Treatment of vascular dementia in female rats with AV-001, an Angiopoietin-1 mimetic peptide, improves cognitive function.

Background: Vascular dementia (VaD) is a complex neurodegenerative disorder. We previously found that treatment of VaD in middle-aged male rats subjected to multiple microinfarction (MMI) with AV-001, a Tie2 receptor agonist, significantly improves cognitive function. Age and sex affect the development and response of VaD to therapeutic intervention.

Early therapeutic effects of an Angiopoietin-1 mimetic peptide in middle-aged rats with vascular dementia.

Background: Vascular Dementia (VaD) refers to dementia caused by cerebrovascular disease and/or reduced blood flow to the brain and is the second most common form of dementia after Alzheimer's disease. We previously found that in middle-aged rats subjected to a multiple microinfarction (MMI) model of VaD, treatment with AV-001, a Tie2 receptor agonist, significantly improves short-term memory, long-term memory, as well as improves preference for social novelty compared to control MMI rats. In this study, we tested the early therapeutic effects of AV-001 on inflammation and glymphatic function in rats subjected to VaD.

Therapeutic effects of CD133 + Exosomes on liver function after stroke in type 2 diabetic mice.

Background And Purpose: Non-alcoholic fatty liver disease (NAFLD) is known to adversely affect stroke recovery. However, few studies investigate how stroke elicits liver dysfunction, particularly, how stroke in type 2 diabetes mellitus (T2DM) exacerbates progression of NAFLD. In this study, we test whether exosomes harvested from human umbilical cord blood (HUCBC) derived CD133 + cells (CD133 + Exo) improves neuro-cognitive outcome as well as reduces liver dysfunction in T2DM female mice.

Treatment With an Angiopoietin-1 Mimetic Peptide Improves Cognitive Outcome in Rats With Vascular Dementia.

Background And Purpose: Vascular dementia (VaD) is a complex neurodegenerative disease affecting cognition and memory. There is a lack of approved pharmacological treatments specifically for VaD. In this study, we investigate the therapeutic effects of AV-001, a Tie2 receptor agonist, in middle-aged rats subjected to a multiple microinfarct (MMI) model of VaD.

Post-Stroke Administration of L-4F Promotes Neurovascular and White Matter Remodeling in Type-2 Diabetic Stroke Mice.

Patients with type 2 diabetes mellitus (T2DM) exhibit a distinct and high risk of ischemic stroke with worse post-stroke neurovascular and white matter (WM) prognosis than the non-diabetic population. In the central nervous system, the ATP-binding cassette transporter member A 1 (ABCA1), a reverse cholesterol transporter that efflux cellular cholesterol, plays an important role in high-density lipoprotein (HDL) biogenesis and in maintaining neurovascular stability and WM integrity. Our previous study shows that L-4F, an economical apolipoprotein A member I (ApoA-I) mimetic peptide, has neuroprotective effects alleviating neurovascular and WM impairments in the brain of db/db-T2DM stroke mice.

Cardiac Dysfunction in a Mouse Vascular Dementia Model of Bilateral Common Carotid Artery Stenosis.

Cardiac function is associated with cognitive function. Previously, we found that stroke and traumatic brain injury evoke cardiac dysfunction in mice. In this study, we investigate whether bilateral common carotid artery stenosis (BCAS), a model that induces vascular dementia (VaD) in mice, induces cardiac dysfunction.

Deficiency of Endothelial Nitric Oxide Synthase (eNOS) Exacerbates Brain Damage and Cognitive Deficit in A Mouse Model of Vascular Dementia.

Vascular Dementia (VaD) accounts for nearly 20% of all cases of dementia. eNOS plays an important role in neurovascular remodeling, anti-inflammation, and cognitive functional recovery after stroke. In this study, we investigated whether eNOS regulates brain damage, cognitive function in mouse model of bilateral common carotid artery stenosis (BCAS) induced VaD.

Treatment with an Angiopoietin-1 mimetic peptide promotes neurological recovery after stroke in diabetic rats.

Aim: Vasculotide (VT), an angiopoietin-1 mimetic peptide, exerts neuroprotective effects in type one diabetic (T1DM) rats subjected to ischemic stroke. In this study, we investigated whether delayed VT treatment improves long-term neurological outcome after stroke in T1DM rats.

Methods: Male Wistar rats were induced with T1DM, subjected to middle cerebral artery occlusion (MCAo) model of stroke, and treated with PBS (control), 2 µg/kg VT, 3 µg/kg VT, or 5.

HUCBC Treatment Improves Cognitive Outcome in Rats With Vascular Dementia.

: Vascular dementia (VaD) is the second common cause of dementia after Alzheimer's disease in older people. Yet, there are no FDA approved drugs specifically for VaD. In this study, we have investigated the therapeutic effects of human umbilical cord blood cells (HUCBC) treatment on the cognitive outcome, white matter (WM) integrity, and glymphatic system function in rats subject to a multiple microinfarction (MMI) model of VaD.

Exosomes derived from bone marrow mesenchymal stem cells harvested from type two diabetes rats promotes neurorestorative effects after stroke in type two diabetes rats.

Background And Purpose: Diabetes elevates the risk of stroke, promotes inflammation, and exacerbates vascular and white matter damage post stroke, thereby hindering long term functional recovery. Here, we investigated the neurorestorative effects and the underlying therapeutic mechanisms of treatment of stroke in type 2 diabetic rats (T2DM) using exosomes harvested from bone marrow stromal cells obtained from T2DM rats (T2DM-MSC-Exo).

Methods: T2DM was induced in adult male Wistar rats using a combination of high fat diet and Streptozotocin.

SUMO1 Deficiency Exacerbates Neurological and Cardiac Dysfunction after Intracerebral Hemorrhage in Aged Mice.

Small ubiquitin-like modifier 1 (SUMO1) reduces cardiac hypertrophy and induces neuroprotective effects. Previous studies have found that intracerebral hemorrhage (ICH) provokes cardiac deficit in the absence of primary cardiac diseases in mice. In this study, we tested the hypothesis that SUMO1 deficiency leads to worse brain and heart dysfunction after ICH and SUMO1 plays a key role in regulating brain-heart interaction after ICH in aged mice.

CD133+Exosome Treatment Improves Cardiac Function after Stroke in Type 2 Diabetic Mice.

Cardiac complications post-stroke are common, and diabetes exacerbates post-stroke cardiac injury. In this study, we tested whether treatment with exosomes harvested from human umbilical cord blood derived CD133+ cells (CD133+Exo) improves cardiac function in type 2 diabetes mellitus (T2DM) stroke mice. Adult (3-4 m), male, BKS.

Brain-Derived Microparticles (BDMPs) Contribute to Neuroinflammation and Lactadherin Reduces BDMP Induced Neuroinflammation and Improves Outcome After Stroke.

Microparticles (MPs, ~size between 0.1 and 1 mm) are lipid encased containers derived from intact cells which contain antigen from the parent cells. MPs are involved in intercellular communication and regulate inflammation.

Spleen associated immune-response mediates brain-heart interaction after intracerebral hemorrhage.

Background And Purpose: Intracerebral hemorrhage (ICH) patients frequently encounter cardiovascular complications which may contribute to increased mortality and poor long term outcome. ICH induces systemic oxidative stress and activates peripheral immune responses which are involved in the pathological cascade leading to cardiac dysfunction and heart failure after ICH. We have previously reported that ICH induces progressive cardiac dysfunction in mice without primary cardiac diseases.

Brain-kidney interaction: Renal dysfunction following ischemic stroke.

Stroke is a leading cause of mortality and morbidity, with long-term debilitating effects. Accumulating evidence from experimental studies as well as observational studies in patients suggests a cross talk between the brain and kidney after stroke. Stroke may lead to kidney dysfunction which can adversely impact patient outcome.

Role of Regulatory T cells in Atorvastatin Induced Absorption of Chronic Subdural Hematoma in Rats.

Chronic subdural hematoma (CSDH) is a neurological disorder with a substantial recurrence rate. Atorvastatin is an effective drug for treating hyperlipidemia and known to improve neurological outcome after intracerebral hemorrhage. Previous studies have reported that atorvastatin treatment promotes hematoma absorption in CSDH, while the underlying mechanisms remain unclear.

Deficiency of tPA Exacerbates White Matter Damage, Neuroinflammation, Glymphatic Dysfunction and Cognitive Dysfunction in Aging Mice.

Tissue plasminogen activator (tPA) is a serine protease primarily involved in mediating thrombus breakdown and regulating catabolism of amyloid-beta (Aβ). The aim of this study is to investigate age-dependent decline of endogenous tPA and the effects of tPA decline on glymphatic function and cognitive outcome in mice. Male, young (3m), adult (6m) and middle-aged (12m) C57/BL6 (wild type) and tPA knockout (tPA) mice were subject to a battery of cognitive tests and white matter (WM) integrity, neuroinflammation, and glymphatic function were evaluated.

MiR-126 Mediates Brain Endothelial Cell Exosome Treatment-Induced Neurorestorative Effects After Stroke in Type 2 Diabetes Mellitus Mice.

Background and Purpose- Stroke patients with type 2 diabetes mellitus (T2DM) exhibit increased vascular and white matter damage and have worse prognosis compared with nondiabetic stroke patients. We investigated the neurorestorative effects of exosomes derived from mouse brain endothelial cells (EC-Exo) as treatment for stroke in T2DM mice and investigated the role of miR-126 in mediating EC-Exo-derived therapeutic benefits in T2DM-stroke mice. Methods- Adult, male BKS.

RP001 hydrochloride improves neurological outcome after subarachnoid hemorrhage.

Subarachnoid hemorrhage (SAH) results in neurological damage, acute cardiac damage and has a high mortality rate. Immunoresponse in the acute phase after SAH plays a key role in mediating vasospasm, edema, inflammation and neuronal damage. The S1P/S1PR pathway impacts multiple cellular functions, exerts anti-inflammatory and anti-apoptotic effects, promotes remyelination, and improves outcome in several central nervous system (CNS) diseases.

Sildenafil treatment of vascular dementia in aged rats.

Background: and purpose: In this study, we employed a multiple microinfarction (MMI) based vascular dementia (VaD) model in aged rats and tested the therapeutic effects of Sildenafil, a phosphodiesterase type 5 inhibitor, on cognitive decline, white matter damage, autophagy and inflammatory response associated with VaD.

Methods: Male, aged (16-18 months) Wistar rats were subjected to MMI (800 ± 100, 70-100 μm cholesterol crystals injected into the internal carotid artery) and treated with or without Sildenafil (2 mg/kg, i.p) starting at 24 h after MMI daily for 28 days.

Intracerebral Hemorrhage Induces Cardiac Dysfunction in Mice Without Primary Cardiac Disease.

Intracerebral hemorrhage (ICH) is a life threatening stroke subtype and a worldwide health problem. In this study, we investigate brain-heart interaction after ICH in mice and test whether ICH induces cardiac dysfunction in the absence of primary cardiac disease. We also investigate underlying mechanisms such as oxidative stress and inflammatory responses in mediating cardiac dysfunction post-ICH in mice.

Inflammatory responses mediate brain-heart interaction after ischemic stroke in adult mice.

Stroke induces cardiac dysfunction which increases post stroke mortality and morbidity particularly in aging population. Here, we investigated the effects of inflammatory responses as underlying mediators of cardiac dysfunction after stroke in adult mice. Adult (eight-to-nine months) male C57BL/6 mice were subjected to photothrombotic stroke.

Role of microRNA-126 in vascular cognitive impairment in mice.

Vascular dementia (VaD) affects cognition and memory. MicroRNA-126 (miR-126) is an angiogenic microRNA that regulates vascular function. In this study, we employ a multiple microinfarction (MMI) model to induce VaD in mice, and investigate VaD-induced cognitive dysfunction, white matter (WM) damage, glymphatic dysfunction and the role of miR-126 in mediating these effects.

Angiopoietin-1 Mimetic Peptide Promotes Neuroprotection after Stroke in Type 1 Diabetic Rats.

Angiopoietin-1 (Ang1) mediates vascular maturation and immune response. Diabetes decreases Ang1 expression and disrupts Ang1/Tie2 signaling activity. Vasculotide is an Ang1 mimetic peptide, and has anti-inflammatory effects.