Osteopontin modulates microglial activation states and attenuates inflammatory responses after subarachnoid hemorrhage in rats.

Aims: Osteopontin (OPN) has demonstrated neuroprotective effects in various stroke models. Its role in neuroinflammation after brain injury remains to be elucidated. This study aims to clarify the effect of OPN on neuroinflammation, particularly on the functional states of microglia after subarachnoid hemorrhage (SAH).

Redox Dysregulation of Vascular Smooth Muscle Sirtuin-1 in Thoracic Aortic Aneurysm in Marfan Syndrome.

Background: Thoracic aortic aneurysms (TAAs) are abnormal aortic dilatations and a major cardiovascular complication of Marfan syndrome. We previously demonstrated a critical role for vascular smooth muscle (VSM) SirT1 (sirtuin-1), a lysine deacetylase, against maladaptive aortic remodeling associated with chronic oxidative stress and aberrant activation of MMPs (matrix metalloproteinases).

Methods: In this study, we investigated whether redox dysregulation of SirT1 contributed to the pathogenesis of TAA using fibrillin-1 hypomorphic mice (Fbn1), an established model of Marfan syndrome prone to aortic dissection/rupture.

Exendin-4 Preserves Blood-Brain Barrier Integrity Glucagon-Like Peptide 1 Receptor/Activated Protein Kinase-Dependent Nuclear Factor-Kappa B/Matrix Metalloproteinase-9 Inhibition After Subarachnoid Hemorrhage in Rat.

In this study, we investigated the role of Exendin-4 (Ex-4), a glucagon-like peptide 1 receptor (GLP-1R) agonist, in blood-brain barrier (BBB) disruption after subarachnoid hemorrhage (SAH) in rats. The endovascular perforation model of SAH was performed in Sprague-Dawley rats. Ex-4 was intraperitoneally injected 1 h after SAH induction.

Dihydrolipoic acid enhances autophagy and alleviates neurological deficits after subarachnoid hemorrhage in rats.

Autophagy is a crucial pathological process in early brain injury (EBI) after subarachnoid hemorrhage (SAH). In this study, we investigated the role of dihydrolipoic acid (DHLA) on enhancing autophagy and alleviating neurological deficits after SAH. SAH was induced by endovascular perforation in male Sprague-Dawley rats.

BCL11B Regulates Arterial Stiffness and Related Target Organ Damage.

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The Role of Sirtuin-1 in the Vasculature: Focus on Aortic Aneurysm.

Sirtuin-1 (SirT1) is a nicotinamide adenine dinucleotide-dependent deacetylase and the best characterized member of the sirtuins family in mammalians. Sirtuin-1 shuttles between the cytoplasm and the nucleus, where it deacetylates histones and non-histone proteins involved in a plethora of cellular processes, including survival, growth, metabolism, senescence, and stress resistance. In this brief review, we summarize the current knowledge on the anti-oxidant, anti-inflammatory, anti-apoptotic, and anti-senescence effects of SirT1 with an emphasis on vascular diseases.

Recombinant OX40 attenuates neuronal apoptosis through OX40-OX40L/PI3K/AKT signaling pathway following subarachnoid hemorrhage in rats.

Subarachnoid hemorrhage (SAH) is the most devastating form of stroke. Reducing neuronal apoptosis is an important countermeasure against early brain injury (EBI) after SAH. Recent evidence indicates that OX40-OX40L coupling is critical for cell survival and proliferation.

Activation of Melanocortin 1 Receptor Attenuates Early Brain Injury in a Rat Model of Subarachnoid Hemorrhage viathe Suppression of Neuroinflammation through AMPK/TBK1/NF-κB Pathway in Rats.

Neuroinflammation plays a vital role in early brain injury (EBI) following subarachnoid hemorrhage (SAH). The hypothesis of this study was that activation of melanocortin 1 receptor (MC1R) with BMS-470539 attenuates EBI by suppression of neuroinflammation after SAH. We utilized BMS-470539, MSG-606, and MRT-68601 to verify the neuroprotective effects of MC1R.

Osteopontin-Enhanced Autophagy Attenuates Early Brain Injury via FAK-ERK Pathway and Improves Long-Term Outcome after Subarachnoid Hemorrhage in Rats.

Osteopontin (OPN) enhances autophagy, reduces apoptosis, and attenuates early brain injury (EBI) after a subarachnoid hemorrhage (SAH). A total of 87 Sprague-Dawley rats were subjected to sham or SAH operations to further investigate the signaling pathway involved in osteopontin-enhanced autophagy during EBI, and the potential effect of recombinant OPN (rOPN) administration to improve long-term outcomes after SAH. Rats were randomly divided into five groups: Sham, SAH + Vehicle (PBS, phosphate-buffered saline), SAH + rOPN (5 μg/rat recombinant OPN), SAH + rOPN + Fib-14 (30 mg/kg of focal adhesion kinase (FAK) inhibitor-14), and SAH + rOPN + DMSO (dimethyl sulfoxide).

Hydrogen gas therapy improves survival rate and neurological deficits in subarachnoid hemorrhage rats: a pilot study.

The high morbidity, high mortality, and significant shortage of effective therapies for subarachnoid hemorrhage (SAH) have created an urgency to discover novel therapies. Human studies in Asia have established the safety of hydrogen gas in the treatment of hepatic, renal, pulmonary, and cardiac diseases. Mechanistically, hydrogen gas has been shown to affect oxidative stress, inflammation, and apoptosis.

FGF-2 Attenuates Neuronal Apoptosis via FGFR3/PI3k/Akt Signaling Pathway After Subarachnoid Hemorrhage.

Neuronal apoptosis is a common and critical pathology following subarachnoid hemorrhage (SAH). We investigated the anti-apoptotic property of fibroblast growth factor (FGF)-2 after SAH in rats. A total of 289 rats underwent endovascular perforation to induce SAH or sham operation.

Mitophagy Reduces Oxidative Stress Via Keap1 (Kelch-Like Epichlorohydrin-Associated Protein 1)/Nrf2 (Nuclear Factor-E2-Related Factor 2)/PHB2 (Prohibitin 2) Pathway After Subarachnoid Hemorrhage in Rats.

Background and Purpose- Mitoquinone has been reported as a mitochondria-targeting antioxidant to promote mitophagy in various chronic diseases. Here, our aim was to study the role of mitoquinone in mitophagy activation and oxidative stress-induced neuronal death reduction after subarachnoid hemorrhage (SAH) in rats. Methods- Endovascular perforation was used for SAH model of male Sprague-Dawley rats.

Activation of retinoid X receptor by bexarotene attenuates neuroinflammation via PPARγ/SIRT6/FoxO3a pathway after subarachnoid hemorrhage in rats.

Background: Subarachnoid hemorrhage (SAH) is a life-threatening subtype of stroke with high mortality and disabilities. Retinoid X receptor (RXR) has been shown to be neuroprotective against ischemia/reperfusion injury. This study aimed to investigate the effects of the selective RXR agonist bexarotene on neuroinflammation in a rat model of SAH.

LRP1 activation attenuates white matter injury by modulating microglial polarization through Shc1/PI3K/Akt pathway after subarachnoid hemorrhage in rats.

White matter injury (WMI) is associated with motor deficits and cognitive dysfunctions in subarachnoid hemorrhage (SAH) patients. Therapeutic strategy targeting WMI would likely improve the neurological outcomes after SAH. Low-density lipoprotein receptor-related protein-1 (LRP1), a scavenger receptor of apolipoprotein E (apoE), is able to modulate microglia polarization towards anti-inflammatory M2 phenotypes during inflammatory and oxidative insult.

TLR7 (Toll-Like Receptor 7) Facilitates Heme Scavenging Through the BTK (Bruton Tyrosine Kinase)-CRT (Calreticulin)-LRP1 (Low-Density Lipoprotein Receptor-Related Protein-1)-Hx (Hemopexin) Pathway in Murine Intracerebral Hemorrhage.

Background and Purpose- Heme and iron are considered to be key factors responsible for secondary insults after intracerebral hemorrhage (ICH). Our previous study showed that LRP1 (low-density lipoprotein receptor-related protein-1)-Hx (hemopexin) facilitates removal of heme. The TLR7 (Toll-like receptor 7)-BTK (Bruton tyrosine kinase)-CRT (calreticulin) pathway regulates the expression of LRP1-Hx.

Neurogenesis changes and the fate of progenitor cells after subarachnoid hemorrhage in rats.

Background: Subarachnoid hemorrhage (SAH) is a devastating cerebrovascular disease that leads to poor outcomes. Neurogenesis, an essential recovery mechanism after brain injury, has not been fully elucidated after SAH.

Methods: A total of 122 SD rats were used in this study.

AVE 0991 attenuates oxidative stress and neuronal apoptosis via Mas/PKA/CREB/UCP-2 pathway after subarachnoid hemorrhage in rats.

Oxidative stress and neuronal apoptosis have been demonstrated to be key features in early brain injury (EBI) after subarachnoid hemorrhage (SAH). Previous studies have indicated that Mas receptor activation initiates an anti-oxidative and anti-apoptotic role in the brain. However, whether Mas activation can attenuate oxidative stress and neuronal apoptosis after SAH remains unknown.

Role of PPAR-β/δ/miR-17/TXNIP pathway in neuronal apoptosis after neonatal hypoxic-ischemic injury in rats.

Activation of peroxisome proliferator-activated receptor beta/delta (PPAR-β/δ), a nuclear receptor acting as a transcription factor, was shown to be protective in various models of neurological diseases. However, there is no information about the role of PPAR-β/δ as well as its molecular mechanisms in neonatal hypoxia-ischemia (HI). In the present study, we hypothesized that PPAR-β/δ agonist GW0742 can activate miR-17-5p, consequently inhibiting TXNIP and ASK1/p38 pathway leading to attenuation of apoptosis.

Osteopontin attenuates inflammation via JAK2/STAT1 pathway in hyperglycemic rats after intracerebral hemorrhage.

Acute intracerebral hemorrhage (ICH) complicated by hyperglycemia is associated with aggravation of post-stroke inflammation, leading to exacerbation of brain edema and predicting poor neurological outcomes and higher mortality of patients. Osteopontin (OPN) is a neuroprotective glycoprotein, which is able to attenuate brain injury induced by hemorrhagic stroke. In the current study we investigated whether OPN will decrease the inflammatory post-ICH response as well as attenuate brain edema and neurological deficits in hyperglycemic rats.