Abstract W P90: Insulin-like Growth Factor-1-mediated Reduction of Stroke-induced Brain Infarction is Preceded by Improvement of Blood Brain Barrier Integrity and Inflammatory Cytokines

Stroke ◽  
2014 ◽  
Vol 45 (suppl_1) ◽  
Author(s):  
Shameena Bake ◽  
Farida Sohrabji
Keyword(s):  
Growth Factor ◽  
Blood Brain Barrier ◽  
Inflammatory Cytokines ◽  
Inflammatory Markers ◽  
Infarct Volume ◽  
Brain Barrier ◽  
Barrier Permeability ◽  
Post Stroke ◽  
Blood Brain ◽  
Brain Barrier Permeability

Background and Purpose: Although insulin-like growth factor (IGF)-1 treatment has been shown to reduce stroke-induced infarct volume, the mechanisms underlying its neuroprotective actions are not fully understood. The present study tested the hypothesis that IGF-1 may regulate the neuroinflammatory cascade initiated by ischemic stroke, specifically, by promoting the integrity of the blood brain barrier. Methods: Middle-aged (10-12 month old) female rats were implanted with a cannula directed toward the lateral ventricle. One week later, animals were anesthetized using isoflurane and the middle-cerebral artery was occluded using an intraluminal suture maintained in place for 90 mins. IGF-1 or vehicle was delivered icv, via a mini-pump, following reperfusion. All animals were terminated at 4h or 24h post MCAo. Blood brain barrier permeability was determined using Evan’s blue extravasation and infarct volumes were determined from TTC-stained brain sections. Inflammatory cytokines were analyzed from brain lysates by ELISA. Results: IGF-1 treatment to middle-aged females resulted in a 39% reduction in infarct volume when measured 24h post MCAo, confirming the neuroprotective action of this peptide hormone. In order to assess the effects of IGF-1 on early stroke induced effects, we next determined blood brain permeability 4h post stroke as well as the expression of cytokines in the ischemic hemisphere. IGF-1 treatment resulted in a significant reduction of blood brain barrier permeability at 4h post-stroke compared to vehicle treated animals. Moreover, multiplex cytokine analysis showed that IGF-1 significantly reduced inflammatory markers such as IL-6, IFN-gamma, TNF-alpha, eotaxin, GM-CSF. Brain infarct volume at 4h was similar in both IGF-1 and vehicle groups, indicating that the effects of IGF-1 on inflammatory markers precede its effects on infarct volume. IGF-1 also suppressed IL-6, MIP-2, GRO-KC, MCP-1, EGF and MIP-1-alpha expression at 24h post stroke, indicating a persistent anti-inflammatory effect for this growth factor. Conclusions: The above findings support the hypothesis that IGF-1 has unique anti-inflammatory action in the aging female brain, and suggest that brain endothelial cells may be a primary target of IGF-1.

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.

Abstract T P84: Beneficial Stroke Outcomes Following Epicatechin Consumption in Young and Older Mice

Stroke ◽  
2014 ◽  
Vol 45 (suppl_1) ◽  
Author(s):  
Christopher Leonardo ◽  
Sylvain Dore
Keyword(s):  
Blood Brain Barrier ◽  
Knockout Mice ◽  
Infarct Volume ◽  
Brain Barrier ◽  
Barrier Permeability ◽  
Blood Brain Barrier Permeability ◽  
Functional Deficits ◽  
Post Stroke ◽  
Brain Barrier Permeability ◽  
Nrf2 Knockout

Background: The consumption of flavanol containing foods, including (-)-epicatechin, has been linked to lower incidence of cardiovascular disease and stroke. We have previously demonstrated that epicatechin prophylaxis reduces stroke-induced anatomical and functional deficits in young, healthy mice; yet clinical stroke is primarily a disease of the elderly. Since neuroinflammation and vascular dysfunction are associated with aging, we aimed to test whether epicatechin is also protective in aging mice subjected to experimental stroke, and if so, whether this results from reduced glial cell activation and blood brain barrier permeability. Methods: Twelve-month-old wildtype and C57BL/6 Nrf2 knockout mice were administered 15mg/kg epicatechin, the minimum effective dose in young, healthy mice, prior to permanent distal middle cerebral artery occlusion. Mice were evaluated for functional recovery at one day post-stroke using the Adhesive Removal Test. Infarct volume, gliosis, and blood brain barrier permeability estimates were conducted seven days following stroke. Additionally, we compared anastomosis in wildtype and Nrf2 knockout mice and assessed hemorrhage frequency in studies using four- and 12-month-old mice. Results: Consistent with previous results in young mice, 12-month-old wildtype mice pretreated with epicatechin showed significant reductions in infarct volume and latency to remove adhesive tape relative to vehicle-treated controls, while Nrf2 knockout mice were not protected by epicatechin. Interestingly, epicatechin did not reduce Iba1 immunoreactivity or mouse IgG extravasation at seven days post-stroke. Similarly, there were no significant differences in anastomosis or spontaneous hemorrhage between wildtype and Nrf2 knockouts, indicating that cerebral vascular physiology is similar and gross vascular integrity was unaffected by treatment. Conclusion: Thus, although epicatechin prophylaxis reduces infarct volume and functional deficits, it does not exert sustained effects on gliosis or cerebrovascular integrity in aging mice.

Ligand and Structure-based Modeling of Passive Diffusion through the Blood-Brain Barrier

2018 ◽  
Vol 25 (9) ◽  
pp. 1073-1089 ◽  
Author(s):  
Santiago Vilar ◽  
Eduardo Sobarzo-Sanchez ◽  
Lourdes Santana ◽  
Eugenio Uriarte
Keyword(s):  
Blood Brain Barrier ◽  
In Silico ◽  
Passive Diffusion ◽  
Brain Barrier ◽  
Barrier Permeability ◽  
Blood Brain Barrier Permeability ◽  
Blood Brain ◽  
Brain Barrier Permeability ◽  
Different Types ◽  
The Brain

Background: Blood-brain barrier transport is an important process to be considered in drug candidates. The blood-brain barrier protects the brain from toxicological agents and, therefore, also establishes a restrictive mechanism for the delivery of drugs into the brain. Although there are different and complex mechanisms implicated in drug transport, in this review we focused on the prediction of passive diffusion through the blood-brain barrier. Methods: We elaborated on ligand-based and structure-based models that have been described to predict the blood-brain barrier permeability. Results: Multiple 2D and 3D QSPR/QSAR models and integrative approaches have been published to establish quantitative and qualitative relationships with the blood-brain barrier permeability. We explained different types of descriptors that correlate with passive diffusion along with data analysis methods. Moreover, we discussed the applicability of other types of molecular structure-based simulations, such as molecular dynamics, and their implications in the prediction of passive diffusion. Challenges and limitations of experimental measurements of permeability and in silico predictive methods were also described. Conclusion: Improvements in the prediction of blood-brain barrier permeability from different types of in silico models are crucial to optimize the process of Central Nervous System drug discovery and development.

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