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.

Impact of ventriculo-cisternal irrigation on prevention of delayed cerebral infarction in aneurysmal subarachnoid hemorrhage: a single-center retrospective study and literature review.

OBJECTIVE: The aim of this study was to evaluate the effectiveness of ventriculo-cisternal irrigation (VCI) in preventing vasospasms and delayed cerebral infarction (DCI) by washing out subarachnoid clots earlier after aneurysm surgery. METHODS: We retrospectively identified 340 subarachnoid hemorrhage (SAH) patients with ruptured intracranial aneurysms treated with postoperative VCI at our institution between December 2010 and January 2020. As VCI therapy, a ventricular drain/cisternal drain was placed during aneurysm surgery, and lactated Ringer's solution was used for irrigation until day 4 of SAH, followed by intracranial pressure control at 5-10 cmH2O until day 14. RESULTS: The median age was 65 years (interquartile range 52-75), with 236 female patients (69%). The World Federation of Neurosurgical Societies grade distribution was as follows: grade I or II, 175 patients (51%); grade III or IV, 84 (25%); and grade V, 81 (24%). With VCI management in all patients, total vasospasm occurred in 162 patients (48%), although the DCI incidence was low (23 patients [6.8%]). Major drainage-related complications were observed in five patients (1.5%). Early surgery, performed on SAH day 0 or 1, was identified as a preventive factor against DCI occurrence (odds ratio (OR) 0.21, 95% confidence interval (CI) 0.07-0.67; P = 0.008), while additional surgery (4.76, 1.62-13.98; P = 0.005) and dyslipidemia (3.27, 1.24-8.63; P = 0.017) were associated with DCI occurrence. CONCLUSION: Managing vasospasms with VCI after SAH is considered a safe and effective method to prevent DCI. Early surgery after SAH may be associated with a decreased risk of DCI with VCI therapy.

The Value of a Management Plan Based on Risk Factors for Cerebral Infarction Patients with Cerebral Hemorrhage.

Cerebral infarction is a neurological disease related to abnormal blood supply to brain tissue. Patients are mainly men between the ages of 50 and 60 years old. In order to explore the value of risk factor-based management programs for preventing hemorrhagic conversion in patients with cerebral infarction, this paper uses single and multifactor methods to analyze the risk factors of cerebral hemorrhage transformation after cerebral infarction and formulate risk factor-based management plans. 240 cases of cerebral infarction who were admitted to our hospital in the past 2 years were evenly divided into an intervention group (intervention based on risk factors) and a routine group (regular care mode) by a simple randomized method. Cerebral hemorrhage is observed in both groups. We assessed the stroke scale of the National Institutes of Health (NIHSS) score. The development of risk factor-based management plans for patients with acute cerebral infarction during the treatment period has important clinical significance for reducing the incidence of hemorrhagic conversion in patients and promoting the recovery of neurological function.

Direct oral anticoagulants versus warfarin for secondary prevention of cerebral infarction and bleeding in older adults with atrial fibrillation.

BACKGROUND: Direct oral anticoagulants (DOACs) have been used for both primary and secondary prevention of cerebral infarction in older patients with atrial fibrillation (AF). However, whether DOACs are more effective and safer than warfarin for secondary prevention of cerebral infarction in older patients with AF remains unclear. METHODS: Using the Japanese Diagnosis Procedure Combination database, we identified patients with AF who were hospitalized for cerebral infarction from January 1, 2015 to March 31, 2019 and were aged ≥75 years at admission. We performed propensity score-stabilized inverse probability of treatment weighting analyses to balance measured confounders between patients with AF receiving DOACs and those receiving warfarin after discharge. The primary outcomes were 365-day readmission for (a) benefit: cerebral infarction or (b) harm: bleeding events after discharge. The secondary outcomes were 365-day readmission for intracranial bleeding or gastrointestinal bleeding after discharge as well as all-cause death during readmission. Using a Fine-Gray model, we compared the subdistribution hazard ratios (SHRs) of readmission between the DOAC group and warfarin group. RESULTS: We identified 101,389 eligible patients, including 80,726 patients receiving DOACs and 20,663 patients receiving warfarin. After the propensity score-stabilized inverse probability of treatment weighting, the adjusted SHRs of readmission (95% confidence interval [CI]) for cerebral infarction, bleeding events, and intracranial bleeding in the DOAC group as compared with the warfarin group were 0.76 (0.71-0.81), 0.78 (0.68-0.90), and 0.69 (0.57-0.82), respectively. There was no significant difference in readmission for gastrointestinal bleeding (SHR, 1.01; 95% CI, 0.72-1.41) between the DOAC and warfarin groups. CONCLUSION: In this retrospective nationwide study, DOACs were more effective and safer than warfarin for preventing reinfarction and bleeding events in patients with AF aged ≥75 years who have a history of cerebral infarction.

Neuroprotective effect of exosomes derived from bone marrow mesenchymal stem cells via activating TGR5 and suppressing apoptosis.

Cerebral infarction has become one of the most common neurovascular diseases, and it leads to a high disability and death rate. The exosomes derived from bone marrow mesenchymal stem cells (BM-MSCs-exo) have been viewed as a potential therapeutic method for some diseases. However, the role of BM-MSCs-exo in cerebral infarction remains unclear. Middle cerebral artery occlusion (MCAO) rat and oxygen and glucose deprived cell models were established. Neurological score, animal behaviors, TTC-staining, HE staining, and immunohistochemical staining were performed to evaluate neuro function recovery. Floy cytometry was applied to detect apoptosis and cell cycle. BM-MSCs-exo significantly improved infarction ratio and neurological function after MCAO, and the influence of BM-MSCs-exo on neuro function recovery could be reversed by knocking down TGR5. Meanwhile, BM-MSCs-exo could remarkably activate TGR5 in vivo. The suppression of apoptosis by BM-MSCs-exo in vivo and in vitro was remarkably reversed by siRNA TGR5. BM-MSCs-exo promoted the animal recovery after MCAO. The neuroprotective effect by BM-MSCs-exo might be achieved by activating TGR5 and inhibiting apoptosis. Our findings provide a potential therapeutic thought for the treatment of cerebral infarction through BM-MSCs-exo targeting TGR5 and inhibiting apoptosis.

Recurrent Cerebral Infarcts Associated with Uterine Adenomyosis: Successful Prevention by Surgical Removal.

Hypercoagulability associated with malignant tumors causes thrombosis, termed Trousseau's syndrome, but is rarely associated with benign gynecological tumors, such as myoma and adenomyosis. We herein report a 47-year-old Japanese woman with uterine adenomyosis who developed multiple cerebral infarcts during menstruation. Edoxaban was initially used for prevention but failed to prevent recurrence of thrombosis. However, hysterectomy and bilateral salpingo-oophorectomy resulted in the successful prevention of recurrence of cerebral infarct for five years without antiplatelet or anticoagulant agents. In our patient, the surgical removal of adenomyosis was highly effective for preventing thrombosis in a patient with adenomyosis.

Effects of co-administration of metformin and evogliptin on cerebral infarct volume in the diabetic rat.

Patients with diabetes suffer more severe ischemic stroke. A combination of metformin and dipeptidyl peptide-4 inhibitors is commonly prescribed to treat diabetes. Therefore, we aimed to determine if pretreatment with a combination of metformin and evogliptin, a dipeptidyl peptidase-4 inhibitor, could reduce cerebral infarct volume in rats with streptozotocin-induced diabetes. After confirming diabetes induction, the rats were treated with vehicle, evogliptin, metformin, or evogliptin/metformin combination for 30 days. Then, stroke was induced by transient middle cerebral artery occlusion (tMCAO). Infarct volume, oxidative stress, levels of methylglyoxal-modified protein, glucagon-like peptide-1 receptor (GLP-1R), AMPK, and Akt/PI3K pathway-related proteins, and post-stroke pancreatic islet cell volume were evaluated. Compared to vehicle, only the co-administration group had significantly reduced infarct volume from the effects of tMCAO; the regimen also improved glycemic control, whereas the individual treatments did not. Co-administration also significantly reduced methylglyoxal-modified protein level in the core of the brain cortex, and the expression of 4-HNE and 8-OHdG was reduced. Co-administration increased p-Akt levels in the ischemic core and mitigated the suppression of Bcl-2 expression. Plasma GLP-1 and dipeptidyl peptidase-4 levels and brain GLP-1R expression remained unaltered. In the pancreas, islet cell damage was reduced by co-administration. These results reveal that metformin and evogliptin co-administration ameliorates cerebral infarction associated with prolonged glycemic control and pancreatic beta cell sparing. Other potential protective mechanisms may be upregulation of insulin receptor signaling or reduction of methylglyoxal-induced neurotoxicity. The combination of metformin and evogliptin should be tested further for its potential against focal cerebral ischemia in diabetes patients.

POTENTIAL PROTECTIVE EFFECTS OF NIMODIPINE FROM CEREBRAI ISCHEMIA REPERFUSION INJURY IN RATS.

OBJECTIVE: The aim: To see whether nimodipine had neuroprotective effects in cerebral ischemia/reperfusion injury. PATIENTS AND METHODS: Materials and methods: A total of 28 adult male Sprauge-dawley rats weighting 200-300 g were distributed randomly into 4 groups (7 animals in each group): sham (neck dissection without bilateral common carotid artery occlusion), control (bilateral common carotid artery occlusion for 30 minutes and reperfusion for 1 hour), vehicle (7 days of daily carboxymethylcellulose by oral gavage followed by bilateral carotid artery occlusion and reperfusion), and nimodipine-treated rats (7 days of 3 mg/kg/day of oral Azelnidipine pretreatment then bilateral common carotid artery occlusion and reperfusion). Besides assessment of histological changes and brain infarct volume, the brain tissues were sectioned to estimate NF-κB p65, IL-6, IL-10, TNF-α, ICAM-1 and total anti-oxidant capacity. RESULTS: Results: Cerebral NF-κB p65, IL-6, IL-10, TNF-α, ICAM-1, in addition to cerebral infarct size were markedly increased in control and vehicle related to sham rats, while total anti-oxidant capacity was considerably decreased. Treatment with nimodipine resulted in remarkable increment of total anti-oxidant capacity, while NF-κB p65, IL-6, TNF-α, and ICAM-1 showed great reduction. Cerebral IL-10 levels didn't change by nimodipine treatment. Histologically, control and vehicle rats showed severe brain ischemic changes which is dramatically reduced by nimodipine treatment. CONCLUSION: Conclusions: Our study results revealed that nimodipine can greatly decrease cerebral infarct size and reduce histological ischemic injury in male rats subjected to cerebral ischemia/ reperfusion. The neuroprotective actions of nimodipine possibly originated from its anti-inflammatory and antioxidative effects. Nimodipine protection was unrelated to IL-10.

[Effect of different shunt strategies on cerebral infarction after carotid endarterectomy].

OBJECTIVE: The key point of anesthesia management in carotid endarterectomy (CEA) is to maintain adequate cerebral perfusion during carotid artery occlusion. Placement of shunt is one of the common surgical methods. This study analyzed the effects of different shunt strategies on cerebral infarction after carotid endarterectomy. METHODS: A total of 443 patients who underwent CEA under general anesthesia within 2 years were divided into imaging group (based on preoperative imaging data as the basis for shunt) and stump pressure group (based on intraoperative stump pressure as the basis for shunt). The preoperative demographic data, past medical history, degree of cervical vascular stenosis, blood pressure at each time point during the perioperative period, vascular blocking time, whether to place the shunt, postoperative hospital stay, cerebral infarction during hospitalization, and other adverse events were collected and compared between the two groups. On this basis, the preoperative and intraoperative conditions with significant differences were matched with propensity scores, and the influence of different shunt strategies on postoperative cerebral infarction was analyzed. RESULTS: In the study, 268 patients in the imaging group and 175 patients in the stump pressure group underwent CEA under general anesthesia. There were statistically significant differences in basic conditions and blood pressure at each time point between the two groups. After matching the propensity scores, 105 patients in each of the two groups were matched. The basic conditions of the patients before surgery and the difference in blood pressure of the two groups at each time point were not statistically significant. There was no significant diffe-rence in the incidence of postoperative cerebral infarction between the two groups (1.9% vs. 1.0%, P>0.999). The intraoperative shunt rate in the imaging group was lower than that in the stump pressure group (0 vs. 22.9%, P < 0.001). The postoperative hospital stay in the imaging group was 8 (7, 8) days, which was longer than the stump pressure group 5 (4, 6) days (P < 0.001). CONCLUSION: The rate of the shunt was lower according to preoperative imaging examination than that according to the residual pressure in our hospital. There is no significant difference in the incidence of cerebral infarction during the postoperative hospital stay. The effect of different shunt strategies on cerebral infarction needs further study.

Efficacy and safety of clopidogrel and/or aspirin for ischemic stroke/transient ischemic attack: An overview of systematic reviews and meta-analysis.

OBJECTIVE: Patients experiencing acute ischemic stroke or transient ischemic attack are commonly treated with clopidogrel and/or aspirin (mono- and dual-antiplatelet therapy) to minimize the risk for recurrent stroke. Updated data from systematic studies can be used to guide practice. The present study aimed to compare findings from systematic reviews and meta-analyses addressing the efficacy and safety of clopidogrel or aspirin - alone or in combination - in patients experiencing acute ischemic stroke or transient ischemic attack. METHODS: The Cochrane Library, PubMed, Ovid, Scopus, EBSCO, and CINAHL databases were searched for relevant studies published from inception to 2020. Data from each study were extracted independently using a predefined data abstraction form. The Risk of Bias in Systematic Reviews tool and A Measurement Tool to Assess Systematic Reviews 2 were used to evaluate risk of bias and the quality of the included studies. RESULTS: Seven studies, published between 2010 and 2020, were eligible for analysis. The included studies evaluated a wide range of outcomes, including recurrent stroke, myocardial infarction, recurrent ischemic stroke, vascular mortality and vascular events, bleeding events, all-cause mortality, functional disability, and quality of life. The risk of bias and methodological validity of the included studies ranged from low to high according to ROBIS and AMSTAR 2 parameters. Results revealed that clopidogrel plus aspirin was more effective than aspirin alone in reducing the risk for recurrent stroke (ischemic or hemorrhagic), with high-quality evidence. However, compared with aspirin, dual treatment increased major bleeding events (intracranial bleeding and extracranial bleeding), supported by high-quality evidence. CONCLUSIONS: High-quality evidence suggested that clopidogrel plus aspirin was more efficient than monotherapy, although the risk for hemorrhagic stroke was relatively higher in combined therapy regimens lasting >1 month.

Benefits and risks of antiplatelet medication in hemodynamically stable adult moyamoya disease.

Revascularization surgery is considered a standard treatment for preventing additional stroke in symptomatic moyamoya disease (MMD). In hemodynamically stable, and asymptomatic or mildly symptomatic patients, however, the treatment strategy is controversial because of the obscure natural course of them. The authors analyzed the benefits and risks of antiplatelet medication in those patients. Medical data were retrospectively reviewed in 439 hemispheres of 243 patients with stable hemodynamic status. Overall, 121 patients (49.8%) with 222 studied hemispheres (50.6%) took antiplatelet medication. Symptomatic cerebral infarction and hemorrhage occurred in 10 (2.3%) and 30 (6.8%) hemispheres, over a mean follow-up of 62.0 ± 43.4 months (range 6-218 months). The use of antiplatelet agents was statistically insignificant in terms of symptomatic infarction, hemorrhage and improvement of ischemic symptoms. In subgroup analyses within the antiplatelet group according to drug potency and duration of medication, a longer duration of antiplatelet medication significantly improved ischemic symptoms (adjusted OR 1.02; 95% CI 1.01-1.03; p = 0.006). Antiplatelet medication failed to prevent symptomatic cerebral infarction or improve ischemic symptoms. However, antiplatelet therapy did not increase the risk of cerebral hemorrhage.

Risk Factors Control and Early Recurrent Cerebral Infarction in Patients with Symptomatic Intracranial Atherosclerotic Disease.

BACKGROUND: The risk of early recurrent cerebral infarction (RCI) is high in patients with symptomatic intracranial atherosclerotic disease (IAD). We sought to determine the relationship between risk factor control and early RCI risk among patients with symptomatic IAD. METHODS: We analyzed participants with symptomatic IAD in the multi-center prospective observational MYRIAD study. Risk factor control was assessed at 6-8-week follow-up. Optimal risk factor control was defined by target systolic blood pressure, being non-smoker, target physical activity, and antiplatelet and antilipidemic therapy compliance. Age-adjusted associations were calculated between risk factor control and RCI determined by MRI-evident new infarcts in the territory of the stenotic vessel at 6-8 weeks from the index event. RESULTS: Among 82 participants with clinical and brain MRI information available 6-8 weeks after the index event (mean age 63.5 ±12.5 years, 62.2% men), RCI occurred in 21 (25.6%) cases. At 6-8-week follow-up, 37.8% had target systolic blood pressure, 92.7% were non-smokers, 51.2% had target physical activity, and 98.8% and 86.6% were compliant with antiplatelet and antilipidemic therapy, respectively. Optimal risk factor control increased from 4.9% at baseline to 19.5% at 6-8-week follow-up (p=0.01). None of the participants with optimal risk factor control at follow-up had RCI (0% vs. 31.8%, p<0.01). CONCLUSIONS: Only one-fifth of MYRIAD participants had optimal risk factor control during early follow-up. Approximately half and two-thirds had physical inactivity and uncontrolled systolic blood pressure, respectively. These risk factors may represent important therapeutic targets to prevent early RCI in patients with symptomatic IAD.

Exercise-Linked Irisin Prevents Mortality and Enhances Cognition in a Mice Model of Cerebral Ischemia by Regulating Klotho Expression.

Irisin, which can be released in the hippocampus after physical exercise, is demonstrated to have beneficial effects on neurovascular diseases. This study investigated the impact of exercise linked-irisin on mortality and cognition in a mice model of cerebral ischemia and further explored its underlying mechanism. The cerebrospinal concentrations of irisin and klotho from ischemic stroke patients were measured with an enzyme-linked immunosorbent assay (ELISA). The cognitive function of mice was evaluated by a series of behavioural experiments. The expressions of klotho, MnSOD, and FOXO3a in the hippocampus of mice were detected by Western blot. Superoxide production in the brain tissue of mice was evaluated with the dihydroethidium (DHE) dying. The results demonstrated that stroke patients showed a positive correlation between their CSF irisin concentration and klotho concentration. In addition, when mice subjected to cerebral ischemia, their cognitive function was impaired, the protein expressions of klotho, MnSOD, and FOXO3a downregulated, and the production of reactive oxygen species (ROS) increased compared with the sham group. After pretreatment with exogenous irisin, improved cognitive impairment, upregulated protein expressions of klotho, MnSOD, and FOXO3a, and reduced ROS generation were observed in mice with MCAO. However, the neuroprotective effects of irisin compromised with the evidence of severe cognitive impairment, decreased protein expressions of MnSOD and FOXO3a, and increased ROS production in klotho knockout mice. Thus, our results indicated that exercise-linked irisin could prevent mortality and improve cognitive impairment after cerebral ischemia by regulating klotho expression.

Role of platelets in the pathogenesis of delayed injury after subarachnoid hemorrhage.

Aneurysmal subarachnoid hemorrhage (aSAH) patients develop delayed cerebral ischemia and delayed deficits (DCI) within 2 weeks of aneurysm rupture at a rate of approximately 30%. DCI is a major contributor to morbidity and mortality after SAH. The cause of DCI is multi-factorial with contributions from microthrombi, blood vessel constriction, inflammation, and cortical spreading depolarizations. Platelets play central roles in hemostasis, inflammation, and vascular function. Within this review, we examine the potential roles of platelets in microthrombi formation, large artery vasospasm, microvessel constriction, inflammation, and cortical spreading depolarization. Evidence from experimental and clinical studies is provided to support the role(s) of platelets in each pathophysiology which contributes to DCI. The review concludes with a suggestion for future therapeutic targets to prevent DCI after aSAH.

New diagnostic algorithm for detection of covert Bow Hunter's Syndrome.

Bow hunter's syndrome (BHS) should not be overlooked as a cause of cerebral infarction in the posterior circulation. However, covert BHS, which does not impair blood flow with simple rotation but only at certain angles, may make the diagnosis of BHS difficult. We propose a new algorithm to detect BHS or covert BHS. We recommend that BHS and covert BHS be detected by noninvasive duplex ultrasonography, which will allow for appropriate treatment.

Pathogenic variants of PROC gene caused type II activity deficiency in a Chinese family: A case report.

RATIONALE: Hereditary Protein C (PC) deficiency is a rare genetic disorder caused by PROC gene mutation. In this article, we report a case of PC deficiency in a Chinese family due to a novel PROC gene mutation. STUDY SUBJECT: The proband presented with recurrent cerebral infarction over the course of the previous 3 years. He was admitted to the hospital due to signs of mental retardation. DIAGNOSES: Physical examination, laboratory tests, and magnetic resonance imaging demonstrated that the proband had a manifestation of PC deficiency that included acute cerebral infarction. DNA sequencing analysis revealed a missense variant, c.1015G > A (p.V339 M from valine to methionine) in exon 9 of the PROC gene. In addition, Sanger sequencing confirmed that the proband's son was heterozygous for the same variant. Therefore, the PROC gene mutation was transmitted in an autosomal dominant inheritance manner. INTERVENTIONS: The patient was treated with a daily dosage of Warfarin (3.5 mg) and was scheduled to undergo regular blood coagulation tests. OUTCOMES: At the 3-month follow-up appointment, the patient showed improvements in his overall health condition. LESSONS: We identified a novel missense mutation in the PROC gene in a Chinese family which caused a decrease in the PC antigen level and recurrent cerebral infarction.

Exosomes containing miR-451a is involved in the protective effect of cerebral ischemic preconditioning against cerebral ischemia and reperfusion injury.

AIM: To study the role of exosomes in the protective effect of cerebral ischemic preconditioning (cerebral-IPC) against cerebral I/R injury. METHOD: Mouse models of cerebral-IPC and MCAO/R were established as described previously, and their behavioral, pathological, and proteomic changes were analyzed. Neuro-2a subjected to OGD/R were treated with exosomes isolated from the plasma of sham-operated and cerebral-IPC mice. The differentially expressed miRNAs between exosomes derived from sham-operated (S-exosomes) and preconditioned (IPC-exosomes) mice were identified through miRNA array, and their targets were identified through database search. The control and OGD/R cells were treated with the IPC-exosomes, miRNA mimic or target protein inhibitor, and their viability, oxidative, stress and apoptosis rates were measured. The activated pathways were identified by analyzing the levels of relevant proteins. RESULTS: Cerebral-IPC mitigated the cerebral injury following ischemia and reperfusion, and increased the number of plasma exosomes. IPC-exosomes increased the survival of Neuro-2a cells after OGD/R. The miR-451a targeting Rac1 was upregulated in the IPC-exosomes relative to S-exosomes. The miR-451a mimic and the Rac1 inhibitor NSC23766 reversed OGD/R-mediated activation of Rac1 and its downstream pathways. CONCLUSION: Cerebral-IPC ameliorated cerebral I/R injury by inducing the release of exosomes containing miR-451a.