Systematic review and meta-analysis of the efficacy and safety of cerebrospinal fluid drainage and lumbar puncture in the treatment of cerebrospinal fluid leakage after craniocerebral injury.

BACKGROUND: Commonly used clinical treatments for intracranial hypertension include continuous lumbar cerebrospinal fluid drainage (CLCFD) and conventional lumbar puncture. However, lumbar puncture is more invasive, requires multiple punctures. CLCFD has less trauma, and drainage can be manipulated to avoid repeated lumbar puncture. However, CLCFD may also lead to complications such as intracranial hematoma and intracranial pneumothorax. Therefore, there is no agreement on which method is more effective. This study evaluated the efficacy of CLCFD and conventional lumbar puncture in the treatment of cerebrospinal fluid leakage after craniocerebral injury. METHODS: The search terms 'brain injury' and 'CLCFD' were used to search CNKI, Wanfang, VIP, Longyuan, PubMed, Embase, Cochrane Library and other databases (from inception to November 1, 2022). Inclusion criteria: (I) randomized controlled trials (RCTs), CLCFD and conventional lumbar puncture drainage for patients with cerebrospinal fluid leakage after craniocerebral injury; (II) evaluation of indicators such as cerebrospinal fluid leakage stop time, clearance time, intracranial infection and complications. Cochrane systematic review was performed to assess the quality of the literature. RevMan 5.3 software was used for systematic analysis. RESULTS: A total of 8 studies, involving 568 patients. There is some publication bias in the statistics. The cessation time of cerebrospinal fluid leakage (95% confidence interval (CI): -3.65 to -2.86, Z=16.21, P<0.00001), the time to return to normal pressure (95% CI: -3.13 to -2.09, Z=9.79, P<0.00001), cerebrospinal fluid clearing time (95% CI: -1.96 to -1.09, Z=6.91, P<0.00001), hospitalization time (95% CI: -1.99 to -0.91, Z=5.27, P<0.00001), incidence of intracranial infection (95% CI: 0.07-0.27, Z=5.84, P<0.00001) and complications (95% CI: 0.10-0.43, Z=4.22, P<0.0001) in the CLCFD group were lower than those in the conventional group. The cure rate of the CLCFD group was significantly higher than that of the conventional group (OR =3.75, 95% CI: 2.26-6.23, Z=5.11, P<0.00001); the difference in mortality between the two groups was not statistically significant (P>0.05). CONCLUSIONS: Compared with conventional lumbar puncture, CLCFD can significantly increase the cure rate, shorten the recovery time of cerebrospinal fluid, and significantly reduce the incidence of intracranial infections, reduce complications, is conducive to the prognosis of patients.

Selective brain hypothermia attenuates focal cerebral ischemic injury and improves long-term neurological outcome in aged female mice.

AIMS: This study aimed to investigate the effects of mild selective brain hypothermia on aged female ischemic mice. METHODS: A distal middle cerebral artery occlusion (dMCAO) model was established in aged female mice, who were then subjected to mild selective brain hypothermia immediately after the dMCAO procedure. Neurological behavioral examinations were conducted prior to and up to 35 days post-ischemia. Infarct volume, brain atrophy, pro-inflammation, and anti-inflammation microglia/macrophages phenotype and white matter injury were evaluated by immunofluorescence staining. Correlations between neurological behaviors and histological parameters were evaluated by Pearson product linear regression analysis. RESULTS: Sensorimotor and cognitive function tests confirmed the protective effect of mild selective brain hypothermia in elderly female ischemic mice. In addition, hypothermia decreased the infarct volume and brain atrophy induced by focal cerebral ischemia. Furthermore, hypothermia alleviated ischemia-induced short-term and long-term white matter injury, which was correlated with behavioral deficits. Finally, hypothermia suppressed the harmful immunological response by promoting the transformation of pro-inflammatory microglia/macrophages to anti-inflammatory phenotype. This polarization was negatively correlated with neuronal loss and white matter injury. CONCLUSION: Mild selective brain hypothermia promoted long-term functional recovery by alleviating white matter damage in an aged female mouse model of ischemia.

Effect of Ginkgolide in Ischemic Stroke patients with large Artery Atherosclerosis: Results from a randomized trial.

BACKGROUND: Dual antiplatelet therapy is considered beneficial in acute ischemic stroke (AIS) patients with intracranial artery stenosis (ICAS), with more bleeding events. Ginkgolide is shown to reduce platelet activation after infarction, which might be of benefit in AIS. We aimed to explore the effect of Ginkgolide in AIS patients with ICAS. METHODS: This was a randomized, double-blinded, placebo-controlled trial conducted at 61 centers in China. Within 72 h after onset, consecutive patients diagnosed as AIS with ICAS were randomized to either Ginkgolide or placebo treatment. The primary outcome was the composite of mortality and recurrent stroke (ischemic or hemorrhagic) during first 4 weeks in an intention-to-treat analysis. Secondary functional outcome was assessed by modified Rankin Scale and improvement of stroke severity was assessed by National Institution of Health Stroke Scale at day 28. Safety outcome was measured by the rate of severe adverse event (SAE). RESULTS: There were 936 patients randomized to either Ginkgolide or placebo treatment. Their average age was 64.2 ± 10.4 years old and 36.0% of the patients were female. The composite index event occurred in six patients in placebo group, and none occurred in Ginkgolide group (risk ratio 1.01; 95% CI 1.00-1.02). There were more patients who achieved favorable outcome in Ginkgolide group, compared with that of the placebo group (OR 2.16, 95%CI 1.37-3.41). SAE occurred in five (1.1%) patients in the Ginkgolide group and three (0.6%) in the placebo group (OR0.60, 95CI% 0.14-2.53). Intracranial hemorrhage occurred in 1/473 (0.2%) in the placebo group. CONCLUSIONS: Ginkgolide, working as PAF antagonist, may reduce recurrent stroke in AIS with ICAS patients within 72 hours after onset. It might be an optional treatment in moderate-to-severe AIS patients with ICAS. (http://www.chictr.org.cn Number as ChiCTR-IPR-17012310).

Naringin Targets NFKB1 to Alleviate Oxygen-Glucose Deprivation/Reoxygenation-Induced Injury in PC12 Cells Via Modulating HIF-1α/AKT/mTOR-Signaling Pathway.

This study was designed to investigate the effect of naringin in oxygen-glucose deprivation/reoxygenation (OGD/R) model and its mechanism. The target gene of naringin and the enriched pathways of the gene were searched and identified using bioinformatics analysis. Then OGD/R model was built using PC12 cells, after which the cells were treated with different concentrations of naringin. Subsequently, cell proliferation and apoptosis were evaluated by cell counting kit-8 (CCK-8) and flow cytometry assays, respectively. Meanwhile, the expression of NFKB1 in PC12 cells underwent OGD/R-induced injury was detected by qRT-PCR, while apoptosis-related and pathway-related proteins were checked by Western blot. DCF-DA kit was utilized to measure the level of ROS. Our results revealed that NFKB1, which was upregulated in MACO rats and OGD/R-treated PC12 cells, was a target gene of naringin. Naringin could alleviate OGD/R-induced injury via promoting the proliferation, and repressing the apoptosis of PC12 cells through regulating the expression of NFKB1 and apoptosis-associated proteins and ROS level. Besides, the depletion of NFKB1 was positive to cell proliferation but negative to cell apoptosis. Moreover, the depletion of NFKB1 enhanced the influences of naringin on cell proliferation and apoptosis as well as the expression of apoptosis-related proteins and ROS level. Western blotting indicated that both naringin treatment and depletion of NFKB1 could increase the expression of HIF-1α, p-AKT, and p-mTOR compared with OGD/R group. What's more, treatment by naringin and si-NFKB1 together could significantly increase these effects. Nevertheless, the expression of AKT and mTOR among each group was almost not changed. In conclusion, naringin could prevent the OGD/R-induced injury in PC12 cells in vitro by targeting NFKB1 and regulating HIF-1α/AKT/mTOR-signaling pathway, which might provide novel ideas for the therapy of cerebral ischemia-reperfusion (I/R) injury.

LncRNA FGD5-AS1 acts as a competing endogenous RNA for miRNA-223 to lessen oxygen-glucose deprivation and simulated reperfusion (OGD/R)-induced neurons injury.

The purpose of this study was to evaluate whether FGD5-AS1 participates in oxygen-glucose deprivation and simulated reperfusion (OGD/R)-induced neurons injury and the detailed mechanism. An OGD/R model was established using the primary cortical neuron isolated from the brains of Sprague-Dawley rats. qRT-PCR and western blot were performed to de-tect the RNA and protein expression levels, respectively. Cell counting kit 8 (CCK8) and flow cytometry assays were used to evaluate the proliferation and apoptosis of neurons. The luciferase reporter assay was used to verify the interaction between lncRNA FGD5-AS1 and miRNA-223. We found that the expression of FGD5-AS1 is decreased in neurons suffering from OGD/R. Up-regulation of FGD5-AS1 could recover proliferation and inhibit apoptosis of OGD/R-injured neurons. In addition, the interaction between FGD5-AS1 and miRNA-223 were verified. The expression of miRNA-223 was negatively correlated with the level of FGD5-AS1. In turn, the expression of insulin-like growth factor-1 receptor (IGFIR, a target gene of miR-223) was positively associated with the level of FGD5-AS1. Simultaneously down-regulating miR-223 and over-expressing FGD5-AS1 as well as IGF1R exhibited an additional effect of extenuating OGD/R damage i.e. increasing neuron proliferation and reducing neuron apoptosis. In conclusion, our findings indicated that FGD5-AS1 may protect the neuron against OGD/R injury via acting as a ceRNA for miR-223 to mediate IGF1R expression, which contributes to a deeper understanding of ischemic stroke and provide a promising therapeutic target for this disease.

miRNA-223 regulates ischemic neuronal injury by targeting the type 1 insulin-like growth factor receptor (IGF1R).

Cerebral ischemia injury seriously endangers human health and its molecular mechanism is still not fully understood. microRNA-223 (miR-223) has been reported to be involved in many physiological functions but the specific role of miRNA-223 in ischemic neuronal injury is still unclear. An oxygen-glucose deprivation and simulated reperfusion (OGD/R) model was constructed here to investigate the possible role miR-223 played in ischemic neuronal injury. The expression of miRNA-223 in the OGD/R model and its effect on cell proliferation were studied by qPCR and CCK8 assay. We observed that miR-223 was significantly over-expressed after OGD/R treatment and it suppressed significantly cortical neurons proliferation. To further study the mechanism involved, we predicted and examined the potential targets of miR-223 by targetscan, qPCR, western blot and luciferase reporter assay. We found that the expression level of type 1 insulin-like growth factor receptor (IGF1R) was negatively associated with the level of miR-223. Furthermore, the relative luciferase activity of pmirGLO-WT was inhibited obviously, while no significant change was observed in the pmirGLO-Mut group, indicating that miR-223 could bind to IGF1R. Similar cell proliferation suppression caused by miR-223 antagomir was observed when IGF1R was silenced. On the contrary, when cortical neurons were co-treated with miR-223 agomir and the cDNA of IGF1R which did not contain 3'- untranslated region, the inhibition caused by miR-223 disappeared. Our results suggested that miR-223 may suppress proliferation of cortical neurons that were treated with OGD/R via inhibiting IGF1R expression.

Emodin suppresses LPS-induced inflammation in RAW264.7 cells through a PPARγ-dependent pathway.

Inflammation is a defense and protective response to multiple harmful stimuli. Over and uncontrolled inflammation can lead to local tissues or even systemic damages and injuries. Actually, uncontrolled and self-amplified inflammation is the fundament of the pathogenesis of a variety of inflammatory diseases, including sepsis shock, acute lung injury and acute respiratory distress syndrome (ALI/ARDS). Our recent study showed that emodin, the main active component of Radix rhizoma Rhei, could significantly ameliorate LPS-induced ALI/ARDS in mice. However, its underlying signal pathway was not still very clear. Then, the aim of current study was to explore whether emodin could attenuate LPS-induced inflammation in RAW264.7 cells, and its involved potential mechanism. The mRNA and protein expression of ICAM-1, MCP-1 and PPARγ were measured by qRCR and western blotting, the production of TNF-α was evaluated by ELISA. Then, the phosphorylation of NF-κB p65 was also detected by western blotting. And NF-κB p65 DNA binding activity was analyzed by ELISA as well. Meanwhile, siRNA-PPARγ transfection was performed to knockdown PPARγ expression in cells. Our data revealed that LPS-induced the up-regulation of ICAM-1, MCP-1 and TNF-α, LPS-induced the down-regulation of PPARγ, and LPS-enhanced NF-κB p65 activation and DNA binding activity were substantially suppressed by emdoin in RAW264.7 cells. Furthermore, our data also figured out that these effects of emdoin were largely abrogated by siRNA-PPARγ transfection. Taken together, our results indicated that LPS-induced inflammation were potently compromised by emodin very likely through the PPARγ-dependent inactivation of NF-κB in RAW264.7 cells.

Edaravone for acute ischaemic stroke.

BACKGROUND: Neuroprotection is a promising therapeutic strategy for the treatment of acute ischaemic stroke. Edaravone is a neuroprotective agent that has been widely used in China, and several studies have suggested that it may be beneficial in acute ischaemic stroke. OBJECTIVES: To assess the efficacy and safety of edaravone for acute ischaemic stroke. SEARCH METHODS: We searched the Cochrane Stroke Group Trials Register (November 2010) and the Chinese Stroke Trials Register (November 2010). In addition, we searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2010, Issue 4), MEDLINE (1950 to November 2010), EMBASE (1980 to November 2010), China National Knowledge Infrastructure (1979 to November 2010), Chinese Biomedical Database (1979 to November 2010), Chinese Evidence-Based Medicine Database (November 2010) and Chinese Science and Technology Journals Database (1980 to November 2010). In an attempt to identify further published, unpublished and ongoing trials we searched reference lists and clinical trials and research registers, and contacted a pharmaceutical company, researchers and study authors. SELECTION CRITERIA: We included randomised controlled trials comparing edaravone with placebo or no intervention in patients with acute ischaemic stroke. DATA COLLECTION AND ANALYSIS: Two review authors selected trials for inclusion, assessed trial quality and independently extracted the data. MAIN RESULTS: We included three trials, involving 496 participants, and defined four trials as waiting assessment. All three included trials were of edaravone plus another treatment compared with the other treatment alone. The dose of edaravone injections in the three trials was the same at 60 mg per day. The course of treatment in all three trials is 14 days. None of the included trials reported the pre-specified primary outcome of death or dependency defined using the modified Rankin scale during the follow-up period. The three trials evaluated the effect of edaravone at different times and using different methods. All three trials reported adverse events; there were no differences between the treatment group and the control group. Overall, edaravone appeared to increase the proportion of participants with marked neurological improvement compared with the control group, and the difference was significant (risk ratio (RR) 1.99, 95% confidence interval (CI) 1.60 to 2.49). AUTHORS' CONCLUSIONS: The risk of bias in the included trials was moderate and the sample was small. Hence, although the data in this review show an effective treatment trend of edaravone for acute ischaemic stroke, further large, high-quality trials are required to confirm this trend.

Acanthopanax for acute ischaemic stroke.

BACKGROUND: Acute ischaemic stroke is a common cause of death and disability. A number of studies published in China have shown that acanthopanax is beneficial for acute ischaemic stroke. OBJECTIVES: To assess the efficacy and safety of acanthopanax in patients with acute ischaemic stroke. SEARCH STRATEGY: We searched the Cochrane Stroke Group Trials Register (last searched January 2008), the Chinese Stroke Trials Register (last searched March 2008), and the Trials Register of the Cochrane Complementary Medicine Field (last searched January 2008). In addition, we searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library Issue 1, 2008), MEDLINE (1966 to March 2008), EMBASE (1980 to March 2008), CINAHL (1982 to March 2008), AMED (1985 to March 2008), and nine Chinese databases, including the China Biological Medicine Database (CBM-disc) (1979 to March 2008). We handsearched three Chinese journals and searched reference lists, relevant clinical trials registers and research databases. In an attempt to identify further published, unpublished, and ongoing trials, we contacted a pharmaceutical company, researchers and study authors. SELECTION CRITERIA: We included randomised controlled trials comparing acanthopanax with placebo or open control (no placebo) in patients with acute ischaemic stroke. DATA COLLECTION AND ANALYSIS: Two review authors selected trials for inclusion, assessed trial quality and extracted the data independently. MAIN RESULTS: We included 13 trials (962 participants); the period of follow up in all included trials ranged from 10 to 30 days. None of the trials reported the pre-specified primary outcome death or dependency during the follow-up period. The outcome measure in all included trials was the improvement of neurological deficit after treatment; acanthopanax was associated with a significant increase in the number of participants whose neurological impairment improved (risk ratio (RR) 1.22, 95% confidence interval (CI) 1.15 to 1.29). Two trials reported adverse events; five trials reported no adverse events. AUTHORS' CONCLUSIONS: The risk of bias in all the included trials was high, and hence the data were not adequate to draw reliable conclusions about the efficacy of acanthopanax in acute stroke. Much larger trials of greater methodological quality are needed.

[A prospective study of stroke recurrence and the risk factors].

OBJECTIVE: To evaluate prognosis of stroke and identify the risk factors for stroke recurrence. METHODS: Based on the West China Hospital stroke register database, we conducted a prospective follow-up study of stroke patients to record the potential risk factors of stroke recurrence and investigate stroke recurrence at 1 year. Analysis of the risk factors was performed using a logistic regression model. RESULTS: A total of 1913 stroke consecutive patients admitted to our department were prospectively registered. Of these patients, 599 (31.3%) were identified to have intracerebral hemorrhage (ICH), and 1314 (68.7%) had ischemic stroke. The total recurrence rate at 1 year was 11.2%, and was 10.5% in ischemic patients and 12.7% in ICH patients. Multivariate analysis adjusted for age and gender identified atrial fibrillation, hypertension, hyperlipemia, family history of stroke, and smoking as the risk factors of stroke recurrence at 1 year. CONCLUSION: The 1 year recurrent rate is about 11%, and monitoring the factors of atrial fibrillation, hyperlipemia, hypertension, and smoking may help reduce the recurrence of stroke.

[Clinical characteristics and long-term prognosis of patients with ischemic and hemorrhagic stroke].

OBJECTIVE: To investigate the risk factors, pathogenesis, cause of death, and outcome of different stroke subtypes. METHODS: The relevant data, including demographics, baseline risk factors, cause of death, and 1-year case fatality, were analyzed among 1913 consecutive hospitalized patients with ischemic and hemorrhagic stroke, 599 (31.3%) with intracerebral hemorrhage (ICH) and 1314 with ischemic stroke (68.7%), including 209 cases (15.9%) of total anterior circulation infarction (TACI), 417 cases (31.7%) of partial anterior circulation infarction (PACI), and 186 cases (14.2%) of posterior circulation infarctions (POCI), and 502 cases (38.2%) of lacunar infarctions (LACI), 1098 males and 815 females, aged 64 +/- 13 (14-98). RESULTS: Multivariate analysis showed that when age and sex were adjusted, atrial fibrillation was the independent predictive factor of TACI [odds ratio (OR) = 1.42, 95% CI = 1.25-2.31), hypertension and alcohol intake were the independent predictive factor LACI (OR = 1.24, 95% CI = 1.02-2.18; 0R = 1.12, 95% CI = 1.03-3.04) and ICH (OR = 1.84, 95% CI = 1.31-3.02; OR = 1.04, 95% CI = 1.01-4.13). A negative association was observed between hypertension and TACI (OR = 0.62, 95% CI = 0.34-0.72), atrial fibrillation and LACI (OR = 0.46, 95% CI = 0.26-0.82), and ICH and diabetes (OR = 0.56, 95% CI = 0.42-0.76). As compared to LACI, TACI and ICH significantly increased the risk of 1-year mortality (OR = 6.21, 95% CI = 2.86-8.42; OR = 5.86; 95% CI = 2.46-8.52). CONCLUSIONS: Stroke subtypes have different risk factor profile, causes and outcome. Information on determinants of the clinical syndromes may impact on the prevention and acute phase interventions.

Association between metabolic syndrome and risk of stroke: a meta-analysis of cohort studies.

BACKGROUND: Our purpose was to investigate the association between metabolic syndrome and risk of stroke by meta-analysis. METHODS: Electronic databases through July 2007 were searched to identify prospective cohort studies that examined the association between metabolic syndrome and risk of stroke. Two reviewers independently assessed eligibility and used a standardized form to collect data from published studies. The study quality was assessed by the Newcastle-Ottawa Scale. RESULTS: We found 13 eligible studies that included 92,732 participants. Compared to individuals without metabolic syndrome, subjects with metabolic syndrome had a 1.6-fold increased risk of stroke (95% CI, 1.48-1.75). The relative risk of stroke associated with metabolic syndrome was 2.2 in the studies using the World Health Organization definition and 1.6 in those using the Adult Treatment Panel III definition, but the difference was not statistically significant. CONCLUSIONS: This analysis shows that metabolic syndrome is an important risk factor for incident stroke. A diagnosis of metabolic syndrome may prove useful in clinical management, and its elements should ultimately become important therapeutic targets for the reduction of the stroke burden in the general population.