scholarly journals Interferon-Beta Blocks Infiltration of Inflammatory Cells and Reduces Infarct Volume after Ischemic Stroke in the Rat

2003 ◽  
Vol 23 (9) ◽  
pp. 1029-1039 ◽  
Author(s):  
Wouter B. Veldhuis ◽  
Joris W. Derksen ◽  
Sarah Floris ◽  
Peter H. van der Meide ◽  
Helga E. de Vries ◽  
...  
Keyword(s):  
Blood Brain Barrier ◽  
Interferon Beta ◽  
Infarct Volume ◽  
Ischemia Reperfusion ◽  
Stroke Onset ◽  
Cerebral Injury ◽  
Brain Barrier ◽  
Similar Degree ◽  
Lesion Volume ◽  
Blood Brain

The inflammatory response that exacerbates cerebral injury after ischemia is an attractive therapeutic target: it progresses over days and strongly contributes to worsening of the neurologic outcome. The authors show that, after transient ischemic injury to the rat brain, systemic application of interferon-beta (IFN-β), a cytokine with antiinflammatory properties, attenuated the development of brain infarction. Serial magnetic resonance imaging (MRI) showed that IFN-β treatment reduced lesion volume on diffusion-weighted MRI by 70% ( P < 0.01) at 1 day after stroke. IFN-β attenuated the leakage of contrast agent through the blood–brain barrier ( P < 0.005), indicating a better-preserved blood–brain barrier integrity. Both control and IFN-β-treated animals showed a similar degree of relative hyperperfusion of the lesioned hemisphere, indicating that neuroprotection by IFN-β was not mediated by improved cerebral perfusion as assessed 24 hours after stroke onset. IFN-β treatment resulted in an 85% reduction ( P < 0.0001) in infarct volume 3 weeks later, as determined from T2-weighted MRI and confirmed by histology. This effect was achieved even when treatment was started 6 hours after stroke onset. Quantitative immunohistochemistry at 24 hours after stroke onset showed that IFN-β almost completely prevented the infiltration of neutrophils and monocytes into the brain. Gelatinase zymography showed that this effect was associated with a decrease in matrix metalloproteinase-9 expression. In conclusion, treatment with the antiinflammatory cytokine IFN-β affords significant neuroprotection against ischemia/reperfusion injury, and within a relatively long treatment window. Because IFN-β has been approved for clinical use, it may be rapidly tested in a clinical trial for its efficacy against human stroke.

Combined Ischemic Preconditioning and Resveratrol Improved Bloodbrain Barrier Breakdown via Hippo/YAP/TAZ Signaling Pathway

2020 ◽  
Vol 18 (9) ◽  
pp. 713-722 ◽  
Author(s):  
Ganji Hong ◽  
Ying Yan ◽  
Yali Zhong ◽  
Jianer Chen ◽  
Fei Tong ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Blood Brain Barrier ◽  
Ischemic Preconditioning ◽  
Infarct Volume ◽  
Ischemia Reperfusion ◽  
Cerebral Infarct ◽  
Brain Barrier ◽  
Binding Motif ◽  
Blood Brain ◽  
Barrier Breakdown

Background: Transient Ischemia/Reperfusion (I/R) is the main reason for brain injury and results in disruption of the Blood-Brain Barrier (BBB). It had been reported that BBB injury is one of the main risk factors for early death in patients with cerebral ischemia. Numerous investigations focus on the study of BBB injury which have been carried out. Objective: The objective of this study was to investigate the treatment function of the activation of the Hippo/Yes-Associated Protein (YAP) signaling pathway by combined Ischemic Preconditioning (IPC) and resveratrol (RES) before brain Ischemia/Reperfusion (BI/R) improves Blood-Brain Barrier (BBB) disruption in rats. Methods: Sprague-Dawley (SD) rats were pretreated with 20 mg/kg RES and IPC and then subjected to 2 h of ischemia and 22 h of reperfusion. The cerebral tissues were collected; the cerebral infarct volume was determined; the Evans Blue (EB) level, the brain Water Content (BWC), and apoptosis were assessed; and the expressions of YAP and TAZ were investigated in cerebral tissues. Results: Both IPC and RES preconditioning reduced the cerebral infarct size, improved BBB permeability, lessened apoptosis, and upregulated expressions of YAP and transcriptional co-activator with PDZ-binding motif (TAZ) compared to the Ischemia/Reperfusion (I/R) group, while combined IPC and RES significantly enhanced this action. Conclusion: combined ischemic preconditioning and resveratrol improved blood-brain barrier breakdown via Hippo/YAP/TAZ signaling pathway.

scholarly journals Dietary Virgin Olive Oil Reduces Blood Brain Barrier Permeability, Brain Edema, and Brain Injury in Rats Subjected to Ischemia-Reperfusion

2010 ◽  
Vol 10 ◽  
pp. 1180-1191 ◽  
Author(s):  
Fatemeh Mohagheghi ◽  
Mohammad Reza Bigdeli ◽  
Bahram Rasoulian ◽  
Ali Asghar Zeinanloo ◽  
Ali Khoshbaten
Keyword(s):  
Brain Edema ◽  
Blood Brain Barrier ◽  
Infarct Volume ◽  
Ischemia Reperfusion ◽  
Virgin Olive Oil ◽  
Brain Barrier ◽  
Barrier Permeability ◽  
Blood Brain Barrier Permeability ◽  
Blood Brain ◽  
Brain Barrier Permeability

Recent studies suggest that dietary virgin olive oil (VOO) reduces hypoxia-reoxygenation injury in rat brain slices. We sought to extend these observations in anin vivostudy of rat cerebral ischemia-reperfusion injury. Four groups, each consisting of 18 Wistar rats, were studied. One group (control) received saline, while three treatment groups received oral VOO (0.25, 0.5, and 0.75 mL/kg/day, respectively). After 30 days, blood lipid profiles were determined, before a 60-min period of middle cerebral artery occlusion (MCAO). After 24-h reperfusion, neurological deficit scores, infarct volume, brain edema, and blood brain barrier permeability were each assessed in subgroups of six animals drawn from each main group. VOO reduced the LDL/HDL ratio in doses of 0.25, 0.5, and 0.75 mL/kg/day in comparison to the control group (p< 0.05), and offered cerebroprotection from ischemia-reperfusion. For controls vs. doses of 0.25 vs. 0.5 vs. 0.75 mL/kg/day, attenuated corrected infarct volumes were 207.82 ± 34.29 vs. 206.41 ± 26.23 vs. 124.21 ± 14.73 vs. 108.46 ± 31.63 mm3; brain water content of the infarcted hemisphere was 82 ±± 0.25 vs. 81.5 ± 0.56 vs. 80.5 ± 0.22 vs. 80.5 ± 0.34%; and blood brain barrier permeability of the infarcted hemisphere was 11.31 ± 2.67 vs. 9.21 ± 2.28 vs. 5.83 ± 1.6 vs. 4.43 ± 0.93 µg/g tissue (p< 0.05 for measures in doses 0.5 and 0.75 mL/kg/day vs. controls). Oral administration of VOO reduces infarct volume, brain edema, blood brain barrier permeability, and improves neurologic deficit scores after transient MCAO in rats.

scholarly journals Neurovascular Protection by Targeting Early Blood–Brain Barrier Disruption with Neurotrophic Factors after Ischemia–Reperfusion in Rats

2013 ◽  
Vol 33 (4) ◽  
pp. 557-566 ◽  
Author(s):  
Deepu R Pillai ◽  
Nagesh C Shanbhag ◽  
Michael S Dittmar ◽  
Ulrich Bogdahn ◽  
Felix Schlachetzki
Keyword(s):  
Blood Brain Barrier ◽  
Ischemia Reperfusion ◽  
Pigment Epithelium ◽  
Neurovascular Unit ◽  
Trophic Factors ◽  
Brain Barrier ◽  
Multiple Time ◽  
Lesion Volume ◽  
Time Points ◽  
Blood Brain

The ‘new penumbra’ concept imbues the transition between injury and repair at the neurovascular unit with profound implications for selecting the appropriate type and timing of neuroprotective interventions. In this conceptual study, we investigated the protective effects of pigment epithelium-derived factor (PEDF) and compared them with the properties of epidermal growth factor (EGF) in a rat model of ischemia–reperfusion injury. We initiated a delayed intervention 3 hours after reperfusion using equimolar amounts of PEDF and EGF. These agents were then administered intravenously for 4 hours following reperfusion after 1 hour of focal ischemia. Magnetic resonance imaging indices were characterized, and imaging was performed at multiple time points post reperfusion. PEDF and EGF reduced lesion volumes at all time points as observed on T2-weighted images (T2-LVs). In addition PEDF selectively attenuated lesion volume expansion at 48 hours after reperfusion and persistently modulated blood–brain barrier (BBB) permeability at all time points. Intervention with peptides is suspected to cause edema formation at distant regions. The observed T2-LV reduction and BBB modulation by these trophic factors is probably mediated through a number of diverse mechanisms. A thorough evaluation of neurotrophins is still necessary to determine their time-dependent contributions against injury and their modulatory effects on repair after stroke.

Comparative changes in the blood-brain barrier and cerebral infarction of SHR and WKY rats

2007 ◽  
Vol 292 (5) ◽  
pp. R1881-R1892 ◽  
Author(s):  
Sharon Hom ◽  
Melissa A. Fleegal ◽  
Richard D. Egleton ◽  
Christopher R. Campos ◽  
Brian T. Hawkins ◽  
...  
Keyword(s):  
Cerebral Infarction ◽  
Blood Brain Barrier ◽  
Infarct Volume ◽  
Brain Barrier ◽  
Ion Transporter ◽  
Transporter Proteins ◽  
Wky Rats ◽  
Blood Brain ◽  
Hypertension Development ◽  
The Brain

Hypertension is involved in the exacerbation of stroke. It is unclear how blood-brain barrier (BBB) tight-junction (TJ) and ion transporter proteins critical for maintaining brain homeostasis contribute to cerebral infarction during hypertension development. In the present study, we investigated cerebral infarct volume following permanent 4-h middle cerebral artery occlusion (MCAO) and characterized the expression of BBB TJ and ion transporter proteins in brain microvessels of spontaneously hypertensive rats (SHR) compared with age-matched Wistar-Kyoto (WKY) rats at 5 wk (prehypertension), 10 wk (early-stage hypertension), and 15 wk (later-stage hypertension) of age. Hypertensive SHR show increased infarct volume following MCAO compared with WKY control rats. BBB TJ and ion transporter proteins, known to contribute to edema and fluid volume changes in the brain, show differential protein expression patterns during hypertension development. Western blot analysis of TJ protein zonula occludens-2 (ZO-2) showed decreased expression, while ion transporter, Na+/H+ exchanger 1 (NHE-1), was markedly increased in hypertensive SHR. Expression of TJ proteins ZO-1, occludin, actin, claudin-5, and Na+-K+-2Cl− cotransporter remain unaffected in SHR compared with control. Selective inhibition of NHE-1 using dimethylamiloride significantly attenuated ischemia-induced infarct volume in hypertensive SHR following MCAO, suggesting a novel role for NHE-1 in the brain in the regulation of ischemia-induced infarct volume in SHR.

scholarly journals The Neuroprotective Effects of Necrostatin-1 on Subarachnoid Hemorrhage in Rats Are Possibly Mediated by Preventing Blood–Brain Barrier Disruption and RIP3-Mediated Necroptosis

2019 ◽  
Vol 28 (11) ◽  
pp. 1358-1372 ◽  
Author(s):  
Jingsen Chen ◽  
Hanghuang Jin ◽  
Hangzhe Xu ◽  
Yucong Peng ◽  
Liyong Jie ◽  
...  
Keyword(s):  
Subarachnoid Hemorrhage ◽  
Blood Brain Barrier ◽  
New Drugs ◽  
Brain Barrier ◽  
Lesion Volume ◽  
Brain Swelling ◽  
Neuroprotective Effects ◽  
Pharmaceutical Therapy ◽  
Blood Brain

Despite the substantial efforts to elucidate the role of early brain injury in subarachnoid hemorrhage (SAH), an effective pharmaceutical therapy for patients with SAH continues to be unavailable. This study aims to reveal the role of necroptosis after SAH, and explore whether the disruption of the blood–brain barrier (BBB) and RIP3-mediated necroptosis following SAH in a rat SAH model are altered by necrostatin-1 via its selective inhibition of receptor-interacting protein kinase 1 (RIP1). Sixty-five rats were used in the experiments. The SAH model was established using endovascular perforation. Necrostatin-1 was intracerebroventricularly injected 1 h before SAH induction. The neuroprotective effects of necrostatin-1 were evaluated with multiple methods such as magnetic resonance imaging (MRI) scanning, immunohistochemistry, propidium iodide (PI) labeling, and western blotting. Pretreatment with necrostatin-1 attenuated brain swelling and reduced the lesion volume on T2 sequence and ventricular volume on MRI 72 h after SAH induction. Albumin leakage and the degradation of tight junction proteins were also ameliorated by necrostatin-1 administration. In addition, necrostatin-1 decreased the number of PI-positive cells in the basal cortex, reduced the levels of the RIP3 and MLKL proteins, and inhibited the production of the pro-inflammatory cytokines IL-1β, IL-6, and TNF-α. Based on the findings from the present study, the selective RIP1 inhibitor necrostatin-1 functioned as a neuroprotective agent after SAH by attenuating brain swelling and BBB disruption. Moreover, the necrostatin-1 pretreatment prevented SAH-induced necroptosis by suppressing the activity of the RIP3/MLKL signaling pathway. These results will provide insights into new drugs and pharmacological targets to manage SAH, which are worth further study.

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.

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