MMP-3 Knockout Induces Global Transcriptional Changes and Reduces Cerebral Infarction in Both Male and Female Models of Ischemic Stroke.

Ischemic stroke followed by reperfusion (IR) leads to extensive cerebrovascular injury characterized by neuroinflammation and brain cell death. Inhibition of matrix metalloproteinase-3 (MMP-3) emerges as a promising therapeutic approach to mitigate IR-induced stroke injury. We employed middle cerebral artery occlusion with subsequent reperfusion (MCAO/R) to model ischemic stroke in adult mice.

Loss of microRNA-15a/16-1 function promotes neuropathological and functional recovery in experimental traumatic brain injury.

The diffuse axonal damage in white matter and neuronal loss, along with excessive neuroinflammation, hinder long-term functional recovery after traumatic brain injury (TBI). MicroRNAs (miRs) are small noncoding RNAs that negatively regulate protein-coding target genes in a posttranscriptional manner. Recent studies have shown that loss of function of the miR-15a/16-1 cluster reduced neurovascular damage and improved functional recovery in ischemic stroke and vascular dementia.

Role of regulatory non-coding RNAs in traumatic brain injury.

Traumatic brain injury (TBI) is a potentially fatal health event that cannot be predicted in advance. After TBI occurs, it can have enduring consequences within both familial and social spheres. Yet, despite extensive efforts to improve medical interventions and tailor healthcare services, TBI still remains a major contributor to global disability and mortality rates.

Genetic ablation of diabetes-associated gene reduces obesity and insulin resistance in mice.

Multiple genome-wide association studies (GWAS) have identified specific genetic variants in the coiled-coil domain containing 92 () locus that is associated with obesity and type 2 diabetes in humans. However, the biological function of CCDC92 in obesity and insulin resistance remains to be explored. Utilizing wild-type (WT) and whole-body knockout (KO) mice, we found that KO reduced obesity and increased insulin sensitivity under high-fat diet (HFD) conditions.

Genetic deletion of Krüppel-like factor 11 aggravates traumatic brain injury.

Background: The long-term functional recovery of traumatic brain injury (TBI) is hampered by pathological events, such as parenchymal neuroinflammation, neuronal death, and white matter injury. Krüppel-like transcription factor 11 (KLF 11) belongs to the zinc finger family of transcription factors and actively participates in various pathophysiological processes in neurological disorders. Up to now, the role and molecular mechanisms of KLF11 in regulating the pathogenesis of brain trauma is poorly understood.

Genetic Deficiency of MicroRNA-15a/16-1 Confers Resistance to Neuropathological Damage and Cognitive Dysfunction in Experimental Vascular Cognitive Impairment and Dementia.

Chronic cerebral hypoperfusion-derived brain damage contributes to the progression of vascular cognitive impairment and dementia (VCID). Cumulative evidence has shown that microRNAs (miRs) are emerging as novel therapeutic targets for CNS disorders. In this study, it is sought to determine the regulatory role of miR-15a/16-1 in VCID.

Non-coding RNAs in the regulation of blood-brain barrier functions in central nervous system disorders.

The blood-brain barrier (BBB) is an essential component of the neurovascular unit that controls the exchanges of various biological substances between the blood and the brain. BBB damage is a common feature of different central nervous systems (CNS) disorders and plays a vital role in the pathogenesis of the diseases. Non-coding RNAs (ncRNAs), such as microRNAs (miRNAs), long non-coding RNA (lncRNAs), and circular RNAs (circRNAs), are important regulatory RNA molecules that are involved in almost all cellular processes in normal development and various diseases, including CNS diseases.

Reduced dopaminergic neuron degeneration and global transcriptional changes in Parkinson's disease mouse brains engrafted with human neural stems during the early disease stage.

Introduction: Current stem cell therapies for Parkinson's disease (PD) focus on a neurorestorative approach that aims to repair the CNS during the symptomatic phase. However, the pleiotropic and supportive effects of human neural stem cells (hNSCs) may make them effective for PD treatment during the disease's earlier stages. In the current study, we investigated the therapeutic effects of transplanting hNSCs during the early stages of PD development when most dopaminergic neurons are still present and before symptoms appear.

Vascular Smooth Muscle Cells in Aortic Aneurysm: From Genetics to Mechanisms.

Aortic aneurysm, including thoracic aortic aneurysm and abdominal aortic aneurysm, is the second most prevalent aortic disease following atherosclerosis, representing the ninth-leading cause of death globally. Open surgery and endovascular procedures are the major treatments for aortic aneurysm. Typically, thoracic aortic aneurysm has a more robust genetic background than abdominal aortic aneurysm.

Modulation of gene expression on a transcriptome-wide level following human neural stem cell transplantation in aged mouse stroke brains.

Introduction: Neural stem cell (NSC) transplantation offers great potential for treating ischemic stroke. Clinically, ischemia followed by reperfusion results in robust cerebrovascular injury that upregulates proinflammatory factors, disrupts neurovascular units, and causes brain cell death. NSCs possess multiple actions that can be exploited for reducing the severity of neurovascular injury.

Neural Stem Cells for Early Ischemic Stroke.

Clinical treatments for ischemic stroke are limited. Neural stem cell (NSC) transplantation can be a promising therapy. Clinically, ischemia and subsequent reperfusion lead to extensive neurovascular injury that involves inflammation, disruption of the blood-brain barrier, and brain cell death.

Long non-coding RNAs mediate cerebral vascular pathologies after CNS injuries.

Central nervous system (CNS) injuries are one of the leading causes of morbidity and mortality worldwide, accompanied with high medical costs and a decreased quality of life. Brain vascular disorders are involved in the pathological processes of CNS injuries and might play key roles for their recovery and prognosis. Recently, increasing evidence has shown that long non-coding RNAs (lncRNAs), which comprise a very heterogeneous group of non-protein-coding RNAs greater than 200 nucleotides, have emerged as functional mediators in the regulation of vascular homeostasis under pathophysiological conditions.

Endothelial Cell Glucose Metabolism and Angiogenesis.

Angiogenesis, a process of new blood vessel formation from the pre-existing vascular bed, is a critical event in various physiological and pathological settings. Over the last few years, the role of endothelial cell (EC) metabolism in angiogenesis has received considerable attention. Accumulating studies suggest that ECs rely on aerobic glycolysis, rather than the oxidative phosphorylation pathway, to produce ATP during angiogenesis.

Regulatory microRNAs and vascular cognitive impairment and dementia.

Vascular cognitive impairment and dementia (VCID) is defined as a progressive dementia disease related to cerebrovascular injury and often occurs in aged populations. Despite decades of research, effective treatment for VCID is still absent. The pathological processes of VCID are mediated by the molecular mechanisms that are partly modulated at the post-transcriptional level.

Transcription factor EB regulates cardiovascular homeostasis.

Cardiovascular diseases (CVDs) are the leading cause of death and a major cause of disability globally. Transcription factor EB (TFEB), as a member of the microphthalmia transcription factor (MITF) family, has been demonstrated to be a master regulator of autophagy and lysosomal biogenesis. Emerging studies suggest that TFEB regulates homeostasis in the cardiovascular system and shows beneficial effects on CVDs, including atherosclerosis, aortic aneurysm, postischemic angiogenesis, and cardiotoxicity, constituting a promising molecular target for the prevention and treatment of these diseases.

Chemical mutagenesis of a GPCR ligand: Detoxifying "inflammo-attraction" to direct therapeutic stem cell migration.

A transplanted stem cell's engagement with a pathologic niche is the first step in its restoring homeostasis to that site. Inflammatory chemokines are constitutively produced in such a niche; their binding to receptors on the stem cell helps direct that cell's "pathotropism." Neural stem cells (NSCs), which express CXCR4, migrate to sites of CNS injury or degeneration in part because astrocytes and vasculature produce the inflammatory chemokine CXCL12.

Endothelial deficiency of insulin-like growth factor-1 receptor reduces endothelial barrier function and promotes atherosclerosis in -deficient mice.

Insulin-like growth factor-1 (IGF-1) decreases atherosclerosis in apolipoprotein E ()-deficient mice when administered systemically. However, mechanisms for its atheroprotective effect are not fully understood. We generated endothelium-specific IGF-1 receptor (IGF1R)-deficient mice on an -deficient background to assess effects of IGF-1 on the endothelium in the context of hyperlipidemia-induced atherosclerosis.

Neurovascular protection by peroxisome proliferator-activated receptor α in ischemic stroke.

Ischemic stroke is a leading cause of death and disability worldwide. Currently, the only pharmacological therapy for ischemic stroke is thrombolysis with tissue plasminogen activator that has a narrow therapeutic window and increases the risk of intracerebral hemorrhage. New pharmacological treatments for ischemic stroke are desperately needed, but no neuroprotective drugs have successfully made it through clinical trials.

Endothelium-targeted deletion of the miR-15a/16-1 cluster ameliorates blood-brain barrier dysfunction in ischemic stroke.

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.

Endothelium-targeted overexpression of Krüppel-like factor 11 protects the blood-brain barrier function after ischemic brain injury.

Microvascular endothelial cell (EC) injury and the subsequent blood-brain barrier (BBB) breakdown are frequently seen in many neurological disorders, including stroke. We have previously documented that peroxisome proliferator-activated receptor gamma (PPARγ)-mediated cerebral protection during ischemic insults needs Krüppel-like factor 11 (KLF11) as a critical coactivator. However, the role of endothelial KLF11 in cerebrovascular function and stroke outcome is unclear.

Human neural stem cells improve early stage stroke outcome in delayed tissue plasminogen activator-treated aged stroke brains.

Introduction: Clinically, significant stroke injury results from ischemia-reperfusion (IR), which induces a deleterious biphasic opening of the blood-brain barrier (BBB). Tissue plasminogen activator (tPA) remains the sole pharmacological agent to treat ischemic stroke. However, major limitations of tPA treatment include a narrow effective therapeutic window of 4.

Neural stem cell therapy for neurovascular injury in Alzheimer's disease.

Alzheimer's disease (AD), the most common form of dementia, is characterized by progressive neurodegeneration leading to severe cognitive decline and eventual death. AD pathophysiology is complex, but neurotoxic accumulation of amyloid-β (Aβ) and hyperphosphorylation of Tau are believed to be main drivers of neurodegeneration in AD. The formation and deposition of Aβ plaques occurs in the brain parenchyma as well as in the cerebral vasculature.

Neural stem cell therapy for subacute and chronic ischemic stroke.

Neural stem cells (NSCs) play vital roles in brain homeostasis and exhibit a broad repertoire of potentially therapeutic actions following neurovascular injury. One such injury is stroke, a worldwide leading cause of death and disability. Clinically, extensive injury from ischemic stroke results from ischemia-reperfusion (IR), which is accompanied by inflammation, blood-brain barrier (BBB) damage, neural cell death, and extensive tissue loss.

Long Non-Coding RNA Regulates Angiogenesis in Hindlimb Ischemia.

Angiogenesis is a complex process that depends on the delicate regulation of gene expression. Dysregulation of transcription during angiogenesis often leads to various human diseases. Emerging evidence has recently begun to show that long non-coding RNAs (lncRNAs) may mediate angiogenesis in both physiological and pathological conditions; concurrently, underlying molecular mechanisms are largely unexplored.