Human-induced pluripotent stem cell-derived neural stem cell exosomes improve blood-brain barrier function after intracerebral hemorrhage by activating astrocytes via PI3K/AKT/MCP-1 axis

Cerebral edema caused by blood-brain barrier injury after intracerebral hemorrhage is an important factor leading to poor prognosis.Human-induced pluripotent stem cell-derived neural stem cell exosomes(hiPSC-NSC-Exos)have shown potential for brain injury repair in central nervous system diseases.In this study,we explored the impact of hiPSC-NSC-Exos on blood-brain barrier preservation and the underlying mechanism.Our results indicated that intranasal delivery of hiPSC-NSC-Exos mitigated neurological deficits,enhanced blood-brain barrier integrity,and reduced leukocyte infiltration in a mouse model of intracerebral hemorrhage.Additionally,hiPSC-NSC-Exos decreased immune cell infiltration,activated astrocytes,and decreased the secretion of inflammatory cytokines like monocyte chemoattractant protein-1,macrophage inflammatory protein-1α,and tumor necrosis factor-αpost-intracerebral hemorrhage,thereby improving the inflammatory microenvironment.RNA sequencing indicated that hiPSC-NSC-Exo activated the PI3K/AKT signaling pathway in astrocytes and decreased monocyte chemoattractant protein-1 secretion,thereby improving blood-brain barrier integrity.Treatment with the PI3K/AKT inhibitor LY294002 or the monocyte chemoattractant protein-1 neutralizing agent C1142 abolished these effects.In summary,our findings suggest that hiPSC-NSC-Exos maintains blood-brain barrier integrity,in part by downregulating monocyte chemoattractant protein-1 secretion through activation of the PI3K/AKT signaling pathway in astrocytes.

Mitophagy in intracerebral hemorrhage:a new target for therapeutic intervention

Intracerebral hemorrhage is a life-threatening condition with a high fatality rate and severe sequelae.However,there is currently no treatment available for intracerebral hemorrhage,unlike for other stroke subtypes.Recent studies have indicated that mitochondrial dysfunction and mitophagy likely relate to the pathophysiology of intracerebral hemorrhage.Mitophagy,or selective autophagy of mitochondria,is an essential pathway to preserve mitochondrial homeostasis by clearing up damaged mitochondria.Mitophagy markedly contributes to the reduction of secondary brain injury caused by mitochondrial dysfunction after intracerebral hemorrhage.This review provides an overview of the mitochondrial dysfunction that occurs after intracerebral hemorrhage and the underlying mechanisms regarding how mitophagy regulates it,and discusses the new direction of therapeutic strategies targeting mitophagy for intracerebral hemorrhage,aiming to determine the close connection between mitophagy and intracerebral hemorrhage and identify new therapies to modulate mitophagy after intracerebral hemorrhage.In conclusion,although only a small number of drugs modulating mitophagy in intracerebral hemorrhage have been found thus far,most of which are in the preclinical stage and require further investigation,mitophagy is still a very valid and promising therapeutic target for intracerebral hemorrhage in the long run.

Spi1 regulates the microglial/macrophage inflammatory response via the PI3K/AKT/mTOR signaling pathway after intracerebral hemorrhage

Preclinical and clinical studies have shown that microglia and macrophages participate in a multiphasic brain damage repair process following intracerebral hemorrhage.The E26 transformation-specific sequence-related transcription factor Spi1 regulates microglial/macrophage commitment and maturation.However,the effect of Spi1 on intracerebral hemorrhage remains unclear.In this study,we found that Spi1 may regulate recovery from the neuroinflammation and neurofunctional damage caused by intracerebral hemorrhage by modulating the microglial/macrophage transcriptome.We showed that high Spi1expression in microglia/macrophages after intracerebral hemorrhage is associated with the activation of many pathways that promote phagocytosis,glycolysis,and autophagy,as well as debris clearance and sustained remyelination.Notably,microglia with higher levels of Soil expression were chara cterized by activation of pathways associated with a variety of hemorrhage-related cellular processes,such as complement activation,angiogenesis,and coagulation.In conclusion,our results suggest that Spi1 plays a vital role in the microglial/macrophage inflammatory response following intracerebral hemorrhage.This new insight into the regulation of Spi1 and its target genes may advance our understanding of neuroinflammation in intracerebral hemorrhage and provide therapeutic targets for patients with intracerebral hemorrhage.

ATAT1 deficiency enhances microglia/macrophage-mediated erythrophagocytosis and hematoma absorption following intracerebral hemorrhage

MIcroglia/macrophage-mediated erythrophagocytosis plays a crucial role in hematoma clearance after intracerebral hemorrhage.Dynamic cytoskeletal changes accompany phagocytosis.However,whether and how these changes are associated with microglia/macrophage-mediated erythrophagocytosis remain unclear.In this study,we investigated the function of acetylatedα-tubulin,a stabilized microtubule form,in microglia/macrophage erythrophagocytosis after intracerebral hemorrhage both in vitro and in vivo.We first assessed the function of acetylatedα-tubulin in erythrophagocytosis using primary DiO GFP-labeled red blood cells co-cultured with the BV2 microglia or RAW264.7 macrophage cell lines.Acetylatedα-tubulin expression was significantly decreased in BV2 and RAW264.7 cells during erythrophagocytosis.Moreover,silencingα-tubulin acetyltransferase 1(ATAT1),a newly discoveredα-tubulin acetyltransferase,decreased Ac-α-tub levels and enhanced the erythrophagocytosis by BV2 and RAW264.7 cells.Consistent with these findings,in ATAT1-/-mice,we observed increased ionized calcium binding adapter molecule 1(Iba1)and Perls-positive microglia/macrophage phagocytes of red blood cells in peri-hematoma and reduced hematoma volume in mice with intracerebral hemorrhage.Additionally,knocking out ATAT1 alleviated neuronal apoptosis and pro-inflammatory cytokines and increased anti-inflammatory cytokines around the hematoma,ultimately improving neurological recovery of mice after intracerebral hemorrhage.These findings suggest that ATAT1 deficiency accelerates erythrophagocytosis by microglia/macrophages and hematoma absorption after intracerebral hemorrhage.These results provide novel insights into the mechanisms of hematoma clearance and suggest ATAT1 as a potential target for the treatment of intracerebral hemorrhage.

Optimization of nursing interventions for postoperative mental status recovery in patients with cerebral hemorrhage

BACKGROUND Hypertensive cerebral hemorrhage(HCH),the most common chronic diseases,has become a topic of global public health discussions.AIM To investigate the role of rehabilitative nursing interventions in optimizing the postoperative mental status recovery phase and to provide clinical value for future rehabilitation of patients with HCH.METHODS This randomized controlled study included 120 patients with cerebral HCH who were contained to our neurosurgery department between May 2021–May 2023 as the participants.The participants have randomly sampled and grouped into the observation and control groups.The observation group received the rehabilitation nursing model,whereas the control group have given conventional nursing.The conscious state of the patients was assessed at 7,14,21,and 30 d postoperatively.After one month of care,sleep quality,anxiety,and depression were compared between the two groups.Patient and family satisfaction were assessed using a nursing care model.RESULTS The results showed that the state of consciousness scores of the patients in both groups significantly increased(P<0.05)after surgical treatment.From the 14th day onwards,differences in the state of consciousness scores between the two groups of patients began to appear(P<0.05).After one month of care,the sleep quality,anxiety state,and depression state of patients were significantly better in the observation group than in the control group(P<0.05).Satisfaction with nursing care was higher in the observation group than in the control group(P<0.05).CONCLUSION The rehabilitation nursing model has a more complete system compared to conventional nursing,which can effectively improve the postoperative quality of life of patients with cerebral hemorrhage and improve the efficiency of mental state recovery;however,further analysis and research are needed to provide more scientific evidence.

Exosomal miR-23b from bone marrow mesenchymal stem cells alleviates oxidative stress and pyroptosis after intracerebral hemorrhage

Our previous studies showed that miR-23b was downregulated in patients with intracerebral hemorrhage(ICH). This indicates that miR-23b may be closely related to the patho-physiological mechanism of ICH, but this hypothesis lacks direct evidence. In this study, we established rat models of ICH by injecting collagenase Ⅶ into the right basal ganglia and treating them with an injection of bone marrow mesenchymal stem cell(BMSC)-derived exosomal miR-23b via the tail vein. We found that edema in the rat brain was markedly reduced and rat behaviors were improved after BMSC exosomal miR-23b injection compared with those in the ICH groups. Additionally, exosomal miR-23b was transported to the microglia/macrophages, thereby reducing oxidative stress and pyroptosis after ICH. We also used hemin to mimic ICH conditions in vitro. We found that phosphatase and tensin homolog deleted on chromosome 10(PTEN) was the downstream target gene of miR-23b, and exosomal miR-23b exhibited antioxidant effects by regulating the PTEN/Nrf2 pathway. Moreover, miR-23b reduced PTEN binding to NOD-like receptor family pyrin domain containing 3(NLRP3) and NLRP3 inflammasome activation, thereby decreasing the NLRP3-dependent pyroptosis level. These findings suggest that BMSC-derived exosomal miR-23b exhibits antioxidant effects through inhibiting PTEN and alleviating NLRP3 inflammasome-mediated pyroptosis, thereby promoting neurologic function recovery in rats with ICH.

Piezo1 suppression reduces demyelination after intracerebral hemorrhage

Piezo1 is a mechanically-gated calcium channel.Recent studies have shown that Piezo1,a mechanically-gated calcium channel,can attenuate both psychosineand lipopolysaccharide-induced demyelination.Because oligodendrocyte damage and demyelination occur in intracerebral hemorrhage,in this study,we investigated the role of Piezo1 in intracerebral hemorrhage.We established a mouse model of cerebral hemorrhage by injecting autologous blood into the right basal ganglia and found that Piezo1 was largely expressed soon(within 48 hours)after intracerebral hemorrhage,primarily in oligodendrocytes.Intraperitoneal injection of Dooku1 to inhibit Piezo1 resulted in marked alleviation of brain edema,myelin sheath loss,and degeneration in injured tissue,a substantial reduction in oligodendrocyte apoptosis,and a significant improvement in neurological function.In addition,we found that Dooku1-mediated Piezo1 suppression reduced intracellular endoplasmic reticulum stress and cell apoptosis through the PERK-ATF4-CHOP and inositol-requiring enzyme 1 signaling pathway.These findings suggest that Piezo1 is a potential therapeutic target for intracerebral hemorrhage,as its suppression reduces intracellular endoplasmic reticulum stress and cell apoptosis and protects the myelin sheath,thereby improving neuronal function after intracerebral hemorrhage.

Knockdown of NADPH oxidase 4 reduces mitochondrial oxidative stress and neuronal pyroptosis following intracerebral hemorrhage

Intracerebral hemorrhage is often accompanied by oxidative stress induced by reactive oxygen species,which causes abnormal mitochondrial function and secondary reactive oxygen species generation.This creates a vicious cycle leading to reactive oxygen species accumulation,resulting in progression of the pathological process.Therefore,breaking the cycle to inhibit reactive oxygen species accumulation is critical for reducing neuronal death after intracerebral hemorrhage.Our previous study found that increased expression of nicotinamide adenine dinucleotide phosphate oxidase 4(NADPH oxidase 4,NOX4)led to neuronal apoptosis and damage to the blood-brain barrier after intracerebral hemorrhage.The purpose of this study was to investigate the role of NOX4 in the circle involving the neuronal tolerance to oxidative stress,mitochondrial reactive oxygen species and modes of neuronal death other than apoptosis after intracerebral hemorrhage.We found that NOX4 knockdown by adeno-associated virus(AAV-NOX4)in rats enhanced neuronal tolerance to oxidative stress,enabling them to better resist the oxidative stress caused by intracerebral hemorrhage.Knockdown of NOX4 also reduced the production of reactive oxygen species in the mitochondria,relieved mitochondrial damage,prevented secondary reactive oxygen species accumulation,reduced neuronal pyroptosis and contributed to relieving secondary brain injury after intracerebral hemorrhage in rats.Finally,we used a mitochondria-targeted superoxide dismutase mimetic to explore the relationship between reactive oxygen species and NOX4.The mitochondria-targeted superoxide dismutase mimetic inhibited the expression of NOX4 and neuronal pyroptosis,which is similar to the effect of AAV-NOX4.This indicates that NOX4 is likely to be an important target for inhibiting mitochondrial reactive oxygen species production,and NOX4 inhibitors can be used to alleviate oxidative stress response induced by intracerebral hemorrhage.

Cyclophilin D-induced mitochondrial impairment confers axonal injury after intracerebral hemorrhage in mice

The mitochondrial permeability transition pore is a nonspecific transmembrane channel.Inhibition of mitochondrial permeability transition pore opening has been shown to alleviate mitochondrial swelling,calcium overload,and axonal degeneration.Cyclophilin D is an important component of the mitochondrial permeability transition pore.Whether cyclophilin D participates in mitochondrial impairment and axonal injury after intracerebral hemorrhage is not clear.In this study,we established mouse models of intracerebral hemorrhage in vivo by injection of autologous blood and oxyhemoglobin into the striatum in Thy1-YFP mice,in which pyramidal neurons and axons express yellow fluorescent protein.We also simulated intracerebral hemorrhage in vitro in PC12 cells using oxyhemoglobin.We found that axonal degeneration in the early stage of intracerebral hemorrhage depended on mitochondrial swelling induced by cyclophilin D activation and mitochondrial permeability transition pore opening.We further investigated the mechanism underlying the role of cyclophilin D in mouse models and PC12 cell models of intracerebral hemorrhage.We found that both cyclosporin A inhibition and short hairpin RNA interference of cyclophilin D reduced mitochondrial permeability transition pore opening and mitochondrial injury.In addition,inhibition of cyclophilin D and mitochondrial permeability transition pore opening protected corticospinal tract integrity and alleviated motor dysfunction caused by intracerebral hemorrhage.Our findings suggest that cyclophilin D is used as a key mediator of axonal degeneration after intracerebral hemorrhage;inhibition of cyclophilin D expression can protect mitochondrial structure and function and further alleviate corticospinal tract injury and motor dysfunction after intracerebral hemorrhage.Our findings provide a therapeutic target for preventing axonal degeneration of white matter injury and subsequent functional impairment in central nervous diseases.

A novel aged mouse model of recurrent intracerebral hemorrhage in the bilateral striatum

The current animal models of stroke primarily model a single intracerebral hemorrhage(ICH)attack,and there is a lack of a reliable model of recurrent ICH.In this study,we established 16-month-old C57 B L/6 male mouse models of ICH by injecting collagenaseⅦ-S into the left striatum.Twenty-one days later,we injected collagenaseⅦ-S into the right striatum to simulate recurrent ICH.Our results showed that mice subjected to bilateral striatal hemorrhage had poorer neurological function at the early stage of hemorrhage,delayed recovery in locomotor function,motor coordination,and movement speed,and more obvious emotional and cognitive dysfunction than mice subjected to unilate ral striatal hemorrhage.These findings indicate that mouse models of bilateral striatal hemorrhage can well simulate clinically common recurrent ICH.These models should be used as a novel tool for investigating the pathogenesis and treatment targets of recurrent ICH.

Lung imaging characteristics in a patient infected with Elizabethkingia miricola following cerebral hemorrhage surgery: A case report

BACKGROUND Elizabethkingia miricola is a non-fermenting gram-negative bacterium,which was first isolated from the condensate of the Russian peace space station in 2003.Most studies on this bacterium have been carried out in the laboratory,and clinical case studies are rare.To date,a total of 6 clinical cases have been reported worldwide.CASE SUMMARY We present the first case of postoperative pulmonary infection in a patient with intracerebral hemorrhage due to Elizabethkingia miricola.The imaging character-istics of pulmonary infection were identified and the formulation and selection of the clinical treatment plan for this patient are discussed.CONCLUSION Elizabethkingia miricola infection is rare.When pulmonary infection occurs,computed tomography imaging may show diffuse distribution of a ground glass density shadow in both lungs,the air containing bronchial sign in local areas,thickening of bronchial vascular bundle,and pleural effusion.

Myocardial ischemic changes of electrocardiogram in intracerebral hemorrhage: A case report and review of literature

BACKGROUND Cardiac injury may occur after acute pathology of central nervous system(CNS)without any evidence of primary cardiac diseases.The resulting structural and/or functional changes are called cerebrocardiac syndrome(CCS).The great majority of studies have been performed in patients with subarachnoid hemorrhage(SAH),while CCS data after intracerebral hemorrhage(ICH)are rare.It may cause diagnostic and therapeutic pitfalls for the clinician due to a lack of specific clinical manifestations and diagnostic methods.Understanding the underlying pathophysiological and molecular mechanism(s)following cerebrovascular incidents will help to implement prevention and treatment strategies to improve the prognosis.CASE SUMMARY A 37-year-old man with a history of hypertension presented to our department on an emergency basis because of a sudden dizziness and left limb weakness.Cerebral computed tomography(CT)suggested ICH in the occipital and parietal lobes,and the chosen emergency treatment was hematoma evacuation.Left ventricular(LV)dysfunction occurred after the next 48 h and the electrocardiogram(ECG)showed non-ST elevation myocardial infarction.CCS was suspected first in the context of ICH due to the negative result of the coronary CT angiogram.CONCLUSION Misinterpretation of ischemic-like ECGs may lead to unnecessary or hazardous interventions and cause undue delay of rehabilitation after stroke.Our objective is to highlight the clinical implications of CCS and we hope the differential diagnoses will be considered in patients with acute CNS diseases.

Cholesterol metabolism: physiological versus pathological aspects in intracerebral hemorrhage

Cholesterol is an important component of plasma membranes and participates in many basic life functions,such as the maintenance of cell membrane stability,the synthesis of steroid hormones,and myelination.Cholesterol plays a key role in the establishment and maintenance of the central nervous system.The brain contains 20%of the whole body’s cholesterol,80%of which is located within myelin.A huge number of processes(e.g.,the sterol regulatory element-binding protein pathway and liver X receptor pathway)participate in the regulation of cholesterol metabolism in the brain via mechanisms that include cholesterol biosynthesis,intracellular transport,and efflux.Certain brain injuries or diseases involving crosstalk among the processes above can affect normal cholesterol metabolism to induce detrimental consequences.Therefore,we hypothesized that cholesterol-related molecules and pathways can serve as therapeutic targets for central nervous system diseases.Intracerebral hemorrhage is the most severe hemorrhagic stroke subtype,with high mortality and morbidity.Historical cholesterol levels are associated with the risk of intracerebral hemorrhage.Moreover,secondary pathological changes after intracerebral hemorrhage are associated with cholesterol metabolism dysregulation,such as neuroinflammation,demyelination,and multiple types of programmed cell death.Intracellular cholesterol accumulation in the brain has been found after intracerebral hemorrhage.In this paper,we review normal cholesterol metabolism in the central nervous system,the mechanisms known to participate in the disturbance of cholesterol metabolism after intracerebral hemorrhage,and the links between cholesterol metabolism and cell death.We also review several possible and constructive therapeutic targets identified based on cholesterol metabolism to provide cholesterol-based perspectives and a reference for those interested in the treatment of intracerebral hemorrhage.

Withaferin A inhibits ferroptosis and protects against intracerebral hemorrhage

Recent studies have indicated that suppressing oxidative stress and ferroptosis can considerably improve the prognosis of intracerebral hemorrhage(ICH).Withaferin A(WFA),a natural compound,exhibits a positive effect on a number of neurological diseases.However,the effects of WFA on oxidative stress and ferroptosis-mediated signaling pathways to ICH remain unknown.In this study,we investigated the neuroprotective effects and underlying mechanism for WFA in the regulation of ICH-induced oxidative stress and ferroptosis.We established a mouse model of ICH by injection of autologous tail artery blood into the caudate nucleus and an in vitro cell model of hemin-induced ICH.WFA was injected intracerebroventricularly at 0.1,1 or 5μg/kg once daily for 7 days,starting immediately after ICH operation.WFA markedly reduced brain tissue injury and iron deposition and improved neurological function in a dose-dependent manner 7 days after cerebral hemorrhage.Through in vitro experiments,cell viability test showed that WFA protected SH-SY5Y neuronal cells against hemin-induced cell injury.Enzyme-linked immunosorbent assays in vitro and in vivo showed that WFA markedly decreased the level of malondialdehyde,an oxidative stress marker,and increased the activities of anti-oxidative stress markers superoxide dismutase and glutathione peroxidase after ICH.Western blot assay,quantitative polymerase chain reaction and immunofluorescence results demonstrated that WFA activated the nuclear factor E2-related factor 2(Nrf2)/heme oxygenase-1(HO-1)signaling axis,promoted translocation of Nrf2 from the cytoplasm to nucleus,and increased HO-1 expression.Silencing Nrf2 with siRNA completely reversed HO-1 expression,oxidative stress and protective effects of WFA.Furthermore,WFA reduced hemin-induced ferroptosis.However,after treatment with an HO-1 inhibitor,the neuroprotective effects of WFA against hemin-induced ferroptosis were weakened.MTT test results showed that WFA combined with ferrostatin-1 reduced hemin-induced SH-SY5Y neuronal cell injury.Our findings reveal that WFA treatment alleviated ICH injury-induced ferroptosis and oxidative stress through activating the Nrf2/HO-1 pathway,which may highlight a potential role of WFA for the treatment of ICH.

Injectable collagen scaffold with human umbilical cordderived mesenchymal stem cells promotes functional recovery in patients with spontaneous intracerebral hemorrhage:phase Ⅰ clinical trial

Animal expe riments have shown that injectable collagen scaffold with human umbilical cord-derived mesenchymal stem cells can promote recovery from spinal cord injury.To investigate whether injectable collagen scaffold with human umbilical cord-derived mesenchymal stem cells can be used to treat spontaneous intracerebral hemorrhage,this non-randomized phase I clinical trial recruited patients who met the inclusion criteria and did not meet the exclusion crite ria of spontaneous intracerebral hemorrhage treated in the Characteristic Medical Center of Chinese People’s Armed Police Force from May 2016 to December 2020.Patients were divided into three groups according to the clinical situation and patient benefit:control(n=18),human umbilical cord-derived mesenchymal stem cells(n=4),and combination(n=8).The control group did not receive any transplantation.The human umbilical cord-derived mesenchymal stem cells group received human umbilical cord-derived mesenchymal stem cell transplantation.The combination group received injectable collagen scaffold with human umbilical cord-derived mesenchymal stem cells.Patients who received injectable collagen scaffold with human umbilical cord-derived mesenchymal stem cells had more remarkable improvements in activities of daily living and cognitive function and smaller foci of intra cerebral hemorrhage-related encephalomalacia.Severe adve rse events associated with cell transplantation were not observed.Injectable collagen scaffold with human umbilical cord-derived mesenchymal stem cells appears to have great potential treating spontaneous intracerebral hemorrhage.

Effect of minimally invasive craniotomy combined with edaravone on cerebral oxygen metabolism, cerebrovascular function and oxidative stress in patients with acute cerebral hemorrhage

Objective:To investigate the effects of minimally invasive craniotomy combined with edaravone on cerebral oxygen metabolism, cerebrovascular function and oxidative stress in patients with acute cerebral hemorrhage.Methods:A total of 100 patients with acute cerebral hemorrhage treated in our hospital from March 2015 to February 2017 were randomly divided into control group and observation group. 50 patients in the control group were treated with minimally invasive craniotomy. On the basis of control group, patients in the observation group were treated with edaravone. Cerebral oxygen metabolism, cerebrovascular function and oxidative stress were measured later in both groups.Results:After treatment, the levels of SOD in both groups increased significantly and MDA levels decreased significantly, and SOD level in the observation group was (97.34±1.95) U/mL, which was significantly higher than the control group, MDA level was (2.77±0.11) mol/L and significantly lower than that of the control group after treatment;After treatment, the levels of ET in both groups were significantly lower than those before treatment, and the levels of CGRP were significantly higher than those before treatment. ET level in observation group was (3.24±0.22) μg/L after treatment, which was significantly lower than that in control group (59.67±0.79) pg/mL, which was significantly higher than the control group;After treatment, the levels of SjvO2, CjvO2 and PbtO2 in both groups were significantly increased compared with before treatment, the levels of Da-jvO2 and CEO2 were significantly lower than the level of before treatment, and the levels of SjvO2, The levels of CjvO2 and PbtO2 were (62.93±1.63)%, (99.31±0.94) mL/L and (28.56±1.55) mmHg, which were significantly higher than the control group. Da-jvO2 and CEO2 levels were (51.31±1.13) mL/L and (30.52±0.43)%, which were significantly lower than the control group.Conclusion: Edaravone combined with minimally invasive craniotomy can effectively reduce the level of oxidative stress, improve endothelial function and cerebral oxygen metabolism, and has reliable curative effect. It is worth further clinical application.

Acupuncture inhibits Notch1 and Hes1 protein expression in the basal ganglia of rats with cerebral hemorrhage

Notch pathway activation maintains neural stem cells in a proliferating state and increases nerve repair capacity. To date, studies have rarely focused on changes or damage to signal transduc- tion pathways during cerebral hemorrhage. Here, we examined the effect of acupuncture in a rat model of cerebral hemorrhage. We examined four groups： in the control group, rats received no treatment. In the model group, cerebral hemorrhage models were established by infusing non-hep-arinized blood into the Brain. In the acupuncture group, modeled rats had Baihui （DU20） and Qubin （GBT） acupoints treated once a day for 30 minutes. In the DAPT group, modeled rats had 0.15 μg/mL DAPT solution （10 mL） infused into the brain. Immunohistochemistry and western blot results showed that acupuncture effectively inhibits Notch 1 and Hesl protein expression in rat basal ganglia. These inhibitory effects were identical to DAPT, a Notch signaling pathway inhibitor. Our results suggest that acupuncture has a neuroprotective effect on cerebral hemorrhage by in- hibiting Notch-Hes signaling pathway transduction in rat basal ganglia after cerebral hemorrhage.

Effect of minimally invasive intracranial hematoma drainage on inflammatory factors, serum ferritin and serum P substance in patients with hypertensive cerebral hemorrhage

Objective:To study the effect of minimally invasive intracranial hematoma drainage on inflammatory factors, serum ferritin and serum P substance in patients with hypertensive cerebral hemorrhage.Methods:92 cases of hypertensive cerebral hemorrhage patients in our hospital were selected and randomly divided into 2 groups: minimally invasive group (51 cases) and routine group (41 cases). Minimally invasive intracranial hematoma drainage was performed on the minimally invasive group. Bone flap decompression or small bone window craniotomy were used in the routine group. Tumor necrosis factorα (TNF-α), interleukin-6 (IL-6), high sensitive C reactive protein (hs-CRP) and serum protein (SF), serum substance P (SP) in the 2 groups were detected before treatment and 2 weeks after treatment.Results: The comparison of TNF-α, IL-6, hs-CRP, SP, and SF in the two groups before treatment was not statistically significant (P>0.05). TNF-α, IL-6, hs-CRP and SF in both groups after treatment significantly decreased, compared with that before treatment (P<0.01,P<0.05). TNF-α, IL-6, and SF in minimally invasive group decreased more significantly than that in routine group (P<0.01);The comparison of SP in the two groups after treatment significantly increased compared with that before treatment (P<0.01,P<0.05). SP in minimally invasive group increased more significantly than that in routine group (P<0.05).Conclusions:Compared with bone flap decompression or small bone window craniotomy, minimally invasive intracranial hematoma drainage can inhibit inflammatory reaction, reduce the degree of nerve damage and alleviate clinical symptoms more effectively.

Effect of early enteral nutrition intervention on nerve function, systemic oxidative stress and inflammatory response in patients with hypertensive cerebral hemorrhage

Objective: To study the effect of early enteral nutrition intervention on nerve function, systemic oxidative stress and inflammatory response in patients with hypertensive cerebral hemorrhage. Methods: A total of 98 patients with hypertensive cerebral hemorrhage who received hospitalization in the hospital between April 2015 and February 2017 were collected and divided into control group and observation group by random number table method, 49 cases in each group. Control group received routine enteral nutrition intervention and observation group received early enteral nutrition intervention. The differences in serum levels of nerve function-related indexes, oxidative stress indexes and inflammatory mediators were compared between the two groups of patients before and after intervention. Results: Before intervention, the differences in serum levels of nerve function-related indexes, oxidative stress indexes and inflammatory mediators were not statistically significant between the two groups of patients. After 1 week of intervention, serum S100B, NSE, GFAP, MBP, LPO, MDA, PCT, IL-1β, IL-6 and TNF-α levels of both groups of patients were lower than those before intervention while GSH-PX levels were higher than those before intervention, and serum S100B, NSE, GFAP, MBP, LPO, MDA, PCT, IL-1β, IL-6 and TNF-α levels of observation group were lower than those of control group while GSH-PX level was higher than that of control group. Conclusion:Early enteral nutrition intervention can effectively optimize the nerve function and suppress the systemic oxidative stress and inflammatory response in patients with hypertensive cerebral hemorrhage.

Effect of urokinase in combined with minimally invasive hematoma puncture with YL-1 type needle on the blood sugar and serum CRP in patients with hypertensive cerebral hemorrhage

Objective:To observe the clinical efficacy of urokinase in combined with minimally invasive hematoma puncture with YL-1 type needle in the treatment of hypertensive cerebral hemorrhage and the effect on blood sugar and serum CRP.Methods:A total of 84 patients with hypertensive cerebral hemorrhage who were admitted in our hospital were included in the study and divided into the minimally invasive group (n=53) and the conservative group (n=31) according to different treatment protocols. The patients in the two groups were given routine drug treatments. The patients in the observation group were given urokinase in combined with minimally invasive hematoma puncture with YL-1 type needle. The blood sugar and serum CRP levels before and after treatment in the two groups were compared. CT was performed to reexamine the cerebral hematoma and edema volume.Results: The serum CRP and blood sugar levels 3, 7 and 14 d after treatment in the minimally invasive group were significantly lower than those in the conservative group (P<0.05). The cerebral hematoma and edema volume 1, 3, 7, and 14 d after treatment in the minimally invasive group was significantly lower than that in the conservative group (P<0.05).Conclusions: Urokinase in combined with minimally invasive hematoma puncture with YL-1 type needle in the treatment of hypertensive cerebral hemorrhage can significantly alleviate the brain tissue injury, reduce the systemic inflammatory reaction and blood sugar level, and contribute to the rehabilitation.