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.

Role of triggering receptor expressed on myeloid cells 1/2 in secondary injury after cerebral hemorrhage

Intracerebral hemorrhage(ICH)is a common severe emergency in neurosurgery,causing tremendous economic pressure on families and society and devastating effects on patients both physically and psychologically,especially among patients with poor functional outcomes.ICH is often accompanied by decreased consciousness and limb dysfunction.This seriously affects patients’ability to live independently.Although rapid advances in neurosurgery have greatly improved patient survival,there remains insufficient evidence that surgical treatment significantly improves long-term outcomes.With in-depth pathophysiological studies after ICH,increasing evidence has shown that secondary injury after ICH is related to long-term prognosis and that the key to secondary injury is various immune-mediated neuroinflammatory reactions after ICH.In basic and clinical studies of various systemic inflammatory diseases,triggering receptor expressed on myeloid cells 1/2(TREM-1/2),and the TREM receptor family is closely related to the inflammatory response.Various inflammatory diseases can be upregulated and downregulated through receptor intervention.How the TREM receptor functions after ICH,the types of results from intervention,and whether the outcomes can improve secondary brain injury and the long-term prognosis of patients are unknown.An analysis of relevant research results from basic and clinical trials revealed that the inhibition of TREM-1 and the activation of TREM-2 can alleviate the neuroinflammatory immune response,significantly improve the long-term prognosis of neurological function in patients with cerebral hemorrhage,and thus improve the ability of patients to live independently.

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.

Cerebral arterial blood flow,attention,and executive and cognitive functions in depressed patients after acute hypertensive cerebral hemorrhage

BACKGROUND Intracerebral hemorrhage mainly occurs in middle-aged and elderly patients with hypertension,and surgery is currently the main treatment for hypertensive cerebral hemorrhage,but the bleeding caused by surgery will cause damage to the patient's nerve cells,resulting in cognitive and motor dysfunction,resulting in a decline in the patient's quality of life.AIM To investigate associations between cerebral arterial blood flow and executive and cognitive functions in depressed patients after acute hypertensive cerebral hemorrhage.METHODS Eighty-nine patients with depression after acute hypertensive cerebral hemorrhage who were admitted to our hospital between January 2019 and July 2021 were selected as the observation group,while 100 patients without depression who had acute hypertensive cerebral hemorrhage were selected as the control group.The attention span of the patients was assessed using the Paddle Pin Test while executive function was assessed using the Wisconsin Card Sorting Test(WCST)and cognitive function was assessed using the Montreal Cognitive Assessment Scale(MoCA).The Hamilton Depression Rating Scale(HAMD-24)was used to evaluate the severity of depression of involved patients.Cerebral arterial blood flow was measured in both groups.RESULTS The MoCA score,net scores I,II,III,IV,and the total net score of the scratch test in the observation group were significantly lower than those in the control group(P<0.05).Concurrently,the total number of responses,number of incorrect responses,number of persistent errors,and number of completed responses of the first classification in the WCST test were significantly higher in the observation group than those in the control group(P<0.05).Blood flow in the basilar artery,left middle cerebral artery,right middle cerebral artery,left anterior cerebral artery,and right anterior cerebral artery was significantly lower in the observation group than in the control group(P<0.05).The basilar artery,left middle cerebral artery,right middle cerebral artery,left anterior cerebral artery,and right anterior cerebral artery were positively correlated with the net and total net scores of each part of the Paddle Pin test and the MoCA score(P<0.05),and negatively correlated with each part of the WCST test(P<0.05).In the observation group,the post-treatment improvement was more prominent in the Paddle Pin test,WCST test,HAMD-24 score,and MoCA score compared with those in the pre-treatment period(P<0.05).Blood flow in the basilar artery,left middle cerebral artery,right middle cerebral artery,left anterior cerebral artery,and right anterior cerebral artery significantly improved in the observation group after treatment(P<0.05).CONCLUSION Impaired attention,and executive and cognitive functions are correlated with cerebral artery blood flow in patients with depression after acute hypertensive cerebral hemorrhage and warrant further study.

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.

Postoperative Care for Patients with Hypertensive Intracerebral Hemorrhage

This article summarizes the postoperative care plan for patients with hypertensive intracerebral hemorrhage(HICH).Nursing strategies are analyzed in terms of the level of consciousness,pupil care,vital sign care,temperature care,complication care,and early rehabilitation care,with the goal of providing reference for follow-up care of HICH patients.

Prognostic value of intracranial pressure monitoring for the management of hypertensive intracerebral hemorrhage following minimally invasive surgery

BACKGROUND:The incidence of hypertensive intracerebral hemorrhage(HICH)has been increasing during the recent years in low-and middle-income countries.With high mortality and morbidity rates,it brings huge burden to the families.It lacks evidence regarding the application of intracranial pressure(ICP)monitoring in HICH.In the current study,the authors aimed to evaluate whether ICP monitoring could make any difference on the prognosis of HICH patients after minimally invasive surgery.METHODS:A retrospective review of 116 HICH patients admitted to the Second Affiliated Hospital of Zhejiang University School of Medicine,between 2014 and 2016,was performed.The effects of ICP monitoring on 6-month mortality and favorable outcomes were evaluated by univariate and logistic regression analysis.RESULTS:ICP monitors were inserted into 50 patients.Patients with ICP monitoring had a significantly better outcome(P<0.05).The average in-hospital duration in patients with ICP monitoring was shorter than that in the patients without ICP monitoring(16.68 days vs.20.47 days,P<0.05).Mortality rates between ICP monitoring and no ICP monitoring did not differ significantly(16.0%vs.15.1%,P=0.901).On univariate analysis,age,Glasgow Coma Scale(GCS)on admission and presence of ICP monitor were independent predictors of 6-month favorable outcomes.CONCLUSION:ICP monitoring is associated with a better 6-month functional outcome compared with no ICP monitoring.Future study is still needed to confirm our results and elucidate which subgroup of HICH patients will benefit most from the minimally invasive surgical intervention and ICP monitoring.

Curative effect of surgery combined with nerve growth factor preparation treatment of acute cerebral hemorrhage

Objective: To study the effect of surgery combined with nerve growth factor preparation treatment of acute cerebral hemorrhage on nerve cytokines and nerve injury. Methods: 68 patients with acute cerebral hemorrhage who received emergency minimally invasive evacuation of hematoma in Zigong No. 4 People's Hospital between August 2014 and September 2016 were selected and randomly divided into mNGF group and control group, mNGF group received postoperative mouse nerve growth factor preparation combined with conventional therapy, and control group accepted routine postoperative treatment. 10d, 20d and 30d after treatment, the serum was collected to determine the levels of nerve cytokines and nerve injury molecules. Results: 10d, 20d and 30d after treatment, serum BDNF (5.29±0.88 vs. 3.58±0.61, 6.94±0.93 vs. 3.78±0.55, 9.28±1.13 vs. 4.57±0.62 ng/ml), NTF-α (2.94±0.52 vs. 1.35±0.18, 3.88±0.58 vs. 1.51±0.20, 5.21±0.72 vs. 2.95±0.46 ng/ml), NGF (0.89±0.11 vs. 0.62±0.08, 1.02±0.15 vs. 0.78±0.09, 1.45±0.18 vs. 0.92±0.12 ng/ml) and VEGF (147.53±19.52 vs. 110.38±14.28, 184.95±22.51 vs. 121.29±17.85, 237.49±31.28 vs. 145.38±18.31 pg/ml) levels of mNGF group were significantly higher than those of control group while S100β (1.27±0.20 vs. 2.19±0.33, 0.94±0.14 vs. 1.76±0.25, 0.71±0.09 vs. 1.32±0.17 ng/ml), GFAP (2.08±0.36 vs. 4.42±0.55, 1.65±0.25 vs. 3.57±0.51, 1.31±0.17 vs. 2.93±0.42 pg/ml), NSE (34.21±5.82 vs. 73.19±9.35, 27.58±4.12 vs. 58.76±8.28, 22.12±3.25 vs. 39.52±5.28 ng/ml), MBP (5.28±0.93 vs. 11.28±1.86, 3.89±0.51 vs. 9.12±1.14, 3.12±0.41 vs. 6.79±0.94 ng/ml), MDA (6.97±0.93 vs. 14.21±1.87, 5.02±0.78 vs. 11.75±1.76, 3.57±0.62 vs. 8.12±0.99 μmol/L), AOPP(65.19±9.68 vs. 155.62±19.63, 48.59±7.21 vs. 118.75±16.85, 37.83±5.28 vs. 82.11±10.18 μmol/L) and 8-OHdG (4.77±0.67 vs. 10.28±1.52, 3.52±0.51 vs. 9.38±1.15, 2.33±0.41 vs. 6.52±0.92 ng/ml) levels were significantly lower than those of control group. Conclusion: Surgery combined with nerve growth factor preparation treatment of acute cerebral hemorrhage can improve neural nutritional status and reduce nerve injury degree, and it is beneficial to the recovery of neural function.

Short-term effect and long-term prognosis of neuroendoscopic minimally invasive surgery for hypertensive int-racerebral hemorrhage

BACKGROUND Hypertensive intracerebral hemorrhage is a common critical disease of the nervous system,comprising one fifth of all acute cerebrovascular diseases and has a high disability and mortality rate.It severely affects the patients’quality of life.AIM To analyze the short-term effect and long-term prognosis of neuroendoscopic minimally invasive surgery for hypertensive intracerebral hemorrhage.METHODS From March 2018 to May 2020,118 patients with hypertensive intracerebral hemorrhage were enrolled in our study and divided into a control group and observation group according to the surgical plan.The control group used a hard-channel minimally invasive puncture and drainage procedure.The observation group underwent minimally invasive neuroendoscopic surgery.The changes in the levels of serum P substances(SP),inflammatory factors[tumor necrosis factor-α,interleukin-6(IL-6),IL-10],and the National Hospital Stroke Scale(NIHSS)and Barthel index scores were recorded.Surgery related indicators and prognosis were compared between the two groups.RESULTS The operation time(105.26±28.35)of the observation group was min longer than that of the control group,and the volume of intraoperative bleeding was 45.36±10.17 mL more than that of the control group.The hematoma clearance rates were 88.58%±4.69%and 94.47%±4.02%higher than those of the control group at 48 h and 72 h,respectively.Good prognosis rate(86.44%)was higher in the observation group than in the control group,and complication rate(5.08%)was not significantly different from that of the control group(P>0.05).The SP level and Barthel index score of the two groups increased(P<0.05)and the inflam-matory factors and NIHSS score decreased(P<0.05).The cytokine levels,NIHSS score,and Barthel index score were better in the observation group than in the control group(P<0.05).CONCLUSION Neuroendoscopic minimally invasive surgery is more complicated than hard channel minimally invasive puncture drainage in the treatment of hypertensive intracerebral hemorrhage;however,hematoma clearance is more thorough,and the short-term effect and long-term prognosis are better than hard channel minimally invasive puncture drainage.

Effects of ulinastatin combined with surgery on nerve injury, oxygen free radicals and inflammatory factors production of patients with hypertensive intracerebral hemorrhage

Objective: To study the effects of ulinastatin combined with surgery on nerve injury, oxygen free radicals and inflammatory factors production of patients with hypertensive intracerebral hemorrhage. Methods: The patients with hypertensive intracerebral hemorrhage received surgical treatment in our hospital during February 2015 - December 2017 were selected and divided into two groups by random number table. The observation group received ulinastatin combined surgery and the control group received conventional medicine combined with surgery. Before treatment and 1 weeks after treatment, serum levels of nerve damage markers, neurotrophic indexes, oxygen free radicals production indexes and inflammatory cytokines were measured. Results: After treatment, the contents of NSE, VILIP-1, GFAP, S100B, MDA, AOPP, 8-OHdG, NO, ET-1, TNF-α, sICAM-1, sVCAM-1, sICAM-1 of two groups were all decreased, the contents of BDNF, NGF, VEGF, IGF-I were all increased and the decreasing trend of NSE, VILIP-1, GFAP, S100B, MDA, AOPP, 8-OHdG, NO, ET-1, TNF-α, sICAM-1, sVCAM-1, sICAM-1 of observation group was more obvious than that of the control group, the increasing trend of BDNF, NGF, VEGF, IGF-I content was more obvious than that of the control group. Conclusion: The use of ulinastatin combined with surgery in the treatment of hypertensive intracerebral hemorrhage can significantly reduce the damage of nerve function and reduce the production of oxygen free radicals and inflammatory factors.

Effects of endoscopic surgery via different approaches on neurological function and complications in patients with hypertensive cerebral hemorrhage

Objective:To study the effects of different approaches of neuroendoscopic treatment on neurological function and complications of patients with hypertensive cerebral hemorrhage.Methods:72 patients with hypertensive cerebral hemorrhage diagnosed and treated in our hospital were selected as research objects.They were divided into the study group(n=37)and the control group(n=35)according to different approaches.The study group was the lateral fissure approach,and the control group was the anterior coronary suture approach.The curative effect,hematoma clearance,postoperative wake time,postoperative cerebral edema,daily living ability,neurological function,and complications in the two groups were observed.Results:The efficacy of the study group was higher than that of the control group,and the differences were statistically significant(P<0.05).The postoperative cerebral edema,postoperative wake time,and postoperative intracranial pressure in the study group were lower than those in the control group,and the hematoma clearance rate in the study group was higher than that in the control group,the differences were statistically significant(P<0.05);At 3 and 6 months after treatment,the daily living ability of the study group was higher than that of the control group,and neurological dysfunction of the study group was lower than that of the control group(P<0.05);The complication rate of the study group was lower than that of the control group(P<0.05);There was no significant difference in mortality rate between the two groups(P>0.05).Conclusion:Different approaches have different effects on patients with hypertensive intracerebral hemorrhage.Compared with the anterior coronary suture approach,the lateral fissure approach has less damage to nerve function,and has less postoperative complications.

Effects of mild hypothermia combined with minimally invasive surgery on the degree of nerve injury and the generation of toxic metabolites in patients with hypertensive cerebral hemorrhage

Objective: To explore the effects of mild hypothermia combined with minimally invasive surgery on the degree of nerve injury and the generation of toxic metabolites in patients with hypertensive cerebral hemorrhage. Methods: A total of 138 patients with hypertensive cerebral hemorrhage who received treatment in the hospital between December 2015 and March 2017 were collected and divided into control group (n=69) and mild hypothermia group (n=69) by random number table method. Control group received conventional minimally invasive surgery, and mild hypothermia group received mild hypothermia combined with minimally invasive surgery. The differences in the serum contents of nerve injury indexes, excitatory amino acids and oxidative metabolites were compared between two groups of patients before treatment and after 1 week of treatment. Results: There was no statistically significant difference in serum levels of nerve injury indexes, excitatory amino acids and oxidative metabolites between the two groups. 1 week after treatment, serum pro-BNP, h-FABP, MBP and NSE levels of mild hypothermia group were lower than those of control group;serum excitatory amino acids Glu and Asp levels were lower than those of control group;oxidative metabolites ROS, MDA, AOPPs and LHP levels were lower than those of control group. Conclusion: Mild hypothermia combined with minimally invasive surgery can effectively relieve the nerve injury and reduce the secretion of excitatory amino acids, oxidative metabolites and so on in patients with hypertensive cerebral hemorrhage.

Therapeutic potential of stem cells in subarachnoid hemorrhage

Aneurysm rupture can result in subarachnoid hemorrhage,a condition with potentially severe consequences,such as disability and death.In the acute stage,early brain injury manifests as intracranial pressure elevation,global cerebral ischemia,acute hydrocephalus,and direct blood–brain contact due to aneurysm rupture.This may subsequently cause delayed cerebral infarction,often with cerebral vasospasm,significantly affecting patient outcomes.Chronic complications such as brain volume loss and chronic hydrocephalus can further impact outcomes.Investigating the mechanisms of subarachnoid hemorrhage-induced brain injury is paramount for identifying effective treatments.Stem cell therapy,with its multipotent differentiation capacity and anti-inflammatory effects,has emerged as a promising approach for treating previously deemed incurable conditions.This review focuses on the potential application of stem cells in subarachnoid hemorrhage pathology and explores their role in neurogenesis and as a therapeutic intervention in preclinical and clinical subarachnoid hemorrhage studies.

Traditional craniotomy versus current minimally invasive surgery for spontaneous supratentorial intracerebral haemorrhage:A propensity-matched analysis

BACKGROUND Minimally invasive surgery(MIS)and craniotomy(CI)are the current treatments for spontaneous supratentorial cerebral haemorrhage(SSTICH).AIM To compare the efficacy and safety of MIS and CI for the treatment of SSTICH.METHODS Clinical and imaging data of 557 consecutive patients with SSTICH who underwent MIS or CI between January 2017 and December 2022 were retrospectively analysed.The patients were divided into two subgroups:The MIS group and CI group.Propensity score matching was performed to minimise case selection bias.The primary outcome was a dichotomous prognostic(favourable or unfavourable)outcome based on the modified Rankin Scale(mRS)score at 3 months;an mRS score of 0–2 was considered favourable.RESULTS In both conventional statistical and binary logistic regression analyses,the MIS group had a better outcome.The outcome of propensity score matching was unexpected(odds ratio:0.582;95%CI:0.281–1.204;P=0.144),which indicated that,after excluding the interference of each confounder,different surgical modalities were more effective,and there was no significant difference in their prognosis.CONCLUSION Deciding between MIS and CI should be made based on the individual patient,considering the hematoma size,degree of midline shift,cerebral swelling,and preoperative Glasgow Coma Scale score.

Henoch-Schonlein purpura with intestinal perforation and cerebral hemorrhage: A case report

Henoch-Schonlein purpura (HSP) with intestinal perforation and cerebral hemorrhage is a very rare clinical condition. There has been no report of HSP complicated with both intestinal perforation and cerebral hemorrhage until October 2012. Here we describe a case of HSP with intestinal perforation and cerebral hemorrhage in a 5-year-old girl. Plain abdominal radiograph in the erect position showed heavy gas in the right subphrenic space with an elevated diaphragm. Partial resection of the small intestine was performed, and pathological analysis suggested chronic suppurative inflammation in all layers of the ileal wall and mesentery. Seventeen days after surgery, cerebral hemorrhage developed and the patient died.

Preventive and therapeutic effect of simvastatin on secondary inflammatory damage of rats with cerebral hemorrhage

Objective:To investigate the preventive and therapeutic effect and mechanism of simvastatin on secondary inflammatory damage of rats with cerebral hemorrhage.Methods:Sixty SD rat aged 9-12 weeks were chosen and divided into the control group,model group and simvastatintreated group randomly with 20 rats in each group.Rats in the model group and simvastatintreated group were infused with autologous fresh uncoagulated blood to the right brain tissue of the basal ganglia to build the cerebral hemorrhage model,while rats in the control group were treated with the same amount of normal saline.Then,rats in the simvastatin-treated group were given a gavage of 3 mg/kg of simvastatin once a day after modeling.Rats in the three groups were given nerve dysfunction score(NDS) and wet-dry weighting method was used to detect the brain water content(BWC) of brain tissues around the lesion of the rats.Then Nissl staining was conducted and the undamaged neurons were counted.Immunohistochemical SP method was applied to count the number of NF-d the immuno fluorκB,TLR4 and IL-1escence method wasβ positive cells in brain tissues around the lesions,an employed to determine the expression levels of NF-κB,TLR4 and IL-1me points were aβ proteins.Results:The NDS results of the simvastatin-treated group at all till significantly higher than those of the model group(P < 0.05);the BWC values of the simvastatin-treated group at all time points were all significantly lower than those of the model group at the same periods(P < 0.05);the number of the undamaged neurons around the lesions of the simvastatin-treated group at all time points were all significantly higher than those of the model group(P < 0.05);seven days after treatment,the number of the NF-κB,TLR4 and IL-1β positive cells in brain tissues around the lesions of the simvastatin-treated group were all significantly lower than those of the model group(P < 0.05),and its expression levels of NF-ower than those of the model group(κB,TLR4 and IL-1P < 0.05).Conclusioβ protein were also significantly lns:Simvastatin can inhibit the expressions of NF-κB,TLR4 and IL-1β proteins in rats with cerebral hemorrhage,and protect neurons and reduce secondary inflammatory damages by down-regulating the above protein-mediated inflammatory responses.

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.

Acupuncture promotes functional recovery after cerebral hemorrhage by upregulating neurotrophic factor expression

Acupuncture is widely used in the treatment of cerebral hemorrhage,and it improves outcomes in experimental animal models and patients.However,the mechanisms underlying the effectiveness of acupuncture treatment for cerebral hemorrhage are still unclear.In this study,a model of intracerebral hemorrhage was produced by injecting 50μL autologous blood into the caudate nucleus in Wistar rats.Acupuncture at Baihui(DU20)and Qubin(GB7)acupoints was performed at a depth of 1.0 inch,12 hours after blood injection,once every 24 hours.The needle was rotated at 200 r/min for 5 minutes,For each 30-minute session,needling at 200 r/min was performed for three sessions,each lasting 5 minutes.For the positive control group,at 6 hours,and 1,2,3 and 7 days after induction of hemorrhage,the rats were intraperitoneally injected with 1 mL aniracetam(0.75 mg/mL),three times a day.The Bederson behavioral test was used to assess palsy in the contralateral limbs.Western blot assay was used to examine the expression levels of Nestin and basic fibroblast growth factor in the basal ganglia.Immunohistochemistry was performed to count the number of Nestin-and glial cell line-derived neurotrophic factor-positive cells in the basal ganglia.Acupuncture effectively reduced hemorrhage and brain edema,elevated the expression levels of Nestin and basic fibroblast growth factor in the basal ganglia,and increased the number of Nestin-and glial cell line-derived neurotrophic factor-positive cells in the basal ganglia.Together,these findings suggest that acupuncture promotes functional recovery after cerebral hemorrhage by increasing the expression of neurotrophic factors.The study was approved by the Committee for Experimental Animals of Heilongjiang Medical Laboratory Animal Center(approval No.2017061001)on June 10,2017.

Nimodipine for treatment of perifocal edema following aspiration and drainage in patients with cerebral hemorrhage

BACKGROUND： After cephalophyma removal, perifocal edema does not disappear subsequently, but progresses occasionally. Nimodipine can improve cerebral blood flow, so it maybe reduce cerebral edema area, and speed up the absorption of edematous fluid. OBJECTIVE： To observe the effect of nimodipine on perifocal edema area and neurologic function in patients with hypertensive intracerebral hemorrhage （HICH） following stereotaxic aspiration. DESIGN： Clinical controlled observation. SETTING： Department of Neurology, Third Hospital Affiliated to Liaoning Medical University. PARTICIPANTS： Totally 116 HICH inpatients admitted to the Department of Neurology, Third Hospital Affiliated to Liaoning Medical University from January 2003 to January 2005 were involved in this experiment. They all met the classification and diagnosis of cerebrovascular disease proposed in 1995 4th National Conference on Cerebrovascular Disease. The bleeding volume ≥ 35 mL was confirmed by skull CT. The involved patients, 64 male and 52 femlae, averaged 63 years old, ranging from 40 to 70 years. All the patients suffered from unilateral cerebral hemisphere hemorrhage, and muscle strength of paralyzed limb was less than degree Ⅲ. Informed consents of therapeutic items were obtained from all the patients and relatives. METHODS： ① According to different wills, the patients were assigned into treatment group （n =60） and control group （n =56）. In the treatment group, the involved patients, 32 male, 28 female, averaged 63 years. They underwent operation and administration of nimodipine. In the control group, the involved patients, 30 male and 26 female, averaged 62 years old. They all underwent operation simply. Patients in the two groups all received stereotaxic aspiration, drainage, dehydration, haemostasis, antiinflammation, blood pressure controlling and other treatments. Patients in the treatment group were also intravenously injected with 0.2 g/L nimodipine（Bayer Medicine Health Care Co., Ltd., Lot No. 021127） at 10 mg/d. One course of treatment was 15 days. ② According to the clinical neurologic function deficit score of stroke proposed in the 4th National Conference on Cerebrovascular Disease （mild： 0-15 points; moderate： 16-30 points; severe： 31-45 points）, neurologic function deficit score and the largest perifocal edema area of patients in two groups were recorded on the 1st, 7th and 15th days after operation. The differences in perifocal edema area and neurologic deficit score between on the 1st and 7th days and between on the 7th and 15th days were calculated. MAIN OUTCOME MEASURES： Changes in the neurologic function deficit score and the largest perifocal edema area. RESULTS： Two of treatment group and 16 of control group died. Finally, 98 patients participated in the final analysis. ①In the treatment group, the difference in the largest perifocal edema area on the postoperative 7th and 15th days and on the 1st day was （1.02±0.07） and （1.86±0.10） cm2, respectively, which changed more significantly as compared with control group, respectively [（0.02±0.04）,（0.61±0.09） cm2,P 〈 0.01]. ② The difference in neurologic function deficit score between on the postoperative 15th and 1st days in the treatment group was larger than that in the control group [（7.23±0.22）,（2.68±0.32） points,P 〈 0.01]. CONCLUSION： Nimodipine obviously reduces perifocal edema area of patients with cerebral hemorrhage following aspiration and drainage, and promotes the recovery of neurologic function.