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bbb stroke

Ekaterina Turlova, Zhong-Ping Feng, Hong-Shuo Sun
Stroke is one of the major causes of mortality and morbidity worldwide, yet novel therapeutic treatments for this condition are lacking. This review focuses on the roles of the transient receptor potential melastatin 2 (TRPM2) ion channels in cellular damage following hypoxia-ischemia and their potential as a future therapeutic target for stroke. Here, we highlight the complex molecular signaling that takes place in neurons, glial cells and the blood-brain barrier following ischemic insult. We also describe the evidence of TRPM2 involvement in these processes, as shown from numerous in vitro and in vivo studies that utilize genetic and pharmacological approaches...
March 15, 2018: Acta Pharmacologica Sinica
Yingying Liu, Yudiao Huang, Yueyue Xu, Peng Qu, Minghua Wang
Increased transendothelial permeability and subsequent blood-brain barrier damage play a key role in the pathological progression of human brain ischemia and secondary reperfusion. Memantine is a licensed drug providing clinically relevant efficacy in patients with Alzheimer's disease. However, little information is known regarding its effects on brain endothelial permeability. In this study, we investigated the effects of memantine on endothelial permeability and the underlying mechanisms in an ischemia-reperfusion (I/R) injury model in primary human brain microvascular endothelial cells...
March 15, 2018: IUBMB Life
Kelly M DeMars, Austin O McCrea, David M Siwarski, Brian D Sanz, Changjun Yang, Eduardo Candelario-Jalil
Ischemic stroke occurs when a clot forms in the brain vasculature that starves downstream tissue of oxygen and nutrients resulting in cell death. The tissue immediately downstream of the blockage, the core, dies within minutes, but the surrounding tissue, the penumbra is potentially salvageable. Prostaglandin E2 binds to four different G-protein coupled membrane receptors EP1-EP4 mediating different and sometimes opposing responses. Pharmacological activation of the EP4 receptor has already been established as neuroprotective in stroke, but the mechanism(s) of protection are not well-characterized...
2018: Frontiers in Neuroscience
Shuai Zhang, Qier An, Tianfu Wang, Shuping Gao, Guangqian Zhou
Post-stroke hyperglycemia during early reperfusion increases blood-brain barrier (BBB) permeability and subsequently aggravates brain injury and clinical prognosis. The decreased level of tight junction proteins (TJPs) has been reported but the underlying mechanism remains largely elusive. Herein we designed to investigate the detailed molecular events in brain microvascular endothelial cells (BMECs) ex and in vivo. After oxygen-glucose deprivation (OGD) for 90 min and reperfusion with 8 or 16 mM glucose for 30 min, glucose at 16 mM caused significant decrease of the TJP expression and particularly ZO-1 redistribution from membrane to cytoplasm of BMECs...
March 7, 2018: Neuroscience
Nicolas Diotel, Thierry D Charlier, Christian Lefebvre d'Hellencourt, David Couret, Vance L Trudeau, Joel C Nicolau, Olivier Meilhac, Olivier Kah, Elisabeth Pellegrini
Sex steroid hormones are synthesized from cholesterol and exert pleiotropic effects notably in the central nervous system. Pioneering studies from Baulieu and colleagues have suggested that steroids are also locally-synthesized in the brain. Such steroids, called neurosteroids, can rapidly modulate neuronal excitability and functions, brain plasticity, and behavior. Accumulating data obtained on a wide variety of species demonstrate that neurosteroidogenesis is an evolutionary conserved feature across fish, birds, and mammals...
2018: Frontiers in Neuroscience
Xian-Ru Lee, Gui-Ling Xiang
OBJECTIVES: Edaravone, a free radical scavenger, alleviates blood-brain barrier disruption in conjunction with suppression of the inflammatory reaction in acute cerebral infarction. Thrombolysis with recombinant tissue plasminogen activator (rtPA) is an established therapy for acute cerebral infarction patients. The purpose of this study was to assess the effects of edaravone on outcomes in acute cerebral infarction patients treated with ultra-early thrombolysis of iv-rt-PA. PATIENTS AND METHODS: We conducted a retrospective cohort study using the database of Ningbo First Hospital...
February 24, 2018: Clinical Neurology and Neurosurgery
Douglas M Bennion, Chad H Jones, Alex N Dang, Jacob D Isenberg, Justin T Graham, Lena Lindblad, Oliver Domenig, Michael F Waters, Marko Poglitsch, Colin Sumners, U Muscha Steckelings
Significant neuroprotective effects of angiotensin II type 2 (AT2 ) receptor agonists in ischemic stroke have been previously demonstrated in multiple studies.  However, the routes of agonist application used in these pre-clinical studies, direct intracerebroventricular and systemic administration, are unsuitable for translation to humans; in the latter case because AT2 receptor agonists are blood brain barrier (BBB) impermeable. To circumvent this problem, in the current study we utilized the nose-to-brain (N2B) route of administration to bypass the blood brain barrier and deliver the selective AT2 receptor agonist Compound 21 (C21) to naïve rats or rats that had undergone endothelin 1-induced ischemic stroke...
March 2, 2018: Clinical Science (1979-)
Berta Anuncibay-Soto, Diego Pérez-Rodriguez, María Santos-Galdiano, Enrique Font-Belmonte, Irene F Ugidos, Paloma Gonzalez-Rodriguez, Marta Regueiro-Purriños, Arsenio Fernández-López
BACKGROUND: Blood reperfusion of the ischemic tissue after stroke promotes increases in the inflammatory response as well as accumulation of unfolded/misfolded proteins in the cell, leading to endoplasmic reticulum (ER) stress. Both Inflammation and ER stress are critical processes in the delayed death of the cells damaged after ischemia. The aim of this study is to check the putative synergic neuroprotective effect by combining anti-inflammatory and anti-ER stress agents after ischemia...
February 27, 2018: Biochemical Pharmacology
Jean-Philippe Desilles, Varouna Syvannarath, Lucas Di Meglio, Célina Ducroux, William Boisseau, Liliane Louedec, Martine Jandrot-Perrus, Jean-Baptiste Michel, Mikael Mazighi, Benoît Ho-Tin-Noé
BACKGROUND: Previous experimental studies have shown that downstream microvascular thromboinflammation is involved in brain damage from acute ischemic stroke. Using intravital microscopy, we investigated and characterized the sequence of downstream microvascular thromboinflammation in an ischemia/reperfusion acute ischemic stroke model. METHODS AND RESULTS: Rats underwent transient monofilament middle cerebral artery (MCA) occlusion. Cerebral microcirculation in the MCA territory was exposed through a craniotomy and analyzed using real-time intravital imaging coupled with laser Doppler interferometry...
March 1, 2018: Journal of the American Heart Association
Yirong Yang, Lisa Y Yang, Lilla Orban, Darnell Cuylear, Jeffrey Thompson, Bruce Simon, Yi Yang
BACKGROUND: Vagus nerve stimulation (VNS) significantly reduces infarct volume in rat models of cerebral ischemia, but the mechanism of this protective effect remains open. HYPOTHESIS: This study tested the hypothesis that non-invasive VNS (nVNS), during transient middle cerebral artery occlusion (MCAO), protects the blood-brain barrier (BBB), leading to reduced infarct size in ischemic brain. METHODS: Spontaneous hypertensive rats (SHRs) were subjected to a 90 min MCAO...
February 15, 2018: Brain Stimulation
Yan-Ping Luo, Hong Zhang, Han-Fei Hu, Ze-Yu Cao, Xin-Zhuang Zhang, Liang Cao, Zhen-Zhong Wang, Wei Xiao
To investigate the protective effects of ginkgo diterpene lactone meglumine injection (GDLMI) on cerebral focal ischemia reperfusion injury induced by middle cerebral artery occlusion (MCAO) in rats, and explore its possible mechanism. One hundred and forty male SD rats were randomly divided into sham operation group, model group, ginkgo biloba extract injection (Ginaton, 1.0 mL•kg⁻¹) group, nimodipine (0.4 mg•kg⁻¹) group, and GDLMI (5.2, 2.6, 1.3 mg•kg⁻¹) groups; All of rats received corresponding drugs by tail vein injection 4 days before operation (normal saline in model group and sham operation group)...
December 2017: Zhongguo Zhong Yao za Zhi, Zhongguo Zhongyao Zazhi, China Journal of Chinese Materia Medica
Angharad Davis, Graeme Meintjes, Robert J Wilkinson
PURPOSE OF REVIEW: Tuberculous meningitis (TBM) is a global health problem. In this review, we systematically evaluate the evidence for current and emerging antimicrobials, host-directed therapies and supportive managements. RECENT FINDINGS: Current antimicrobial regimes do not factor the differing ability of drugs to cross the blood-brain barrier. Rifampicin may be more effective at higher doses yet the most recent clinical trial failed to demonstrate survival benefit at 15 mg/kg/day...
February 28, 2018: Current Treatment Options in Neurology
Yi Yang, Shihoko Kimura-Ohba, Jeffrey F Thompson, Victor M Salayandia, Melissa Cosse, Limor Raz, Fakhreya Y Jalal, Gary A Rosenberg
Vascular cognitive impairment is a major cause of dementia caused by chronic hypoxia, producing progressive damage to white matter (WM) secondary to blood-brain barrier (BBB) opening and vascular dysfunction. Tight junction proteins (TJPs), which maintain BBB integrity, are lost in acute ischemia. Although angiogenesis is critical for neurovascular remodeling, less is known about its role in chronic hypoxia. To study the impact of TJP degradation and angiogenesis during pathological progression of WM damage, we used the spontaneously hypertensive/stroke prone rats with unilateral carotid artery occlusion and Japanese permissive diet to model WM damage...
February 24, 2018: Neurobiology of Disease
Zhong-Song Shi, Gary R Duckwiler, Reza Jahan, Satoshi Tateshima, Viktor Szeder, Jeffrey L Saver, Doojin Kim, Latisha K Sharma, Paul M Vespa, Noriko Salamon, J Pablo Villablanca, Fernando Viñuela, Lei Feng, Yince Loh, David S Liebeskind
BACKGROUND AND PURPOSE: The impact of blood-brain barrier (BBB) disruption can be detected by intraparenchymal hyperdense lesion on the computed tomography (CT) scan after endovascular stroke therapy. The purpose of this study was to determine whether early BBB disruption predicts intracranial hemorrhage and poor outcome in patients with acute ischemic stroke treated with mechanical thrombectomy. METHODS: We analyzed patients with anterior circulation stroke treated with mechanical thrombectomy and identified BBB disruption on the noncontrast CT images immediately after endovascular treatment...
February 27, 2018: Journal of Neuroimaging: Official Journal of the American Society of Neuroimaging
Natalia Chmielewska, Janusz Szyndler, Karolina Makowska, Dawid Wojtyna, Piotr Maciejak, Adam Płaźnik
The role of blood brain barrier (BBB) is to preserve a precisely regulated environment for proper neuronal signaling. In many of the central nervous system (CNS) pathologies, the function of BBB is altered. Thus, there is a necessity to evaluate a fast, noninvasive and reliable method for monitoring of BBB condition. It seems that revealing the peripheral diagnostic biomarker whose release pattern (concentration, dynamics) will be correlated with clinical symptoms of neurological disorders offers significant hope...
February 13, 2018: Neurologia i Neurochirurgia Polska
Hannah Aucott, Johan Lundberg, Henna Salo, Lena Klevenvall, Peter Damberg, Lars Ottosson, Ulf Andersson, Staffan Holmin, Helena Erlandsson Harris
BACKGROUND: Neuroinflammation triggered by infection or trauma is the cause of central nervous system dysfunction. High-mobility group box 1 protein (HMGB1), released from stressed and dying brain cells, is a potent neuroinflammatory mediator. The proinflammatory functions of HMGB1 are tightly regulated by post-translational redox modifications, and we here investigated detailed neuroinflammatory responses induced by the individual redox isoforms. METHODS: Male Dark Agouti rats received a stereotactic injection of saline, lipopolysaccharide, disulfide HMGB1, or fully reduced HMGB1, and were accessed for blood-brain barrier modifications using magnetic resonance imaging (MRI) and inflammatory responses by immunohistochemistry...
February 23, 2018: Journal of Innate Immunity
Mika Takarada-Iemata, Akifumi Yoshikawa, Hieu Minh Ta, Nahoko Okitani, Takumi Nishiuchi, Yasuhiro Aida, Tomoya Kamide, Tsuyoshi Hattori, Hiroshi Ishii, Takashi Tamatani, Thuong Manh Le, Jureepon Roboon, Yasuko Kitao, Tomohiro Matsuyama, Mitsutoshi Nakada, Osamu Hori
Disruption of the blood-brain barrier (BBB) following cerebral ischemia is closely related to the infiltration of peripheral cells into the brain, progression of lesion formation, and clinical exacerbation. However, the mechanism that regulates BBB integrity, especially after permanent ischemia, remains unclear. Here, we present evidence that astrocytic N-myc downstream-regulated gene 2 (NDRG2), a differentiation- and stress-associated molecule, may function as a modulator of BBB permeability following ischemic stroke, using a mouse model of permanent cerebral ischemia...
February 24, 2018: Glia
Chang Liu, Feina Shi, Zhicai Chen, Shenqiang Yan, Xinfa Ding, Min Lou
Background: Previous studies demonstrated that cardioembolism (CE) was prone to develop hemorrhagic transformation (HT), whereas hyper-permeability of blood-brain barrier (BBB) might be one reason for the development of HT. We, thus, aimed to investigate whether the BBB permeability (BBBP) was higher in CE stroke than other stroke subtypes in acute ischemic stroke (AIS) patients. Methods: This study was a retrospective review of prospectively collected clinical and imaging database of AIS patients who underwent CT perfusion...
2018: Frontiers in Neurology
Chunggab Choi, Hye Min Kim, Jeeheun Shon, Jiae Park, Hyeong-Taek Kim, Seung-Hun Oh, Nam Keun Kim, Ok-Joon Kim
The blood-brain barrier (BBB) is major obstacle in drug or stem cell treatment in chronic stroke. We hypothesized that adding mannitol to temozolomide (TMZ) is a practically applicable method for resolving the low efficacy of intravenous mannitol therapy. In this study, we investigated whether BBB permeability could be increased by this combined treatment. First, we established a chronic ischemic stroke rat model and examined changes in leakage of Evans blue dye within a lesion site, and in expression of tight junction proteins (TJPs), by this combined treatment...
February 17, 2018: Biochemical and Biophysical Research Communications
Marina S Hernandes, Bernard Lassègue, Lula L Hilenski, Jonathan Adams, Ning Gao, Chia-Yi Kuan, Yu-Yo Sun, Lihong Cheng, Daniel S Kikuchi, Manuel Yepes, Kathy K Griendling
BACKGROUND: Polymerase δ-interacting protein 2 (Poldip2) is a multifunctional protein that regulates vascular extracellular matrix composition and matrix metalloproteinase (MMP) activity. The blood-brain barrier (BBB) is a dynamic system assembled by endothelial cells, basal lamina, and perivascular astrocytes, raising the possibility that Poldip2 may be involved in maintaining its structure. We investigated the role of Poldip2 in the late BBB permeability induced by cerebral ischemia...
February 17, 2018: Journal of Neuroinflammation
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