scholarly journals Temporal analysis of blood–brain barrier disruption and cerebrospinal fluid matrix metalloproteinases in rhesus monkeys subjected to transient ischemic stroke

2016 ◽  
Vol 37 (8) ◽  
pp. 2963-2974 ◽  
Author(s):  
Yingqian Zhang ◽  
Feng Fan ◽  
Guojun Zeng ◽  
Linlin Zhou ◽  
Yinbing Zhang ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Blood Brain Barrier ◽  
Dynamic Change ◽  
Fold Increase ◽  
Temporal Analysis ◽  
Brain Barrier ◽  
Infarction Size ◽  
Blood Brain Barrier Disruption ◽  
Blood Brain ◽  
Bbb Permeability

Blood–brain barrier (BBB) disruption plays an important role in pathophysiological progress of ischemic stroke. However, our knowledge of the dynamic change of BBB permeability and its mechanism remains limited. In the current study, we used a non-human primate (NHP) MCAO model and a serial CSF sampling method that allowed us to determine the dynamic change of BBB permeability by calculating the CSF/serum albumin ratio (AR). We showed that AR increased rapidly and significantly after ischemia, and the fold increase of AR is highly correlated with the infarction size during the subacute phase. Moreover, we determined the temporal change of MMP-1, MMP-2, MMP-3, MMP-9, MMP-10, MMP-13, TIMP-1, and TIMP-2 in CSF and serum. Each MMP and TIMP showed different change patterns when comparing their values in CSF and serum. Based on the longitudinal dataset, we showed that the fold increase of MMP-9 in serum and CSF are both correlated to infarction size. Among the measured MMPs and TIMPs, only MMP-2, MMP-13, and TIMP-2 in CSF correlated with AR to some extent. Our data suggest there is no single MMP or TIMP fully responsible for BBB breakdown, which is regulated by a much more complicated signal network and further investigations of the mechanisms are needed.

Early Blood‐Brain Barrier Disruption after Mechanical Thrombectomy in Acute Ischemic Stroke

2018 ◽  
Vol 28 (3) ◽  
pp. 283-288 ◽  
Author(s):  
Zhong‐Song Shi ◽  
Gary R. Duckwiler ◽  
Reza Jahan ◽  
Satoshi Tateshima ◽  
Viktor Szeder ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Acute Ischemic Stroke ◽  
Blood Brain Barrier ◽  
Mechanical Thrombectomy ◽  
Brain Barrier ◽  
Barrier Disruption ◽  
Blood Brain Barrier Disruption ◽  
Blood Brain ◽  
Brain Barrier Disruption

Abstract TP80: Panaxatriol Saponins Attenuates Blood-brain Barrier Disruption and Promotes Angiogenesis After Ischemic Stroke in Rats

Stroke ◽  
2017 ◽  
Vol 48 (suppl_1) ◽  
Author(s):  
Hui Yang ◽  
Zhen Hui ◽  
Du Juan Sha ◽  
Yun Xu
Keyword(s):  
Ischemic Stroke ◽  
Blood Brain Barrier ◽  
Cerebral Perfusion ◽  
Infarct Volume ◽  
Immunofluorescence Staining ◽  
Brain Barrier ◽  
Shh Pathway ◽  
Blood Brain Barrier Disruption ◽  
Blood Brain ◽  
Brain Barrier Disruption

Background: The induction of angiogenesis and maintain the integrity of the blood brain barrier (BBB) after stroke may enhance neurorestorative processes. Panaxatriol Saponins (PTS), extracted from traditional Chinese herb Panaxnotoginseng, could noticeably prevent BBB disruption and promote angiogenesis in rodent stroke model. Methods: Middle cerebral artery occlusion (MCAO) model were applied to mimic acute stroke in vivo. Ischemic infarct volume and neurological functions were evaluated through 2,3,5-triphenyltetrazolium chloride (TTC) staining and Longa Scores (LS) respectively. The micro-PET scan was adopted to assess cerebral perfusion; evans blue extravasation assay was used to test BBB permeability; real time PCR and Western blot were used to evaluate the level of vascular growth factors, pro-inflammation factors, the components of Sonic hedgehog (Shh) pathway and NF-κB pathway. Enzyme Linked Immunosorbent Assay (ELISA) was used to detect the levels of pro-inflammation factors in the brain. The capillaries density in ischemic penumbra and tight junction in BBB were measured by immunofluorescence staining. Results: PTS treatment improved neurological function and reduced infarct volume in MCAO-rats. The result of micro-PET scan indicated that PTS could significantly enhance cerebral perfusion after MCAO operation. Treatment of PTS significantly attenuated BBB destruction. PTS could significantly increase the VEGF, Ang-1, VEGFR-2, Tie-2, CD31 and α-SMA mRNA expression at 3 d and 7 d after MCAO compared to vehicle group. Moreover, the expression levels of inflammation factors were decreased after PTS treatment. The co-immunofluorescence staining of α-SMA and Brdu with CD31 respectively showed that PTS promotes angiogenesis and endothelial cell proliferation after MCAO. Meanwhile, co-immunofluorescence staining of Claudin-5, Occludin and ZO-1 with CD31 respectively showed that PTS could protect tight junction from ischemia/reperfusion injury. PTS could also activate Shh pathway and inhibited NF-κB pathway. Conclusions: PTS alleviated ischemic stroke injury through attenuates blood-brain barrier disruption and promotes angiogenesis. PTS could be a potential medication for combating ischemic brain injury.

scholarly journals Early Blood–Brain Barrier Disruption in Ischemic Stroke Initiates Multifocally Around Capillaries/Venules

Stroke ◽  
2018 ◽  
Vol 49 (6) ◽  
pp. 1479-1487 ◽  
Author(s):  
Angelika Hoffmann ◽  
Tassilo Dege ◽  
Reiner Kunze ◽  
Anne-Sophie Ernst ◽  
Holger Lorenz ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Blood Brain Barrier ◽  
Brain Barrier ◽  
Barrier Disruption ◽  
Blood Brain Barrier Disruption ◽  
Blood Brain ◽  
Brain Barrier Disruption

scholarly journals Borneol for Regulating the Permeability of the Blood-Brain Barrier in Experimental Ischemic Stroke: Preclinical Evidence and Possible Mechanism

2019 ◽  
Vol 2019 ◽  
pp. 1-15 ◽  
Author(s):  
Zi-xian Chen ◽  
Qing-qing Xu ◽  
Chun-shuo Shan ◽  
Yi-hua Shi ◽  
Yong Wang ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Blood Brain Barrier ◽  
Ischemic Injury ◽  
Brain Barrier ◽  
Brain Diseases ◽  
Glycoprotein P ◽  
Blood Brain ◽  
Cerebral Ischemic Injury ◽  
Bbb Permeability ◽  
Cerebral Ischemic

Borneol, a natural product in the Asteraceae family, is widely used as an upper ushering drug for various brain diseases in many Chinese herbal formulae. The blood-brain barrier (BBB) plays an essential role in maintaining a stable homeostatic environment, while BBB destruction and the increasing BBB permeability are common pathological processes in many serious central nervous system (CNS) diseases, which is especially an essential pathological basis of cerebral ischemic injury. Here, we aimed to conduct a systematic review to assess preclinical evidence of borneol for experimental ischemic stroke as well as investigate in the possible neuroprotective mechanisms, which mainly focused on regulating the permeability of BBB. Seven databases were searched from their inception to July 2018. The studies of borneol for ischemic stroke in animal models were included. RevMan 5.3 was applied for data analysis. Fifteen studies investigated the effects of borneol in experimental ischemic stroke involving 308 animals were ultimately identified. The present study showed that the administration of borneol exerted a significant decrease of BBB permeability during cerebral ischemic injury according to brain Evans blue content and brain water content compared with controls (P<0.01). In addition, borneol could improve neurological function scores (NFS) and cerebral infarction area. Thus, borneol may be a promising neuroprotective agent for cerebral ischemic injury, largely through alleviating the BBB disruption, reducing oxidative reactions, inhibiting the occurrence of inflammation, inhibiting apoptosis, and improving the activity of lactate dehydrogenase (LDH) as well as P-glycoprotein (P-GP) and NO signaling pathway.

scholarly journals Role of MicroRNA29b in Blood–Brain Barrier Dysfunction during Hyperhomocysteinemia: An Epigenetic Mechanism

2014 ◽  
Vol 34 (7) ◽  
pp. 1212-1222 ◽  
Author(s):  
Anuradha Kalani ◽  
Pradip K Kamat ◽  
Anastasia Familtseva ◽  
Pankaj Chaturvedi ◽  
Nino Muradashvili ◽  
...  
Keyword(s):  
Blood Brain Barrier ◽  
Epigenetic Mechanism ◽  
Brain Barrier ◽  
Barrier Dysfunction ◽  
Blood Brain Barrier Disruption ◽  
Blood Brain ◽  
Qpcr Array ◽  
Bbb Permeability ◽  
Brain Barrier Disruption ◽  
Junction Proteins

Although blood–brain barrier (BBB) integrity is maintained by the cross-talk of endothelial cells, junction proteins, and neurogliovascular network, the epigenetic mechanisms behind BBB permeability are largely unknown. We are reporting for the first time miR29b-mediated regulation of BBB, which is a novel mechanism underlying BBB integrity. We hypothesize that miR29b regulates BBB dysfunction by regulating DNMT3b, which consequently regulates the levels of metalloproteinases, that can eat up the membrane and junction proteins leading to leaky vasculature. In addition, 5′-azacytidine (5′-aza) was used to test its efficacy on BBB permeability. Blood–brain barrier disruption model was created by using homocysteine, and in the models miR29b was identified to be most affected, by using microRNA RT 2 -qPCR array. MiR29b mimics and inhibitors also confirmed that miR29b regulates the levels DNMT3b and MMP9. In hyperhomocysteinemic cystathionine-β-synthase deficient (CBS+/−) mice with high brain vessel permeability, miR29b levels were also high as compared with wild-type (WT) mice. Interestingly, 5′-aza improved BBB permeability by decreasing the expression of miR29b. In conclusion, our data suggested miR29b-mediated regulation of BBB dysfunction through DNMT3b and MMP9. It also potentiates the use of microRNAs as candidates for future epigenetic therapies in the improvement of BBB integrity.

Abstract WP137: Time-Course Characterization of Blood-Brain Barrier Disruption in Secondary Thalamic Injury After Stroke

Stroke ◽  
2020 ◽  
Vol 51 (Suppl_1) ◽  
Author(s):  
Zhijuan Cao ◽  
Sean Harvey ◽  
Arjun Pendharkar ◽  
Terrance Chiang ◽  
Michelle Cheng ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Blood Brain Barrier ◽  
Stroke Recovery ◽  
Brain Barrier ◽  
Tube Length ◽  
Left Middle Cerebral Artery ◽  
Vessel Morphology ◽  
Blood Brain ◽  
Branching Points ◽  
Bbb Permeability

Introduction: A secondary degenerative injury occurs in the thalamus after primary cortical ischemic stroke. This secondary thalamic injury progresses long-term and is associated with somatosensory dysfunctions. Blood-brain barrier (BBB) disruption is one of the feature pathological changes in primary ischemic stroke, but whether BBB disruption happens in the secondary thalamic injury is unclear. In this study, we aim to investigate the BBB changes during the development of secondary thalamic injury after stroke. Methods: Cortical ischemic stroke was generated by permanent occlusion of the left middle cerebral artery on male C57BL6J mice (12-15 weeks). BBB permeability was assessed by Biocytin-TMR (869 Da, 1mg/mL) at post-stroke days (PD) 1, 3, 7, 14, 28, 56, and 84. Immunostainings of CD68 (inflammation) and CD31 (vascular morphology) were performed. Brain sections were imaged with Confocal LSM800 and quantified by NIH ImageJ and Wimasis Image Analysis. BBB permeability related genes were quantified by real-time PCR among naïve, PD7 and PD28. Results: In ipsilesional thalamus (iTH), the Biocytin-TMR was detected as early as PD3 in the secondary thalamic injury area and persisted until at least PD84. The fluorescence intensity of Biocytin-TMR significantly increased during PD28-84 and peaked at PD56, suggesting the BBB is chronically disrupted in iTH. Compared to naïve animals, stroke animals exhibited significant increase in tube length, total number of tubes and total number of branching points at PD56 and PD84. mRNA expression of ZO-2 significantly down-regulated at PD7 and returned to baseline levels by PD28. mRNA of Angiopoietin-1 ( Ang-1 ), VEGFa and Adam10 were significantly increased at PD28. Conclusion: Our data demonstrate that the BBB disruption begins early at PD3 and continues to progress until PD84 in the secondary degenerative thalamus. This BBB disruption is accompanied by changes in blood vessel morphology and permeability related genes. Current studies are examining the expression of key genes at PD56 using qPCR and immunohistochemistry. Our results will elucidate the cellular and molecular changes of BBB disruption involved in thalamic injury, which will provide potential targets for enhancing stroke recovery.

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