scholarly journals DL-3n-Butylphthalide Improves Blood–Brain Barrier Integrity in Rat After Middle Cerebral Artery Occlusion

2021 ◽  
Vol 14 ◽  
Author(s):  
Muyassar Mamtilahun ◽  
Zhenyu Wei ◽  
Chuan Qin ◽  
Yongting Wang ◽  
Yaohui Tang ◽  
...  
Keyword(s):  
Enzyme Activity ◽  
Ischemic Stroke ◽  
Blood Brain Barrier ◽  
Infarct Volume ◽  
Artery Occlusion ◽  
Brain Barrier ◽  
Barrier Integrity ◽  
Aqp4 Expression ◽  
Blood Brain ◽  
Blood Brain Barrier Integrity

Objective: DL-3n-butylphthalide (NBP) has beneficial effects in different stages of ischemic stroke. Our previous studies have demonstrated that NBP promoted angiogenesis in the perifocal region of the ischemic brain. However, the molecular mechanism of NBP for blood–brain barrier protection in acute ischemic stroke was unclear. Here, we explored the neuroprotective effects of NBP on blood–brain barrier integrity in the acute phase of ischemic stroke in a rat model.Methods: Adult male Sprague–Dawley rats (n = 82) underwent 2 h of transient middle cerebral artery occlusion and received 90 mg/kg of NBP for 3 days. Brain edema, infarct volume, surface blood flow, and neurological severity score were evaluated. Blood–brain barrier integrity was evaluated by Evans blue leakage and changes in tight junction proteins. We further examined AQP4 and eNOS expression, MMP-9 enzyme activity, and possible signaling pathways for the role of NBP after ischemic stroke.Results: NBP treatment significantly increased eNOS expression and surface blood flow in the brain, reduced brain edema and infarct volume, and improved neurological severity score compared to the control group (p < 0.05). Furthermore, NBP attenuated Evans blue and IgG leakage and increased tight junction protein expression compared to the control after 1 and 3 days of ischemic stroke (p < 0.05). Finally, NBP decreased AQP4 expression, MMP-9 enzyme activity, and increased MAPK expression during acute ischemic stroke.Conclusion: NBP protected blood–brain barrier integrity and attenuated brain injury in the acute phase of ischemic stroke by decreasing AQP4 expression and MMP-9 enzyme activity. The MAPK signaling pathway may be associated in this process.

scholarly journals Plasma from healthy donors protects blood–brain barrier integrity via FGF21 and improves the recovery in a mouse model of cerebral ischaemia

2021 ◽  
pp. svn-2020-000774
Author(s):  
Muyassar Mamtilahun ◽  
Lu Jiang ◽  
Yaying Song ◽  
Xiaojing Shi ◽  
Chang Liu ◽  
...  
Keyword(s):  
Ischaemic Stroke ◽  
Plasma Treatment ◽  
Blood Brain Barrier ◽  
Infarct Volume ◽  
Brain Barrier ◽  
Plasma Therapy ◽  
Barrier Integrity ◽  
Blood Brain ◽  
Plasma Injection ◽  
Blood Brain Barrier Integrity

BackgroundHealthy plasma therapy reverses cognitive deficits and promotes neuroplasticity in ageing brain disease. However, whether healthy plasma therapy improve blood–brain barrier integrity after stroke remains unknown.MethodsHere, we intravenously injected healthy female mouse plasma into adult female ischaemic stroke C57BL/6 mouse induced by 90 min transient middle cerebral artery occlusion for eight consecutive days. Infarct volume, brain atrophy and neurobehavioural tests were examined to assess the outcomes of plasma treatment. Cell apoptosis, blood–brain barrier integrity and fibroblast growth factor 21 knockout mice were used to explore the underlying mechanism.ResultsPlasma injection improved neurobehavioural recovery and decreased infarct volume, brain oedema and atrophy after stroke. Immunostaining showed that the number of transferase dUTP nick end labelling+/NeuN+ cells decreased in the plasma-injected group. Meanwhile, plasma injection reduced ZO-1, occluding and claudin-5 tight junction gap formation and IgG extravasation at 3 days after ischaemic stroke. Western blot results showed that the FGF21 expression increased in the plasma-injected mice. However, using FGF21 knockout mouse plasma injecting to the ischaemic wild-type mice diminished the neuroprotective effects.ConclusionsOur study demonstrated that healthy adult plasma treatment protected the structural and functional integrity of blood–brain barrier, reduced neuronal apoptosis and improved functional recovery via FGF21, opening a new avenue for ischaemic stroke therapy.

scholarly journals Changes in Background Blood–Brain Barrier Integrity Between Lacunar and Cortical Ischemic Stroke Subtypes

Stroke ◽  
2008 ◽  
Vol 39 (4) ◽  
pp. 1327-1332 ◽  
Author(s):  
Joanna M. Wardlaw ◽  
Andrew Farrall ◽  
Paul A. Armitage ◽  
Trevor Carpenter ◽  
Francesca Chappell ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Blood Brain Barrier ◽  
Brain Barrier ◽  
Barrier Integrity ◽  
Stroke Subtypes ◽  
Blood Brain ◽  
Blood Brain Barrier Integrity

scholarly journals Mice deficient in endothelial α5 integrin are profoundly resistant to experimental ischemic stroke

2016 ◽  
Vol 37 (1) ◽  
pp. 85-96 ◽  
Author(s):  
Jill Roberts ◽  
Leon de Hoog ◽  
Gregory J Bix
Keyword(s):  
Endothelial Cell ◽  
Blood Brain Barrier ◽  
Infarct Volume ◽  
Ischemic Injury ◽  
Glucose Deprivation ◽  
Brain Barrier ◽  
Barrier Integrity ◽  
Blood Brain ◽  
Blood Brain Barrier Integrity

Stroke is a disease in dire need of better therapies. We have previously shown that a fragment of the extracellular matrix proteoglycan, perlecan, has beneficial effects following cerebral ischemia via the α5β1 integrin receptor. We now report that endothelial cell selective α5 integrin deficient mice (α5 KO) are profoundly resistant to ischemic infarct after transient middle cerebral artery occlusion. Specifically, α5 KOs had little to no infarct 2–3 days post-stroke, whereas controls had an increase in mean infarct volume over the same time period as expected. Functional outcome is also improved in the α5 KOs compared with controls. Importantly, no differences in cerebrovascular anatomy or collateral blood flow were noted that could account for this difference in ischemic injury. Rather, we demonstrate that α5 KOs have increased blood-brain barrier integrity (increased expression of claudin-5, and absent brain parenchymal IgG extravasation) after stroke compared with controls, which could explain their resistance to ischemic injury. Additionally, inhibition of α5 integrin in vitro leads to decreased permeability of brain endothelial cells following oxygen-glucose deprivation. Together, these findings indicate endothelial cell α5 integrin plays an important role in stroke outcome and blood-brain barrier integrity, suggesting that α5 integrin could be a novel therapeutic target for stroke.

scholarly journals Activation of PDGF-CC by tissue plasminogen activator impairs blood-brain barrier integrity during ischemic stroke

2008 ◽  
Vol 14 (7) ◽  
pp. 731-737 ◽  
Author(s):  
Enming J Su ◽  
Linda Fredriksson ◽  
Melissa Geyer ◽  
Erika Folestad ◽  
Jacqueline Cale ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Plasminogen Activator ◽  
Tissue Plasminogen Activator ◽  
Blood Brain Barrier ◽  
Brain Barrier ◽  
Barrier Integrity ◽  
Blood Brain ◽  
Tissue Plasminogen ◽  
Blood Brain Barrier Integrity
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