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.

“Baihui”(DU20)-penetrating “Qubin”(GB7) acupuncture on blood–brain barrier integrity in rat intracerebral hemorrhage models via the RhoA/ROCK Ⅱ/MLC 2 signaling pathway

Background: Blocking the Rho A/ROCK Ⅱ/MLC 2(Ras homolog gene family member A/Rho kinase Ⅱ/myosin light chain 2) signaling pathway can initiate neuroprotective mechanisms against neurological diseases such as stroke, cerebral ischemia, and subarachnoid hemorrhage. Nevertheless, it is not clear whether and how disrupting the Rho A/ROCK Ⅱ/MLC 2 signaling pathway changes the pathogenic processes of the blood–brain barrier(BBB) after intracerebral hemorrhage(ICH). The present investigation included the injection of rat caudal vein blood into the basal ganglia area to replicate the pathophysiological conditions caused by ICH. Methods: Scalp acupuncture(SA) therapy was performed on rats with ICH at the acupuncture point “Baihui”-penetrating “Qubin,” and the ROCK selective inhibitor fasudil was used as a positive control to evaluate the inhibitory effect of acupuncture on the Rho A/ROCK Ⅱ/MLC 2 signaling pathway. Post-assessments included neurological deficits, brain edema, Evans blue extravasation, Western blot, quantitative polymerase chain reaction, and transmission electron microscope imaging. Results: We found that ROCK Ⅱ acts as a promoter of the Rho A/ROCK Ⅱ/MLC 2 signaling pathway, and its expression increased at 6 h after ICH, peaked at 3 days, and then decreased at 7 days after ICH, but was still higher than the preintervention level. According to some experimental results, although 3 days is the peak, 7 days is the best time point for acupuncture treatment. Starting from 6 h after ICH, the neurovascular structure and endothelial cell morphology around the hematoma began to change. Based on the changes in the promoter ROCK Ⅱ, a 7-day time point was selected as the breakthrough point for treating ICH model rats in the main experiment. The results of this experiment showed that both SA at “Baihui”-penetrating “Qubin” and treatment with fasudil could improve the expression of endothelial-related proteins by inhibiting the Rho A/ROCK Ⅱ/MLC 2 signaling pathway and reduce neurological dysfunction, brain edema, and BBB permeability in rats. Conclusion: This study found that these experimental data indicated that SA at “Baihui”-penetrating “Qubin” could preserve BBB integrity and neurological function recovery after ICH by inhibiting Rho A/ROCK Ⅱ/MLC 2 signaling pathway activation and by regulating endothelial cell–related proteins.

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.

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.

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.

Time-effect relationship of acupuncture on histopathology, ultrastructure, and neuroethology in the acute phase of cerebral hemorrhage

Many clinical studies have addressed the treatment of acute cerebral hemorrhage using acupuncture. However, few studies have examined the relationship between time of acupuncture and curative effect on cerebral hemorrhage. By observing the effect of acupuncture on changes in histopathology, ultrastructure, and neuroethology in a cerebral hemorrhage model of rats, we have directly examined the time-effect relationship of acupuncture. The rat model of cerebral hemorrhage was produced by slowly injecting autologous blood to the right caudate nucleus. The experimental groups were: 3-, 9-, 24-, and 48-hour model groups; and 3-, 9-, 24-, and 48-hour acupuncture groups. The sham-operation group was used for comparison. Acupuncture was performed at the Neiguan(PC6) and Renzhong(DU26) acupoints, twice a day, 6 hours apart, for 5 consecutive days. Brain tissue changes were observed by light microscopy and transmission electron microscopy. Neuroethology was assessed using Bederson and Longa scores. Our results show that compared with the sham-operation and model groups, Bederson and Longa scores were lower in each acupuncture group, with visibly improved histopathology and brain tissue ultrastructure. Further, the results were better in the 3-and 9-hour acupuncture groups than the 24-and 48-hour acupuncture groups. Our findings show that acupuncture treatment can relieve pathological and ultrastructural deterioration and neurological impairment caused by the acute phase of cerebral hemorrhage, and may protect brain tissue during this period. In addition, earlier acupuncture intervention following cerebral hemorrhage(by 3 or 9 hours) is associated with a better treatment outcome.

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.

Clinical Study on the Needling and Drug Treatment of Acute Cerebral Hemorrhage

Researches in recent years have shown that cellular immune factor plays an important role in the generation and development of cerebral hemorrhage1-3.

Effect of Xinglou Chengqi Decoction on the blood brain barrier permeability, nerve damage and neurotrophy in rats with cerebral hemorrhage

Objective: To study the effect of Xinglou Chengqi Decoction on the blood brain barrier permeability, nerve damage and neurotrophy in rats with cerebral hemorrhage. Methods:Adult male SD rats were chosen as the experimental animals and randomly divided into control group, model group and intervention group, model group were made into cerebral hemorrhage models, and intervention group were made into cerebral hemorrhage models and given intragastric administration of Xinglou Chengqi Decoction for intervention. After 14 d of intervention, the blood brain barrier permeability, the expression of apoptosis genes as well as the contents of oxidative products, inflammatory products and nerve cytokines in brain tissues were determined. Results: The blood brain barrier permeability parameter EB level in brain tissue of model group was significantly higher than that of control group, and Bax, FasL, Fas and Caspase-3 mRNA expression as well as MDA, AOPP, TNF-α, HMGB1 and MCP-1 contents in brain tissue were significantly higher than those of control group whereas BDNF, NTF, VEGF and IGF-1 contents were significantly lower than those of control group;the blood brain barrier permeability parameter EB level in brain tissue of intervention group was significantly lower than that of model group, and Bax, FasL, Fas and Caspase-3 mRNA expression as well as MDA, AOPP, TNF-α, HMGB1 and MCP-1 contents in brain tissue were significantly lower than those of model group whereas BDNF, NTF, VEGF and IGF-1 contents were significantly higher than those of model group. Conclusion: Xinglou Chengqi Decoction intervention can reduce the blood brain barrier permeability, relieve the nerve damage and improve the neurotrophy in rat model with cerebral 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.

Bone marrow-derived mesenchymal stem cell-derived exosomeloaded miR-129-5p targets high-mobility group box 1 attenuates neurological-impairment after diabetic cerebral hemorrhage

BACKGROUND Diabetic intracerebral hemorrhage(ICH)is a serious complication of diabetes.The role and mechanism of bone marrow mesenchymal stem cell(BMSC)-derived exosomes(BMSC-exo)in neuroinflammation post-ICH in patients with diabetes are unknown.In this study,we investigated the regulation of BMSC-exo on hyperglycemia-induced neuroinflammation.AIM To study the mechanism of BMSC-exo on nerve function damage after diabetes complicated with cerebral hemorrhage.METHODS BMSC-exo were isolated from mouse BMSC media.This was followed by transfection with microRNA-129-5p(miR-129-5p).BMSC-exo or miR-129-5poverexpressing BMSC-exo were intravitreally injected into a diabetes mouse model with ICH for in vivo analyses and were cocultured with high glucoseaffected BV2 cells for in vitro analyses.The dual luciferase test and RNA immunoprecipitation test verified the targeted binding relationship between miR-129-5p and high-mobility group box 1(HMGB1).Quantitative polymerase chain reaction,western blotting,and enzyme-linked immunosorbent assay were conducted to assess the levels of some inflammation factors,such as HMGB1,interleukin 6,interleukin 1β,toll-like receptor 4,and tumor necrosis factorα.Brain water content,neural function deficit score,and Evans blue were used to measure the neural function of mice.RESULTS Our findings indicated that BMSC-exo can promote neuroinflammation and functional recovery.MicroRNA chip analysis of BMSC-exo identified miR-129-5p as the specific microRNA with a protective role in neuroinflammation.Overexpression of miR-129-5p in BMSC-exo reduced the inflammatory response and neurological impairment in comorbid diabetes and ICH cases.Furthermore,we found that miR-129-5p had a targeted binding relationship with HMGB1 mRNA.CONCLUSION We demonstrated that BMSC-exo can reduce the inflammatory response after ICH with diabetes,thereby improving the neurological function of the brain.

A Comparative Study of Automated Segmentation Methods for Use in a Microwave Tomography System for Imaging Intracerebral Hemorrhage in Stroke Patients

Microwave technology offers the possibility for pre-hospital stroke detection as we have previously demonstrated using non-imaging diagnostics. The focus in this paper is on image-based diagnostics wherein the technical and computational complexities of image reconstruction are a challenge for clinical realization. Herein we investigate whether information about a patient’s brain anatomy obtained prior to a stroke event can be used to facilitate image-based stroke diagnostics. A priori information can be obtained by segmenting the patient’s head tissues from magnetic resonance images. Expert manual segmentation is presently the gold standard, but it is laborious and subjective. A fully automatic method is thus desirable. This paper presents an evaluation of several such methods using both synthetic magnetic resonance imaging (MRI) data and real data from four healthy subjects. The segmentation was performed on the full 3D MRI data, whereas the electromagnetic evaluation was performed using a 2D slice. The methods were evaluated in terms of: i) tissue classification accuracy over all tissues with respect to ground truth, ii) the accuracy of the simulated electromagnetic wave propagation through the head, and iii) the accuracy of the image reconstruction of the hemorrhage. The segmentation accuracy was measured in terms of the degree of overlap (Dice score) with the ground truth. The electromagnetic simulation accuracy was measured in terms of signal deviation relative to the simulation based on the ground truth. Finally, the image reconstruction accuracy was measured in terms of the Dice score, relative error of dielectric properties, and visual comparison between the true and reconstructed intracerebral hemorrhage. The results show that accurate segmentation of tissues (Dice score = 0.97) from the MRI data can lead to accurate image reconstruction (relative error = 0.24) for the intracerebral hemorrhage in the subject’s brain. They also suggest that accurate automated segmentation can be used as a surrogate for manual segmentation and can facilitate the rapid diagnosis of intracerebral hemorrhage in stroke patients using a microwave imaging system.

Effects of scalp acupuncture intervention combined with rehabilitation training on the neurotrophy status and nerve injury in patients with convalescent period of cerebral hemorrhage

Objective: To investigate the effects of scalp acupuncture intervention combined with rehabilitation training on the neurotrophy status and nerve injury in patients with convalescent period of cerebral hemorrhage. Methods: A total of 78 patients with convalescent period of cerebral hemorrhage who were treated in West China Hospital between January 2016 and March 2017 were divided into the control group and the experimental group by random number table, each with 39 cases. Control group received the routine rehabilitation training, and the experimental group received scalp acupuncture intervention combined with rehabilitation training. The differences in neurotrophy status and nerve injury were compared between the two groups before and after intervention. Results: Before intervention, there was no statistically significant difference in neurotrophy status and nerve injury between the two groups. After 1 week of intervention and after 2 weeks of intervention, serum neurotrophy indexes NGF and BDNF contents of experimental group were higher than those of control group;serum nerve injury indexes GFAP, NSE and S100B contents were lower than those of control group;serum inflammatory mediators IL-18, HMGB1 and IFN-γ contents were lower than those of control group. Conclusion: scalp acupuncture intervention combined with rehabilitation training can effectively improve the neurotrophy state and reduce the nerve injury in patients with convalescent period of cerebral hemorrhage.

Effect of minimally invasive evacuation of hematoma combined with Xingnaojing therapy on neurological function injury and cytokine level in patients with hypertensive cerebral hemorrhagen

Objective:To study the effect of minimally invasive evacuation of hematoma combined with Xingnaojing therapy on neurological function damage and cytokine level in patients with hypertensive cerebral hemorrhage.Methods:A total of 80 patients with hypertensive cerebral hemorrhage treated in our hospital between June 2010 and September 2015 were selected as the research subjects, the treatment methods and test results were reviewed, and then they were divided into the control group (n=45) who accepted minimally invasive evacuation of hematoma alone and the observation group (n=35) who accepted minimally invasive evacuation of hematoma combined with Xingnaojing therapy. Before and after treatment, cerebral blood flow detector was used to detect cerebral blood flow parameters;ELISA method was used to detect serum levels of neurological function indexes and inflammatory cytokines;high performance liquid chromatograph was used to detect serum neurotransmitter levels. Results: Before treatment, the differences in cerebral blood flow parameters, neurological function indexes, inflammatory cytokines and neurotransmitters were not statistically significant between two groups of patients. After treatment, cerebral blood flow parameters Q and V levels of observation group were higher than those of control group while R level was lower than that of control group;serum NSE, NPY, IL-1β, IL-4, IL-6, TNF-α, Glu and Asp contents of observation group were lower than those of control group while BDNF and Gly contents were higher than those of control group.Conclusion: Minimally invasive evacuation of hematoma combined with Xingnaojing therapy can improve the neurological function and regulate the synthesis of inflammatory cytokines and neurotransmitters in patients with hypertension cerebral hemorrhage.