Attenuated Blood-Brain Barrier Dysfunction by XQ-1H Following Ischemic Stroke in Hyperlipidemic Rats

The blood-brain barrier (BBB) maintains a stable brain microenvironment. Breakdown of BBB integrity during cerebral ischemia initiates a devastating cascade of events that eventually leads to neuronal loss. MicroRNAs are small noncoding RNAs that suppress protein expression, and we previously showed that the miR-15a/16-1 cluster is involved in the pathogenesis of ischemic brain injury. Here, we demonstrated that when subjected to experimentally induced stroke, mice with an endothelial cell (EC)–selective deletion of miR-15a/16-1 had smaller brain infarcts, reduced BBB leakage, and decreased infiltration of peripheral immune cells. These mice also showed reduced infiltration of proinflammatory M1-type microglia/macrophage in the peri-infarct area without changes in the number of resolving M2-type cells. Stroke decreases claudin-5 abundance, and we found that EC-selective miR-15a/16-1 deletion enhanced claudin-5 mRNA and protein abundance in ischemic mouse brains. In cultured mouse brain microvascular ECs (mBMECs), the miR-15a/16-1 cluster directly bound to the 3′ untranslated region (3′UTR) of Claudin-5, and lentivirus-mediated ablation of miR-15a/16-1 diminished oxygen-glucose deprivation (OGD)–induced down-regulation of claudin-5 mRNA and protein abundance and endothelial barrier dysfunction. These findings suggest that genetic deletion of endothelial miR-15a/16-1 suppresses BBB pathologies after ischemic stroke. Elucidating the molecular mechanisms of miR-15a/16-1–mediated BBB dysfunction may enable the discovery of new therapies for ischemic stroke.

Download Full-text

Blood-brain barrier dysfunction and recovery after ischemic stroke

Progress in Neurobiology ◽

10.1016/j.pneurobio.2017.10.001 ◽

2018 ◽

Vol 163-164 ◽

pp. 144-171 ◽

Cited By ~ 137

Author(s):

Xiaoyan Jiang ◽

Anuska V. Andjelkovic ◽

Ling Zhu ◽

Tuo Yang ◽

Michael V.L. Bennett ◽

...

Keyword(s):

Ischemic Stroke ◽

Blood Brain Barrier ◽

Brain Barrier ◽

Barrier Dysfunction ◽

Blood Brain

Download Full-text

Vitamin D deficiency increases blood-brain barrier dysfunction after ischemic stroke in male rats

Experimental Neurology ◽

10.1016/j.expneurol.2018.11.005 ◽

2019 ◽

Vol 312 ◽

pp. 63-71 ◽

Cited By ~ 14

Author(s):

Iqbal Sayeed ◽

Nefize Turan ◽

Donald G. Stein ◽

Bushra Wali

Keyword(s):

Vitamin D ◽

Ischemic Stroke ◽

Vitamin D Deficiency ◽

Blood Brain Barrier ◽

Brain Barrier ◽

Male Rats ◽

Barrier Dysfunction ◽

Blood Brain

Download Full-text

Bone marrow-derived cells are the major source of MMP-9 contributing to blood–brain barrier dysfunction and infarct formation after ischemic stroke in mice

Brain Research ◽

10.1016/j.brainres.2009.07.070 ◽

2009 ◽

Vol 1294 ◽

pp. 183-192 ◽

Cited By ~ 37

Author(s):

Guangming Wang ◽

Qingmin Guo ◽

Mohammed Hossain ◽

Vince Fazio ◽

Emil Zeynalov ◽

...

Keyword(s):

Bone Marrow ◽

Ischemic Stroke ◽

Blood Brain Barrier ◽

Brain Barrier ◽

Barrier Dysfunction ◽

Blood Brain ◽

Bone Marrow Derived Cells

Download Full-text

Blood-brain barrier dysfunction in ischemic stroke and diabetes: the underlying link, mechanisms and future possible therapeutic targets

Anatomy & Cell Biology ◽

10.5115/acb.20.290 ◽

2021 ◽

Author(s):

Piyawadee Wicha ◽

Srijit Das ◽

Pasuk Mahakkanukrauh

Keyword(s):

Ischemic Stroke ◽

Blood Brain Barrier ◽

Therapeutic Targets ◽

Brain Barrier ◽

Barrier Dysfunction ◽

Blood Brain

Download Full-text

Blood-brain barrier dysfunction in hemorrhagic transformation: a therapeutic opportunity for nanoparticles and melatonin.

Journal of Neurophysiology ◽

10.1152/jn.00638.2020 ◽

2021 ◽

Author(s):

Esteban Figueroa ◽

Alejandro González-Candia ◽

Aitor Caballero-Román ◽

Cristina Fornaguera ◽

Elvira Escribano-Ferrer ◽

...

Keyword(s):

Oxidative Stress ◽

Ischemic Stroke ◽

Blood Brain Barrier ◽

Medical Condition ◽

Brain Area ◽

Hemorrhagic Transformation ◽

Brain Barrier ◽

World Population ◽

Barrier Dysfunction ◽

Blood Brain

Stroke is the second leading cause of death worldwide, estimated that 1/6 of the world population will suffer it once in their life. The most common type of this medical condition is the ischemic stroke (IS), produced by a thrombotic or embolic occlusion of a major cerebral artery or its branches, leading to the formation of a complex infarct region caused by oxidative stress, excitotoxicity and endothelial dysfunction. Nowadays, the immediate treatment for IS involves thrombolytic agents or mechanical thrombectomy, depending on the integrity of the blood-brain barrier (BBB). A common stroke complication is the hemorrhagic transformation (HT), which consists of bleeding into the ischemic brain area. Currently, better treatments for IS are urgently needed. As such, the neurohormone melatonin has been proposed as a good candidate due to its antioxidant, anti-inflammatory and neuroprotective effects, particularly against lipid peroxidation and oxidative stress during brain ischemia. Here, we proposed to develop intravenous or intranasal melatonin nanoformulation to specifically target the brain in stroke patients. Nowadays, the challenge is to find a formulation able to cross the barriers and reach the target organ in an effective dose to generate the pharmacological effect. In this review, we discuss the current literature about stroke pathophysiology, melatonin properties and its potential use in nanoformulations as a novel therapeutic approach for ischemic stroke.

Download Full-text