Protective Effect of Bendavia (SS-31) Against Oxygen/Glucose-Deprivation Stress-Induced Mitochondrial Damage in Human Brain Microvascular Endothelial Cells.

Mitochondria play a key role in cell survival by perfoming functions such as adenosine tri-phosphate (ATP) synthesis, regulation of apoptotic cell death, calcium storage. Hypoxic conditions induce mitochondrial dysfunction, which leads to endothelial injury in cerebral ischemia. Functional disorders include the following: collapse of mitochondrial membrane potential, reduction of ATP synthesis, and generation of reactive oxygen species (ROS).

Cilostazol ameliorates collagenase-induced cerebral hemorrhage by protecting the blood-brain barrier.

Intracranial hemorrhage remains a devastating disease. Among antiplatelet drugs, cilostazol, a phosphodiesterase 3 inhibitor, was recently reported to prevent secondary hemorrhagic stroke in patients in a clinical trial. The aim of this study was to evaluate whether pre-treatment with cilostazol could decrease the intracranial hemorrhage volume and examine the protective mechanisms of cilostazol.

The phosphodiesterase III inhibitor cilostazol ameliorates ethanolinduced endothelial dysfunction.

Intracranial hemorrhage (ICH) remains a devastating disease, and heavy alcohol consumption is an underlying risk factor. The aim of this study was to study the mechanism of ethanol-induced endothelial cell damage and to evaluate the protective effect of cilostazol against ethanol-induced damage. We first evaluated transendothelial electrical resistance (TEER) and cell viability of human brain microvascular endothelial cells at the ethanol concentration shown to cause mild-to-moderate intoxication in the clinic.

Diabetes mellitus aggravates hemorrhagic transformation after ischemic stroke via mitochondrial defects leading to endothelial apoptosis.

Diabetes is a crucial risk factor for stroke and is associated with increased frequency and poor prognosis. Although endothelial dysfunction is a known contributor of stroke, the underlying mechanisms have not been elucidated. The aim of this study was to elucidate the mechanism by which chronic hyperglycemia may contribute to the worsened prognosis following stroke, especially focusing on mitochondrial alterations.

Involvement of Mincle and Syk in the changes to innate immunity after ischemic stroke.

Accumulating evidence shows that post-ischemic inflammation originated by Toll-like receptors (TLR) plays critical roles in ischemic stroke. However, the functions of other innate immune receptors are poorly understood in cerebral ischemia. Macrophage-inducible C-type lectin, Mincle, is one of the innate immune receptor C-type lectin-like receptor (CLR) to response against dying cells.

The growth factor progranulin attenuates neuronal injury induced by cerebral ischemia-reperfusion through the suppression of neutrophil recruitment.

Background: To improve the clinical outcome of patients who suffered ischemic stroke, cerebral ischemia-reperfusion (I/R) injury is one of the major concerns that should be conquered. Inflammatory reactions are considered a major contributor to brain injury following cerebral ischemia, and I/R exacerbates these reactions. The aim of this study was to investigate the possible ameliorative effects of progranulin (PGRN) against I/R injury in mice.

Cilostazol ameliorates warfarin-induced hemorrhagic transformation after cerebral ischemia in mice.

Background And Purpose: Although long-term treatment with the oral anticoagulant warfarin is widely used to prevent cardioembolic ischemic stroke, it has been reported that warfarin can exacerbate hemorrhagic transformation (HT) after cerebral ischemia. We investigated whether cilostazol, a phosphodiesterase-III inhibitor, suppressed the warfarin-induced HT after cerebral ischemia in mice.

Methods: Male ddY mice were treated with oral warfarin before 3-hour middle cerebral artery occlusion followed by 21-hour reperfusion to induce HT.

Pharmacological inhibition of TLR4-NOX4 signal protects against neuronal death in transient focal ischemia.

Recent data have shown that TLR4 performs a key role in cerebral ischemia-reperfusion injury which serves as the origin of the immunological inflammatory reactions. However, the therapeutic effects of pharmacological inhibitions of TLR4 and its immediate down-stream pathway remain to be uncovered. In the present study, on mice, intracerebroventricular injection of resatorvid (TLR4 signal inhibitor; 0.

Tissue plasminogen activator prevents restoration of tight junction proteins through upregulation of angiopoietin-2.

We examined the temporal profiles of changes in the expressions of tight junction proteins (TJPs; namely, claudin-5, occludin, and ZO-1) after focal cerebral ischemia/reperfusion in mice. We also examined the effects of delayed treatment with tissue plasminogen activator (tPA) on the expressions of TJPs and angiopoietin (Ang) -1/2/Tie2. Mice subjected to a 6-h filamental middle cerebral artery (MCA) occlusion were treated with tPA (10 mg/kg, intravenously, just after the start of reperfusion) or vehicle.

The conditioned medium of murine and human adipose-derived stem cells exerts neuroprotective effects against experimental stroke model.

This study investigated the possible ameliorative effects of adipose-derived stem cells-conditioned medium (ASC-CM) on experimental ischemic stroke. In vivo ischemic stroke was induced in mice after 2h of middle cerebral artery occlusion (MCAO) followed by 22 h reperfusion. Culture of SH-SY5Y human neuroblastoma cells with 100 μM glutamate for 24h was used as an in vitro neuronal apoptosis model.

Blockade of phosphodiesterase-III protects against oxygen-glucose deprivation in endothelial cells by upregulation of VE-cadherin.

We recently reported that a phosphodiesterase-III inhibitor, cilostazol, prevented the hemorrhagic transformation induced by focal cerebral ischemia in mice treated with tissue plasminogen activator (tPA) and that it reversed tPA-induced cell damage by protecting the neurovascular unit, particularly endothelial cells. However, the mechanisms of cilostazol action are still not clearly defined. The adheren junction (AJ) protein, VE-cadherin, is a known mediator of endothelial barrier sealing and maintenance.

Phosphodiesterase-III inhibitor prevents hemorrhagic transformation induced by focal cerebral ischemia in mice treated with tPA.

The purpose of the present study was to investigate whether cilostazol, a phosphodiesterase-III inhibitor and antiplatelet drug, would prevent tPA-associated hemorrhagic transformation. Mice subjected to 6-h middle cerebral artery occlusion were treated with delayed tPA alone at 6 h, with combined tPA plus cilostazol at 6 h, or with vehicle at 6 h. We used multiple imaging (electron microscopy, spectroscopy), histological and neurobehavioral measures to assess the effects of the treatment at 18 h and 7 days after the reperfusion.