Background and Purpose— Multipotent mesenchymal stromal cell (MSC) harvested exosomes are hypothesized as the major paracrine effectors of MSCs. In vitro, miR-17–92 cluster promotes oligodendrogenesis, neurogenesis, axonal outgrowth. We, therefore, investigated whether cluster–enriched from MSCs transfected with an plasmid enhance neurological recovery compared control MSC-derived exosomes. Methods— Rats subjected to 2 hours transient middle cerebral artery occlusion were intravenously...

MicroRNAs are small RNAs that attenuate protein expression by complementary binding to the 3'-UTR of a target mRNA. Currently, very little is known about microRNAs after cerebral ischemia. In particular, microRNA-21 (miR-21) strong antiapoptotic factor in some biological systems. We investigated role miR-21 stroke rat. employed situ hybridization and laser capture microdissection combination with real-time RT-PCR investigate stroke. revealed was upregulated neurons ischemic boundary zone,...

Background and Purpose— Axonal remodeling is critical to brain repair after stroke. The present study investigated axonal outgrowth stroke the signaling pathways mediating in cortical neurons. Methods— Using a rodent model of middle cerebral artery occlusion, we examined high-molecular weight neurofilament (NFH) immunoreactive axons myelin basic protein-positive oligodendrocytes peri-infarct area. In vitro, using cultured neurons microfluidic chamber challenged by oxygen-glucose deprivation...

Carbamylated erythropoietin (CEPO), a well characterized (EPO) derivative, does not bind to the classical EPO receptor and stimulate erythropoiesis. Using neural progenitor cells derived from subventricular zone of adult mouse, we investigated effect CEPO on neurogenesis associated signaling pathways in vitro. We found that significantly increased cell proliferation promoted differentiation into neurons, which was with up-regulation Sonic hedgehog (Shh), its ptc, mammalian achaete-scute...

We demonstrate that tissue plasminogen activator (tPA) and its inhibitors contribute to neurite outgrowth in the central nervous system (CNS) after treatment of stroke with multipotent mesenchymal stromal cells (MSCs). In vivo, administration MSCs mice subjected middle cerebral artery occlusion (MCAo) significantly increased activation tPA downregulated PAI-1 levels ischemic boundary zone (IBZ) compared control PBS treated mice, concurrently increases myelinated axons synaptophysin. vitro,...

The unique cellular and vascular architecture of the adult ventricular-subventricular zone (V/SVZ) neurogenic niche plays an important role in regulating neural stem cell function. However, vivo identification cells their relationship to blood vessels within this response stroke remain largely unknown. Using whole-mount preparation lateral ventricle wall, we examined V/SVZ mouse over course 3 months after onset focal cerebral ischemia. Stroke substantially increased number glial fibrillary...

MicroRNAs (miRNAs) serve as important regulators of inflammatory and immune responses are implicated in several disorders including gouty arthritis. The expression miR-146a is upregulated the peripheral blood mononuclear cells patients with inter-critical gout when compared to normouricemic hyperuricemic controls those acute flares. However, role development remains unknown. Here, we used knockout (KO) mice test function a monosodium urate (MSU)-induced arthritis model. footpad or ankle...

Background— Microvascular dysfunction posttreatment of stroke with recombinant human tissue-type plasminogen activator (rht-PA) constrains the therapeutic window to 3 hours. Statins (3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors) promote vascular thrombolysis and reduce inflammation response. We therefore investigated neuroprotective effects a combination atorvastatin delayed rht-PA treatment in rat model embolic stroke. Methods Results— Rats subjected middle cerebral artery...

Objective— Activation of the toll-like receptor (TLR) signaling pathway exacerbates ischemic brain damage. The present study tested hypothesis that combination treatment with VELCADE and tissue plasminogen activator (tPA) modulates TLR on cerebral vasculature, which leads to neuroprotection in aged rats after stroke. Methods Results— Focal ischemia acutely increased TLR2, TLR4, interleukin-1 receptor–activated kinases 1 immunoreactivity fibrin/fibrinogen-positive vessels rats. Monotherapy...

Adult neural stem cells give rise to neurons, oligodendrocytes and astrocytes. Aging reduces cells. Using an inducible nestin-CreERT2/R26R-yellow fluorescent protein (YFP) mouse, we investigated the effect of Sildenafil, a phosphodiesterase type 5 (PDE5) inhibitor, on nestin lineage their progeny in ischemic brain middle-aged mouse. We showed that focal cerebral ischemia induced subventricular zone (SVZ) lateral ventricles expressing NeuN positive neurons adenomatous polyposis coli (APC)...

Cerebral endothelial cells (CECs) and axons of neurons interact to maintain vascular neuronal homeostasis axonal remodeling in normal ischemic brain, respectively. However, the role exosomes interaction CECs brain under conditions after stroke is unknown.

Abstract Neurogenesis contributes to poststroke recovery. Long noncoding RNAs (lncRNAs) participate in the regulation of stem cell self-renewal and differentiation. However, role lncRNAs stroke-induced neurogenesis remains unknown. In this study, we found that H19 was most highly upregulated lncRNA neural cells (NSCs) subventricular zone (SVZ) rats subjected focal cerebral ischemia. Deletion suppressed proliferation, promoted death, blocked NSC RNA sequencing analysis revealed genes...

Background: Vascular cognitive impairment (VCI) is the second most frequent subtype of dementia following Alzheimer's disease. However, underlying mechanism has not been fully understood and there no effective treatment for VCI. MicroRNAs (miRNAs) play critical roles in pathologies cerebral ischemia dementia. This study aims to identify key miRNAs that may mediate outcomes using multiple microinfarction (MMI), a VCI model. Methods: MMI was induced by administration cholesterol crystals...

Background and Purpose: Gut microbiota dysfunction is associated with diabetic cognitive impairment (DCI). However, the mechanisms underlying interaction of gut dysbiosis DCI remain poorly understood. We tested hypothesis that extracellular vesicles generated by exacerbate promoting cerebral vascular function. Methods: Gut-EVs from stools male non-diabetic dm (dm-gut-EVs) (db/db mice) (db-gut-EVs) mice at 20 weeks age (20W) were isolated characterized means ultracentrifugation 16S rRNA...

Treatment with a selective proteasome inhibitor, VELCADE, in combination tissue plasminogen activator (tPA) extended the therapeutic window to 6 hours young rats after stroke. However, stroke is major cause of death and disability elderly. The present study investigated effect VELCADE low-dose tPA on aged embolic stroke.Male Wistar at age 18 20 months were treated (0.2 mg/kg) alone, (5 tPA, or saline 2 middle cerebral artery occlusion. To test contribution endothelial nitric oxide synthase...

Axonal miRNAs locally regulate axonal growth by modulating local protein composition. Whether localized in the axon mediate inhibitory effect of Chondroitin sulfate proteoglycans (CSPGs) on remains unknown. We showed that cultured cortical neurons, application CSPGs inhibited and altered miRNA profiles, whereas elevation cyclic guanosine monophosphate (cGMP) levels sildenafil reversed inhibition profiles. Specifically, elevated reduced miR-29c integrin β1 (ITGB1) proteins, respectively,...

Summary Stroke elicits a progressive vascular dysfunction, which contributes to the evolution of brain injury. Thrombolysis with tissue plasminogen activator (tPA) promotes adverse events that limit therapeutic window stroke three hours. Proteasome inhibitors reduce thrombotic and inflammatory events, consequently protect function. The present study evaluated neuroprotective effect bortezomib,a potent selective inhibitor proteasome, alone in combination delayed thrombolytic therapy on rat...

Multipotent mesenchymal stromal cells (MSCs) increase tissue plasminogen activator (tPA) activity in astrocytes of the ischemic boundary zone, leading to increased neurite outgrowth brain. To probe mechanisms that underlie MSC-mediated activation tPA, we investigated morphogenetic gene, sonic hedgehog (Shh) pathway. In vitro oxygen and glucose deprivation coculture MSCs were used mimic an vivo condition. Both real-time-PCR western blot showed MSC significantly Shh level concomitantly tPA...