a-modified-mouse-model-intracranial-aneurysm-based-on-hemodynamic

A Modified Mouse Model of Intracranial Aneurysm Based on Hemodynamic Change and Hypertension

Intracranial aneurysm (IA) poses a significant health risk due to morbidity and mortality associated with aneurysm rupture. However, the molecular ...

Zaozhuang Municipal Hospital

Different endovascular modalities have been applied to the treatment of vertebral artery dissecting aneurysms, the most commonly used being internal trapping and stent-assisted coiling, although the ideal treatment remains controversial.

Endovascular treatment for ruptured and unruptured vertebral artery dissecting aneurysms: a meta-analysis.

Posterior circulation ischemic stroke (PCIS), accounting for approximately 20% of total ischemic stroke, is a sever disease that associated with high rate of morbidity and mortality. Though the effectiveness of endovascular mechanical thrombectomy has been well demonstrated in many types of ischemic stroke, it is still unclear what the outcome is in posterior circulation ischemic stroke.

Evaluation of recanalisation treatment on posterior circulation ischemic stroke by Solitaire device-A multicenter retrospective study.

To investigate the morphological and hemodynamic parameters associated with middle cerebral artery (MCA)bifurcation aneurysm rupture.

Morphological and Hemodynamic Parameters for Middle Cerebral Artery Bifurcation Aneurysm Rupture Risk Assessment.

Traumatic brain injury is now a major contributor to the global healthcare burden. Migraine is another debilitating disease with a global health impact. While most researchers agree that traumatic brain injury is a risk factor for migraine, whether migraine is a risk factor for traumatic brain injury still remains under debate. We therefore aimed to investigate whether migraine was a risk factor for developing traumatic brain injury.

Migraine and traumatic brain injury: a cohort study in Taiwan.

Exosome and microRNAs (miRs) are implicated in ischemia/reperfusion (I/R) process. In this study, I/R mouse model was established, and exosomes derived from human umbilical cord mesenchymal stem cells (hUCMSCs) were isolated, identified, and injected to I/R mice to observe nerve injury and microglia M1 polarization. The differentially expressed genes in I/R microglia from databases were analyzed, and miRs differentially expressed in exosomes-treated microglia were analyzed by microarray. miR-26b-5p expression in hUCMSCs was intervened. Besides, microglia was extracted and co-cultured with SH-SY5Y or PC12 cells in oxygen-glucose deprivation/reperfusion (OGD/R) models to simulate I/R . Additionally, Toll-like receptor (TLR) activator GS-9620 was added to microglia. Exosomes alleviated nerve injury and inhibited M1 polarization in microglia. After I/R modeling, CH25H expression in microglia was upregulated but decreased after exosome treatment. miR-26b-5p was upregulated in microglia after exosome treatment and could target CH25H. Reduction in exosomal miR-26b-5p reversed the effects of hUCMSCs-exos on microglia. TLR pathway was activated in microglia after I/R but exosomes prevented its activation. Exosomal miR-26b-5p could repress M1 polarization of microglia by targeting CH25H to inactivate the TLR pathway, so as to relieve nerve injury after cerebral I/R. This investigation may offer new approaches for I/R treatment.

Exosomes-carried microRNA-26b-5p regulates microglia M1 polarization after cerebral ischemia/reperfusion.

Keloids are characterized by disturbance of fibroblast proliferation and apoptosis, deposition of collagen, and upregulation of dermal inflammation cells. This benign dermal fibro-proliferative scarring condition is a recognized skin inflammation disorder. Chronic inflammation is a well-known contributor to bone loss and its sequelae, osteoporosis. They both shared a similar pathogenesis through chronic inflammation. We assessed whether keloids increase osteoporosis risk through using National Health Insurance Research Database.

The association between keloid and osteoporosis: real-world evidence.

Fibroproliferative lesions with intractable pruritus, pain and hyperesthesia that cause uncontrolled scar growth are known as keloids. Migraines are common upsetting headache disorders characterised by frequent recurrence and attacks aggravated by physical activity. Both keloids and migraines can cause physical exhaustion and discomfort in patients; they have similar pathophysiological pathways, that is, the transforming growth factor-β1 gene and neurogenic inflammation.

Migraines and keloids: a 15-year Taiwan claim database analysis.

Oxygen-glucose deprivation and reoxygenation (OGD/R)-induced impairment of astrocytes may lead to neuronal dysfunction in the central nervous system (CNS). Apremilast is a phosphodiesterase 4 (PDE4) inhibitor primarily used for the treatment of psoriasis and psoriatic arthritis that has demonstrated certain neuroprotective properties. PDE4 is an isoenzyme that degrades 3'-5'-cyclic adenosine monophosphate (cAMP), which serves as a neuroprotective agent by promoting neuronal recovery through protein kinase (PKA)-mediated phosphorylation of cAMP response element-binding protein (CREB) and subsequent expression of the neurotrophic factor brain-derived neurotrophic factor (BDNF) and anti-apoptotic B cell lymphoma (Bcl-2). However, the effects of apremilast in astrocytes have not been elucidated. In the present study, we employed an in vitro model of ischemic stroke using oxygen-glucose deprivation and reoxygenation (OGD/R)-challenged astrocytes to investigate the effects of apremilast against apoptosis (the flow cytometry assay), cell death (the lactate dehydrogenase release assay), oxidative stress (2', 7' dichlorofluorescin diacetate staining), and the expression of the key neuroprotective factors CREB and BDNF (Western blot analysis). Our findings show that treatment with apremilast could significantly reduce astrocyte apoptosis and cell death induced by OGD/R as evidenced by reduced release of glial fibrillary acidic protein (GFAP) and improvement of the Bax/Bcl-2 ratio. The results of MTT assay, measurement of lactate dehydrogenase (LDH) release, and flow cytometry confirmed the improvement in cell viability mediated by apremilast. Importantly, we found that CREB phosphorylation was required for the increases in BDNF and Bcl-2 induced by apremilast as well as the decrease in astrocyte apoptosis. These preliminary findings indicate that apremilast may have the potential to prevent astrocyte cell death and promote neuronal healing in cerebral ischemic injury. Further in vivo research will expand our understanding of these promising results.

The Protective Effects of Apremilast Against Oxygen-Glucose Deprivation/Reperfusion (OGD/R)-Induced Inflammation and Apoptosis in Astroglia Mediated by CREB/BDNF.

The basic function of the blood-brain barrier (BBB) is to selectively regulate the infiltration of solutes from the circulating blood into the central nervous system (CNS). Impaired BBB activity is related to brain damage caused by stroke, traumatic injury, neurodegenerative diseases, etc. Comprised of a monolayer of endothelial cells, the integrity of the BBB is determined by the expression of tight junction proteins and the contractile activity of the perijunctional apical actomyosin ring. Irbesartan, an AT1R antagonist, has been widely used for the treatment of hypertension. However, the pharmacological function of Irbesartan in the balance of the BBB is still unknown. In the present study, we performed both in-vivo and in-vitro experiments using lipopolysaccharide (LPS) to explore the mechanism behind the protective effects of Irbesartan against the BBB impairment. The results of our mouse model study revealed that Irbesartan could reduce BBB permeability, restore the expression of Occludin, and suppress the expression of inflammatory mediators, including interleukin-6, monocyte chemoattractant protein-1, and intercellular adhesion molecule-1. Additionally, Irbesartan improved LPS-induced depressive-like behavior. In our in vitro experiments, human brain microvascular endothelial cells (HBMVECs) stimulated with LPS demonstrated decreased endothelial permeability and increased occludin expression in response to Irbesartan treatment. Importantly, we found that the protective effects of Irbesartan were mediated through the NF-κB/MLC/MLCK signaling pathway, as blockage of NF-κB abolished the effects of Irbesartan. Our findings provide a basis for further research into the neuroprotective mechanism of Irbesartan.

Irbesartan suppresses lipopolysaccharide (LPS)-induced blood-brain barrier (BBB) dysfunction by inhibiting the activation of MLCK/MLC.

Phosphatase and tensin homolog (PTEN) is known to be involved in the pathogenesis of intracranial aneurysm (IA). This study investigated the molecular mechanism of exosomal miR-144-5p (ex-miR-144-5p) and PTEN in IA. Ex-miR-144-5p expression was assessed in serum from individuals with ruptured intracranial aneurysm (RA) or unruptured intracranial aneurysm (UA), and healthy controls (HC). Vascular endothelial cells (VECs) were co-cultured with exosomes isolated from mesenchymal stem cells (MSCs) with transfection of miR-144-5p mimic or miR-144-5p inhibitor. IA rats were induced by combing systemic hypertension and intrathecal elastase injection. VECs were transfected with miR-144-5p mimic or inhibitor to verify the impacts of miR-144-5p on cell viability and proliferation. The connection between miR-144-5p and PTEN was verified by luciferase activity assay. Our data proved that ex-miR-144-5p was decreased in both UA and RA patients. MiR-144-5p overexpression in MSCs-derived exosome promoted VEC viability, inhibited VEC proliferation of VEs, and decreased the protein levels of matrix metalloproteinase-9 (MMP-9), proliferating cell nuclear antigen (PCNA) and osteopontin (OPN). IA rats injected with ex-miR-144-5p mimic showed significant luminal dilation, declined smooth muscle layers, and thinned vascular wall. Besides, inhibited cell apoptosis and decreased protein expressions were also observed. However, ex-miR-144-5p inhibitor had the opposite effects both in vivo and in vitro. We validated that miR-144-5p directly targeted PTEN. MiR-144-5p mimic increased cell viability and proliferation and reduced protein expressions, which could be blunted by PTEN overexpression. This study suggests that miR-144-5p elevates PTEN expression, thereby boosting apoptosis and attenuating viability of VECs in IA.

Hao Qin

Department of Neurosurgery

Zaozhuang Municipal Hospital

A Modified Mouse Model of Intracranial Aneurysm Based on Hemodynamic Change and Hypertension

Hao Qin

.css-o250i3{font-size:18px;font-family:Open Sans,sans-serif;line-height:21.6px;}Department of Neurosurgery

Zaozhuang Municipal Hospital

A Modified Mouse Model of Intracranial Aneurysm Based on Hemodynamic Change and Hypertension

Department of Neurosurgery