直接干预物质与能量的代谢过程,进而触发心肌细胞的凋亡或坏死,对心脏组织构成显著损害,因此,清除或降低活性氧水平被视为有效遏制心肌缺血再灌注损伤发展的重要治疗策略。传统药物半衰期短、生物利用度低、缺乏靶向性,再加上肝脏和脾脏的螯合作用以及心肌部位血流的持续冲刷,严重影响了临床药物的预期疗效。纳米药物在突破上述局限方面展现出非凡的潜力,为缺血性疾病的治疗开辟了新方向。通过精确设计的纳米颗粒可实现对药物的靶向递送,显著提高药物在受损心肌部位的浓度与滞留时间,从而增强治疗效果。此外,纳米药物作为抗氧化剂、生长因子或细胞疗法的载体有效减轻了氧化应激,促进了心肌细胞的修复与再生,为心肌功能的恢复带来了希望。

Houshiheisan compound prescription protects neurovascular units after cerebral ischemia

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.

Tall gastrodis tuber combined with antiepileptic drugs repairs abnormal perfusion foci in focal epilepsy

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.

Brain natriuretic peptide and optimal management of heart failure

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.

Gene therapy with caspase-3 small interfering RNA-nanoparticles is neuroprotective after optic nerve damage

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).

Brainstem abscesses caused by Listeria monocytogenes:A case report

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.

Effects of neuroprotectant cocktails on focal cerebral ischemia in rats

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.

Heat shock protein 72 normothermic ischemia,and the impact of congested portal blood reperfusion on rat liver

INTRODUCTIONFrom the technical aspect of liver surgery ,control of bleeding during hepatic parenchymal resection is one of the most important procedures in hepatectomy .Pringle,s maneuver ,a temporary cross-clamping of the hepatoduodnal ligament ,has often been used for this purpose[1],This is the simplest and userul technique to reduce intraoperative blood loss .

EFFECT OF RADIX SALVIAE MILTIORRHIZAE ON THE GENE EXPRESSION OF NITRIC OXIDE SYNTHASE IN ISCHEMIC RAT BRAINS

The effect of Radix Salviae Miltiorrhizae (RSM) on the gene expression of nitric oxide synthase (NOS) in rat brains during 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

严重下肢缺血患者围手术期的合理用药

严重下肢缺(CLI)血患者常合并多种慢性疾病,血运重建围手术期的药物管理是疾病治疗的重要内容,不合理的多重用药直接影响患者的治疗结局。本研究针对CLI患者围手术期常见的用药问题进行探讨,重点关注围手术期血栓的预防与治疗、基础疾病防治与多重用药管理、镇痛方案制定与调整,以期为临床医师和药师给患者制定个体化用药方案提供参考。

Suppressing Wnt signaling of the blood-tumor barrier to intensify drug delivery and inhibit lipogenesis of brain metastases

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.

基于数据挖掘对中医药治疗CKD合并脑卒中的组方用药分析

基于数据挖掘方法探讨中医药治疗慢性肾脏病(CKD)合并脑卒中(CS)的临床用药规律。收集2017年10月至2022年10月天津中医药大学第一附属医院门诊治疗CKD合并CS的处方,建立中药处方数据库。统计分析用药频次、性味及归经,对处方中的药物进行聚类分析,利用SPSS Modeler 18 Apriori算法对所有药物进行关联分析。最终纳入544个处方,涉及中药258味,总用药频次8 886次。药性以寒性、温性、平性居多;药味以苦味、甘味、辛味为主;归经多为脾经、肝经;得出13个关联组合药对和5个核心药物组合。中医药对CKD合并CS患者的治疗,根据气虚血瘀、脾肾两虚的病机特点,主要采用健脾益气、补肾活血的组方用药。

脑类器官在药物研发中的研究进展

近年来,随着再生医学与组织工程学的飞速发展,脑类器官作为一种创新的体外模型系统,逐渐成为神经科学研究和药物研发领域的热点。脑类器官通过模拟人类大脑的复杂结构和功能,在体外重现了大脑发育的关键过程,为理解神经系统疾病机制、评估药物疗效及毒性提供了前所未有的平台。本文综述了脑类器官技术的最新进展,特别是其在药物研发中的应用,并探讨了该领域面临的挑战与未来发展方向。

重度抑郁症患者脑网络有效连接的磁共振成像研究进展

重度抑郁症(major depressive disorder,MDD)是一种以持续悲伤为特征,以精力缺乏、情绪低落、睡眠异常、思维迟缓等为主要表现的精神障碍类疾病。有效连接(effective connectivity,EC)作为一种可以揭示脑区间因果关系的研究方法,在MDD的研究中起着重要作用。本文将对EC分析方法、EC在MDD不同脑网络和重要脑区节点中的研究及临床治疗后变化进行综述,旨在进一步揭示MDD的发病机制以及为治疗靶点的研究提供参考与技术支持。

从肠道菌群探讨健脾益智法治疗缺血性脑卒中的机制研究

中医脾与脑相关理论是健脾益智法治疗缺血性脑卒中的理论基础,而肠道菌群-肠-脑轴是脾脑相关理论的微观机制体现。肠道菌群因定植于肠道,与中医脾脏有着天然的相关性:脾主运化与肠道菌群的消化、吸收作用相关,脾胃气机升降与肠道菌群促进肠蠕动相关;脾主为卫与肠道菌群促进免疫系统的发育与功能的成熟相关。肠道菌群属于中医脾藏功能范畴,为治疗缺血性脑卒中提供了新的思路。从肠道菌群的角度来看,健脾益智法治疗缺血性脑卒中具有坚实的理论及现实依据,健脾益智法治疗缺血性脑卒中值得展开深入研究。

药物治疗在肝切除术中预防缺血再灌注损伤的研究进展

肝切除术中常采用肝门阻断和控制中心静脉压的方法减少出血,保证手术视野清晰,从而使手术顺利进行,但在肝门阻断和开放过程中会导致肝脏缺血再灌注损伤(hepatic ischemia-reperfusion injury,HIRI)、胃肠道淤血、肠源性细菌移位等问题。因此,围术期采取各种措施减轻因肝门阻断引起的HIRI进而提高手术的安全性成为肝切除术的研究热点。缺血预处理、亚低温处理、药物治疗、抗凋亡基因治疗等方法应运而生,其中药物治疗具有可操作性强、相对安全、临床上易操作等优势,因而受到广泛关注。本文对有助于改善HIRI的部分代表药物及作用机制进行总结,为HIRI的临床诊治提供参考。