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bbb edema

Tongyu Zhang, Shancai Xu, Pei Wu, Keren Zhou, Lingyun Wu, Zhiyi Xie, Weilin Xu, Xu Luo, Peng Li, Umut Ocak, Pinar Eser Ocak, Zachary D Travis, Jiping Tang, Huaizhang Shi, John H Zhang
BACKGROUND AND PURPOSE: Mitochondrial dysfunction is involved in the mechanism of early brain injury (EBI) following subarachnoid hemorrhage (SAH). Blood-brain barrier disruption is a devastating outcome in the early stage of SAH. In this study, we aimed to investigate the role of a mitochondria-related drug Mitoquinone (MitoQ) in blood-brain barrier disruption after SAH in rats. METHODS: A total of 181 male Sprague-Dawley SAH rats with the endovascular perforation model were utilized...
February 16, 2019: Experimental Neurology
Abhijit Nirwane, Jessica Johnson, Benjamin Nguyen, Jeffrey H Miner, Yao Yao
At the blood-brain barrier (BBB), laminin-α5 is predominantly synthesized by endothelial cells and mural cells. Endothelial laminin-α5 is dispensable for BBB maintenance under homeostatic conditions but inhibits inflammatory cell extravasation in pathological conditions. Whether mural cell-derived laminin-α5 is involved in vascular integrity regulation, however, remains unknown. To answer this question, we generated transgenic mice with laminin-α5 deficiency in mural cells (α5-PKO). Under homeostatic conditions, no defects in BBB integrity and cerebral blood flow (CBF) were observed in α5-PKO mice, suggesting that mural cell-derived laminin-α5 is dispensable for BBB maintenance and CBF regulation under homeostatic conditions...
February 18, 2019: Acta Neuropathologica Communications
Jiang Shao, Qi Wu, Sheng-Yin Lv, Xiao-Ming Zhou, Xiang-Sheng Zhang, Li-Li Wen, Jin Xue, Xin Zhang
Early Brain Injury, rather than Cerebral Vasospasm, has been demonstrated to be more important for patients with Subarachnoid hemorrhage. It is considered that allicin can make sense in a wide range of pharmacological areas and can be taken as a therapeutic method in many pathologic situations. We have explored the potential effect of allicin and possible mechanisms in Early Brain Injury after Experimental Subarachnoid Hemorrhage in Rats. With therapy (70 mg/kg Allicin, rather than 30 mg/kg) 30 min post SAH, groups showed better neurological scores in 24 h...
February 15, 2019: Journal of Clinical Neuroscience: Official Journal of the Neurosurgical Society of Australasia
Eva-Verena Griemert, Jana Hedrich, Tobias Hirnet, Serge Christian Thal
Plasminogen activator inhibitor type 2 (PAI-2 / SerpinB2) inhibits extracellular urokinase plasminogen activator (uPA). Under physiological conditions PAI-2 is expressed at low levels, but is rapidly induced by inflammatory triggers. It is a negative regulator of fibrinolysis and serves to stabilize clots. In the present study PAI-2 expression is upregulated 25-fold in pericontusional brain tissue at 6h after traumatic brain injury (TBI) with a maximum increase of 87-fold at 12h. To investigate a potentially detrimental influence of PAI-2 on secondary posttraumatic processes, male PAI-2 deficient (PAI-2-KO) and wild-type mice (WT) were subjected to TBI by controlled cortical impact injury (CCI)...
February 13, 2019: Journal of Neurotrauma
Benjamin M Aertker, Akshita Kumar, Karthik S Prabhakara, Philippa Smith, Naama E Toledano Furman, Xue Hasen, Charles S Cox, Supinder S Bedi
Traumatic brain injury (TBI) effects both the brain and the immune system. Circulating monocytes/macrophages (Mo /Ma ) after a TBI may play an important role in preserving the blood-brain barrier (BBB), reducing brain edema, and interacting with resident microglia. To elucidate the role of circulating Mo /Ma , we utilized a monocyte/macrophage depletion model in response to TBI in male rats. Clodronate liposomes (CL) were used to deplete circulating Mo /Ma . A controlled cortical impact (CCI) injury model was used to create a TBI...
February 12, 2019: Journal of Neuroscience Research
Martin Krueger, Bianca Mages, Constance Hobusch, Dominik Michalski
In the setting of stroke, ischemia-related blood-brain barrier (BBB) dysfunction aggravates the cerebral edema, which critically impacts on the clinical outcome. Further, an impaired vascular integrity is associated with the risk of intracranial bleeding, especially after therapeutic recanalization. Therefore, the present study was aimed to investigate early vascular alterations from 30 min to 4 h after experimental middle cerebral artery occlusion (MCAO) in mice. Here, an extravasation of the permeability marker FITC-albumin was detectable in animals 2 and 4 h after MCAO...
February 11, 2019: Acta Neuropathologica Communications
Ran Li, Poornima Venkat, Michael Chopp, Qiang Zhang, Tao Yan, Jieli Chen
Subarachnoid hemorrhage (SAH) results in neurological damage, acute cardiac damage and has a high mortality rate. Immunoresponse in the acute phase after SAH plays a key role in mediating vasospasm, edema, inflammation and neuronal damage. The S1P/S1PR pathway impacts multiple cellular functions, exerts anti-inflammatory and anti-apoptotic effects, promotes remyelination, and improves outcome in several central nervous system (CNS) diseases. RP001 hydrochloride is a novel S1PR agonist, which sequesters lymphocytes within their secondary tissues and prevents infiltration of immune cells into the CNS thereby reducing immune response...
February 5, 2019: Journal of the Neurological Sciences
George W Farr, Christopher H Hall, Susan M Farr, Ramon Wade, Joshua M Detzel, Amielia G Adams, Jasen M Buch, Derek L Beahm, Christopher A Flask, Kui Xu, Joseph C LaManna, Paul R McGuirk, Walter F Boron, Marc F Pelletier
Cerebral edema in ischemic stroke can lead to increased intracranial pressure, reduced cerebral blood flow and neuronal death. Unfortunately, current therapies for cerebral edema are either ineffective or highly invasive. During the development of cytotoxic and subsequent ionic cerebral edema water enters the brain by moving across an intact blood brain barrier and through aquaporin-4 (AQP4) at astrocyte endfeet. Using AQP4-expressing cells, we screened small molecule libraries for inhibitors that reduce AQP4-mediated water permeability...
February 6, 2019: Neuroscience
Qing-Song Lin, Wei-Xiong Wang, Yuan-Xiang Lin, Zhang-Ya Lin, Liang-Hong Yu, Yin Kang, De-Zhi Kang
OBJECTIVEGlutamate excitotoxicity and neuronal apoptosis are suggested to contribute to early brain injury after subarachnoid hemorrhage (SAH). Annexin A7 (ANXA7) has been shown to regulate glutamate release. However, the role of ANXA7 in early brain injury after SAH has not been illustrated. In this study, we aimed to investigate the effect of ANXA7 knockdown in reducing the severity of early brain injury after SAH, and determine the underlying mechanisms.METHODSEndovascular perforation was performed to induce SAH in male Sprague-Dawley rats...
February 1, 2019: Journal of Neurosurgery
Yin Cheng, Wan Lung Yeung, Ping De Zhang, Ning Li, Mei Yee Kiang, Ka Kit Leung
OBJECTIVE: Dexamethasone (DEXA) is widely used in the management of peri-tumoral brain edema. DEXA, however, has many systemic side-effects, and may interact negatively with glioma therapy. Progesterone (PROG), on the other hand, is a well-tolerated and readily accessible anti-inflammatory and anti-edema agent with potent neuroprotective properties. We investigated if PROG can serve as a viable alternative to DEXA in the management of peri-tumoral brain edema. METHODS: We used an orthotopic C6 glioblastoma model with male Sprague-Dawley (SD) rats...
January 30, 2019: World Neurosurgery
Anis Talebi, Mehdi Rahnema, Mohammad Reza Bigdeli
Stroke is one of the leading causes of death in the world, but the underlying molecular mechanism of this disease remains elusive, thus it will be great challenges to finding appropriate protection. MicroRNAs are short, single-stranded, non-coding RNAs and recent studies have shown that they are aberrantly expressed in ischemic condition. Due to the fact that miR-1 has harmful effects on neural damages during brain ischemia, limited miR-1 has been proven to be protective in middle cerebral artery occlusion (MCAO)...
February 1, 2019: Molecular Biology Reports
Yu-Long Lan, Xun Wang, Yu-Jie Zou, Jin-Shan Xing, Jia-Cheng Lou, Shuang Zou, Bin-Bin Ma, Yan Ding, Bo Zhang
OBJECTIVE: Traumatic brain injury (TBI) is a significant cause of death and long-term deficits in motor and cognitive functions for which there are currently no effective chemotherapeutic drugs. Bazedoxifene (BZA) is a third-generation selective estrogen receptor modulator (SERM) and has been investigated as a treatment for postmenopausal osteoporosis. It is generally safe and well tolerated, with favorable endometrial and breast safety profiles. Recent findings have shown that SERMs may have therapeutic benefits; however, the role of BZA in the treatment of TBI and its molecular and cellular mechanisms remain poorly understood...
January 31, 2019: Inflammation Research: Official Journal of the European Histamine Research Society ... [et Al.]
Qiang Tan, Yuhan Li, Peiwen Guo, Jiru Zhou, Zhouyang Jiang, Xin Liu, Zhi Chen, Hua Feng
Arginine-vasopressin (AVP) is believed to be positively correlated with the brain edema formation, but the underlying mechanism is still unclear. In this study, we explored the role of the V2 receptors antagonist tolvaptan on brain edema following intracerebral hemorrhage (ICH) with a rat model. Animals were randomly given tolvaptan or vehicle through oral gavage at 12h, 36h, and 60h after ICH surgery. Brain swelling (%), brain water content(BWC), neurological scores, Evans blue fluorescence and blood-brain barrier (BBB) tight junction proteins were measured to evaluate the effect of tolvaptan in ICH...
January 28, 2019: Brain Research
Shotaro Michinaga, Yutaka Koyama
The blood-brain barrier (BBB) is a major functional barrier in the central nervous system (CNS), and inhibits the extravasation of intravascular contents and transports various essential nutrients between the blood and the brain. After brain damage by traumatic brain injury, cerebral ischemia and several other CNS disorders, the functions of the BBB are disrupted, resulting in severe secondary damage including brain edema and inflammatory injury. Therefore, BBB protection and recovery are considered novel therapeutic strategies for reducing brain damage...
January 29, 2019: International Journal of Molecular Sciences
Jyoti Gautam, Jeffrey H Miner, Yao Yao
Endothelial cells make laminin-411 and laminin-511. Although laminin-411 is well studied, the role of laminin-511 remains largely unknown due to the embryonic lethality of lama5-/- mutants. In this study, we generated endothelium-specific lama5 conditional knockout (α5-TKO) mice and investigated the biological functions of endothelial lama5 in blood-brain barrier (BBB) maintenance under homeostatic conditions and the pathogenesis of intracerebral hemorrhage (ICH). First, the BBB integrity of α5-TKO mice was measured under homeostatic conditions...
January 29, 2019: Translational Stroke Research
Xin Zhang, Yunhe Gu, Peitong Li, Anqi Jiang, Xiaomeng Sheng, Xin Jin, Yue Shi, Guozhong Li
BACKGROUND It is well documented that the Blood-Brain barrier (BBB) can be damaged by matrix metalloproteases (MMPs) after intracerebral hemorrhage (ICH), but little is known about the mechanism of this effect. MATERIAL AND METHODS We established an ICH model in rats by injecting collagenase VII into the striatum. Afterwards, intraperitoneal injection of these rats with 40 mg/kg GM6001 (a MMPs inhibitor). The effects of GM6001 on ICH were investigated by neurological severity score, brain water content, Evans blue staining, hematoxylin-eosin staining, immunohistochemical staining, and Western blot assays...
January 28, 2019: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
Xinzhi Wang, Shuyue Li, Jinbang Ma, Chuangang Wang, Anzhong Chen, Zhenxue Xin, Jianjun Zhang
Gastrodin is a phenolic glycoside that has been demonstrated to provide neuroprotection in preclinical models of central nervous system disease, but its effect in subarachnoid hemorrhage (SAH) remains unclear. In this study, we showed that intraperitoneal administration of gastrodin (100 mg/kg per day) significantly attenuated the SAH-induced neurological deficit, brain edema, and increased blood-brain barrier permeability in rats. Meanwhile, gastrodin treatment significantly reduced the SAH-induced elevation of glutamate concentration in the cerebrospinal fluid and the intracellular Ca2+ overload...
January 23, 2019: Neuroscience Bulletin
Natsuko Imakita, Masahiro Kitabatake, Noriko Ouji-Sageshima, Atsushi Hara, Shoko Morita-Takemura, Kei Kasahara, Akihiro Matsukawa, Akio Wanaka, Keiichi Mikasa, Toshihiro Ito
Influenza-associated encephalopathy (IAE) is a serious complication that can follow influenza virus infection. Once a cytokine storm is induced during influenza virus infection, tight junction protein disruption occurs, which consequently leads to blood-brain barrier (BBB) breakdown. However, the details of IAE pathogenesis are not well understood. Here, we established a murine IAE model by administration of lipopolysaccharide following influenza virus infection. Brains from IAE model mice had significantly higher expression of type I interferons and inflammatory cytokines...
January 22, 2019: Scientific Reports
Philipp Eisele, Simon Konstandin, Kristina Szabo, Anne Ebert, Christina Roßmanith, Nadia Paschke, Martin Kerschensteiner, Michael Platten, Stefan O Schoenberg, Lothar R Schad, Achim Gass
BACKGROUND: Several studies have reported the characteristics of acute multiple sclerosis (MS) lesions on diffusion-weighted magnetic resonance imaging (DWI MRI). Current publications reported a transient reduction of the apparent diffusion coefficient (ADC) delineating an early phase of lesion evolution, before increased diffusion occurs in parallel to blood-brain-barrier (BBB) breakdown. Sodium MRI might provide another perspective on lesion development, but clinical applications have been limited to high field MR systems...
January 17, 2019: Multiple Sclerosis and related Disorders
Junyi Yang, Weiliang Gong
Approximately 3-5% of patients with non-small cell lung cancer (NSCLC)belonged to anaplastic lymphoma kinase (ALK)-positive NSCLC. The treatment drugs of ALK-positive NSCLC mainly included crizotinib, ceritinib, alectinib and brigatinib. Although these drugs had some effects, most of them were usually easy to develop drug resistance. Lorlatinib is a new inhibitor of ALK for treating ALK-positive NSCLC,the effect is obvious, and not easy to develop resistance. Areas covered: The main mechanism of action, pharmacokinetics, clinical efficacy and safety of lorlatinib were introduced in this paper...
January 18, 2019: Expert Review of Clinical Pharmacology
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