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neurovascular unit* AND cerebral ischemia

Masato Kanazawa, Tetsuya Takahashi, Masanori Ishikawa, Osamu Onodera, Takayoshi Shimohata, Gregory J Del Zoppo
The ischemic penumbra is both a concept in understanding the evolution of cerebral tissue injury outcome of focal ischemia and a potential therapeutic target for ischemic stroke. In this review, we examine the evidence that angiogenesis can contribute to beneficial outcomes following focal ischemia in model systems. Several studies have shown that, following cerebral ischemia, endothelial proliferation and subsequent angiogenesis can be detected beginning four days after cerebral ischemia in the border of the ischemic core, or in the ischemic periphery, in rodent and non-human primate models, although initial signals appear within hours of ischemia onset...
March 6, 2019: Journal of Cerebral Blood Flow and Metabolism
Michał Wiciński, Maciej Socha, Bartosz Malinowski, Eryk Wódkiewicz, Maciej Walczak, Karol Górski, Maciej Słupski, Katarzyna Pawlak-Osińska
Liraglutide is a GLP-1 analog (glucagon like peptide-1) used primarily in the treatment of diabetes mellitus type 2 (DM2) and obesity. The literature starts to suggest that liraglutide may reduce the effects of ischemic stroke by activating anti-apoptotic pathways, as well as limiting the harmful effects of free radicals. The GLP-1R expression has been reported in the cerebral cortex, especially occipital and frontal lobes, the hypothalamus, and the thalamus. Liraglutide reduced the area of ischemia caused by MCAO (middle cerebral artery occlusion), limited neurological deficits, decreased hyperglycemia caused by stress, and presented anti-apoptotic effects by increasing the expression of Bcl-2 and Bcl-xl proteins and reduction of Bax and Bad protein expression...
February 28, 2019: International Journal of Molecular Sciences
Rebecca Ward, Weiguo Li, Yasir Abdul, LaDonya Jackson, Guangkuo Dong, Sarah Jamil, Jessica Filosa, Susan C Fagan, Adviye Ergul
Diabetes increases the risk and worsens the progression of cognitive impairment via the greater occurrence of small vessel disease and stroke. Yet, the underlying mechanisms are not fully understood. It is now accepted that cardiovascular health is critical for brain health and any neurorestorative approaches to prevent/delay cognitive deficits should target the conceptual neurovascular unit (NVU) rather than neurons alone. We have recently shown that there is augmented hippocampal NVU remodeling after a remote ischemic injury in diabetes...
February 25, 2019: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
Bikei Ryu, Hidekazu Sekine, Jun Homma, Tomonori Kobayashi, Eiji Kobayashi, Takakazu Kawamata, Tatsuya Shimizu
OBJECTIVEStem cell therapy is a promising strategy for the treatment of severe cerebral ischemia. However, targeting sufficient grafted cells to the affected area remains challenging. Choosing an adequate transplantation method for the CNS appears crucial for this therapy to become a clinical reality. The authors used a scaffold-free cell sheet as a translational intervention. This method involves the use of cell sheet layers and allows the transplantation of a large number of cells, locally and noninvasively...
February 22, 2019: Journal of Neurosurgery
Dan Mi, De-Cheng Wang, Chong Pan
OBJECTIVE: To observe the effect of eye-acupuncture intervention on cerebro-cortical apoptosis of microvascular endothelial cells, neurons and astrocytes (main components of neurovascular unit) and the expression of Bad (an apoptosis promoter) and B-cell lymphoma-extra large(Bcl-xL) proteins in focal cerebral ischemia-reperfusion injury (CIRI) rats, so as to explore its mechanisms underlying improvement of CIRI. METHODS: SD rats were randomly divided into control, sham-operation, model 3 h, model 24 h, model 72 h, eye-acupuncture 3 h, eye-acupuncture 24 h and eye-acupuncture 72 h groups( n =12 in each group)...
January 25, 2019: Zhen Ci Yan Jiu, Acupuncture Research
Vincent J Huber, Hironaka Igarashi, Satoshi Ueki, Mika Terumitsu-Tsujita, Chikako Nito, Ken Ohno, Yuji Suzuki, Kosuke Itoh, Ingrid L Kwee, Tsutomu Nakada
Matrix metalloproteinases (MMPs) damage the neurovascular unit, promote the blood-brain barrier (BBB) disruption following ischemic stroke, and play essential roles in hemorrhagic transformation (HT), which is one of the most severe side effects of thrombolytic therapy. However, no biomarkers have presently been identified that can be used to track changes in the distribution of MMPs in the brain. Here, we developed a new 19 F-molecular ligand, TGF-019, for visualizing the distribution of MMPs in vivo using 19 F-magnetic resonance spectroscopic imaging (19 F-MRSI)...
2019: Contrast Media & Molecular Imaging
Amy M Dagro, K T Ramesh
An increase in arterial pressure within the cerebral vasculature appears to coincide with ischemia and dysfunction of the neurovascular unit in some cases of traumatic brain injury. In this study, we examine a new mechanism of brain tissue damage that results from excessive cerebral arteriole pressurization. We begin by considering the morphological and material properties of normotensive and hypertensive arterioles and present a computational model that captures the interaction of neighboring pressurized arterioles and the surrounding brain tissue...
January 2, 2019: Biomechanics and Modeling in Mechanobiology
Sandra Schöniger, Enrika Schütze, Dominik Michalski, Joana Puchta, Matthias Kaiser, Wolfgang Härtig
BACKGROUND: This case report describes a focal brain lesion in an alpaca (Vicugna pacos). Although this is a restricted study based on a single animal, neuropathological features are reported that are most likely attributed to a vascular event with either ischemic or hemorrhagic pathology. Concerning translational issues, these findings extend neurovascular unit concept to the alpacas' brain and qualify a larger panel of stroke tissue markers for further exploration of ischemic or hemorrhagic consequences beyond the usually used small animal models in stroke research...
January 3, 2019: Acta Veterinaria Scandinavica
Bahram Bibak, Manouchehr Teymouri, Ameneh Mohammadi, Ali Haghbin, Yanshu Pan, Jamal Kasaian, Peiman Alesheikh
The pressing need to discover more effective drugs for various CNS disorders has resurrected the idea of investigating the effectiveness of traditional medicines in modern science. Tongluojiunao (TLJN) is an example of revived modern herbal preparation based on traditional Chinese medicine (TCM) with a long history of administration for various types of cerebrovascular injuries and neurodegenerative diseases. TLJN is prepared from the herbal roots of Panax notoginseng (Sanchi) and dried fruits of Gardenia jasminoides (Cape Jasmine), and so far, it has demonstrated promising results in patients with vascular dementia and cerebral ischemic stroke...
December 27, 2018: Biomedicine & Pharmacotherapy
Beilei Chen, Liu Yang, Jian Chen, Yingzhu Chen, Lingling Zhang, Liangzhu Wang, Xiaobo Li, Yuping Li, Hailong Yu
Functional disruption of the neurovascular unit may lead to aggravation of ischemic cerebral injury. Connexin43 (Cx43)-dependent gap junctional channels (GJCs) are critical in maintaining brain homeostasis. However, excessive opening of hemichannels (HCs) after cerebral ischemia may cause apoptosis and finally lead to amplification of ischemic injury. Previous studies indicated that Cx43 mimetic peptides Gap26 and Gap27 may protect cerebral ischemic injury, but the latest studies showed they also inhibit the opening of GJCs, which are beneficial for neuroprotection...
December 26, 2018: Brain Research Bulletin
Yu Liu, Yong Li, Meixiao Zhan, Yongkang Liu, Zhongliang Li, Jihua Li, Guangsen Cheng, Gaojun Teng, Ligong Lu
20-Hydroxyeicosatetraenoic acid (20-HETE), a cytochrome P450 4A (CYP4A) metabolite of arachidonic acid, is one of the primary eicosanoids in most of microcirculatory beds. Studies have indicated that 20-HETE has important functions in the modulation of vascular tone, ion transport, inflammation reaction, and cellular proliferation. Both we and others have demonstrated that 20-HETE plays an important role in acute phase of ischemic stroke. However, little is known about the effect of 20-HETE on recovery phase of stroke...
December 17, 2018: Brain Research
Ivan Presta, Marco Vismara, Fabiana Novellino, Annalidia Donato, Paolo Zaffino, Elisabetta Scali, Krizia Caterina Pirrone, Maria Francesca Spadea, Natalia Malara, Giuseppe Donato
Recent studies have clarified many still unknown aspects related to innate immunity and the blood-brain barrier relationship. They have also confirmed the close links between effector immune system cells, such as granulocytes, macrophages, microglia, natural killer cells and mast cells, and barrier functionality. The latter, in turn, is able to influence not only the entry of the cells of the immune system into the nervous tissue, but also their own activation. Interestingly, these two components and their interactions play a role of great importance not only in infectious diseases, but in almost all the pathologies of the central nervous system...
December 3, 2018: International Journal of Molecular Sciences
Ana-Maria Zagrean, Dirk M Hermann, Ioan Opris, Leon Zagrean, Aurel Popa-Wagner
Restorative strategies after stroke are focused on the remodeling of cerebral endothelial cells and brain parenchymal cells. The latter, i.e., neurons, neural precursor cells and glial cells, synergistically interact with endothelial cells in the ischemic brain, providing a neurovascular unit (NVU) remodeling that can be used as target for stroke therapies. Intercellular communication and signaling within the NVU, the multicellular brain-vessel-blood interface, including its highly selective blood-brain barrier, are fundamental to the central nervous system homeostasis and function...
2018: Frontiers in Neuroscience
Yingzhu Chen, Liangzhu Wang, Lingling Zhang, Beilei Chen, Liu Yang, Xiaobo Li, Yuping Li, Hailong Yu
Connexin 43 (Cx43) widely exists in all components of the neurovascular unit (NVU) and is a constituent of gap junctions and hemichannels. In physiological states, gap junctions are open for regular intercellular communication, and the hemichannels present low open probability in astrocytes. After cerebral ischemia, a large number of hemichannels are unusually opened, leading to cell swelling and even death. Most known hemichannel blockers also inhibit gap junctions and sequentially obstruct normal electrical cell-cell communication...
2018: Frontiers in Cellular Neuroscience
Paolo Bazzigaluppi, Evelyn M Lake, Tina L Beckett, Margaret M Koletar, Iliya Weisspapir, Stefan Heinen, James Mester, Aaron Lai, Rafal Janik, Adrienne Dorr, JoAnne McLaurin, Greg J Stanisz, Peter L Carlen, Bojana Stefanovic
Background and Purpose- Recent evidence suggests great potential of metabolically targeted interventions for treating neurological disorders. We investigated the use of the endogenous ketone body β-hydroxybutyrate (BHB) as an alternate metabolic substrate for the brain in the acute phase of ischemia because postischemic hyperglycemia and brain glucose metabolism elevation compromise functional recovery. Methods- We delivered BHB (or vehicle) 1 hour after ischemic insult induced by cortical microinjection of endothelin-1 in sensorimotor cortex of rats...
September 2018: Stroke; a Journal of Cerebral Circulation
Camille Blochet, Lara Buscemi, Tifenn Clément, Sabrina Gehri, Jérôme Badaut, Lorenz Hirt
Complex cellular and molecular events occur in the neurovascular unit after stroke, such as blood-brain barrier (BBB) dysfunction and inflammation that contribute to neuronal death, neurological deterioration and mortality. Caveolin-1 (Cav-1) has distinct physiological functions such as caveolae formation associated with endocytosis and transcytosis as well as in signaling pathways. Cav-1 has been proposed to be involved in BBB dysfunction after brain injury; however, its precise role is poorly understood. The goal of this study was to characterize the expression and effect of Cav-1 deletion on outcome in the first week in a transient Middle Cerebral Artery Occlusion stroke model...
October 24, 2018: Journal of Cerebral Blood Flow and Metabolism
Jingyan Zhao, Hongfeng Mu, Liqiang Liu, Xiaoyan Jiang, Di Wu, Yejie Shi, Rehana K Leak, Xunming Ji
Ischemic injury can be alleviated by the judicious use of hypothermia. However, the optimal regimens and the temporal kinetics of post-stroke neurovascular responses to hypothermic intervention have not been systematically studied. These gaps slow the clinical translation of hypothermia as an anti-stroke therapy. Here, we characterized the effects of transient selective brain hypothermia (TSBH) from the hyperacute to chronic stages of focal ischemia/reperfusion brain injury induced by transient middle cerebral artery occlusion in mice...
October 18, 2018: Journal of Cerebral Blood Flow and Metabolism
Kun-Wei Wu, Ling-Ling Lv, Yu Lei, Cheng Qian, Feng-Yan Sun
Brain microvascular endothelial cells (BMEC) are highly complex regulatory cells that communicate with other cells in the neurovascular unit. Cerebral ischemic injury is known to produce detectable synaptic dysfunction. This study aims to investigate whether endothelial cells in the brain regulate postnatal synaptic development and to elucidate their role in functional recovery after ischemia. Here, we found that in vivo engraftment of endothelial cells increased synaptic puncta and excitatory postsynaptic currents in layers 2/3 of the motor cortex...
October 9, 2018: Neurobiology of Disease
Shuai Jiang, Tian Li, Ting Ji, Wei Yi, Zhi Yang, Simeng Wang, Yang Yang, Chunhu Gu
5'-AMP-activated protein kinase (AMPK), a member of the serine/threonine (Ser/Thr) kinase group, is universally distributed in various cells and organs. It is a significant endogenous defensive molecule that responds to harmful stimuli, such as cerebral ischemia, cerebral hemorrhage, and, neurodegenerative diseases (NDD). Cerebral ischemia, which results from insufficient blood flow or the blockage of blood vessels, is a major cause of ischemic stroke. Ischemic stroke has received increased attention due to its '3H' effects, namely high mortality, high morbidity, and high disability...
2018: Theranostics
Zachary A King, Kevin N Sheth, W Taylor Kimberly, J Marc Simard
Glyburide (also known as glibenclamide) is a second-generation sulfonylurea drug that inhibits sulfonylurea receptor 1 (Sur1) at nanomolar concentrations. Long used to target KATP (Sur1-Kir6.2) channels for the treatment of diabetes mellitus type 2, glyburide was recently repurposed to target Sur1-transient receptor potential melastatin 4 (Trpm4) channels in acute central nervous system injury. Discovered nearly two decades ago, SUR1-TRPM4 has emerged as a critical target in stroke, specifically in large hemispheric infarction, which is characterized by edema formation and life-threatening brain swelling...
2018: Drug Design, Development and Therapy
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