جستجوی مقالات مرتبط با کلیدواژه « blood brain barrier » در نشریات گروه « پزشکی »

Chronic alcohol abuse causes cognitive deficits. Huangqi Gegen Decoction (HGD), a traditional Chinese herbal formula comprising Huangqi and Gegen, has been documented for its therapeutic efficacy in the treatment of alcoholic liver injury. However, its potential neuroprotective effects against alcohol-induced brain injury remain unexplored. This study aims to evaluate the neuroprotection of HGD on alcohol-induced cognitive dysfunction and the associated mechanism.

Wistar rats were orally administered 50% ethanol for 10 weeks, followed by treatment with HGD at doses of 16, 32, or 64 mg/kg/day for an additional 6 weeks. The spatial learning and memory abilities of rats were assessed through the Morris Water Maze experiment. The pathological condition in the hippocampus was assessed using H&E and Nissl staining. Tight junction proteins, oxidative stress, and inflammation cytokines were measured by IF, ELISA, PCR, and western blot. The mRNA and protein expression of Keap1, Nrf-2, HO-1, and NQO-1 were tested by PCR and western blot.

Results showed that HGD effectively mitigated cognitive dysfunction and pathological changes in alcohol-induced rats while enhancing the expression of ZO-1, Occludin, and Claudin-5. Furthermore, HGD effectively mitigated oxidative stress by reducing levels of ROS and MDA, while elevating levels of SOD, CAT, and GSH-PX in brain tissue. Moreover, HGD significantly suppressed microglial activation and down-regulated expressions of IL-1β, IL-6, and TNF-α. Mechanistically, HGD remarkably up-regulated the expression of Nrf-2, HO-1, and NQO-1 while down-regulating Keap1 expression.

These findings suggest that HGD may be a promising therapeutic agent for alleviating alcohol-induced cognitive dysfunction.

Vascular endothelial growth factor (VEGF) signaling pathway plays an important role in the pathogenesis of seizure. The oxidant/antioxidant factors and miRNA expression in the brain are differentially regulated in seizure.

We aim to investigate the potential mechanism of action for the recombinant human VEGF (rhVEGF) in mice with maximal electroshock (MES)-induced seizure.

A total of 40 male mice (weight: 20-25 g) were treated intraperitoneally with normal saline, or rhVEGF (50, 100, and 150 µg/kg, daily for 4 consecutive days). One hour after the last injection, seizures were induced in each animal by MES. The latency for the onset of the first clonus and the duration of hind limb extension (HLE) were recorded. The levels of nitric oxide (NO), total antioxidant capacity (TAC), and micoRNA-142-5p expression were determined in the hippocampus of mice. Blood-brain barrier (BBB) permeability was also estimated by Evans blue dye extravasation method.

The administration of rhVEGF at all doses significantly reduced the HLE duration. However, latency for the seizure onset increased after administration of 50 and 150 μg/kg rhVEGF and decreased after administration of 100 μg/kg rhVEGF. In the brain, the NO level decreased, while TAC level and microRNA-142-5p expression increased by rhVEGF treatment in mice with MES-induced seizure. Pretreatment with rhVEGF at doses of 100 and 150 μg/kg reversed the increase in BBB leakage induced by MES-induced seizures.

The rhVEGF administration can prevent MES-induced seizures by regulating NO, TAC, and miR-142-5 expression levels in the hippocampus and reducing BBB leakage in mice.

Stem cells isolated from the amniotic membrane can produce and release substances that can regenerate damaged tissues and contain proteins and other factors that via numerous major and minor mechanisms lead to increasing angiogenesis and tissue survival. This research was conducted to prove the defensive characteristics of the secretome in the face of temporary focal cerebral ischemia in mouse stroke models.

Cerebral ischemia protocol in a specific area was implemented in rats with middle cerebral artery occlusion for 60 minutes and then reperfusion was given for 6, 20, and 30 minutes. Within 30 minutes after the start of reperfusion, conditioned medium derived from the human amniotic membrane (AMSC-CM) was poured into the right ventricle (ICV) at a dose of 0.5 µL. Finally, the volume of the injury, cerebral tissue water, sensorimotor activity, and the strength of the blood-brain barrier integrity were evaluated 24 hours after drug injection.

ICV injection of conditioned medium at the start of reperfusion phase considerably decreased the volume of the injury 6, 20, and 30 hours after reperfusion compared to the MCAO-operated group (P<0.01). Cerebral tissue water in the treatment group decreased considerably after the intervention in comparison with the MCAO group in the core and penumbral area not in the subcortical area (P<0.05). Also, the amount of Evans blue infiltration at all times in the core and half-foot area in the AMSC-CM group was significantly reduced in parallel with the MCAO group (P<0.05). 

Treatment with AMSC-CM during 6-30 h after ischemia-reperfusion insult exerts some beneficial effects against ischemia-reperfusion injury. These findings provide an important vision for more complementary research and treatment of stroke.

Schizophrenia is one of the most severely debilitating mental disorders that affects 1.1% of the world's population. The exact cause of the disease is not known, but genetics, environmental factors (such as infectious agents, season and region of birth, exposure to viruses, low birth weight, advanced paternal age, and tobacco), and immune system dysfunction can all contribute to the development of schizophrenia. Recently, the role of the immune system in schizophrenia has received much attention. Both acquired and innate immune systems are involved in the pathogenesis of schizophrenia and facilitate the disease's progression. Almost all cells of the immune system including microglia, B cells, and T cells play an important role in the blood-brain barrier damage, inflammation, and in the progression of this disease. In schizophrenia, the integrity of the blood-brain barrier is reduced and then the immune cells are recruited into the endothelium following an increase in the expression of cell adhesion molecules. The entry of immune cells and cytokines leads to inflammation and antibody production in the brain. Accordingly, the results of this study strengthen the hypothesis that the innate and acquired immune systems are involved in the pathogenesis of schizophrenia.

Brain, predisposed to local and metastasized tumors, has always been the focus of oncological studies. Glioblastoma multiforme (GBM), the most common invasive primary tumor of the brain, is responsible for 4% of all cancer-related deaths worldwide. Despite novel technologies, the average survival rate is 2 years. Physiological barriers such as blood-brain barrier (BBB) prevent drug molecules penetration into brain. Most of the pharmaceuticals present in the market cannot infiltrate BBB to have their maximum efficacy and this in turn imposes a major challenge. This mini review discusses GBM and physiological and biological barriers for anticancer drug delivery, challenges for drug delivery across BBB, drug delivery strategies focusing on SLNs and NLCs and their medical applications in on-going clinical trials. Numerous nanomedicines with various characteristics have been introduced in the last decades to overcome the delivery challenge. Solid lipid nanoparticles (SLNs) and nanostructured lipid carriers (NLCs) were introduced as oral drug delivery nanomedicines which can be encapsulated by both hydrophilic and lipophilic pharmaceutical compounds. Their biocompatibility, biodegradability, lower toxicity and side effects, enhanced bioavailability, solubility and permeability, prolonged half-life and stability and finally tissue-targeted drug delivery makes them unique among all.

A neurodevelopmental disorder, autism is typically identified with three primary behavioral consequences, such as social impairment, communication problems, and limited or stereotypical behavior. Because of its co-morbidity and lack of therapeutic options, autism is a global economic burden. A short chain of fatty acid, propionic acid is formed biologically by the gut microbiome. Propionic acid levels that are too high can cause leaky intestines, which can lead to autism-like symptoms.

To induce autism, male Albino Wistar rats were given propionic acid (250 mg/kg/po on the 21st, 22nd, and 23rd postnatal days). Rats also received a ryanodine receptor antagonist (Ruthenium red: 3 mg/kg/po; postnatal 21st to 50th day) to see what influence it had on propionic acid-induced autism. Anxiety, social behavior, and repeated behaviors were all assessed, as well as oxidative stress, inflammatory indicators, neuro signaling proteins, and blood-brain barrier permeability.

Ruthenium red was found to counter the propionic acid-induced increases in anxiety, repetitive behavior prefrontal cortex levels of IL-6, TNF-α, TBARS, Evans blue leakage, and water content along with decreases in social behavior, IL-10, and GSH followed by hippocampus CREB and BDNF levels. 

Ryanodine receptor antagonists presented a neuroprotective effect in propionic acid-induced conditions like autism by modulatory effects on social and repetitive behavior, oxidative stress, neuroinflammation, and neuroprotein changes. Ryanodine receptors can be further explored in depth to manage autism as a condition.

Intracerebroventricular (ICV) injections of mesenchymal stem cells (MSCs) may improve the function and structure of blood-brain barrier (BBB), possibly by preserving the BBB integrity. This study examined the impact of Wharton’s jelly (WJ)-MSCs on cognitive dysfunction and BBB disruption following a protracted hypoxic state. Twenty-four male Wistar rats were randomly studied in four groups: Control (Co): Healthy animals, Sham (Sh): Rats were placed in the cage without hypoxia induction and with ICV injection of vehicle, Hypoxic (Hx)+vehicle: Hypoxic rats with ICV injection of vehicle (5 μl of PBS), and Hx+MSCs: Hypoxic rats with ICV injection of MSCs. Spatial learning and memory were evaluated one week after WJ-MSCs injection, and then animals were sacrificed for molecular research. Hypoxia increased latency and lowered the time and distance required reaching the target quarter, according to the findings. Furthermore, hypoxic rats had lower gene expression and protein levels of hippocampus vascular endothelial (VE)-cadherin, claudin 5, and tricellulin gene expression than Co and Sh animals (P<0.05). Finally, administering WJ-MSCs after long-term hypoxia effectively reversed the cognitive deficits and prevented the BBB breakdown via the upregulation of VE-cadherin, claudin 5, and tricellulin genes (P<0.05). These findings suggest that prolonged hypoxia induces spatial learning and memory dysfunction and increases BBB disruption, the potential mechanism of which might be via reducing VE-cadherin, claudin 5, and tricellulin genes. Hence, appropriate treatment with WJ-MSCs could reverse ischemia adverse effects and protect the BBB integrity following prolonged hypoxia.

The delivery of chemotherapies to brain tumors faces the difficult task of crossing the blood-brain barrier (BBB).1-4 The brain capillary endothelial cells (BCECs) along with other cell lines, such as astrocytes and pericytes, form the BBB. This highly selective semipermeable barrier separates the blood from the brain parenchyma. The BBB controls the movement of drug molecules in a selective manner5 and maintains central nervous system (CNS) homeostasis. Depending on the properties of drugs such as their hydrophilic-lipophilic balance (HLB), some can cross the BBB through passive diffusion.6 However, this approach alone has not led to successful drug developments due to low net diffusion rates and systemic toxicity. Although the use of nanomedicine has been proposed to overcome these drawbacks, many recent studies still rely on the so-called ‘enhanced permeability and retention (EPR)’ effect though there is a realization in the field of drug delivery that EPR effect may not be sufficient for successful drug delivery to brain tumors. Since, compared to many other solid tumors, brain tumors pose additional challenges such as more restrictive blood-tumor barrier as well as the well-developed lymphatic drainage, the selection of functional moieties on the nanocarriers under consideration must be carried out with care to propose better solutions to this challenge.

In our previous studies, the effect of sex hormones on brain edema reduction after traumatic brain injury (TBI) was demonstrated. In the current study, alone and combined effects of 17-β estradiol (E2) and vitamin D (Vit D) on TBI in male rats were investigated. Male rats were divided into six groups, including sham, TBI, vehicle, E2, Vit D, and E2+Vit D. In all groups except sham, moderate-intensity diffuse TBI was induced by the Marmarou’s method. Vehicle, E2, Vit D and their combination were intramusculary injected one and 12 hours after the TBI. The brain water content, permeability of blood brain barrier (BBB) and histopathological outcome were assessed 24h after TBI. The neurological outcome score was determined using the veterinary coma scale (VCS). Significant reductions in brain water content (P<0.001, P<0.05 and P<0.01, respectively) and BBB permeability (P<0.001) appeared in the treated groups with E2, Vit D, and E2+Vit D compared to the vehicle group. Twenty-four hours after the injury, the neurological scores in the E2, Vit D, and E2+Vit D groups increased significantly compared to the vehicle group (P<0.05). Dramatic improvement in histopathological outcome was also observed in the treated groups compared to the vehicle group. Alone and combined consumption of estrogen and vitamin D may similarly decrease the development of brain edema and improve the neurological and histopathological consequences of TBI. Therefore, consumption of vitamin D did not enhance the neuroprotective effect of estrogen in TBI.

Neurological disorders such as Alzheimer’s disease, Parkinson’s disease, dementia, epilepsy,depression, migraine etc. are affecting more and more elderly people’s day by day. Conventionalroute of administration to treat these diseases has to face a major hindrance that is bloodbrain and blood-cerebrospinal fluid (CSF) barrier to achieve desired concentration of drug atthe site of action for therapeutic effect. Hence, intranasal route of delivery is considered aspromising and alternative route to achieve desired goals. In last four decades, brain targetingstrategies are widely studied and considered having great potential by researchers; especiallyintranasal delivery owing to its benefits. Various nano formulations such as nanoemulsions,nanosuspensions, hydrogels, in situ gels, dendrimers and lipidic formulations are studiedwidely. Lipid nano formulations especially second generation nanostructured lipid carriersoffer greater advantages in terms of stability, fabrication techniques, scalability, drug loadingand drug targeting. Nanostructured lipid carrier (NLCs) constitute of two major componentsviz solid lipid and liquid lipid in a specific ratio. In this review, authors have discussed aboutthe possible synergistic actions of oils/liquid lipids with synthetic drugs resulting into greattherapeutic benefits.

Schizophrenia is a neuropsychiatric disorder mainly affecting the central nervous system (CNS), presented with auditory and visual hallucinations, delusion and withdrawal from society. Abnormal dopamine levels mainly characterise the disease; various theories of neurotransmitters explain the pathophysiology of the disease. The current therapeutic approach deals with the systemic administration of drugs other than the enteral route, altering the neurotransmitter levels within the brain and providing symptomatic relief. Fluid biomarkers help in the early detection of the disease, which would improve the therapeutic efficacy. However, the major challenge faced in CNS drug delivery is the blood-brain barrier (BBB). Nanotherapeutic approaches may overcome these limitations, which will improve safety, efficacy, and targeted drug delivery. This review article addresses the main challenges faced in CNS drug delivery and the significance of current therapeutic strategies and nanotherapeutic approaches for a better understanding and enhanced drug delivery to the brain, which improve the quality of life of schizophrenia patients.

blood-brain barrier (BBB) is made of specialized cells that are responsible for the selective passage of substances directed to the brain. The integrated BBB is essential for precise controlling of the different substances passage as well as protecting the brain from various damages. In this article, we attempted to explain the role of liver X receptor (LXR) in maintaining BBB integrity as a possible drug target.

In this study, various databases, including PubMed, Google Scholar, and Scopus were searched using the following keywords: blood-brain barrier, BBB, liver X receptor, and LXR until July, 2020. Additionally, contents close to the subject of our study were surveyed.

LXR is a receptor the roles of which in various diseases have been investigated. LXR can affect maintaining BBB by affecting various ways such as ATP-binding cassette transporter A1 (ABCA1), matrix metalloproteinase-9 (MMP9), insulin-like growth factor 1 (IGF1), nuclear factor-kappa B (NF-κB) signaling, mitogen-activated protein kinase (MAPK), tight junction molecules, both signal transducer and activator of transcription 1 (STAT1), Wnt/β-catenin Signaling, transforming growth factor beta (TGF-β) signaling, and expressions of Smad 2/3 and Snail.

LXR could possibly be used either as a target for drug delivery to brain tissue or as a target for maintaining the BBB integrity in different diseases; thereby the drug will be conducted to tissues, other than the brain. If it is verified that only LXRα is necessary for protecting BBB, some specific LXRα ligands must be found and then used in medication.