Letter to editor: Serum concentration-guided intravenous magnesium sulfate administration for neuroprotection in patients with aneurysmal subarachnoid hemorrhage: A retrospective evaluation of a 12-year single-center experience.

This critique examines a 12-year retrospective study on serum magnesium concentration-guided administration of magnesium sulfate in 548 patients with aneurysmal subarachnoid hemorrhage (aSAH). The study reported that maintaining serum magnesium levels between 2 and 2.5 mmol/L reduced rates of delayed cerebral infarction and improved clinical outcomes. However, limitations due to its retrospective nature, single-center design, and unequal treatment group sizes may affect generalizability. Future multicentric randomized controlled trials are recommended to validate these findings and refine magnesium dosing strategies for aSAH treatment.

Predictive model for the risk of hemorrhagic transformation after rt-PA intravenous thrombolysis in patients with acute ischemic stroke: A systematic review and meta-analysis.

OBJECTIVE: To systematically review the risk prediction model of Hemorrhages Transformation (HT) after intravenous thrombolysis in patients with Acute Ischemic Stroke (AIS). METHODS: Web of Science, The Cochrane Library, PubMed, Embase, CINAHL, CNKI, CBM, WanFang, and VIP were searched from inception to February 25, 2023 for literature related to the risk prediction model for HT after thrombolysis in AIS. RESULTS: A total of 17 included studies contained 26 prediction models, and the AUC of all models at the time of modeling ranged from 0.662 to 0.9854, 16 models had AUC>0.8, indicating that the models had good predictive performance. However, most of the included studies were at risk of bias. the results of the Meta-analysis showed that atrial fibrillation (OR=2.72, 95% CI:1.98-3.73), NIHSS score (OR=1.09, 95% CI:1.07-1.11), glucose (OR=1.12, 95% CI:1.06-1.18), moderate to severe leukoaraiosis (OR=3.47, 95% CI:1.61-7.52), hyperdense middle cerebral artery sign (OR=2.35, 95% CI:1.10-4.98), large cerebral infarction (OR=7.57, 95% CI:2.09-27.43), and early signs of infarction (OR=4.80, 95% CI:1.74-13.25) were effective predictors of HT after intravenous thrombolysis in patients with AIS. CONCLUSIONS: The performance of the models for HT after thrombolysis in patients with AIS in the Chinese population is good, but there is some risk of bias. Future post-intravenous HT conversion prediction models for AIS patients in the Chinese population should focus on predictors such as atrial fibrillation, NIHSS score, glucose, moderate to severe leukoaraiosis, hyperdense middle cerebral artery sign, massive cerebral infarction, and early signs of infarction.

Effects of uric acid on ischemic diseases, stratified by lipid levels: a drug-target, nonlinear Mendelian randomization study.

Although uric acid-lowering agents such as xanthine oxidase inhibitors have potential cardioprotective effects, studies on their use in preventing cardiovascular diseases are lacking. We investigated the genetically proxied effects of reducing uric acid on ischemic cardiovascular diseases in a lipid-level-stratified population. We performed drug-target Mendelian randomization (MR) analyses using UK Biobank data to select genetic instruments within a uric acid-lowering gene, xanthine dehydrogenase (XDH), and construct genetic scores. For nonlinear MR analyses, individuals were stratified by lipid level. Outcomes included acute myocardial infarction (AMI), ischemic heart disease, cerebral infarction, transient cerebral ischemic attack, overall ischemic disease, and gout. We included 474,983 non-gout individuals with XDH-associated single-nucleotide polymorphisms. The XDH-variant-induced uric acid reduction was associated with reduced risk of gout (odds ratio [OR], 0.85; 95% confidence interval [CI], 0.78-0.93; P < 0.001), cerebral infarction (OR, 0.86; 95% CI, 0.75-0.98; P = 0.023), AMI (OR, 0.79; 95% CI, 0.66-0.94; P = 0.010) in individuals with triglycerides ≥ 188.00 mg/dL, and cerebral infarction in individuals with low-density lipoprotein cholesterol (LDL-C) ≤ 112.30 mg/dL (OR, 0.76; 95% CI, 0.61-0.96; P = 0.020) or LDL-C of 136.90-157.40 mg/dL (OR, 0.67; 95% CI, 0.49-0.92; P = 0.012). XDH-variant-induced uric acid reduction lowers the risk of gout, AMI for individuals with high triglycerides, and cerebral infarction except for individuals with high LDL-C, highlighting the potential heterogeneity in the protective effects of xanthine oxidase inhibitors for treating AMI and cerebral infarction depending on the lipid profiles.

The efficacy and safety of diterpene ginkgolides meglumine injection for cerebral infarction: A meta-analysis of randomized controlled trials.

OBJECTIVE: To systemically evaluate the efficacy and safety of diterpene ginkgolides meglumine injection (DGMI) on cerebral infarction (CI). METHODS: Comprehensively collect randomized controlled trials of DGMI in the treatment of CI in 7 databases including Embase, PubMed, the Cochrane Library, the China National Knowledge Infrastructure Database, the WanFang Database, the China Science and Technology Journal Database, and the China Biology Medicinedisc as of January 2023. The studies were screened according to the inclusion and exclusion criteria and evaluated according to the criteria recommended by the Cochrane Handbook, then RevMan 5.3, Stata 12.0 software were used for Meta-analysis. RESULTS: A total of 22 randomized controlled trials with 2194 patients were included. Meta analysis showed that: the total effective rate of treatment (relative risk = 1.29, 95% confidence interval (1.21, 1.38), P < .001), National Institute of Health stroke scale score, Barthel index and Modified Rankin Scale were better in DGMI group than in Conventional Western Medicine Treatment group. The included studies reported 42 adverse events, 25 of which belonged to DGMI groups. CONCLUSION: Available evidence suggested that DGMI can significantly improve the clinical efficiency in the treatment of CI. DGMI is an ideal treatment for CI, which has high clinical application value.

Risks of nimodipine dose reduction during the high-risk period for delayed cerebral ischemia after aneurysmal subarachnoid hemorrhage.

Nimodipine dose reduction is recommended in case of high vasopressor demand after aneurysmal subarachnoid hemorrhage (aSAH). The aim of this study was to assess potential adverse effects of nimodipine reduction during the high-risk period for delayed cerebral ischemia (DCI) and cerebral vasospasm (CVS) between days 5 and 10 after hemorrhage. Demographic and clinical data as well as daily nimodipine dose of aSAH patients admitted between 2010 and 2019 were retrospectively analyzed. Univariable and multivariable regression analyses were performed to identify factors associated with DCI, angiographic CVS, DCI-related infarction, and unfavorable outcome. A total of 205 patients were included. Nimodipine dose reduction occurred in 108 (53%) patients ('nimodipine reduction group'), while 97 patients (47%) received the full dose ('no nimodipine reduction group'), Patients in the 'nimodipine reduction group' had significant worse WFNS and Fisher grades and developed significantly more often DCI and angiographic CVS. DCI-related infarction and unfavorable outcome were also significantly increased in the 'nimodipine reduction group.' 'Reduced nimodipine dose' was the only independent predictor for the occurrence of DCI and angiographic CVS in multivariable regression analysis. 'Poor WFNS grade' and 'reduced nimodipine dose' were identified as independent risk factors for DCI-related infarction while 'older age,' 'poor WFNS grade,' and 'reduced nimodipine dose' were associated with unfavorable outcome at 3 months after discharge. Nimodipine dose reduction during the high-risk period of DCI and CVS between days 5 and 10 after hemorrhage might abrogate the positive prognostic effects of nimodipine and should be critically evaluated.

Effect of the Factor XIa Inhibitor Asundexian According to Baseline Infarct Pattern and on MRI Covert Infarct Outcomes.

BACKGROUND: Exploratory analysis of the phase 2 PACIFIC-Stroke (Program of Anticoagulation via Inhibition of FXIa by the Oral Compound BAY 2433334-Non-Cardioembolic Stroke) randomized trial suggested that asundexian, an oral factor XIa inhibitor, prevents recurrent stroke and transient ischemic attacks in patients with atherosclerotic stroke. In this post hoc exploratory analysis, we hypothesized that asundexian would be more effective in patients enrolled with large, multiple, or cortical acute infarcts on magnetic resonance imaging than in patients enrolled with a single small subcortical acute infarct, and asundexian would prevent incident cortical covert infarcts. METHODS: In this placebo-controlled double-blinded randomized controlled trial, patients with mild-to-moderate noncardioembolic ischemic stroke were assigned to asundexian (10, 20, or 50 mg once daily) or placebo, in addition to antiplatelet therapy. Brain magnetic resonance imagings were required within 72 hours of randomization and repeated at 26 weeks or at discontinuation of the study drug. RESULTS: Of 1808 randomized patients, 1780 (98.5%) had interpretable baseline magnetic resonance imagings, of which 1628 (91.5%) had ≥1 diffusion-weighted imaging positive acute infarcts. Magnetic resonance imaging follow-up was obtained in 1439 patients, of whom 1358 had no symptomatic stroke during the trial period. Compared with placebo, asundexian 50 mg daily conferred a trend toward reduced risk of recurrent ischemic stroke or incident covert infarcts (hazard ratio, 0.71 [95% CI, 0.45-1.11]) and recurrent ischemic stroke or transient ischemic attack (secondary outcome; hazard ratio, 0.59 [95% CI, 0.33-1.06]) that was not evident in patients with single small subcortical infarcts (hazard ratios, 1.14 [95% CI, 0.62-2.10] and 0.93 [95% CI, 0.28-3.06]). Incident cortical covert infarcts were reduced in patients taking asundexian 50 mg, but the difference was not statistically significant (crude incidence ratio, 0.56 [95% CI, 0.28-1.12]). CONCLUSIONS: These exploratory, unconfirmed results suggest that asundexian may prevent new embolic infarcts but not small artery occlusion. The hypothesis that subtypes of covert brain infarcts respond differently to anticoagulant prevention should be tested in future trials. REGISTRATION: URL: https://clinicaltrials.gov; Unique identifier: NCT04304508.

Effects of isosakuranetin on cerebral infarction and blood brain barrier damage from cerebral ischemia/reperfusion injury in a rat model.

This study investigated the effects of isosakuranetin (5,7-dihydroxy-4'-methoxyflavanone) on cerebral infarction and blood brain barrier (BBB) damage in cerebral ischemia and reperfusion (I/R) in a rat model. The right middle cerebral artery was occluded for 2 h followed by reperfusion. The experimental rats were divided into five groups: a sham, or control group; vehicle group; and 5 mg/kg, 10 mg/kg, and 20 mg/kg bodyweight isosakuranetin-treated I/R groups. After 24 h of reperfusion, the rats were tested using a six-point neurological function score. The percentage of cerebral infarction was evaluated using 2,3,5-triphenyltetrazolium chloride (TTC) staining. BBB leakage was determined by Evan Blue injection assay and brain morphology changes were observed under light microscopy following staining with hematoxylin and eosin (H&E). The results of neurological function score revealed that isosakuranetin reduced the severity of neurological damage. A dose of 10 and 20 mg/kg bodyweight of isosakuranetin significantly decreased the infarct volume. All three doses of isosakuranetin significantly decreased Evan Blue leakage. The penumbra area of the I/R brains revealed the characteristics of apoptotic cell death. Therefore, isosakuranetin-treated I/R attenuated the brain damage from cerebral I/R injury and further investigation of the mechanisms warrant further investigation to assist in the development of protective strategies against cerebral I/R injury in clinical trials.Communicated by Ramaswamy H. Sarma.

Prolonged paradoxical reaction requiring over 5 years of corticosteroid administration in a patient with severe tuberculous meningitis.

Tuberculous meningitis (TBM) is a rare disease in low-incidence countries like Japan, where general physicians have fewer experience with TBM. Despite its proper treatment and early improvement of the condition, TBM often causes paradoxical reactions (PRs), which can lead to severe complications such as stroke. As PRs in the brain are difficult to detect without regular neuroimaging surveillance and have a later onset than in other organs, delayed treatment can be fatal. We report a case of a 54-year-old, human immunodeficiency virus (HIV)-negative man who presented with TBM and miliary tuberculosis (TB) in an unconscious state. Standard anti-tuberculous therapy with adjunctive systemic high-dose dexamethasone brought rapid clinical and microbiological improvement, which allowed the dexamethasone to be tapered. However, he developed cerebral infarction with left hemiplegia due to a TBM-related PR five months after admission. Therefore, the initial high-dose dexamethasone was again added to the anti-tuberculous drugs, achieving the significant effects on the PR-related lesions. Anti-tuberculous drugs had been administered for 3 years and the dexamethasone was carefully tapered. Nevertheless, enlargement of PR-related lesions in the brain recurred 5 years later. Accordingly, the dose of corticosteroid was again increased, resulting in resolving the lesions. It is important to note that severe TBM may cause prolonged PRs, which require a long-term neuroimaging follow-up and anti-inflammatory drugs for the successful management of the TBM-related PR.

Calpain as a Therapeutic Target for Hypoxic-Ischemic Encephalopathy.

Hypoxic-ischemic encephalopathy (HIE) is a complex pathophysiological process with multiple links and factors. It involves the interaction of inflammation, oxidative stress, and glucose metabolism, and results in acute and even long-term brain damage and impairment of brain function. Calpain is a family of Ca2+-dependent cysteine proteases that regulate cellular function. Calpain activation is involved in cerebral ischemic injury, and this involvement is achieved by the interaction among Ca2+, substrates, organelles, and multiple proteases in the neuronal necrosis and apoptosis pathways after cerebral ischemia. Many calpain inhibitors have been developed and tested in the biochemical and biomedical fields. This study reviewed the potential role of calpain in the treatment of HIE and related mechanism, providing new insights for future research on HIE.

Kaempferol-3-O-(2″-O-galloyl-ß-D-glucopyranoside): a novel neuroprotective agent from Diospryros kaki against cerebral ischemia-induced brain injury.

Our previous study demonstrated neuroprotective and therapeutic effects of a standardized flavonoid extract from leaves of Diospyros kaki L.f. (DK) on middle cerebral artery occlusion-and-reperfusion (MCAO/R)-induced brain injury and its underlying mechanisms. This study aimed to clarify flavonoid components responsible for the effects of DK using in vitro and in vivo transient brain ischemic models. Organotypic hippocampal slice cultures (OHSCs) subjected to oxygen- and glucose-deprivation (OGD) were performed to evaluate in vitro neuroprotective activity of DK extract and nine isolated flavonoid components. MCAO/R mice were employed to elucidate in vivo neuroprotective effects of the flavonoid component that exhibited the most potent neuroprotective effect in OHSCs. DK extract and seven flavonoids [quercetin, isoquercetin, hyperoside, quercetin-3-O-(2″-O-galloyl-ß-D-galactopyranoside), kaempferol, astragalin, and kaempferol-3-O-(2″-O-galloyl-ß-D-glucopyranoside) compound (9)] attenuated OGD-induced neuronal cell damage and compound (9) possessed the most potent neuroprotective activity in OHSCs. The MCAO/R mice showed cerebral infarction, massive weight loss, characteristic neurological symptoms, and deterioration of neuronal cells in the brain. Compound (9) and a reference drugs, edaravone, significantly attenuated these physical and neurological impairments. Compound (9) mitigated the blood-brain barrier dysfunction and the change of glutathione and malondialdehyde content in the MCAO mouse brain. Edaravone suppressed the oxidative stress but did not significantly affect the blood-brain barrier permeability. The present results indicated that compound (9) is a flavonoid constituent of DK with a potent neuroprotective activity against transient ischemia-induced brain damage and this action, at least in part, via preservation of blood-brain barrier integrity and suppression of oxidative stress caused by ischemic insult.

[Atrial fibrillation and dementia: not everything is clear ]. / Fibrillazione atriale e demenza: non tutto è chiaro...

The prevalence of dementia is ever increasing, as well as the prevalence of atrial fibrillation (AF). Several studies and systematic reviews evaluated the association between AF and dementia, highlighting an increased risk for dementia (with odds ratios from 1.4 to 1.6), with robust results in patients with previous stroke. In fact, not only vascular dementia, but also Alzheimer's disease seems more frequent in patients with AF, even though the very high heterogeneity of the results does not allow for solid conclusions. One of the mechanisms by which AF can cause dementia is the presence of silent embolic cerebral infarctions, and therefore treatment with oral anticoagulants could reduce the incidence of dementia. The results of several studies and systematic reviews show that this therapy, particularly with the new oral anticoagulants, is associated with a reduction of approximately one third of dementia. Rhythm control, obtained either with pharmacological therapy or catheter ablation, is associated with a reduction of dementia impact as well. The association between AF and cognitive deficit is therefore well documented, being more evident in patients with previous stroke but also present in cohorts of patients without prior vascular events. The development of dementia in AF patients can be due to cerebral infarctions, both clinically evident or silent, as well as by microembolism, microbleeds and hypoperfusion. Oral anticoagulation, particularly with the use of new oral anticoagulants, as well as a rhythm control strategy can reduce the incidence of dementia. More recently, it has been shown that atrial cardiomyopathy is significantly associated with the incidence of dementia, also in patients with no history of AF or stroke.

[Initial Treatment of Cerebral Hemorrhage:Determining the Cause without Preconceived Notions].

In Japan, cerebral hemorrhage accounts for 19.5% of stroke patients, and its prognosis is poorer than that of cerebral infarction, with a mortality rate of 14.6%. In the initial treatment of cerebral hemorrhage, the airway, respiration, and circulation should be stabilized, and the intracranial pressure and body temperature should be controlled. Hypertensive cerebral hemorrhage is the most common cause; however, the cause should be carefully examined, and the treatment method should be selected according to the degree of urgency. Cerebral hemorrhage patients undergoing antithrombotic therapy show poor outcomes owing to increased hematoma. Therefore, antithrombotic drugs should be discontinued immediately. Blood products and neutralizing drugs should be administered in response to the administration of antithrombotic drugs. In young individuals, cerebrovascular disorders may be caused by the abuse of sympathomimetic drugs, such as stimulants and cocaine. Whether individuals or their family members are using illegal drugs should be confirmed.

[Application Effect of Continuous Lumbar Cistern Fluid Drainage Combined With Decompressive Craniectomy in the Treatment of Severe Craniocerebral Injury].

Objective: To analyze the application effect of continuous lumbar cistern fluid drainage combined with decompressive craniectomy in the treatment of severe craniocerebral injury. Methods: A total of 87 patients with severe craniocerebral injury admitted to our hospital between March 2016 and March 2021 were retrospectively enrolled. They were divided into two groups according to the decompression methods applied, with 42 patients who received standard decompressive craniectomy assigned to the control group and 45 patients who received continuous lumbar cistern fluid drainage combined with standard decompressive craniectomy assigned to the observation group. The primary indicators that were monitored and compared between the two group included the amount of time for patient CT imaging to be clear of subarachnoid hemorrhage, the length-of-stay, the duration of post-operative intubation, the mannitol dose, scores for Glasgow Coma Scale (GCS), prognosis, the incidence of cerebral edema and cerebral infarction, and complications. The secondary indicators that were monitored and compared included intracranial pressure, cerebrospinal fluid antinucleosome protein SP100, and red blood cell count of the two groups before treatment and after continuous drainage for 7 days. Results: The amount of time for CT imaging to be clear of subarachnoid hemorrhage and the length-of-stay of the observation group were shorter than those of the control group, the mannitol dose of the observation group was lower than that of the control group, the incidence of cerebral edema and the incidence of complications of the observation group were lower than those of the control group, and the rate of patients with good prognosis in the observation group was higher than that in the control group ( P<0.05). There was no significant difference in the rate of poor prognosis or mortality between the two groups ( P>0.05). The duration of postoperative intubation of the observation group was (8.24±1.09) d, while that of the control group was (9.22±1.26) d, and the difference between the two groups was statistically significant ( t=3.887, P<0.05). There were 2 cases (4.44%) of cerebral infarction in the observation group, with the infarct volume being (8.36±1.87) cm 3, while there were 9 cases (21.43%) of cerebral infarction in the control group, with the infarct volume being (8.36±1.87) cm 3, and there were statistically significant differences in the incidence and volume of cerebral infarction between the two groups ( χ 2=5.674, t=9.609, P<0.05). After treatment, the intracranial pressure and red blood cell count decreased in both groups and the intracranial pressure, cerebrospinal fluid SP100, and red blood cell count of the observation group were significantly lower than those of the control group ( P<0.05). The cerebrospinal fluid SP100 of the observation group decreased after treatment in comparison with the level before treatment ( P<0.05), while the pre- and post-treatment levels of the control group did not demonstrate any significant difference. Conclusion: Continuous lumbar cistern fluid drainage in patients with severe craniocerebral injury effectively shortens the time required for the body to recover, significantly reduces the level of intracranial pressure, improves the levels of cerebral edema and cerebral infarction, and has a high degree of safety for prognosis and recovery.

Predictive factors for early neurological deterioration after intravenous thrombolysis of single subcortical infarction in the territory of the middle cerebral artery.

INTRODUCTION: Patients with a single subcortical infarction (SSI) in the territory of the middle cerebral artery (MCA) often experience early neurological deterioration (END) despite receiving intravenous thrombolytic therapy (IVT). In this study, predictors of END were investigated in patients with SSI in the MCA after IVT. METHODS: Patients with SSI in the MCA territory who had received IVT between June 2020 and 2022 were included. END was defined as an increase in the total National Institutes of Health Stroke Scale (NIHSS) score by ≥2 or in the motor NIHSS score by ≥1 within the first 72 h of admission. Patients with proximal (pSSI) and distal SSI (dSSI) were analyzed to determine SSI type-specific predictors for END. RESULTS: We evaluated 174 patients with SSI in the MCA territory who underwent IVT. Multivariable logistic regression analysis showed that pSSI (odds ratio [OR] = 0.242; 95% confidence interval [CI], 0.104-0.564; p = .001), lower high-density lipoprotein cholesterol (HDL-C) (OR = 0.150; 95% CI, 0.033-0.682; p = .014), higher blood glucose (OR = 0.858; 95% CI, 0.752-0.979; p = .023), and higher red blood cells count (OR = 1.966; 95% CI, 1.154-3.349; p = .013) were risk factors for END. In patients with pSSI, HDL-C and blood glucose were associated with END. No variable related to END was found in the dSSI group. CONCLUSIONS: The proportion of END in patients with SSI in the MCA territory after IVT was not low; therefore, pSSI, HDL-C, blood glucose, and red blood cells should be monitored closely. The frequency and predictors of SSI in the MCA territory differed between pSSI and dSSI.

Effect of sacubitril/valsartan on brain natriuretic peptide level and prognosis of acute cerebral infarction.

BACKGROUND AND PURPOSE: Previous studies demonstrated that elevated brain natriuretic peptide (BNP) level is associated with adverse clinical outcomes of acute cerebral infarction (ACI). Researchers hypothesized that BNP might be a potential neuroprotective factor against cerebral ischemia because of the antagonistic effect of the natriuretic peptide system on the renin-angiotensin system and regulation of cardiovascular homeostasis. However, whether decreasing the BNP level can improve the prognosis of ACI has not been studied yet. The main effect of sacubitril/valsartan is to enhance the natriuretic peptide system. We investigated whether the intervention of plasma BNP levels with sacubitril/valsartan could improve the prognosis of patients with ACI. METHODS: In a randomized, controlled, parallel-group trial of patients with ACI within 48 hours of symptom onset and need for antihypertensive therapy, patients have randomized within 24 hours to sacubitril/valsartan 200mg once daily (the intervention group) or to conventional medical medication (the control group). The primary outcome was a change in plasma BNP levels before and after sacubitril/valsartan administration. The secondary outcomes included plasma levels of brain-derived neurotrophic factor (BDNF), Corin and neprilysin (NEP) before and after medication, the modified Rankin scale, and the National Institutes of Health Stroke Scale (at onset, at discharge, 30 days, and 90 days after discharge). RESULTS: We evaluated 80 eligible patients admitted to the Stroke Center of Lianyungang Second People's Hospital between 1st May, 2021 and 31st June, 2022. Except for 28 patients excluded before randomization and 14 patients who did not meet the criteria or dropped out or lost to follow-up during the trial, the remaining 38 patients (intervention group: 17, control group: 21) had well-balanced baseline features. In this trial, we found that plasma BNP levels (P = 0.003) decreased and NEP levels (P = 0.006) increased in enrolled patients after treatment with sacubitril/valsartan. There were no differences in plasma BDNF and Corin levels between the two groups. Furthermore, no difference in functional prognosis was observed between the two groups (all P values>0.05). CONCLUSIONS: Sacubitril/valsartan reduced endogenous plasma BNP levels in patients with ACI and did not affect their short-term prognosis.

The effect of butylphthalide on improving the neurological function of patients with acute anterior circulation cerebral infarction after mechanical thrombectomy.

Butylphthalide can improve blood circulation in patients with acute cerebral infarction. Complement 3a receptor 1 (C3aR1) is involved in the regulation of innate immune response and pathogen monitoring, which is closely related to the pathophysiological processes of breast cancer, neurogenesis and lipid catabolism. Our study explored the therapeutic effect of butylphthalide on improving the neurological function of patients with acute anterior circulation cerebral infarction after mechanical thrombectomy, and evaluated the correlation between serum C3aR1 and butylphthalide on improving the neurological function after mechanical thrombectomy. 288 patients with acute anterior circulation cerebral infarction who were admitted to our hospital from January 2019 to November 2022 and were treated with mechanical thrombectomy for the first time were included in this retrospective study and divided into the butylphthalide group and control group that they received treatment methods. The National Institutes of Health Stroke Scale (NIHSS) scale was used to evaluate the patient neurological function treatment efficacy, and the modified Rankin Scale (mRS) scale was used to measure the patient neurological function status 3 months after surgery. Enzyme-linked immunosorbent assay method was used to determine the content of C3aR1 in serum. Two weeks after thrombus removal, the NIHSS efficacy of the butylphthalide group and the control group were 94.44% and 72.22%, respectively. The butylphthalide group was significantly higher than the control group (P < .001). Three months after the operation, the mRS score of the butylphthalide group was significantly lower than that of the control group (P = .001), and the excellent and good rate was significantly higher than that of the control group (P < .001). The serum C3aR1 level of the butylphthalide group was significantly lower than that of the control group 2 weeks after operation and 3 months after operation (P < .001). The serum C3aR1 was positively correlated with the efficacy of NIHSS (R = 0.815, P = .004), which was positively correlated with mRS score (R = 0.774, P = .007). Butylphthalide can improve the therapeutic effect of neurological function in patients with acute anterior circulation cerebral infarction after mechanical thrombus removal. The patient serum C3aR1 is related to the patient neurotherapy efficacy and neurological function status, and its level can reflect the patient neurological function recovery to a certain extent.

Correlation Study of Chronic Renal Insufficiency and Long-Term Prognosis of Patients with Acute Ischemic Cerebral Apoplexy After Intravenous rt-PA Thrombolysis.

Objective: To investigate the correlation between chronic renal insufficiency and the long-term prognosis of patients with acute ischemic cerebral apoplexy after intravenous recombinant tissue plasminogen activator (rt-PA) thrombolysis. Methods: 290 patients (194 males and 96 females) with acute cerebral infarction who received intravenous rt-PA thrombolysis were admitted to Ningbo Medical Center Lihuili Hospital from May 2018 to December 2020. Their clinical baseline data were recorded. According to the estimated glomerular filtration rate (eGFR) level, patients were divided into the control group (252 cases) and the chronic kidney disease (CKD) group (38 cases). The prognosis of patients was evaluated by a modified Rankin Scale (mRS) 90 days after cerebral apoplexy by telephone interview or outpatient following-up (mRS ≤ 2 reflected good prognosis, mRS >2 reflected unfavorable prognosis). Multivariate logistic regression was used to analyze the prognosis risk relationship of acute ischemic cerebral apoplexy patients with intravenous rt-PA thrombolysis with CKD. Results: Acute ischemic cerebral apoplexy patients with intravenous rt-PA thrombolysis with CKD were older ((79.08 ± 8.96) years vs (65.84 ± 13.31) years, P = .00052, 95% CI = 0.00031-0.00072) than who without CKD, and were more likely to be suffering from hypertension (94.7% (36/38) and 66.3% (167/252), P = .00023, 95% CI = 0.00011-0.00033), atrial fibrillation (50.0% (19/38) and 26.6% (67/252), P = .007, 95% CI = 0.001-0.009), high Uric acidemia (68.4% (26/38) and 17.9% (45/252), P = .00044, 95% CI = 0.00027-0.00061), hyperhomocysteinemia (47.4% (18/38) and 13.1% (33/252), P = .00032, 95% CI=0.00022-0.00053), history of malignant tumor (13.2% (5/38) and 4.4% (11/252), P = .044, 95% CI = 0.0023-0.0053), cardiogenic embolism (Trial of ORG 10172 in Acute Stroke Treatment (TOAST) classification of cerebral infarction) (47.4% (18/38) and 29.0% (73/252), P = .038, 95% CI = 0.029-0.055). The mortality rate of the CKD group was higher than the control group (13.2% (5/38) and 4.0% (10/252), P = .033, 95% CI = 0.021-0.053), and the good prognosis rate in the CKD group was significantly lower than in the control group (42.1% (16/38) and 73.8% (186/252), P = .00032, 95% CI = 0.00012-0.00043). Multivariate logistic regression analysis showed that CKD was an independent risk factor for acute ischemic cerebral apoplexy patients undergoing intravenous rt-PA thrombolysis (OR = 4.606, 95%CI 1.176~18.041, P = .028, 95% CI = 0.022-0.043). Conclusion: CKD is an independent risk factor for acute ischemic cerebral apoplexy patients with intravenous rt-PA thrombolysis.

The efficacy of different nimodipine administration route for treating subarachnoid hemorrhage: A network meta-analysis.

BACKGROUND: A systematic review and network meta-analysis (NMA) were conducted to explore the optimal administration route of nimodipine for treatment subarachnoid hemorrhage. METHODS: Electronic databases (Pubmed, Embase, Web of Science and Cochrane databases) were systematically searched to identify randomized controlled trials evaluating different administration route of nimodipine (intravenous and enteral) versus placebo for treatment subarachnoid hemorrhage. Outcomes included case fatality at 3 months, poor outcome measured at 3 months (defined as death, vegetative state, or severe disability), incidence of delayed cerebral ischemia (DCI), delayed ischemic neurological deficit. A random-effect Bayesian NMA was conducted for outcomes of interest, and results were presented as odds ratios (ORs) and 95% credible intervals. The NMA was performed using R Software with a GeMTC package. A Bayesian NMA was performed and relative ranking of agents was assessed using surface under the cumulative ranking (SUCRA) probabilities. RESULTS: Nine randomized controlled trials met criteria for inclusion and finally included in this NMA. There was no statistically significant between intravenous and enteral in terms of case fatality, the occurrence of DCI, delayed ischemic neurologic deficit and poor outcomes (P > .05). Both intravenous and enteral could reduce case fatality, the occurrence of DCI, delayed ischemic neurologic deficit and poor outcomes (P < .05). The SUCRA shows that enteral ranked first, intravenous ranked second and placebo ranked the last for case fatality, the occurrence of DCI and poor outcomes. The SUCRA shows that intravenous ranked first, enteral ranked second and placebo ranked the last for delayed ischemic neurologic deficit. CONCLUSIONS: It is possible that both enteral and intravenous nimodipine have comparable effectiveness in preventing poor outcomes, DCI, and delayed ischemic neurological deficits. However, further investigation may be necessary to determine the exact role of intravenous nimodipine in current clinical practice.

Study on the Difference of Protective Efficacy and Mechanism of Radix Aconiti Coreani and Rhizoma Typhonii in Gerbils with Ischemic Stroke.

Ischemic stroke is a common type of stroke, but effective treatment methods are still imperfect and new effective therapies need to be explored. Radix Aconiti Coreani and Rhizoma Typhonii used as Baifuzi in the treatment of stroke or symptoms associated with stroke have been recorded in ancient Chinese books and are widely used. Modern pharmacological studies have demonstrated that both of them have antioxidant and anti-inflammatory effects. The purpose of this study is to investigate whether Radix Aconiti Coreani and Rhizoma Typhonii have therapeutical effects on gerbils with ischemic stroke, to investigate their potential mechanisms of action, and to provide a reference for rational clinical application by comparing the differences between them. In this manuscript, the right unilateral ligation of the carotid artery of gerbils was used to cause an ischemic stroke model. The neurological deficits of gerbils in each group were scored by Longa scale. The area of cerebral infarction was detected by 2,3,5-tribenzotetrazolchloride staining. The levels of inflammatory factors, oxidative stress indexes, and vascular endothelial function indexes in brain homogenate and serum were determined by ELISA. The expression levels of P-Akt PI3K, HO-1, and KEAP1 proteins in brain tissue were determined by Western blot. Immunofluorescence staining was used to observe the recovery of neuronal cells in the hippocampal CA1 region of the gerbil brain tissue and the expression of proteins related to PI3K/Akt and KEAP1/Nrf2 signaling pathways in neuronal cells in the hippocampal CA1 region. It was found that Radix Aconiti Coreani and Rhizoma Typhonii could improve neurological deficits and reduce cerebral infarction rate in gerbils. The results showed that Radix Aconiti Coreani and Rhizoma Typhonii could significantly decrease the expression of inflammatory factors, increase the expression of antioxidative stress indexes and vascular endothelial function factors, activate the PI3K/Akt, KEAP1/Nrf2 signaling pathway, reduce the inflammatory response, inhibit the oxidative stress, enhance the vascular endothelial cell function, and thus protect against ischemic brain injury. From the experimental results, both Radix Aconiti Coreani and Rhizoma Typhonii had neuroprotective effects on ischemic brain injury. Compared with Rhizoma Typhonii, the effects of Radix Aconiti Coreani on anti-inflammatory and antioxidative stress were more significant, while Rhizoma Typhonii had showed more significant effects in promoting angiogenesis after ischemic stroke by increasing the level of NO.