scholarly journals Opening the Blood-Brain Barrier and Improving the Efficacy of Temozolomide Treatments of Glioblastoma Using Pulsed, Focused Ultrasound with a Microbubble Contrast Agent

2018 ◽  
Vol 2018 ◽  
pp. 1-9 ◽  
Author(s):  
Qian Dong ◽  
Lin He ◽  
Linbo Chen ◽  
Qiongzhen Deng
Keyword(s):  
Western Blot ◽  
Contrast Agent ◽  
Blood Brain Barrier ◽  
Evans Blue ◽  
Wistar Rats ◽  
Blue Staining ◽  
Control Group ◽  
Microbubble Contrast Agent ◽  
Bbb Permeability ◽  
Temozolomide Chemotherapy

Objective.To explore the effects of pulsed, focused, and microbubble contrast agent-enhanced ultrasonography (mCEUS) on blood-brain barrier (BBB) permeability and the efficacy temozolomide for glioblastoma.Methods.Wistar rats (n = 30) were divided into three groups (n = 10 per group) to determine optimal CUES conditions for achieving BBB permeability, as assessed by ultrastructure transmission electron microscopy (TEM) and western blot assays for the tight junction protein claudin-5. Optimized mCEUS effects on BBB permeability were subsequently confirmed with Evans blue staining (2 groups of 10 rats). The glioma cell line 9L was injected into the brain striatum of Wistar rats. After temozolomide chemotherapy, we detected glial fibrillary acidic protein (GFAP) levels in serum by enzyme-linked immunosorbent assay (ELISA) and in brain tissue by western blot, immunocytochemistry, and real-time quantitative polymerase chain reaction (qPCR).Results.BBB permeability was maximized with 1 ml/kg contrast agent mCEUS delivered via 10-min intermittent launches with a 400-ms interval. Evans blue staining confirmed BBB permeability following ultrasonic cavitation in the control group (P < 0.05). Following temozolomide chemotherapy, levels of the tumor marker GFAP were increased in the group with ultrasonic cavitation compared with the control group (P < 0.05).Conclusions.When rats were treated by mCEUS with intermittent launches (interval, 400 ms) and injected with 1 mg/kg contrast agent, BBB permeability was increased and temozolomide BBB penetration was enhanced, therapeutic enhancement for glioblastoma.

scholarly journals The Role and Mechanism of Borneol to Open the Blood-Brain Barrier

2018 ◽  
Vol 17 (3) ◽  
pp. 806-812 ◽  
Author(s):  
Tao Wu ◽  
Aiqin Zhang ◽  
Hongyang Lu ◽  
Qiaoyuan Cheng
Keyword(s):  
Blood Brain Barrier ◽  
Evans Blue ◽  
Corn Oil ◽  
Malignant Tumors ◽  
Brain Barrier ◽  
Control Group ◽  
High Dose ◽  
Total Density ◽  
Sd Rats ◽  
Blood Brain

Background: The blood-brain barrier (BBB) is the greatest challenge in the treatment of intracranial malignant tumors. Objective: The aim of this study is to determine the role of borneol in opening the BBB and elucidate the underlying mechanisms. Materials and Methods: Twenty Sprague-Dawley (SD) rats were randomized into borneol group intragastrically administered with 10% borneol corn oil (2 mL/kg) and control group. After 30 minutes, 2% Evans blue (4 mL/kg) was injected. Thirty minutes later, brain tissue was analyzed using the Evans blue standard curve. Another 40 SD rats were randomized into high-, medium-, and low-dose borneol groups and a control group. Each rat in the experimental groups was intragastrically administered with 10% borneol corn oil (2 mL/kg, 1.25 mL/kg, and 0.5 mL/kg, respectively). The control group was injected with corn oil of 1.25 mL/kg. After 30 minutes, the rats were killed, and the brain tissues were collected. The expression of occludin, occludens-1, nitric oxide synthase, P-glycoprotein, and intercellular cell adhesion molecule-1 (ICAM-1) was detected by immunohistochemy. Results: The concentration of Evans blue in the borneol group was higher than in the control group ( P < .05). The mean density of ICAM-1 expression was higher in the experimental group than in the control group ( P < .05). In contrast, significant differences of positive area and total density of ICAM-1 were shown only between the high-dose group and the control group ( P < .05). Conclusion: Borneol can open the BBB, which might be related with the increased expression of ICAM-1.

IMMUNOHISTOCHEMICAL STUDIES OF BLOOD BRAIN BARRIER AFTER ADMINISTRATION OF ABHRAK BHASM IN WISTAR RATS

2021 ◽  
pp. 13-19
Author(s):  
Amita Singh ◽  
Raj Kumar ◽  
S. K. Kannaujia ◽  
Manikrishna Manikrishna ◽  
N. P. Singh
Keyword(s):  
Blood Brain Barrier ◽  
Wistar Rats ◽  
Brain Parenchyma ◽  
Brain Barrier ◽  
Major Constituent ◽  
Control Group ◽  
Blood Brain ◽  
Biological Studies ◽  
Immunohistochemical Studies ◽  
The Brain

Abhrak bhasma (AB) is a type of bhasma prepared from repeated incineration of mineral mica with decoctions of about 72 herbs. The particle size of Abhrak bhasm has been shown to be in the range of 29-88 nanometers and Fe, Ca, Si, Mg and K are found to be as major constituent. Many drugs developed to treat Central Nervous System (CNS) disorders are unable to reach the brain parenchyma in therapeutically relevant concentrations. The blood brain barrier protects brain parenchyma from the uctuation of plasma composition, from pathogenic agents and maintains homeostasis of the brain parenchyma by restricting non-specic ux of ions, peptides, proteins and even cells into and out the brain. Immunohistochemistry is being widely employed as a tool for biological studies. This study is conducted to examine the change in the continuity of Blood brain barrier by using immunohistochemistry, once Abhrak bhasm drug is given in experimental animal and also to examine the histology of organs. In this study a total of 30 adult albino Wistar rats of approximately 4 months age (approx. 150-200 gms) of either sex selected randomly to see the effect of Abhrak bhasm, an ayurvedic drug on Wistar rats. The rats were weighed, marked and divided into 5 groups each consisting of six animals. In normal control group (Group E), no drug was administered and in rest of the four treated groups (Group-A,B,C,D), Abhrak bhasm @ 36 mg/kg B.wt. was administered orally once in each rat. Brain, liver, kidneys,spleen and blood samples were collected in 10% formalin solution after euthanizing the rats at 0.5,2,6 & 12 hours of Abhrak bhasma drug intervention. The alterations in any of the biochemical parameters are within the tolerable limits of liver and kidney since the dose of abhrak bhasm did not affect liver and kidneys. In the present study, the increase in ALP level may be the result of alterations in metabolisms that occurred without any signicant alteration in histology of liver. After applying the immunohistochemistry with the research markers GFAP, CD 34, S 100, GLUT-1 and RECA-1 on the rats in groups A,B,C and D, there was no change in the intensity of immunohistochemistry, with respect to control. While on applying the Occludin, the intensity of immunohistochemistry was reduced in all the treatment groups as compared to the control group. On the basis of ndings of present study it can be concluded that the therapeutic dose of Abhrak bhasma causes changes at the level of tight junctions present in blood brain barrier in rats which is shown by immunohistochemistry with occludin research marker. There is no toxic effect of drug on different organs of rats as no signicant changes in histology of organs are seen. More studies need to be done to check the permeability of blood brain barrier for Abhrak bhasma drug, like calculating its concentration in brain tissues and other vital organs of rat.

EXTH-07. TEMPORAL ASSESSMENT OF ALTERED PERI-ABLATION BLOOD-BRAIN BARRIER PERMEABILITY FOLLOWING TUMOR CYTOREDUCTION BY THERMAL THERAPY IN A RAT ORTHOTOPIC GLIOBLASTOMA MODEL

2021 ◽  
Vol 23 (Supplement_6) ◽  
pp. vi164-vi164
Author(s):  
Tavarekere Nagaraja ◽  
Seamus Bartlett ◽  
Glauber Cabral ◽  
Katelynn Farmer ◽  
Robert Knight ◽  
...  
Keyword(s):  
Blood Brain Barrier ◽  
Evans Blue ◽  
Thermal Therapy ◽  
Female Rats ◽  
Brain Barrier ◽  
Gadolinium Contrast ◽  
Dce Mri ◽  
Blood Brain ◽  
Bbb Permeability ◽  
Bbb Opening

Abstract Laser interstitial thermal therapy (LITT) is a minimally invasive tumor cytoreductive treatment for recurrent gliomas, brain tumors in eloquent regions and/or otherwise inaccessible. Following reports of persistent peri-ablation blood-brain barrier (BBB) opening in humans, we examined this phenomenon using a rat glioblastoma model. Athymic female rats were implanted with U251 tumor cells in one brain hemisphere. Tumor growth was monitored using magnetic resonance imaging (MRI) and dynamic contrast enhanced (DCE)-MRI. When tumors reached about 4 mm in diameter, they were ablated under supervision of diffusion-weighted MRI using Visualase®, a clinical LITT system. Four rats were used as controls. Longitudinal MRI data were obtained before LITT, and at post-LITT 2 (n=9), 3 (n=3) and 4 (n=9) weeks. After the terminal MRI at each time point, rats were injected intravenously with fluorescent isothiocyanate dextran (FITC-dextran; 2000 kDa) and Evans Blue (68 kDa after binding to plasma albumin) and the brains immersion fixed in 10% paraformaldehyde. The brains were cut into 100 μM thick slices in a vibratome and examined for the distribution of the two fluorophores. All rats survived the LITT procedure. The sham controls showed increased tumor burden by 2 weeks and were sacrificed. DCE-MRI data and fluorescent data showed elevated BBB permeability in peri-ablation regions, with leakage of a gadolinium contrast on DCE-MRI and of Evans Blue, but not of FITC-dextran. Histology showed little tumor tissue at 2 weeks, but evidence of recurrence at ablation margins at later times. These data demonstrate that LITT is adaptable to rat glioma models and can be performed under MRI monitoring. Peri-ablation regions showed selective increase in BBB permeability acutely due to sublethal heating, but later increases in permeability may be due to tumor recurrence. We suggest this model is useful for examining the temporal and spatial development of peri-ablation BBB opening following LITT.

scholarly journals BMSCs Regulate Astrocytes through TSG-6 to Protect the Blood-Brain Barrier after Subarachnoid Hemorrhage

2021 ◽  
Vol 2021 ◽  
pp. 1-18
Author(s):  
Yilv Wan ◽  
Min Song ◽  
Xun Xie ◽  
Zhen Chen ◽  
Ziyun Gao ◽  
...  
Keyword(s):  
Subarachnoid Hemorrhage ◽  
Blood Brain Barrier ◽  
Mapk Signaling ◽  
Brain Barrier ◽  
Inflammatory Factors ◽  
Blue Staining ◽  
Nissl Staining ◽  
Blood Brain ◽  
Bbb Permeability

Background. In patients with subarachnoid hemorrhage (SAH), the damage of the blood-brain barrier (BBB) can be life-threatening. Mesenchymal stem cells are widely used in clinical research due to their pleiotropic properties. This study is aimed at exploring the effect of BMSCs regulating astrocytes on the BBB after SAH. Methods. The SAH model was established by perforating the blood vessels. BMSCs were transfected with TSG-6 inhibitor plasmid and cocultured with astrocytes. Intravenous transplantation of BMSCs was utilized to treat SAH rats. We performed ELISA, neurological scoring, Evans blue staining, NO measurement, immunofluorescence, BBB permeability, Western blot, HE staining, Nissl staining, and immunohistochemistry to evaluate the effect of BMSCs on astrocytes and BBB. Results. SAH rats showed BBB injury, increased BBB permeability, and brain histological damage. BMSCs will secrete TSG-6 after being activated by TNF-α. Under the influence of TSG-6, the NF-κB and MAPK signaling pathways of astrocytes were inhibited. The expression of iNOS was reduced, while occludin, claudin 3, and ZO-1 expression was increased. The production of harmful substances NO and ONOO- decreased. The level of inflammatory factors decreased. The apoptosis of astrocytes was weakened. TSG-6 secreted by BMSCs can relieve inflammation caused by SAH injury. The increase in BBB permeability of SAH rats was further reduced and the risk of rebleeding was reduced. Conclusion. BMSCs can regulate the activation of astrocytes through secreting TSG-6 in vivo and in vitro to protect BBB.

scholarly journals Protection Against Blood-brain Barrier Permeability as a Possible Mechanism for Protective Effects of Thymoquinone Against Sickness Behaviors Induced by Lipopolysaccharide in Rats

2021 ◽  
Vol 16 (2) ◽  
Author(s):  
Rahimeh Bargi ◽  
Mahmoud Hosseini ◽  
Fereshteh Asgharzadeh ◽  
Majid Khazaei ◽  
Mohammad Naser Shafei ◽  
...  
Keyword(s):  
Blood Brain Barrier ◽  
Active Role ◽  
Brain Barrier ◽  
Control Group ◽  
Protective Effects ◽  
Blood Brain ◽  
Immobility Time ◽  
Sickness Behaviors ◽  
Bbb Permeability ◽  
The Brain

Background: Blood-brain barrier (BBB), as well-known protection for the brain, plays an active role in normal homeostasis. It might be changed by a range of inflammatory mediators to have a role in sickness behaviors. Objectives: Regarding the anti-inflammatory effects of thymoquinone (TQ), its protection against BBB permeability, as a possible mechanism for protective effects against sickness behaviors elicited by lipopolysaccharide (LPS), was evaluated in rats. Methods: The animals were grouped as follows and treated (n = 10 in each): (1) control (saline); (2) LPS 1 mg/kg, was injected two hours before behavioral tests for two weeks; (3-5) 2, 5, and 10 mg/kg TQ, respectively was injected 30 min before LPS injection. Open-field (OF), elevated plus-maze (EPM) and Forced Swimming test (FST) were done. Finally, the animals were anesthetized to evaluate for BBB permeability using Evans blue (EB) dye method. Results: Compared with control, LPS decreased the peripheral distance and crossing and also total crossing and distance in OF, (P < 0.01 - P < 0.001). The central crossing and distance and central time in all three treatment groups were more than LPS (P < 0.05 - P < 0.001). LPS also reduced the entries and the time spent in the open arm while increased the time spent in the closed arm in EPM (P < 0.05 - P < 0.001). The effects of LPS were reversed by TQ (P < 0.05 - P < 0.001). In FST, the immobility time and active time were increased and decreased by LPS compared with control (P < 0.001), respectively. In all three TQ-treated groups, the active and climbing times were more while the immobility time was fewer than the LPS (P < 0.05 - P < 0.001). The animals of the LPS group showed more EB dye content in their brain tissue than the control group (P < 0.05 - P < 0.001). TQ significantly reduced EB dye content of the brain tissues (P < 0.05 - P < 0.001). Conclusions: According to this study, protection against BBB permeability as a possible mechanism for the protective effects of TQ against sickness behaviors induced by LPS might be suggested.

Autoradiographic Observation of Platelets in Cerebrovascular Injuries Induced by Arachidonic Acid and its Prevention by Ticlopidine

1988 ◽  
Vol 60 (02) ◽  
pp. 319-323 ◽  
Author(s):  
Tsukasa Fujimoto ◽  
Hidenori Suzuki ◽  
Kenjiro Tanoue ◽  
Yoshiharu Fukushima ◽  
Hiroh Yamazaki
Keyword(s):  
Arachidonic Acid ◽  
Carotid Artery ◽  
Internal Carotid Artery ◽  
Blood Brain Barrier ◽  
Evans Blue ◽  
Internal Carotid ◽  
Antiplatelet Agent ◽  
Blue Staining ◽  
Activated Platelets ◽  
The Brain

SummaryThe behavior of circulating 111In-labeled platelets in cerebrovascular injuries induced by arachidonic acid injection was studied. Fourteen rabbits were pretreated with the antiplatelet agent ticlopidine, and 10 rabbits were used for controls. Arachidonic acid (AA, 0.7 mg/kg) was injected into the internal carotid artery. Prior to the injection, platelets labeled with 111In- oxine were injected for autoradiography of the brain. Evans blue was injected as an indicator of blood-brain barrier disturbance. Nine control animals showed marked blue staining, and one showed slight blue staining. Seven out of the 14 pretreated animals showed slight or no staining, while 7 showed intensive staining. The distributions of the blue staining and the radioactivity showed high correlation. In the rabbits whose platelet aggrega- bility was depressed by ticlopidine, lower blue staining as well as lower radioactivity was observed. Our findings suggest that activated platelets have an important role in the genesis of cerebrovascular injuries.

Opening of the Blood-Brain Barrier by Intravenous Contrast Media in Euvolemic and Dehydrated Rabbits

1989 ◽  
Vol 30 (4) ◽  
pp. 439-444 ◽  
Author(s):  
K. Hayakawa ◽  
T. M. Morris ◽  
R. W. Katzberg
Keyword(s):  
Contrast Media ◽  
Blood Brain Barrier ◽  
Evans Blue ◽  
Plasma Osmolality ◽  
Iodine Concentration ◽  
Brain Barrier ◽  
Blue Staining ◽  
Intravenous Contrast ◽  
Blood Brain ◽  
Bbb Opening

It has been suggested that intravenous injections of hypertonic contrast media when used in computed tomography and digital subtraction angiography might raise plasma osmolality sufficiently to open the blood-brain barrier (BBB). The current investigation establishes the threshold of plasma osmolality that causes the the opening of the BBB in euvolemic and dehydrated rabbits. Euvolemic rabbits were allowed food and water ad libitum. Dehydrated rabbits received 4.0 mg/kg of furosemide intramuscularly and were deprived of water for 72 hours. Meglumine/sodium diatrizoate 76 per cent (n=28) or mannitol 20 per cent (n= 12) was administrated intravenously, at a rate of 25 mmol/kg body weight/hour for 2, 3 or 4 hours. Plasma osmolality, blood iodine concentration, blood pressure, heart rate and hematocrit were assessed at regular intervals. Evans blue and 99Tcm-DTPA were used simultaneously as tracers for BBB opening. Rating of BBB opening with 99Tcm-DTPA correlated well with Evans blue staining (r=0.863, p<0.001; n=42). BBB opening was related to plasma osmolality and was similar for both contrast media and mannitol. Widespread BBB opening occurred above 400 mmol/kg while focal BBB opening occurred above 370 mmol/kg. Dehydration per se increased plasma osmolality but did not reduce the threshold for BBB opening.

The Influence of the Calcium Antagonist Nimodipine and Induced Hypertension on the Behavior of the Cerebral Pial Arteries, the Blood-Brain Barrier, Cerebral Edema, and Cerebral Infarction in Cats with One-Hour Occlusion of the Middle Cerebral Artery

Neurosurgery ◽  
1991 ◽  
Vol 28 (2) ◽  
pp. 267-272 ◽  
Author(s):  
Toshisuke Sakaki ◽  
Shigeru Tsunoda ◽  
Tetsuya Morimoto
Keyword(s):  
Middle Cerebral Artery ◽  
Blood Brain Barrier ◽  
Cerebral Artery ◽  
Cerebral Edema ◽  
Evans Blue ◽  
Control Group ◽  
Blue Dye ◽  
Pial Arteries ◽  
Evans Blue Dye ◽  
Induced Hypertension

Abstract Thirty anesthetized cats were randomly assigned to one of three groups of 10 cats each: nimodipine treatment, nimodipine treatment combined with induced hypertension, or a control group. The behavior of the cerebral pial arteries was measured by means of microscopic observation through a cranial window. The middle cerebral artery of each cat was clipped for 1 hour via the transorbital approach. Five hours after circulation was reestablished in the middle cerebral artery. Evans blue dye was injected intravenously: 30 minutes later, the animal was killed. Administration of nimodipine or saline in the treated or control group was started 5 minutes before the middle cerebral artery was clipped and maintained until the end of the experiment. Induced hypertension was produced by administration of dopamine during the occlusion. Damage to the blood-brain barrier (BBB) was judged by extravasation of Evans blue dye. Cerebral edema and infarction were evaluated from histological findings. They were most prominent in the control group; the extent of the hemisphere affected was as follows (mean ± standard error): extravasation. 40.5 ± 8.8%: edema, 43.2 ± 5.7%: infarction, 35.5 ± 9.6%. On the other hand, the extravasation of Evans blue dye and cerebral edema were significantly more extensive in the group treated with nimodipine and induced hypertension (extravasation, 28.2 ± 9.6% of the hemisphere; edema, 30.3 ± 7.1%) than in the group treated with nimodipine alone (extravasation. 18.5 ± 8.7% of the hemisphere; edema, 19.4 ± 6.3%). but the infarction size was similar in both groups (16.6 ± 4.9% of the hemisphere in the former; 17.0 ± 6.2 in the latter). Based on these results, we arc cautious in combining calcium entry blocking agents such as nimodipine with induced hypertension in patients with acute cerebral ischemia.

scholarly journals Lactobacillus plantarum IS-20506 Probiotic Restores Galectin-4 and Myosin-1a Expressions in Duodenum, Jejunum and Ileum of Lipopolysaccharide-induced Rats

2020 ◽  
Vol 12 (3) ◽  
pp. 283-7
Author(s):  
Reza Gunadi Ranuh ◽  
Alpha Fardah Athiyyah ◽  
Andy Darma ◽  
Wibi Riawan ◽  
Ingrid Suryanti Surono ◽  
...  
Keyword(s):  
Western Blot ◽  
Lactobacillus Plantarum ◽  
Brush Border ◽  
Barrier Function ◽  
Wistar Rats ◽  
Control Group ◽  
Intestinal Segment ◽  
Gut Health ◽  
Intestinal Brush Border ◽  
Male Wistar Rats

BACKGROUND: Galectin-4 and Myosin-1a are important proteins for normal intestinal brush border structure and composition. Damage of these proteins by inflammation may alter digestion, absorption and barrier function. Probiotic has been widely known in maintaining gut health. However, the molecular mechanism of Lactobacillus plantarum IS-2056 probiotic in repairing intestinal brush border is not well defined. Therefore, current study was conducted by investigating the Galectin-4 and Myosin-1a expressions in a rodent model.METHODS: Male Wistar rats were induced with/without lipopolysaccharide (LPS) and treated with/without L. plantarum IS-2056 probiotic. On the seventh day, duodenum, jejunum, and ileum were collected and analyzed with western blot and immunohistochemistry for Galectin-4 and Myosin-1a expressions.RESULTS: Rats administrated with L. plantarum IS-2056 probiotic showed significant increase of Galectin-4 and Myosin-1a expressions in duodenum, jejunum, and ileum compared to the control group (p<0.05). While in control group, Galectin-4 level tended to increase in more distal of intestinal segment and Myosin-1a level tended to decrease in more distal intestinal segment.CONCLUSION: L. plantarum IS-20506 probiotic may facilitate the repairment of damaged intestinal brush border as demonstrated by significant restoration of Galectin-4 and Myosin-1a expressions in duodenum, jejunum, and ileum of LPS-induced rats.KEYWORDS: Lactobacillus plantarum, IS-20506, probiotic, galectin-4, myosin-1a, duodenum, jejunum, ileum

scholarly journals Ultrasound Combined With Microbubbles Loading BDNF Retrovirus to Open Blood–Brain Barrier for Treatment of Alzheimer’s Disease

2021 ◽  
Vol 12 ◽  
Author(s):  
Feng Wang ◽  
Xi-Xi Wei ◽  
Lian-Sheng Chang ◽  
Lei Dong ◽  
Yong-Ling Wang ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Nerve Growth Factor ◽  
Growth Factor ◽  
Western Blot ◽  
Blood Brain Barrier ◽  
Brain Barrier ◽  
Control Group ◽  
Nerve Growth ◽  
Blood Brain

Background: Brain-derived nerve growth factor (BDNF) is a promising effective target for the treatment of Alzheimer’s disease (AD). BDNF, which has a high molecular weight, has difficulty in crossing the blood–brain barrier (BBB). The study aimed to prepare microbubbles loading brain-derived nerve growth factor (BDNF) retrovirus (MpLXSN-BDNF), to verify the characteristics of the microbubbles, and to study the therapeutic effect of the microbubbles combined with ultrasound on the opening of the blood–brain barrier in an AD rat model.Methods: 32 adult male SD rats were randomly divided into four groups: control group, ultrasound + pLXSN-EGFP microbubble group (U + MpLXSN-BDNF), ultrasound + pLXSN-BDNF microbubble group, and ultrasound + microbubble + pLXSN-BDNF virus group (U + MpLXSN-BDNF), with eight rats in each group. At the same time, the left hippocampus of rats was irradiated with low-frequency focused ultrasound guided by MRI to open the blood–brain barrier (BBB). The effects of BDNF overexpression on AD rats were evaluated behaviorally before and 1 month after the treatment. The number of acetylcholinesterase (ChAT)-positive cells and the content of acetylcholine (ACh) in brain tissues were determined by immunohistochemistry and high-performance liquid chromatography (HPLC), respectively. IF staining of synaptic spines and Western blot of synaptophysin presented herein detected synaptic density recovery.Results: Signal intensity enhancement at the BBB disruption sites could be observed on the MR images. The behavioral evaluation showed that the times of crossing the original platform in the U + MpLXSN-BDNF group increased significantly after treatment. Immunohistochemistry and HPLC revealed that the number of ChAT-positive neurons and the contents of ACh in the brain were significantly decreased in the treated groups compared with the controls. IF staining of synaptic spines and Western blot data of synaptophysin showed that the U + MpLXSN-BDNF group can recover the synaptic loss better by BDNF supplementation than the other treatment groups.Conclusion: Ultrasound combined with viral microbubbles carrying BDNF can increase the transfection efficiency of brain neurons, promote the high expression of exogenous gene BDNF, and play a therapeutic role in the AD model rats.

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