Intracerebral hemorrhage (ICH) is a subtype of stroke characterized by high mortality and disability rates. To date, the exact etiology of ICH-induced brain injury is still unclear. Moreover, there is no effective treatment to delay or prevent disease progression currently. Increasing evidence suggests that ferroptosis plays a dominant role in the pathogenesis of ICH injury. Baicalin is a main active ingredient of Chinese herbal medicine Scutellaria baicalensis. It has been reported to exhibit neuroprotective effects against ICH-induced brain injury as well as reduce iron deposition in multiple tissues. Therefore, in this study, we focused on the protective mechanisms of baicalin against ferroptosis caused by ICH using a hemin-induced in vitro model and a Type IV collagenase-induced in vivo model. Our results revealed that baicalin enhanced cell viability and suppressed ferroptosis in rat pheochromocytoma PC12 cells treated with hemin, erastin and RSL3. Importantly, baicalin showed anti-ferroptosis effect on primary cortical neurons (PCN). Furthermore, baicalin alleviated motor deficits and brain injury in ICH model mice through inhibiting ferroptosis. Additionally, baicalin existed no obvious toxicity towards the liver and kidney of mice. Evidently, ferroptosis is a key pathological feature of ICH and baicalin can prevent the development of ferroptosis in ICH. As such, baicalin is a potential therapeutic drug for ICH treatment.

Polymer nanoparticles (NPs) increase resveratrol (Res) oral bioavailability in intracerebral hemorrhage (ICH) and the anti-ferroptosis mechanism of Res-NPs.

Background Intracerebral hemorrhage (ICH) is a form of severe stroke, the pathology of which is tied closely to a recently discovered form of programmed cell death known as ferroptosis. Curcumin (Cur) is a common phenolic compound extracted from the rhizome of Curcuma longa capable of hematoma volume and associated neurological damage in the context of ICH. Despite exhibiting therapeutic promise, the efficacy of Cur is challenged by its poor water solubility, limited oral bioavailability and inability to efficiently transit across the physiological barriers. Polymer-based nanoparticles (NPs) have widely been employed to aid in drug delivery efforts owing to their ideal biocompatibility and their ability to improve the bioavailability and pharmacokinetics of specific drugs of interest. Methods In this study, we encapsulated Cur in NPs (Cur-NPs) and explored the effect of these Cur-NPs to enhance Cur delivery both in vitro and in vivo. Furthermore, we evaluated the anti-ferroptosis effect of Cur-NPs in ICH model mice and erastin-treated HT22 murine hippocampal cells. Results The resultant Cur-NPs were spherical and exhibited a particle size of 127.31±2.73 nm, a PDI of 0.21±0.01 and a zeta potential of −0.25±0.02 mV. When applied to Madin Darby canine kidney (MDCK) cells in vitro, these Cur-NPs were nonspecifically internalized via multiple endocytic pathways, with plasma membrane microcapsules and clathrin-mediated uptake being the dominant mechanisms. Within cells, these NPs accumulated in lysosomes, endoplasmic reticulum and mitochondria. Cur-NPs were capable of passing through physiological barriers in a zebrafish model system. When administrated to C57BL/6 mice, they significantly improved Cur delivery to the brain. Most notably, when administered to ICH model mice, Cur-NPs achieved superior therapeutic outcomes relative to other treatments. In a final series of experiments, these Cur-NPs were shown to suppress erastin-induced ferroptosis in HT22 murine hippocampal cells. Conclusion These Cur-NPs represent a promising means of improving Cur delivery to the brain and thereby better treating ICH.

Background: Approximately 60% of patients experience moderate-to-severe pain after neurosurgery, which primarily occurs in the first 24–72 h. Despite this, improved postoperative analgesia solutions after neurosurgery have not yet been devised. This retrospective study was conducted to evaluate the effect of intra- and post-operative infusions of dexmedetomidine (DEX) plus sufentanil on the quality of postoperative analgesia in patients undergoing neurosurgery.Methods: One hundred and sixty-three post-neurosurgery patients were divided into two groups: Group D (DEX infusion at 0.5 μg·kg−1 for 10 min, then adjusted to 0.3 μg·kg−1·h−1 until incision suturing) and Group ND (no DEX infusion during surgery). Patient-controlled analgesia was administered for 72 h after surgery (Group D: sufentanil 0.02 μg·kg−1·h−1 plus DEX 0.02 μg·kg−1·h−1, Group ND: sufentanil 0.02 μg·kg−1·h−1) in this retrospective study. The primary outcome measure was postoperative sufentanil consumption. Hemodynamics, requirement of narcotic, and vasoactive drugs, recovery time and the incidence of concerning adverse effects were recorded. Pain intensity [Visual Analogue Scale (VAS)], Ramsay sedation scale (RSS) and Bruggemann comfort scale (BCS) were also evaluated at 1, 4, 8, 12, 24, 48, and 72 h after surgery.Results: Postoperative sufentanil consumption was significantly lower in Group D during the first 72 h after surgery (P < 0.05). Compared with Group ND, heart rate (HR) in Group D was significantly decreased from intubation to 20 min after arriving at post anesthesia care unit (PACU), while mean arterial pressure (MAP) in Group D was significantly decreased from intubation to 5 min after arriving at PACU (P < 0.05). The intraoperative requirements for sevoflurane, remifentanil, and fentanyl were approximately 35% less in Group D compared with Group ND. VAS at rest at 1, 4, and 8 h and with cough at 12, 24, 48, and 72 h after surgery were significantly lower in Group D (P < 0.05). Compared with Group ND, patients in Group D showed lower levels of overall incidence of tachycardia, hypertension, nausea, and vomiting (P < 0.05). There were no significant differences between the two groups in terms of baseline clinical characteristics, recovery time, RSS, and BCS (P > 0.05).Conclusions: DEX (0.02 μg·kg−1·h−1) plus sufentanil (0.02 μg·kg−1·h−1) could reduce postoperative opioid consumption and concerning adverse adverse effects, while improving pain scores. However, it did not influence RSS and BCS during the first 72 h after neurosurgery.

Several studies have reported the use of dexmedetomidine (DEX) plus opioids for flexible bronchoscopy in both adults and children. To determine whether DEX plus sufentanil (SF) is safe for children, 142 children undergoing flexible bronchoscopy were assigned to one of three groups, each of which received the same SF loading dose and similar DEX and SF maintenance doses, but different loading doses of DEX: DS1 (DEX 0.5 μg·kg–1), DS2 (DEX 1.0 μg·kg–1), and DS3 (DEX 1.5 μg·kg–1). The Ramsay sedation scale was maintained at 3 in all groups. Results showed that anesthesia onset time was shorter, and the perioperative hemodynamic profile was more stable, in the DS3 group. The number of intraoperative movements was also lowest in the DS3 group. The time to first dose of rescue midazolam and lidocaine was significantly longer, but the total corresponding accumulated doses were lower in the DS3 group. Although the time to recovery prior to discharge from the post anesthesia care unit was longer, the overall incidence of tachycardia was lower in the DS3 group, and it received the highest bronchoscopist satisfaction score among the three groups. We therefore conclude that high-dose DEX plus SF can be safely and efficaciously used in children undergoing flexible bronchoscopy.

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Depression is a prevalent mental disease characterized by persistent low mood, lack of pleasure, and exhaustion. Acupoint catgut embedding (ACE) is a kind of modern acupuncture treatment, which has been widely used for the treatment of a variety of neuropsychiatric diseases. To investigate the effects and underlying mechanism of ACE on depression, in this study, we applied ACE treatment at the Baihui (GV20) and Dazhui (GV14) acupoints of corticosterone (CORT)-induced depression model mice. The results showed that ACE treatment significantly attenuated the behavioral deficits of depression model mice in the open field test (OFT), elevated-plus-maze test (EPMT), tail suspension test (TST), and forced swimming test (FST). Moreover, ACE treatment reduced the serum level of adreno-cortico-tropic-hormone (ACTH), enhanced the serum levels of 5-hydroxytryptamine (5-HT), and noradrenaline (NE). Furthermore, metabolomics analysis revealed that 23 differential metabolites in the brain of depression model mice were regulated by ACE treatment for its protective effect. These findings suggested that ACE treatment ameliorated depression-related manifestations in mice with depression through the attenuation of metabolic dysfunction in brain.