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Repair BBB

Tosol Yu, Bong Jun Cho, Eun Jung Choi, Ji Min Park, Dan Hyo Kim, In Ah Kim
Trastuzumab has been widely used for the treatment of human epidermal growth factor receptor 2 (HER2)-overexpressing breast cancer, however, it cannot easily cross the blood-brain barrier (BBB) and is known to increase the incidence of brain metastases. In contrast, lapatinib has a low molecular weight and can cross the BBB and it could be useful to treat brain metastases in patients with HER2-positive breast cancer.To explore the impact of lapatinib on radiation response, we conducted an in vitro experiment using SKBR3 and BT474 breast carcinoma cells exhibiting HER2/neu amplification...
October 12, 2016: Oncotarget
Andrew T Placzek, Skylar J Ferrara, Meredith D Hartley, Hannah S Sanford-Crane, J Matthew Meinig, Thomas S Scanlan
There is currently great interest in developing drugs that stimulate myelin repair for use in demyelinating diseases such as multiple sclerosis. Thyroid hormone plays a key role in stimulating myelination during development and also controls the expression of important genes involved in myelin repair in adults. Because endogenous thyroid hormone in excess lacks a generally useful therapeutic index, it is not used clinically for indications other than hormone replacement; however, selective thyromimetics such as sobetirome offer a therapeutic alternative...
September 16, 2016: Bioorganic & Medicinal Chemistry
Yan Zhao, Yuan Zuo, Jianming Jiang, Huibo Yan, Xiliang Wang, Hunjun Huo, Yulong Xiao
Spinal cord injury (SCI) comprises nerve and motor function disorders that may be caused by a variety of damaging factors and is challenging to treat. The aim of the present study was to investigate the regenerative effects of neural stem cell (NSC) transplantation combined with intraperitoneal injection of erythropoietin (EPO) on cross-sectional SCI in rats. A model of SCI was induced in 40 adult Wistar rats via the complete transection of the 10th thoracic vertebra (T10). The rats were allocated at random into 4 groups: Control, NSC, EPO and NSC + EPO groups (n=10 per group)...
October 2016: Experimental and Therapeutic Medicine
Slava Rom, Viviana Zuluaga-Ramirez, Nancy L Reichenbach, Holly Dykstra, Sachin Gajghate, Pal Pacher, Yuri Persidsky
BACKGROUND: Blood-brain barrier (BBB) dysfunction/disruption followed by leukocyte infiltration into the brain causes neuroinflammation and contributes to morbidity in multiple sclerosis, encephalitis, traumatic brain injury, and stroke. The identification of pathways that decreases the inflammatory potential of leukocytes would prevent such injury. Poly(ADP-ribose) polymerase 1 (PARP) controls various genes via its interaction with myriad transcription factors. Selective PARP inhibitors have appeared lately as potent anti-inflammatory tools...
September 27, 2016: Journal of Neuroinflammation
Devesh Jalan, Neginder Saini, Mohammad Zaidi, Alexandra Pallottie, Stella Elkabes, Robert F Heary
OBJECTIVE In acute traumatic brain injury, decompressive craniectomy is a common treatment that involves the removal of bone from the cranium to relieve intracranial pressure. The present study investigated whether neurological function following a severe spinal cord injury improves after utilizing either a durotomy to decompress the intradural space and/or a duraplasty to maintain proper flow of cerebrospinal fluid. METHODS Sixty-four adult female rats (n = 64) were randomly assigned to receive either a 3- or 5-level decompressive laminectomy (Groups A and B), laminectomy + durotomy (Groups C and D), or laminectomy + duraplasty with graft (Group E and F) at 24 hours following a severe thoracic contusion injury (200 kilodynes)...
September 16, 2016: Journal of Neurosurgery. Spine
Samir Alkabie, Jayasree Basivireddy, Lixin Zhou, Jane Roskams, Peter Rieckmann, Jacqueline A Quandt
BACKGROUND: SPARC (secreted protein acidic and rich in cysteine) is a nonstructural, cell-matrix modulating protein involved in angiogenesis and endothelial barrier function, yet its potential role in cerebrovascular development, inflammation, and repair in the central nervous system (CNS) remains undetermined. METHODS: This study examines SPARC expression in cultured human cerebral microvascular endothelial cells (hCMEC/D3)-an in vitro model of the blood-brain barrier (BBB)-as they transition between proliferative and barrier phenotypes and encounter pro-inflammatory stimuli...
2016: Journal of Neuroinflammation
Dapeng Zhang, Guozhang Ma, Mingming Hou, Tao Zhang, Limin Chen, Chengbin Zhao
BACKGROUND: Acute spinal cord injury (SCI) leads to permanent disabilities. This study evaluated the neuroprotective effect of puerarin, a natural extract, in a rat model of SCI. METHODS: Acute SCI models were established in rats using a modified Allen's method. Locomotor function was evaluated using the BBB test. The histological changes in the spinal cord were observed by H&E staining. Neuron survival and glial cells activation were evaluated by immunostaining...
2016: Cellular Physiology and Biochemistry
Aruna Sharma, Preeti Menon, Dafin F Muresanu, Asya Ozkizilcik, Z Ryan Tian, José V Lafuente, Hari Sharma
The BBB is a physiological regulator of transport of essential items from blood to brain for the maintenance of homeostasis of the central nervous system (CNS) within the narrow limit. The BBB is also responsible for export of harmful or metabolic products from brain to blood to keep the fluid microenvironment of the CNS healthy. However, following any noxious insult to the brain caused by trauma, ischemia or environmental/chemical toxins the function of the BBB is altered to small as well as to large molecules e...
August 19, 2016: CNS & Neurological Disorders Drug Targets
Xiaojing Lin, Tingbao Zhao, Melissa Walker, Aishi Ding, Shide Lin, Yongcheng Cao, Jinfeng Zheng, Xiaohong Liu, Ming Geng, Xiao-Ming Xu, Shaojun Liu
Spinal cord injury (SCI) is a significant clinical challenge and, to date, no effective treatment is available. Oligodendrocyte progenitor cell (OPC) transplantation has been a promising strategy for SCI repair. However, the poor post-transplantation survival and deficiency in differentiation into myelinating oligodendrocytes (OLs) are two major challenges that limit the use of OPCs as donor cells. Here we report the generation of an OL lineage population, i.e. pro-oligodendroblast (proOL) that is relatively more mature than OPC, for transplantation after SCI...
August 1, 2016: Cell Transplantation
Syed Faraz Kazim, Khalid Iqbal
Alzheimer's disease (AD) is an incurable and debilitating chronic progressive neurodegenerative disorder which is the leading cause of dementia worldwide. AD is a heterogeneous and multifactorial disorder, histopathologically characterized by the presence of amyloid β (Aβ) plaques and neurofibrillary tangles composed of Aβ peptides and abnormally hyperphosphorylated tau protein, respectively. Independent of the various etiopathogenic mechanisms, neurodegeneration is a final common outcome of AD neuropathology...
2016: Molecular Neurodegeneration
Berta Rodríguez-Frutos, Laura Otero-Ortega, Jaime Ramos-Cejudo, Patricia Martínez-Sánchez, Inés Barahona-Sanz, Teresa Navarro-Hernanz, María Del Carmen Gómez-de Frutos, Exuperio Díez-Tejedor, María Gutiérrez-Fernández
Ultrasound-targeted microbubble destruction (UTMD) has been shown to be a promising tool to deliver proteins to select body areas. This study aimed to analyze whether UTMD was able to deliver brain-derived neurotrophic factor (BDNF) to the brain, enhancing functional recovery and white matter repair, in an animal model of subcortical stroke induced by endothelin (ET)-1. UTMD was used to deliver BDNF to the brain 24 h after stroke. This technique was shown to be safe, given there were no cases of hemorrhagic transformation or blood brain barrier (BBB) leakage...
September 2016: Biomaterials
Thomas I-H Park, Vaughan Feisst, Anna E S Brooks, Justin Rustenhoven, Hector J Monzo, Sheryl X Feng, Edward W Mee, Peter S Bergin, Robyn Oldfield, E Scott Graham, Maurice A Curtis, Richard L M Faull, P Rod Dunbar, Mike Dragunow
The human brain is a highly vascular organ in which the blood-brain barrier (BBB) tightly regulates molecules entering the brain. Pericytes are an integral cell type of the BBB, regulating vascular integrity, neuroinflammation, angiogenesis and wound repair. Despite their importance, identifying pericytes amongst other perivascular cell types and deciphering their specific role in the neurovasculature remains a challenge. Using primary adult human brain cultures and fluorescent-activated cell sorting, we identified two CD73(+)CD45(-) mesenchymal populations that showed either high or low CD90 expression...
2016: Scientific Reports
Hemant Kumar, Alexander E Ropper, Soo-Hong Lee, Inbo Han
The blood-spinal cord barrier (BSCB) is a specialized protective barrier that regulates the movement of molecules between blood vessels and the spinal cord parenchyma. Analogous to the blood-brain barrier (BBB), the BSCB plays a crucial role in maintaining the homeostasis and internal environmental stability of the central nervous system (CNS). After spinal cord injury (SCI), BSCB disruption leads to inflammatory cell invasion such as neutrophils and macrophages, contributing to permanent neurological disability...
May 18, 2016: Molecular Neurobiology
Jianzhong Hu, Ye Lang, Tao Zhang, Shuangfei Ni, Hongbin Lu
Peroxisome proliferator-activated receptor-γ coactivator-1 alpha (PGC-1α) is a crucial neuronal regulator in the brain. However, its role in the spinal cord and the underlying regulating mechanisms remain poorly understood. Our previous study demonstrated that PGC-1α is significantly down-regulated following acute spinal cord injury (SCI) in rats. The current study aimed to explore the effects of PGC-1α overexpression on the injured spinal cord by establishing a contusive SCI model in adult Sprague-Dawley rats, followed by immediate intraspinal injection of lentiviral vectors at rostral and caudal sites 3mm from the lesion epicenter...
July 22, 2016: Neuroscience
Birgit Obermeier, Ajay Verma, Richard M Ransohoff
In autoimmune neurologic disorders, the blood-brain barrier (BBB) plays a central role in immunopathogenesis, since this vascular interface is an entry path for cells and effector molecules of the peripheral immune system to reach the target organ, the central nervous system (CNS). The BBB's unique anatomic structure and the tightly regulated interplay of its cellular and acellular components allow for maintenance of brain homeostasis, regulation of influx and efflux, and protection from harm; these ensure an optimal environment for the neuronal network to function properly...
2016: Handbook of Clinical Neurology
Avijit Dey, Xu Kang, Jiange Qiu, Yifeng Du, Jianxiong Jiang
As a crucial component of brain innate immunity, neuroinflammation initially contributes to neuronal tissue repair and maintenance. However, chronic inflammatory processes within the brain and associated blood-brain barrier (BBB) impairment often cause neurotoxicity and hyperexcitability. Mounting evidence points to a mutual facilitation between inflammation and epilepsy, suggesting that blocking the undesired inflammatory signaling within the brain might provide novel strategies to treat seizures and epilepsy...
June 2016: Trends in Pharmacological Sciences
Alexander Gianaris, Nai-Kui Liu, Xiao-Fei Wang, Eddie Oakes, John Brenia, Thomas Gianaris, Yiwen Ruan, Ling-Xiao Deng, Maria Goetz, Sasha Vega-Alvarez, Qing-Bo Lu, Riyi Shi, Xiao-Ming Xu
Although lipid peroxidation has long been associated with spinal cord injury (SCI), the specific role of lipid peroxidation-derived byproducts such as acrolein in mediating damage remains to be fully understood. Acrolein, an α-β unsaturated aldehyde, is highly reactive with proteins, DNA, and phospholipids and is considered as a second toxic messenger that disseminates and augments initial free radical events. Previously, we showed that acrolein increased following traumatic SCI and injection of acrolein induced tissue damage...
June 21, 2016: Neuroscience
Oak Z Chi, Scott J Mellender, Sylviana Barsoum, Xia Liu, Stacey Damito, Harvey R Weiss
The mammalian target of rapamycin (mTOR) pathway is essential in neuronal survival and repair in cerebral ischemia. Decreases in blood-brain barrier (BBB) disruption are associated with a decrease in neuronal damage in cerebral ischemia. This study was performed to investigate how pre-inhibition of the mTOR pathway with rapamycin would affect BBB disruption and the size of the infarcted cortical area in the early stage of focal cerebral ischemia-reperfusion using quantitative analysis of BBB disruption. Rats were treated with 20mg/kg of rapamycin i...
May 4, 2016: Neuroscience Letters
Avinash Parimisetty, Anne-Claire Dorsemans, Rana Awada, Palaniyandi Ravanan, Nicolas Diotel, Christian Lefebvre d'Hellencourt
First seen as a storage organ, the white adipose tissue (WAT) is now considered as an endocrine organ. WAT can produce an array of bioactive factors known as adipokines acting at physiological level and playing a vital role in energy metabolism as well as in immune response. The global effect of adipokines in metabolic activities is well established, but their impact on the physiology and the pathophysiology of the central nervous system (CNS) remains poorly defined. Adipokines are not only produced by the WAT but can also be expressed in the CNS where receptors for these factors are present...
2016: Journal of Neuroinflammation
M M Tenreiro, R Ferreira, L Bernardino, M A Brito
Endothelial cells are the main component of the blood-brain barrier (BBB), a vital structure for maintaining brain homeostasis that is seriously disrupted in various neurological pathologies. Therefore, vascular-targeted therapies may bring advantages for the prevention and treatment of brain disorders. In this sense, novel methods to identify and evaluate endothelial damage have been developed and include the detection of circulating endothelial cells, endothelial progenitor cells, endothelial microparticles and exosomes...
July 2016: Neurobiology of Disease
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