Leonurus japonicus Houtt. modulates neuronal apoptosis in intracerebral hemorrhage: Insights from network pharmacology and molecular docking.

ETHNOPHARMACOLOGICAL RELEVANCE: Leonurus japonicus Houtt. (Labiatae), commonly known as Chinese motherwort, is a herbaceous flowering plant that is native to Asia. It is widely acknowledged in traditional medicine for its diuretic, hypoglycemic, antiepileptic properties and neuroprotection. Currently, Leonurus japonicus (Leo) is included in the Pharmacopoeia of the People's Republic of China. Traditional Chinese Medicine (TCM) recognizes Leo for its myriad pharmacological attributes, but its efficacy against ICH-induced neuronal apoptosis is unclear. AIMS OF THE STUDY: This study aimed to identify the potential targets and regulatory mechanisms of Leo in alleviating neuronal apoptosis after ICH. MATERIALS AND METHODS: The study employed network pharmacology, UPLC-Q-TOF-MS technique, molecular docking, pharmacodynamic studies, western blotting, and immunofluorescence techniques to explore its potential mechanisms. RESULTS: Leo was found to assist hematoma absorption, thus improving the neurological outlook in an ICH mouse model. Importantly, molecular docking highlighted JAK as Leo's potential therapeutic target in ICH scenarios. Further experimental evidence demonstrated that Leo adjusts JAK1 and STAT1 phosphorylation, curbing Bax while augmenting Bcl-2 expression. CONCLUSION: Leo showcases potential in mitigating neuronal apoptosis post-ICH, predominantly via the JAK/STAT mechanism.

Buyang huanwu decoction promotes remyelination via miR-760-3p/GPR17 axis after intracerebral hemorrhage.

ETHNOPHARMACOLOGICAL RELEVANCE: The repairment of myelin sheaths is crucial for mitigating neurological impairments of intracerebral hemorrhage (ICH). However, the current research on remyelination processes in ICH remains limited. A representative traditional Chinese medicine, Buyang Huanwu decoction (BYHWD), shows a promising therapeutic strategy for ICH treatment. AIM OF THE STUDY: To investigate the pro-remyelination effects of BYHWD on ICH and explore the underlying mechanisms. MATERIALS AND METHODS: The collagenase-induced mice ICH model was created for investigation. BYHWD's protective effects were assessed by behavioral tests and histological staining. Transmission electron microscopy was used for displaying the structure of myelin sheaths. The remyelination and oligodendrocyte differentiation were evaluated by the expressions of myelin proteolipid protein (PLP), myelin basic protein (MBP), MBP/TAU, Olig2/CC1, and PDGFRα/proliferating cell nuclear antigen (PCNA) through RT-qPCR and immunofluorescence. Transcriptomics integrated with disease database analysis and experiments in vivo and in vitro revealed the microRNA-related underlying mechanisms. RESULTS: Here, we reported that BYHWD promoted the neurological function of ICH mice and improved remyelination by increasing PLP, MBP, and TAU, as well as restoring myelin structure. Besides, we showed that BYHWD promoted remyelination by boosting the differentiation of PDGFRα+ oligodendrocyte precursor cells into olig2+/CC1+ oligodendrocytes. Additionally, we demonstrated that the remyelination effects of BYHWD worked by inhibiting G protein-coupled receptor 17 (GPR17). miRNA sequencing integrated with miRNA database prediction screened potential miRNAs targeting GPR17. By applying immunofluorescence, RNA in situ hybridization and dual luciferase reporter gene assay, we confirmed that BYHWD suppressed GPR17 and improved remyelination by increasing miR-760-3p. CONCLUSIONS: BYHWD improves remyelination and neurological function in ICH mice by targeting miR-760-3p to inhibit GPR17. This study may shed light on the orchestration of remyelination mechanisms after ICH, thus providing novel insights for developing innovative prescriptions with brain-protective properties.

Yi-Qi-Huo-Xue decoction alleviates intracerebral hemorrhage injury through inhibiting neuronal autophagy of ipsilateral cortex via BDNF/TrkB pathway.

BACKGROUND: Yi-Qi-Huo-Xue Decoction (YQHXD), a traditional Chinese medicine formula, has demonstrated efficacy in the clinical treatment of intracerebral hemorrhage (ICH) for over a decade. Nevertheless, the precise pharmacotherapeutic compounds of YQHXD capable of penetrating into cerebral tissue and the pharmacological underpinnings of YQHXD remain ambiguous. METHODS: The active components of YQHXD in rat brains was analyzed by ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry. The potential targets, pathways and biological progresses of YQHXD ameliorating ICH induced injury was predicted by network pharmacology. Moreover, collagenase-induced ICH rat model, primary cortex neurons exposed to hemin and molecular docking were applied to validate the molecular mechanisms of YQHXD. RESULTS: Eleven active components of YQHXD were identified within the brains. Employing the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) databases, our investigation concentrated on the roles of autophagy and the BDNF/TrkB signaling pathway in the pharmacological context. The pharmacological results revealed that YQHXD alleviated neurological dysfunction, brain water content, brain swelling, and pathological injury caused by ICH. Meanwhile, YQHXD inhibited autophagy influx and autophagosome in vivo, and regulated cortex neuronal autophagy and TrkB/BDNF pathway both in vivo and in vitro. Subsequently, N-acetyl serotonin (NAS), a selective TrkB agonist, was employed to corroborate the significance of the BDNF/TrkB pathway in this process. The combination of NAS and YQHXD did not further enhance the protective efficacy of YQHXD in ICH rats. Additionally, outcomes of molecular docking analysis revealed that nine compounds of YQHXD exhibited potential regulatory effects on TrkB. CONCLUSIONS: Ipsilateral neuronal autophagy and BDNF/TrkB pathway were activated 72 h after ICH. YQHXD effectively resisted injury induced by ICH, which was related with suppression of ipsilateral neuronal autophagy via BDNF/TrkB pathway. This study provides novel insights into the therapeutic mechanisms of traditional Chinese medicine in the context of ICH treatment.

Registration study for the prevention and treatment of cerebral hemorrhage using naoxueshu oral liquid: Protocol for a research study.

BACKGROUND: Naoxueshu oral liquid is the only approved drug for acute treatment of cerebral hemorrhage in China. It has been used widely for the treatment of acute ischemic stroke and acute hemorrhagic stroke. However, safety and efficacy data on the early use of Naoxueshu oral liquid are lacking. The main purpose of this study is to observe the benefit and safety of early use of Naoxueshu oral liquid (< 72 h of cerebral hemorrhage) and offer evidence into the potential superiority of Naoxueshu oral liquid in patients with hemorrhagic stroke, and its healthcare costs. METHODS: This registration study for the prevention and treatment of cerebral hemorrhage using Naoxueshu oral liquid will be a quantitative, prospective, multicenter, observational clinical registry study. We aim to register 2000 patients with cerebral hemorrhage within 7 days of disease onset. This study will be an observational study and not interfere with the medication regimen of participants. Hence, we will not allocate patients. The main observation indicators will be the hematoma volume and the proportion of reduction 14 days post-cerebral hemorrhage (or at hospital discharge), onset of new stroke (ischemic stroke, hemorrhagic stroke) within 12 months of disease onset, independence in everyday life activities (modified Rankin Scale score ≤ 2), total cost during hospitalization, and treatment costs. CONCLUSION: This registration study will offer strong evidence for the efficacy and safety of Naoxueshu oral liquid for the prevention and treatment of cerebral hemorrhage, particularly with regard to early use (72 h after onset). It will offer evidence into the potential advantages of Naoxueshu oral liquid in patients with hemorrhagic stroke, including healthcare costs.

The mechanism of Zhenzhu Pills treating intracerebral hemorrhage secondary injury based on network pharmacology and molecular docking.

BACKGROUND: Intracerebral hemorrhage (ICH) secondary injury is serious and affects patient's prognosis. The Zhenzhu Pills used to treat subacute ICH in Tibet has shown to have a certain curative effect. Network pharmacology and molecular docking technology are employed to explore the potential mechanism of Zhenzhu Pills. The components and potential targets of Zhenzhu Pills were screened from the Traditional Chinese Medicine Systems Pharmacology database. The Gene Expression Omnibus Series 24265 was used to screen differentially expressed genes between perihematomal tissue and normal brain. METHODS: The herbs-components-targets network was established, with weighted eigenvalue to identify the core components and targets of Zhenzhu Pills treatment of ICH secondary injury. Targets' bioinformatics enrichment was proceeded by gene ontology and Kyoto Encyclopedia of Genes and Genome (KEGG) pathway analysis. Finally, molecular docking was used to identify the hydrogen bonding activity between the key components and action targets. RESULTS: Five herbal drugs were screened from Traditional Chinese Medicine Systems Pharmacology database, with a total of 48 components and 234 targets. The Gene Expression Omnibus Series 24265 dataset was evaluated and 920 differentially expressed genes were identified. A total of 29 intersection targets of Zhenzhu Pills were explored in the treatment of ICH secondary injury. Drugs-components-targets network analysis showed that the pivotal targets were prostaglandin G/H synthase 2, interleukin 6, heme oxygenase-1, vascular endothelial growth factor, and vascular cell adhesion molecule 1, and the core components were quercetin, luteolin, and kaempferol. Gene ontology and KEGG pathway enrichment analysis showed that biological processes such as cell chemotaxis, wound healing, leukocyte migration, and regulation of body fluid levels played an important role in the secondary injury of ICH. The results of KEGG pathway analysis were mainly related to advanced glycation end products-receptor for advanced glycation end products signal pathway and tumor necrosis factor signal pathway. Molecular docking of 3 flavonoids with 5 core targets with the results also showed active hydrogen bonding. CONCLUSIONS: This study provides insights into the potential mechanisms of Zhenzhu Pills in the treatment of secondary injuries resulting from ICH and highlights specific components, targets, and molecular pathways involved in this therapeutic effect. These possible therapeutic mechanisms include inhibiting inflammation, edema, oxidative stress, and so on.

Efficacy and safety of bedside percutaneous three-millimeter twist-drill trephination under local anesthesia-a retrospective study of 1000 patients.

PURPOSE: Percutaneous 3-mm twist-drill trephination (TDT) under local anesthesia as a bedside operative technique is an alternative to the conventional open surgical trephination in the operating theatre. The aim of this study was to verify the efficacy and safety of this minimal invasive procedure. METHODS: This retrospective study comprises 1000 patients who were treated with TDT under local anesthesia at bedside due to chronic subdural hematoma (cSDH), intracerebral hemorrhage (ICH), and hydrocephalus (HYD) as a result of subarachnoid hemorrhage or non-hemorrhagic causes, increased intracranial pressure (IIP) in traumatic brain injury or non-traumatic brain edema, and other pathologies (OP) requiring drainage. Medical records, clinical outcome, and results of pre- and postoperative computed tomography (CT) and/or magnetic resonance tomography (MRT) were analyzed. RESULTS: Indications for TDT were cSDH (n = 275; 27.5%), ICH (n = 291; 29.1%), HYD (n = 316; 31.6%), IIP (n = 112; 11.2%), and OP (n = 6; 0.6%). Overall, primary catheter placement was sufficient in 93.8% of trephinations. Complication rate was 14.1% and mainly related to primary catheter malposition (6.2%), infections (5.2%), and secondary hemorrhage (2.7%); the majority of which were clinically inapparent puncture channel bleedings not requiring surgical intervention. The revision rate was 13%. CONCLUSIONS: Bedside TDT under local anesthesia has proven to be an effective and safe alternative to the conventional burr-hole operative technique as usually performed under general anesthesia in the operation theatre, and may be particularly useful in emergency cases as well as in elderly and multimorbid patients.

[Resting tremor of Parkinson's disease changing into Holmes' tremor by cerebellar hemorrhage: an examination of the pathophysiological mechanism of tremor].

A 71-year-old male who suffered from Hoehn and Yahr stage III Parkinson's disease with bradykinesia, rigidity and a 5-6-Hz tremor at rest in the right extremities was admitted to our hospital due to the sudden onset of vertigo. Right cerebellar hemorrhage was confirmed by CT. The patient's resting tremor in the right extremities disappeared immediately following the cerebellar hemorrhage. Six days later, MRI showed Wallerian degeneration in the cerebello-rubro-thalamic tract. Approximately 5 months later, a 2-3-Hz Holmes' tremor gradually appeared in the right upper extremity. This tremor was improved by increasing L-dopa doses. Case reports of the disappearance of Parkinson's resting tremor and subsequent emergence of Holmes' tremor due to cerebellar lesion are rare. Furthermore, the Wallerian degeneration of the cerebello-rubro-thalamic tract identified on MRI between tremors of the different frequencies is very rare. We hypothesize that the cause of the tremor frequency change was simultaneous damage to the nigro-striatal network and the cerebello-thalamo-cerebral network.

Prevalence, patterns, and predictors of patient-reported non-motor outcomes at 30 days after acute stroke: Prospective observational hospital cohort study.

BACKGROUND: Adverse non-motor outcomes are common after acute stroke and likely to substantially affect quality of life, yet few studies have comprehensively assessed their prevalence, patterns, and predictors across multiple health domains. AIMS: We aimed to identify the prevalence, patterns, and the factors associated with non-motor outcomes 30 days after stroke. METHODS: This prospective observational hospital cohort study-Stroke Investigation in North and Central London (SIGNAL)-identified patients with acute ischemic stroke or intracerebral hemorrhage (ICH) admitted to the Hyperacute Stroke Unit (HASU) at University College Hospital (UCH), London, between August 1, 2018 and August 31, 2019. We assessed non-motor outcomes (anxiety, depression, fatigue, sleep, participation in social roles and activities, pain, bowel function, and bladder function) at 30-day follow-up using the Patient-Reported Outcome Measurement Information System-Version 29 (PROMIS-29) scale and Barthel Index scale. RESULTS: We obtained follow-up data for 605/719 (84.1%) eligible patients (mean age 72.0 years; 48.3% female; 521 with ischemic stroke, 84 with ICH). Anxiety (57.0%), fatigue (52.7%), bladder dysfunction (50.2%), reduced social participation (49.2%), and pain (47.9%) were the commonest adverse non-motor outcomes. The rates of adverse non-motor outcomes in ⩾ 1, ⩾ 2 and ⩾ 3 domains were 89%, 66.3%, and 45.8%, respectively; in adjusted analyses, stroke due to ICH (compared to ischemic stroke) and admission stroke severity were the strongest and most consistent predictors. There were significant correlations between bowel dysfunction and bladder dysfunction (κ = 0.908); reduced social participation and bladder dysfunction (κ = 0.844); and anxiety and fatigue (κ = 0.613). We did not identify correlations for other pairs of non-motor domains. CONCLUSION: Adverse non-motor outcomes were very common at 30 days after stroke, affecting nearly 90% of evaluated patients in at least one health domain, about two-thirds in two or more domains, and almost 50% in three or more domains. Stroke due to ICH and admission stroke severity were the strongest and most consistent predictors. Adverse outcomes occurred in pairs of domains, such as with anxiety and fatigue. Our findings emphasize the importance of a multi-domain approach to effectively identify adverse non-motor outcomes after stroke to inform the development of more holistic patient care pathways after stroke.

Azithromycin reduces hemoglobin-induced innate neuroimmune activation.

Neonatal intraventricular hemorrhage (IVH) releases blood products into the lateral ventricles and brain parenchyma. There are currently no medical treatments for IVH and surgery is used to treat a delayed effect of IVH, post-hemorrhagic hydrocephalus. However, surgery is not a cure for intrinsic brain injury from IVH, and is performed in a subacute time frame. Like many neurological diseases and injuries, innate immune activation is implicated in the pathogenesis of IVH. Innate immune activation is a pharmaceutically targetable mechanism to reduce brain injury and post-hemorrhagic hydrocephalus after IVH. Here, we tested the macrolide antibiotic azithromycin, which has immunomodulatory properties, to reduce innate immune activation in an in vitro model of microglial activation using the blood product hemoglobin (Hgb). We then utilized azithromycin in our in vivo model of IVH, using intraventricular blood injection into the lateral ventricle of post-natal day 5 rat pups. In both models, azithromycin modulated innate immune activation by several outcome measures including mitochondrial bioenergetic analysis, cytokine expression and flow cytometric analysis. This suggests that azithromycin, which is safe for neonates, could hold promise for modulating innate immune activation after IVH.

[Mechanism of Zhongfeng Xingnao Decoction in improving microcirculatory disorders in cerebral hemorrhage based on network pharmacology and molecular docking techniques].

This study aimed to explore the mechanism of Zhongfeng Xingnao Decoction(ZFXN) in intervening microcirculatory di-sorders in cerebral hemorrhage by network pharmacology and molecular docking techniques. The information on the components of ZFXN was obtained through the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP) database, and the predicted targets of chemical components were obtained from PubChem and SwissTargetPrediction. The relevant targets of cerebral hemorrhage and microcirculatory disorders were collected from the GeneCards database, and the common targets of the components and diseases were analyzed by the Database for Annotation, Visualization, and Integrated Discovery(DAVID) for Gene Ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG) enrichment analyses. Visualization of the correlation network was carried out using Cytoscape software to further screen important chemical components for molecular docking prediction with disease targets. The animal experiment validation was performed using modified neurological severity score(mNSS), enzyme-linked immunosorbent assay(ELISA), quantitative real-time polymerase chain reaction(qRT-PCR), immunofluorescence, and Western blot to detect the effects of ZFXN intervention in mice with cerebral hemorrhage. The results showed that there were 31 chemical components and 856 targets in the four drugs contained in ZFXN, 173 targets for microcirculatory disorders in cerebral hemorrhage, and 57 common targets for diseases and components. The enrichment analysis showed that common targets were mainly involved in biological processes, such as cell proliferation and apoptosis, and signaling pathways, such as tumor pathway, viral infection, phosphoinositide-3-kinase/protein kinase B(PI3K/AKT) signaling pathway, and mitogen-activated protein kinase(MAPK) signaling pathway. Molecular docking results revealed that the common components ß-sitosterol of Rhei Radix et Rhizoma, Notoginseng Radix et Rhizoma, and Ginseng Radix et Rhizoma Rubra showed good docking with proto-oncogene tyrosine-protein kinase(SRC), signal transducer and activator of transcription 3(STAT3), phosphoinositide-3-kinase catalytic alpha polypeptide gene(PIK3CA), recombinant protein tyrosine phosphatase non receptor type 11(PTPN11), AKT1, epidermal growth factor receptor(EGFR), calcium adhesion-associated protein beta 1(CTNNB1), vascular endothelial growth factor A(VEGFA), and tumor protein p53(TP53). Moreover, sennoside E of Rhei Radix et Rhizoma showed good docking with MAPK1. The results revealed that the ZFXN relieved the neural injury in mice with cerebral hemorrhage, decreased the expression of S100 calcium-binding protein B(S100ß), neuron specific enolase(NSE), matrix metalloproteinase 9(MMP9), tumor necrosis factor α(TNF-α), interleukin 1ß(IL-1ß), SRC, EGFR, CTNNB1, VEGFA, TP53, glial fibrillary acidic protein(GFAP), and leukocyte differentiation antigen 86(CD86), and increased the expression of p-PI3K, p-AKT, and zona occludens 1(ZO-1). The results indicate that ZFXN may inhibit neuronal apoptosis and inflammatory response through PI3K/AKT/p53 pathway to protect the blood-brain barrier, thereby slowing down microcirculatory impairment in cerebral hemorrhage.

Therapeutic effect of allicin in a mouse model of intracerebral hemorrhage.

Natural compounds with sulfur moiety produce various biological actions that may be beneficial for the therapies of several devastative disorders of the central nervous system. Here we investigated potential therapeutic effect of allicin, an organosulfur compound derived from garlic, in a mouse model of intracerebral hemorrhage (ICH) based on intrastriatal collagenase injection. Daily intraperitoneal administration of allicin (50 mg/kg) from 3 h after induction of ICH afforded neuroprotective effects, as evidenced by the increase of surviving neurons in the hematoma, reduction of axonal transport impairment, and prevention of axon tract injury. In addition, allicin inhibited accumulation of activated microglia/macrophages around the hematoma and infiltration of neutrophils within the hematoma. Allicin also suppressed ICH-induced mRNA upregulation of pro-inflammatory factors such as interleukin 6 and C-X-C motif ligand 2 in the brain, suggesting its anti-inflammatory effect. Moreover, ICH-induced increase of malondialdehyde as well as decrease of total glutathione in the brain was attenuated by allicin. Finally, allicin-treated mice showed better recovery of sensorimotor functions after ICH than vehicle-treated mice. These results indicate that allicin produces a therapeutic effect on ICH pathology via alleviation of neuronal damage, inflammatory responses and oxidative stress in the brain.

The effects of astragaloside IV on gut microbiota and serum metabolism in a mice model of intracerebral hemorrhage.

BACKGROUND: Astragaloside IV (AS-IV) is the main active component of "Astragalus membranaceus (Fisch.) Bunge, a synonym of Astragalus propinquus Schischkin (Fabaceae)", which demonstrated to be useful for the treatment of intracerebral hemorrhage (ICH). However, due to the low bioavailability and barrier permeability of AS-IV, the gut microbiota may be an important key regulator for AS-IV to work. OBJECTIVE: To explore the influences of gut microbiota on the effects of AS-IV on ICH. METHODS: Mice were randomly divided into five groups: sham, ICH, and AS-IV-treated groups (25 mg/kg, 50 mg/kg, and 100 mg/kg). Behavioral tests, brain histopathology, and immunohistochemistry analysis were used to evaluate the degree of brain injury. Western blot was employed to verify peri­hematoma inflammation. The plasma lipopolysaccharide (LPS) leakage, the fluorescein isothiocyanate-dextran permeability, the colonic histopathology, and immunohistochemistry were detected to evaluate the barrier function of intestinal mucosal. Moreover, 16S rDNA sequencing and metabolomic analysis was applied to screen differential bacteria and metabolites, respectively. The correlation analysis was adopted to determine the potential relationship between differential bacteria and critical metabolites or neurological deficits. RESULTS: AS-IV alleviated neurological deficits, neuronal injury and apoptosis, and blood-brain barrier disruption. This compound reduced tumor necrosis factor (TNF)-α expression, increased arginase (Arg)-1 and interleukin (IL)-33 levels around the hematoma. Next, 16S rRNA sequencing indicated that AS-IV altered the gut microbiota, and inhibited the production of conditional pathogenic bacteria. Metabolomic analysis demonstrated that AS-IV regulated the serum metabolic profiles, especially the aminoacid metabolism and peroxisome proliferator-activated receptor (PPAR) signaling pathway. Additionally, AS-IV mitigated intestinal barrier damage and LPS leakage. CONCLUSION: This study provides a new perspective on the use of AS-IV for the treatment of ICH. Among them, gut microbiota and its metabolites may be the key regulator of AS-IV in treating ICH.

[Efficacy of electroacupuncture on acute intracerebral hemorrhage and its effect on serum AQP4 in patients].

OBJECTIVE: To observe the effects on neural function, living ability and mental state of the patients with acute intracerebral hemorrhage (ICH), as well as aquaporin 4 (AQP4) in the serum after treated with electroacupuncture (EA) on the base of routine therapy of western medicine. METHODS: Seventy-two acute ICH patients were randomized into an observation group (36 cases, 4 cases dropped off) and a control group (36 cases, 2 cases dropped off). In the control group, the conventional treatment was delivered such as stopping bleeding, preventing re-hemorrhage, controlling blood pressure, mitigating neural edema and reducing intracranial pressure. In the observation group, on the base of the treatment in the control group, EA was supplemented. Acupoints included Shuigou (GV 26), bilateral Neiguan (PC 6) and Sanyinjiao (SP 6) etc. Electric stimulation was operated at Neiguan (PC 6) and Sanyinjiao (SP 6) on the same side, with disperse-dense wave, and 2 Hz/100 Hz in frequency, tolerable current intensity. Electric stimulation was delivered for 30 min in each treatment, once daily and for 6 times per week. The duration of treatment was 2 weeks in the two groups. Before and after treatment, changes of the scores of National Institutes of Health stroke scale (NIHSS), modified Barthel index (MBI) and mini-mental state examination (MMSE), as well as AQP4 content in the serum were observed in the two groups; the efficacy and safety were compared between the two groups. RESULTS: The NIHSS scores and the serum AQP4 content decreased after treatment when compared with those before treatment in the two groups (P<0.05), while, MBI and MMSE scores increased (P<0.05). In the observation group, NIHSS score and serum AQP4 content were lower than those of the control group (P<0.05), and MBI and MMSE scores were higher (P<0.05). The total effective rate of the observation group was 93.8% (30/32), higher than that of the control group (73.5%, 25/34, P<0.05). The treatment in the two groups was safe, without adverse reactions and events occurring in the patients. CONCLUSION: Electroacupuncture, on the base of conventional treatment of western medicine, can effectively improve the neural function, living ability, mental state and serum AQP4 content of the patients with acute ICH. It is suggested that the effective treatment by electroacupuncture may be related to the regulation of the serum AQP4 content.

Photostimulation of brain lymphatics in male newborn and adult rodents for therapy of intraventricular hemorrhage.

Intraventricular hemorrhage is one of the most fatal forms of brain injury that is a common complication of premature infants. However, the therapy of this type of hemorrhage is limited, and new strategies are needed to reduce hematoma expansion. Here we show that the meningeal lymphatics is a pathway to remove red blood cells from the brain's ventricular system of male human, adult and newborn rodents and is a target for non-invasive transcranial near infrared photobiomodulation. Our results uncover the clinical significance of phototherapy of intraventricular hemorrhage in 4-day old male rat pups that have the brain similar to a preterm human brain. The course of phototherapy in newborn rats provides fast recovery after intraventricular hemorrhage due to photo-improvements of lymphatic drainage and clearing functions. These findings shed light on the mechanisms of phototherapy of intraventricular hemorrhage that can be a clinically relevant technology for treatment of neonatal intracerebral bleedings.

Hyperbaric oxygen ameliorates neuronal injury and neurological function recovery in rats with intracerebral hemorrhage by silencing microRNA-204-5p-targeted chloride channel protein 3.

Hyperbaric oxygen (HBO) therapy is of clinical utility in patients with transient cerebral ischemia. The investigatory study was to identify the potential regulatory mechanism of HBO treatment on neuronal injury and neurological function recovery in rats with intracerebral hemorrhage (ICH). Firstly, the rat model of ICH was established by collagenase, and the experimental rats were treated with HBO at 2.5 absolute atmospheres for 60 min each time. Next, lentivirus interfering with microRNA (miR)-204-5p or chloride channel protein 3 (CLCN3) expression was injected via the tail vein. Afterward, neurological function assessment was conducted, serum S100ß and NSE contents were detected by enzymer-linked immunosorbent assay, and pathological conditions of brain tissue were observed by hematoxylin-eosin staining. Terminal deoxynucleotidyl transferase mediated dUTP nick end labeling staining was used to detect neuronal apoptosis. The results showed that HBO alleviated neuronal injury and neurological function recovery in ICH rats and reduced serum S100ß and NSE content (all P<0.05). At the same time, overexpressing miR-204-5p or depleting CLCN3 further promoted the therapeutic effect of HBO on ICH rats (all P<0.05), while silencing miR-204-5p or elevating CLCN3 did oppositely (all P<0.05). In conclusion, HBO alleviates neuronal injury and neurological function recovery in ICH rats by silencing miR-204-5p-targeted CLCN3.

Electro-nape-acupuncture regulates the differentiation of microglia through PD-1/PD-L1 reducing secondary brain injury in acute phase intracerebral hemorrhage rats.

INTRODUCTION: This study aimed to investigate the effect of electro-nape-acupuncture (ENA) on the differentiation of microglia and the secondary brain injury in rats with acute-phase intracerebral hemorrhage (ICH) through the programmed cell death protein-1/ligand-1 (PD-1/PD-L1) pathway. METHODS: A total of 27 male Sprague-Dawley rats were randomly divided into three groups: sham group, ICH group, and ENA group. The autologous blood infusion intracerebral hemorrhage model was used to study the effects of ENA by administering electroacupuncture at GB20 (Fengchi) and Jiaji (EX-B2) acupoints on 24 h after the modeling, once per day for 3 days. The neurological function damage, hematoma lesion, and inflammatory cell infiltration were measured by the beam walking test and hematoxylin-eosin staining. The expression of PD-1, PD-L1, CD86, CD206, and related cytokines around the hematoma was measured by western blot, quantitative reverse transcription polymerase chain reaction, and immunofluorescence. RESULTS: The ICH group had significant neurological deficits (p < .001), hematoma lesions, and inflammatory cell infiltration. The levels of CD86 protein, inflammatory factors tumor necrosis factors (TNF)-α, interleukin (IL)-1ß, and IL-6 were increased (p < .001), while CD206 protein was reduced (p < .01), and the number of CD86+ /CD11b+ cells was also increased (p < .001) compared to the sham group. However, after ENA intervention, there was a significant reduction in neurological function damage (p < .05), infiltration of inflammatory cells, and the expression levels of CD86+ /CD11b+ cells (p < .05), resulting in the increased expression of PD-1 protein and differentiation of M2 phenotype significantly (p < .001). CONCLUSION: The study concludes that ENA could reduce neurological function damage, inhibit the expression of pro-inflammatory cytokines, and improve the infiltration of inflammatory cells to improve secondary brain injury in acute-phase intracerebral hemorrhage rats. These effects could be related to the increased expression of PD-1 around the lesion, promoting the differentiation of microglia from M1 to M2 phenotype.

[Modulation of autophagy in the rats with acute intracerebral hemorrhage by acupuncture based on JNK pathway].

OBJECTIVE: To investigate the effects of acupuncture on JNK pathway and autophagy level in rats with intracerebral hemorrhage （ICH） and explore the partial mechanism of acupuncture against ICH. METHODS: SD rats were randomly divided into blank group, model group and acupuncture group. Each group was divided into Day 1, Day 3 and Day 7 subgroups respectively, with 5 rats in each group. The autologous blood injection was adopted to duplicate rat model of ICH. In the acupuncture group, the needle was inserted from "Baihui" （GV20） towards "Qubin" （GB7） on the affected side, stimulating for 30 min each time, once daily； the same acupuncture technique was opera-ted in each subgroup for 1, 3 and 7 days, separately. Using Bederson scale, the neurological deficit was evaluated in each group. Western blot was adopted to detect the protein expression levels of Beclin1, LC3Ⅰ/Ⅱ, phosphorylated c-Jun amino-terminal kinase （p-JNK） and the phosphorylated （p）-c-Jun around hematoma lesion of the brain tissue of rats in each group. RESULTS: After treatment, the neurological deficit score of rats in the model group was higher than that of the blank group at each time point （P<0.05）, and the score of the acupuncture group started declining since the 3rd day of treatment when compared with the model group （P<0.05）. At each time point, compared with the blank group, the protein expression levels of LC3Ⅰ/Ⅱ, Beclin1, p-c-Jun and p-JNK was increased （P<0.01）. Compared with the model group, the protein expression level of LC3Ⅰ/Ⅱ was reduced （P<0.05）； the protein expression levels of Beclin1, p-c-Jun and p-JNK was increased （P<0.05, P<0.01） on day 3 and 7 in the acupuncture group. CONCLUSION: Acupuncture can activate the JNK pathway in the brain tissue of rats with ICH and increase the level of autophagy, thereby improving the neurological function of the rats with ICH.

Combined Effect of Early Physical Exercise and Stereotactic Hematoma Evacuation in Patients with Cerebral Hemorrhage Undergoing Hemodialysis.

Objective: This study investigated the combined effect of stereotactic hematoma evacuation and early postoperative physical function exercise in hemodialysis patients with cerebral hemorrhage. Methods: A retrospective study was conducted, including a total of 78 hemodialysis patients with cerebral hemorrhage treated at our hospital between January 2021 and June 2022. The patients were equally allocated to two groups based on different postoperative rehabilitation methods. The control group underwent stereotactic hematoma evacuation, while the study group received additional early postoperative physical function exercise in addition to the intervention provided to the control group. The operative conditions of both groups were recorded, and comparisons were made concerning neural function, limb function, daily activity ability, and complications. Results: There were no significant differences between the two groups regarding operation time, intraoperative blood loss, and hematoma removal rate (P > .05). However, the study group demonstrated a significantly shorter hospital stay (12.98 ± 2.01 days) compared to the control group (15.02 ± 2.07 days), P < .05. Post-treatment, the study group exhibited substantially lower neurological function scores (NIHSS score) (6.37 ± 1.02) compared to the control group (10.03 ± 1.09), P < .05. Additionally, the study group showed significantly higher limb function scores (P < .05) and daily activity ability scores (P < .05) compared to the control group. Moreover, the incidence of complications in the study group was significantly lower than that in the control group (P < .05). Conclusions: Early postoperative physical function exercise following stereotactic hematoma evacuation showed beneficial effects in hemodialysis patients with cerebral hemorrhage. It effectively reduced operation time, restored nerve and limb function, improved daily activity ability, and reduced the incidence of related complications. These approaches hold crucial clinical significance.

Integrated Nursing and Targeted Functional Training for Cerebral Hemorrhage Recovery.

Objective: This study aimed to investigate the impact of integrating medical nursing with targeted functional training interventions on neurological and limb motor function and self-care ability in patients diagnosed with cerebral hemorrhage. Methods: A retrospective cohort study was conducted, including 100 patients diagnosed with cerebral hemorrhage who received interventions at our hospital between January 2020 and June 2022. The patients were divided into two groups: the research group (50 cases) and the reference group (50 cases), based on different intervention methods. The reference group received targeted functional training intervention, while the research group implemented the integration of medical nursing in addition to the reference group intervention. Differences in the National Institutes of Health Stroke Scale (NIHSS) score, Barthel index, Modified Barthel Index (MBI) score, Glasgow Coma Scale (GCS) score, Edinburgh Speech Scale (ESS) score, Fugl-Meyer score, Ability of Daily Living (ADL) score, and efficacy evaluation were observed and compared between the two groups of patients. Results: After nursing, the Fugl-Meyer score and Barthel index score were significantly higher in both groups compared to before nursing, with the research group showing higher scores than the reference group (P < 0.05). There was no significant difference in limb motor function scores between the two groups before nursing (P > 0.05). After the integrated nursing intervention, the NIHSS and ADL scores of both groups were significantly higher than before nursing, with the research group demonstrating higher scores than the reference group (P < 0.05). Conclusions: Integrating medical nursing with targeted functional training interventions has the potential to significantly improve cognitive function, neurological function, and daily activity engagement in patients with cerebral hemorrhage, thereby enhancing their overall quality of life.