scholarly journals Theobromine Improves Working Memory by Activating the CaMKII/CREB/BDNF Pathway in Rats

Nutrients ◽  
2019 ◽  
Vol 11 (4) ◽  
pp. 888 ◽  
Author(s):  
Rafiad Islam ◽  
Kentaro Matsuzaki ◽  
Eri Sumiyoshi ◽  
Md Emon Hossain ◽  
Michio Hashimoto ◽  
...  
Keyword(s):  
Working Memory ◽  
Camp Response Element Binding ◽  
Normal Diet ◽  
Learning Ability ◽  
Enzyme Linked Immunosorbent Assay ◽  
Mrna Levels ◽  
Object Recognition Test ◽  
Male Wistar Rats ◽  
Neurotropic Factor ◽  
Bdnf Pathway

Theobromine (TB) is a primary methylxanthine found in cacao beans. cAMP-response element-binding protein (CREB) is a transcription factor, which is involved in different brain processes that bring about cellular changes in response to discrete sets of instructions, including the induction of brain-derived neurotropic factor (BDNF). Ca2+/calmodulin-dependent protein kinase II (CaMKII) has been strongly implicated in the memory formation of different species as a key regulator of gene expression. Here we investigated whether TB acts on the CaMKII/CREB/BDNF pathway in a way that might improve the cognitive and learning function in rats. Male Wistar rats (5 weeks old) were divided into two groups. For 73 days, the control rats (CN rats) were fed a normal diet, while the TB-fed rats (TB rats) received the same food, but with a 0.05% TB supplement. To assess the effects of TB on cognitive and learning ability in rats: The radial arm maze task, novel object recognition test, and Y-maze test were used. Then, the brain was removed and the medial prefrontal cortex (mPFC) was isolated for Western Blot, real-time PCR and enzyme-linked immunosorbent assay. Phosphorylated CaMKII (p-CaMKII), phosphorylated CREB (p-CREB), and BDNF level in the mPFC were measured. In all the behavior tests, working memory seemed to be improved by TB ingestion. In addition, p-CaMKII and p-CREB levels were significantly elevated in the mPFC of TB rats in comparison to those of CN rats. We also found that cortical BDNF protein and mRNA levels in TB rats were significantly greater than those in CN rats. These results suggest that orally supplemented TB upregulates the CaMKII/CREB/BDNF pathway in the mPFC, which may then improve working memory in rats.

scholarly journals The Effect of Soy Milk on Mounting Latency, Mounting Frequency, and Reproductive Development in Male Wistar Rats (Rattus Norvegicus)

2021 ◽  
Vol 9 (B) ◽  
pp. 670-678
Author(s):  
Nurdiana Nurdiana ◽  
Pradnyawati Chania ◽  
Rifzi Nurvitasari ◽  
Azmiatun Nisa ◽  
Styan Wahyu Diana ◽  
...  
Keyword(s):  
Rattus Norvegicus ◽  
Wistar Rats ◽  
Reproductive Development ◽  
Normal Diet ◽  
Male Rats ◽  
Male Rat ◽  
Enzyme Linked Immunosorbent Assay ◽  
Control Group ◽  
Soy Milk ◽  
Male Wistar Rats

AIM: This research aims to examine the effects of soy milk on mounting latency (ML), mounting frequency (MF), estrogen levels, androgen-binding protein (ABP) expression, and spermatogenesis in male rats (Rattus norvegicus). METHODS: Twenty-four male wistar rats (Rattus norvegicus) aged 4 weeks were divided into four groups. Control group (given a normal diet), P1; P2; P3 (given the normal diet and soy milk powder at doses of 7.1; 14.2; 21.3 g/KgBW/day, respectively) for 6 weeks. Observation of ML and MF were performed at 9 weeks 5 days of age, and rat surgery was performed at 10 weeks of age. Analysis of estrogen hormone levels was conducted by enzyme-linked immunosorbent assay (ELISA), ABP staining was using immunohistochemistry method, testicular spermatogenesis was observed using histopathological methods, and observation of spermatozoa was performed under the microscope.  RESULTS: The results showed no significant reduction of ML and MF, estrogen levels, and ABP expression (p ≤ 0.256; 0.865; 0.959, respectively) in male rat, but there was a significant decrease in the number, morphology, motility of spermatozoa, and testicular histophatology, (p ≤ 0.000, 0.003, 0.008, 0.000, respectively). CONCLUSION: The administrassion of soy milk in various doses (7.1;14.2;21.3 g/KgBW/day) in male Wistar rats (Rattus norvegicus) had showed significantly difference on histopathological evaluation using Johnson’s scoring system, sperm quantity and quality, while on mounting latency and frequency, estrogen levels, and ABP expressions did not show significantly difference between groups. That describe of isoflavone in soy milk can affect several aspects related to male endocrine and reproductive development.

scholarly journals Standardized Extract (HemoHIM) Protects against Scopolamine-Induced Amnesia in a Murine Model

2021 ◽  
Vol 2021 ◽  
pp. 1-11
Author(s):  
Seul-Ki Kim ◽  
Da-Ae Kwon ◽  
Yong Sang Kim ◽  
Hak Sung Lee ◽  
Hyun Kyu Kim ◽  
...  
Keyword(s):  
Murine Model ◽  
Memory Impairment ◽  
Therapeutic Potential ◽  
Muscarinic Acetylcholine Receptor ◽  
Camp Response Element Binding ◽  
Avoidance Task ◽  
Mrna Levels ◽  
Object Recognition Test ◽  
Y Maze ◽  
Element Binding Protein

HemoHIM is a medicinal herbal preparation of Angelica gigas Nakai (Apiaceae), Cnidium officinale Makino (Umbelliferae), and Paeonia lactiflora Pallas (Paeoniaceae) designed for immune regulation. In the present study, the memory-enhancing effects of a standardized extract (HemoHIM) on scopolamine-induced memory impairment in a murine model was investigated. To induce amnesia, scopolamine (1 mg/kg) was intraperitoneally (i.p.) injected into mice 30 min before the start of behavioral tests. The Y-maze, novel object recognition test (NORT), and passive avoidance task (PAT) were used to evoke memory functions. HemoHIM significantly improved scopolamine-induced memory impairment in ICR mice, which was evidenced by an improvement of spontaneous alternation in the Y-maze, recognition index in NORT, and latency time in PAT. To elucidate the possible mechanism, the cholinergic activity and mRNA levels of choline acetyltransferase (ChAT), muscarinic acetylcholine receptor (mAchR), brain-derived neurotrophic factor (BDNF), and cAMP response element-binding protein (CREB) were measured using reverse transcription (RT-PCR) and western blot analyses, respectively. HemoHIM treatment attenuated the scopolamine-induced hyperactivation of acetylcholinesterase (AchE) activity. In addition, ChAT, mAchR, and CREB mRNA levels were increased in the hippocampus compared with the scopolamine group. Furthermore, HemoHIM treatment resulted in elevated BDNF protein expression. These results indicate that HemoHIM may exert antiamnesic activity by increasing Ach and inhibiting AchE in the hippocampus. In addition, HemoHIM has therapeutic potential by upregulating ChAT, mAchR, and BDNF, which is apparently mediated by activation of the CREB and ERK signaling pathways.

Epinephrine and AICAR-induced PGC-1α mRNA expression is intact in skeletal muscle from rats fed a high-fat diet

2012 ◽  
Vol 302 (12) ◽  
pp. C1772-C1779 ◽  
Author(s):  
Bruce C. Frier ◽  
Zhongxiao Wan ◽  
Deon B. Williams ◽  
Amanda L. Stefanson ◽  
David C. Wright
Keyword(s):  
Skeletal Muscle ◽  
Protein Kinase ◽  
High Fat Diet ◽  
Camp Response Element Binding ◽  
Peroxisome Proliferator ◽  
Mrna Levels ◽  
High Fat ◽  
Peroxisome Proliferator Activated Receptor ◽  
Male Wistar Rats ◽  
Amp Activated Protein Kinase

Peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α) is a master regulator of mitochondrial biogenesis and is controlled, at least in part, through AMP-activated protein kinase and p38-dependent pathways. There is evidence demonstrating that activation of these kinases and induction of PGC-1α in skeletal muscle are regulated by catecholamines. The purpose of the present study was to determine if consumption of a high-fat diet (HFD) impairs epinephrine and 5-aminoimidazole-4-carboxamide-1β-d-ribofuranoside (AICAR) signaling and induction of PGC-1α in rat skeletal muscle. Male Wistar rats were fed chow or a HFD for 6 wk and then given a weight-adjusted bolus injection of epinephrine (20, 10, or 5 μg/100 g body wt sc) or saline, and triceps muscles were harvested 30 min (signaling) or 2 and 4 h (gene expression) postinjection. Despite blunted increases in p38 phosphorylation, the ability of epinephrine to induce PGC-1α was intact in skeletal muscle from HFD-fed rats and was associated with normal increases in activation of PKA and phosphorylation of cAMP response element-binding protein, reputed mediators of PGC-1α expression. The attenuated epinephrine-mediated increase in p38 phosphorylation was independent of increases in MAPK phosphatase 1. At 2 h following AICAR treatment (0.5 g/kg body wt sc), AMP-activated protein kinase and acetyl-CoA carboxylase phosphorylation were similar in skeletal muscle from chow- and HFD-fed rats. Surprisingly, AICAR-induced increases in PGC-1α mRNA levels were greater in skeletal muscle from HFD-fed rats. Our results demonstrate that the ability of epinephrine and AICAR to induce PGC-1α remains intact in skeletal muscle from HFD-fed rats. These results question the existence of reduced β-adrenergic responsiveness in diet-induced obesity and demonstrate that increases in p38 phosphorylation are not required for induction of PGC-1α in muscle from obese rats.

The Effects of Vitamin K1 and Warfarin on Prothrombin Expression in Human Hepatoblastoma (HepG2) Cells

1992 ◽  
Vol 68 (01) ◽  
pp. 040-047 ◽  
Author(s):  
C Scott Jamison ◽  
Bryan F Burkey ◽  
Sandra J Friezner Degen
Keyword(s):  
Total Protein ◽  
Hepg2 Cells ◽  
Enzyme Linked Immunosorbent Assay ◽  
Response Analysis ◽  
Secreted Protein ◽  
Mrna Levels ◽  
Vitamin K1 ◽  
Maximal Increase ◽  
Protein Levels ◽  
Warfarin Treatment

SummaryCultures of human hepatoblastoma (HepG2) cells were treated with vitamin K1 or warfarin and prothrombin antigen and mRNA levels were determined. With 3 and 6 h of 10 µg vitamin K1 treatment secreted prothrombin antigen levels, relative to total secreted protein levels, were increased 1.5-fold and 2.1-fold, respectively, over ethanol-treated control levels as determined by an enzyme-linked immunosorbent assay. Dose-response analysis with 3 h of 25 µg/ml vitamin K1 treatment demonstrated a maximal increase of 2.0-fold in secreted prothrombin antigen levels, relative to total secreted protein levels, over ethanol-treated control levels. Pulse-chase analysis with 35S-methionine and immunoprecipitation of 35S-labelled prothrombin demonstrated that, with vitamin K1 treatment (25 µg/ml, 3 h), the rate of prothrombin secretion increased approximately 2-fold and the total amount (intra- and extracellular) of prothrombin synthesized increased approximately 50% over ethanol-treated control levels. Warfarin treatment (1, 5, or 10 µg/ml, 24 h) resulted in decreases in secreted prothrombin antigen levels, relative to total protein levels to approximately 85%, 87% or 81% of ethanol-treated control levels. Analysis of total RNA isolated from these cultures by Northern and solution hybridization techniques demonstrated that prothrombin mRNA was approximately 2.1 kb and that neither vitamin K1 nor warfarin treatment affected the quantity of prothrombin mRNA (ranging from 240–350 prothrombin mRNA molecules per cell). These results demonstrate that vitamin K1 and warfarin, in addition to effects on γ-carboxylation, affect prothrombin synthesis post-transcriptionally, perhaps influencing translation, post-translational processing and/or secretion mechanisms.

Berberine Alleviates Amyloid-beta Pathogenesis Via Activating LKB1/AMPK Signaling in the Brain of APP/PS1 Transgenic Mice

2019 ◽  
Vol 19 (5) ◽  
pp. 342-348 ◽  
Author(s):  
Zhi-You Cai ◽  
Chuan-Ling Wang ◽  
Tao-Tao Lu ◽  
Wen-Ming Yang
Keyword(s):  
Transgenic Mice ◽  
Western Blotting ◽  
Amyloid Β ◽  
Adenosine Monophosphate ◽  
Camp Response Element Binding ◽  
Enzyme Linked Immunosorbent Assay ◽  
Synaptic Density ◽  
Ampk Signaling ◽  
The Brain ◽  
Post Synaptic Density

Background:Liver kinase B1 (LKB1)/5’-adenosine monophosphate-activated protein kinase (AMPK) signaling, a metabolic checkpoint, plays a neuro-protective role in the pathogenesis of Alzheimer’s disease (AD). Amyloid-β (Aβ) acts as a classical biomarker of AD. The aim of the present study was to explore whether berberine (BBR) activates LKB1/AMPK signaling and ameliorates Aβ pathology.Methods:The Aβ levels were detected using enzyme-linked immunosorbent assay and immunohistochemistry. The following biomarkers were measured by Western blotting: phosphorylated (p-) LKB1 (Ser334 and Thr189), p-AMPK (AMPKα and AMPKβ1), synaptophysin, post-synaptic density protein 95 and p-cAMP-response element binding protein (p-CREB). The glial fibrillary acidic protein (GFAP) was determined using Western blotting and immunohistochemistry.Results:BBR inhibited Aβ expression in the brain of APP/PS1 mice. There was a strong up-regulation of both p-LKB1 (Ser334 and Thr189) and p-AMPK (AMPKα and AMPKβ1) in the brains of APP/PS1 transgenic mice after BBR-treatment (P<0.01). BBR promoted the expression of synaptophysin, post-synaptic density protein 95 and p-CREB(Ser133) in the AD brain, compared with the model mice.Conclusion:BBR alleviates Aβ pathogenesis and rescues synapse damage via activating LKB1/AMPK signaling in the brain of APP/PS1 transgenic mice.

scholarly journals Caloric Restriction Prevents Metabolic Dysfunction and the Changes in Hypothalamic Neuropeptides Associated with Obesity Independently of Dietary Fat Content in Rats

Nutrients ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 2128
Author(s):  
Marina Martín ◽  
Amaia Rodríguez ◽  
Javier Gómez-Ambrosi ◽  
Beatriz Ramírez ◽  
Sara Becerril ◽  
...  
Keyword(s):  
Weight Loss ◽  
Caloric Restriction ◽  
Normal Diet ◽  
Energy Restriction ◽  
Metabolic Dysfunction ◽  
Gut Hormone ◽  
Male Wistar Rats ◽  
Food Efficiency Ratio ◽  
Hypothalamic Neuropeptides ◽  
Ad Libitum

Energy restriction is a first therapy in the treatment of obesity, but the underlying biological mechanisms have not been completely clarified. We analyzed the effects of restriction of high-fat diet (HFD) on weight loss, circulating gut hormone levels and expression of hypothalamic neuropeptides. Ten-week-old male Wistar rats (n = 40) were randomly distributed into four groups: two fed ad libitum a normal diet (ND) (N group) or a HFD (H group) and two subjected to a 25% caloric restriction of ND (NR group) or HFD (HR group) for 9 weeks. A 25% restriction of HFD over 9 weeks leads to a 36% weight loss with regard to the group fed HFD ad libitum accompanied by normal values in adiposity index and food efficiency ratio (FER). This restriction also carried the normalization of NPY, AgRP and POMC hypothalamic mRNA expression, without changes in CART. Caloric restriction did not succeed in improving glucose homeostasis but reduced HFD-induced hyperinsulinemia. In conclusion, 25% restriction of HFD reduced adiposity and improved metabolism in experimental obesity, without changes in glycemia. Restriction of the HFD triggered the normalization of hypothalamic NPY, AgRP and POMC expression, as well as ghrelin and leptin levels.

scholarly journals Age-related decline in the expression of GDF9 and BMP15 genes in follicle fluid and granulosa cells derived from poor ovarian responders

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Yan Gong ◽  
Jesse Li-Ling ◽  
Dongsheng Xiong ◽  
Jiajing Wei ◽  
Taiqing Zhong ◽  
...  
Keyword(s):  
Granulosa Cells ◽  
Enzyme Linked Immunosorbent Assay ◽  
Mrna Levels ◽  
Clinical Trial Registry ◽  
Altered Expression ◽  
Vitro Fertilization ◽  
Age Related ◽  
Tertiary Teaching ◽  
Poor Ovarian Responders

Abstract Background Growth differentiation factor 9 (GDF9) and bone morphogenetic protein 15 (BMP15) genes play important roles in folliculogenesis. Altered expression of the two have been found among patients with poor ovarian response (POR). In this prospective cohort study, we have determined the expression of the GDF9 and BMP15 genes in follicle fluid (FF) and granulosa cells (GCs) derived from poor ovarian responders grouped by age, and explored its correlation with the outcome of in vitro fertilization and embryo transfer (IVF-ET) treatment. Methods A total of 196 patients with POR were enrolled from a tertiary teaching hospital. The patients were diagnosed by the Bologna criteria and sub-divided into group A (< 35 year old), group B (35–40 year old), and group C (> 40 year old). A GnRH antagonist protocol was conducted for all patients, and FF and GCs were collected after oocyte retrieval. Expression of the GDF9 and BMP15 genes in the FF and GCs was determined with enzyme-linked immunosorbent assay (ELISA), quantitative real-time polymerase chain reaction (qRT-PCR) and Western blotting. Results Compared with group C, groups A and B had significantly more two pronuclei (2PN) oocytes and transplantable embryos, in addition with higher rates of implantation and clinical pregnancy (P <  0.05). The expression level of GDF9 and BMP15 genes in the FF and GCs differed significantly among the three groups (P <  0.05), showing a trend of decline along with age. The ratio of GDF9/BMP15 mRNA levels were similar among the three groups (P > 0.05). The relative levels of GDF9 and BMP15 proteins in GCs have correlated with the relative mRNA levels in GCs and protein concentrations in FF (P <  0.05). Conclusions For poor ovarian responders, in particular those over 40, the expression of GDF9 and BMP15 is declined along with increased age and in accompany with poorer oocyte quality and IVF outcome, whilst the ratio of GDF9/BMP15 mRNA levels remained relatively constant. Trial registration Chinese Clinical Trial Registry Center (ChiCTR1800016107). Registered on 11 May 2018.

scholarly journals Altered mRNA Levels of Stress-Related Peptides in Mouse Hippocampus and Caudate-Putamen in Withdrawal after Long-Term Intermittent Exposure to Tobacco Smoke or Electronic Cigarette Vapour

2021 ◽  
Vol 22 (2) ◽  
pp. 599
Author(s):  
Lucia Carboni ◽  
Luisa Ponzoni ◽  
Daniela Braida ◽  
Mariaelvina Sala ◽  
Cecilia Gotti ◽  
...  
Keyword(s):  
Public Health Problem ◽  
Mrna Levels ◽  
Obsessive Compulsive ◽  
Bdnf Mrna ◽  
Object Recognition Test ◽  
Caudate Putamen ◽  
Molecular Alterations ◽  
Marble Burying ◽  
Cigarette Withdrawal

Nicotine addiction is a severe public health problem. The aim of this study was to investigate the alterations in key neurotransmissions after 60 days of withdrawal from seven weeks of intermittent cigarette smoke, e-cigarette vapours, or an e-cigarette vehicle. In the nicotine withdrawal groups, increased depressive and anxiety/obsessive–compulsive-like behaviours were demonstrated in the tail suspension, sucrose preference and marble burying tests. Cognitive impairments were detected in the spatial object recognition test. A significant increase in Corticotropin-releasing factor (Crf) and Crf1 mRNA levels was observed, specifically after cigarette withdrawal in the caudate-putamen nucleus (CPu). The nociceptin precursor levels were reduced by cigarette (80%) and e-cigarette (50%) withdrawal in the CPu. The delta opioid receptor showed a significant reduction in the hippocampus driven by the exposure to an e-cigarette solubilisation vehicle, while the mRNA levels doubled in the CPu of mice that had been exposed to e-cigarettes. Withdrawal after exposure to e-cigarette vapour induced a 35% Bdnf mRNA decrease in the hippocampus, whereas Bdnf was augmented by 118% by cigarette withdrawal in the CPu. This study shows that long-term withdrawal-induced affective and cognitive symptoms associated to lasting molecular alterations in peptidergic signalling may determine the impaired neuroplasticity in the hippocampal and striatal circuitry.

Tissue Deposition of Zinc from a Zinc Chelate and from Inorganic Zinc in Rats

1994 ◽  
Vol 1994 ◽  
pp. 171-171 ◽  
Author(s):  
Ronan Power ◽  
Kevin Cashman ◽  
Albert Flynn
Keyword(s):  
Amino Acids ◽  
Tissue Distribution ◽  
Wistar Rats ◽  
Gel Filtration ◽  
Normal Diet ◽  
Farm Animals ◽  
Trace Minerals ◽  
Inorganic Salts ◽  
Male Wistar Rats ◽  
Differential Tissue

Some reports have suggested differential tissue deposition of dietary trace minerals such as Zinc (Zn) when supplied to farm animals either chelated to amino acids or as inorganic salts. To test this hypothesis, an experiment was conducted to determine the ultimate tissue distribution of Zinc in rats fed either a radioactively-labeled 65Zn-chelate or 65ZnSO4. The 65Zn-chelate was prepared by heating a solution of 65ZnSO4 and an equimolar mixture of glycine and methionine for 5 minutes at 90°C. The resulting chelate was then separated from unincorporated 65ZnSO4 by gel filtration chromatography. Ten 25-d old male wistar rats (mean weight 34.5 g) were randomized by weight into two groups (n = 5/group), fasted for 18 hours and given 0.4 ml (8 μg Zn, 1 μCi65Zn) of one or other labelled solution by gavage. Four hours later, animals were returned to their normal diet for the duration of the experiment. The 65Zn activity of the animals was determined two hours after administration and daily thereafter for 7 days.

Thrombospondin-1 Modulates the Angiogenic Phenotype of Human Cerebral Arteriovenous Malformation Endothelial Cells

Neurosurgery ◽  
2011 ◽  
Vol 68 (5) ◽  
pp. 1342-1353 ◽  
Author(s):  
Christopher J. Stapleton ◽  
Don L. Armstrong ◽  
Raphael Zidovetzki ◽  
Charles Y. Liu ◽  
Steven L. Giannotta ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Arteriovenous Malformation ◽  
Immunosorbent Assay ◽  
Cerebral Arteriovenous Malformation ◽  
Enzyme Linked Immunosorbent Assay ◽  
Boyden Chamber ◽  
Mrna Levels ◽  
Tubule Formation ◽  
Thrombospondin 1 ◽  
And Migration

Abstract BACKGROUND: The management of cerebral arteriovenous malformation (AVM) is challenging, and invasive therapies place vital intracranial structures at risk of injury. The development of noninvasive, pharmacologic approaches relies on identifying factors that mediate key angiogenic processes. Previous studies indicate that endothelial cells (ECs) derived from cerebral AVM (AVM-ECs) are distinct from control brain ECs with regard to important angiogenic characteristics. OBJECTIVE: To determine whether thrombospondin-1 (TSP-1), a potent angiostatic factor, regulates critical angiogenic features of AVM-ECs and to identify factors that modulate TSP-1 production in AVM-ECs. METHODS: EC proliferation, migration, and tubule formation were evaluated with bromodeoxyuridine incorporation, Boyden chamber, and Matrigel studies, respectively. TSP-1 and inhibitor of DNA binding/differentiation 1 (Id1) mRNA levels were quantified with microarray and quantitative real-time polymerase chain reaction analyses. TSP-1 protein expression was measured using Western blotting, immunohistochemical, and enzyme-linked immunosorbent assay techniques. The mechanistic link between Id1 and TSP-1 was established through small interfering RNA-mediated knockdown of Id1 in AVM-ECs followed by Western blot and enzyme-linked immunosorbent assay experiments assessing TSP-1 production. RESULTS: AVM-ECs proliferate faster, migrate more quickly, and form disorganized tubules compared with brain ECs. TSP-1 is significantly down-regulated in AVM-ECs. The addition of TSP-1 to AVM-EC cultures normalizes the rate of proliferation and migration and the efficiency of tubule formation, whereas brain ECs are unaffected. Id1 negatively regulates TSP-1 expression in AVM-ECs. CONCLUSION: These data highlight a novel role for TSP-1 in the pathobiology of AVM angiogenesis and provide a context for its use in the clinical management of brain AVMs.

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