PCSK9 inhibitor protects against ischemic cerebral injury by attenuating inflammation via the GPNMB/CD44 pathway.

BACKGROUND: Ischemic stroke is the second leading cause of death worldwide, and neuroinflammation has been recognized as a critical player in its progression. Meanwhile, proprotein convertase subtilisin/kexin type 9 inhibitor (PCSK9i) has been demonstrated to inhibit inflammatory response. However, the effects of PCSK9i on ischemic stroke remain unclear and require further investigation. METHODS: Temporary middle cerebral artery occlusion (tMCAO) was performed to establish animal models of ischemic stroke in C57BL/6 mice. The PCSK9i were administered subcutaneously after 2 h tMCAO. Neurological function and cerebral infarct volume were measured by mNSS and TTC staining, respectively. RNA-seq was performed to investigate the changes in mechanistic pathways. Western blotting and immunofluorescence were applied to detect expression of GPNMB, CD44, IL-6, and iNOS. RESULTS: Treatment with PCSK9i significantly improved neurological deficits and reduced the volume of cerebral infarction. PCSK9i suppressed neuroinflammation by activating the GPNMB/CD44 signaling pathway, further exerting their protective effects. CONCLUSION: Taken together, treatment with PCSK9i is an effective way to prevent ischemic stroke-induced brain injury.

Derivation of induced pluripotent stem cell SHEHDNi002-A from a 68-year-old Chinese Han Parkinson's disease patient carrying LRRK2 and DNAJC6 mutations.

Parkinson's disease (PD) is a common movement disorder. In this study, we generated an induced pluripotent stem cell (iPSC) line from the dermal fibroblasts of a 68-year-old female patient, carrying LRRK2 and DNAJC6 mutations. This iPSC line will be a useful tool for investigating the pathogenesis and for developing treatment for PD.

Effect of intravenous thrombolysis on core growth rate in patients with acute cerebral infarction.

Objective: This study aimed to investigate the effects of recombinant tissue plasminogen activator intravenous thrombolysis (IVT) on the core growth rate of acute ischemic stroke. Methods: Stroke patients with large vessel occlusion and non-recanalization from IVT treatment were retrospectively included in this study and divided into two groups: IVT and non-IVT. The core growth rate was estimated by the acute core volume on perfusion CT divided by the last known well time from stroke to CT perfusion. The primary endpoint was the core growth rate, the tissue outcome was 24 h-ASPECTS, and the clinical outcome was a 3-month modified Rankin score. Results: A total of 94 patients were included with 53 in the IVT group and 41 in the non-IVT group. There was no significant difference in age, gender, hypertension, diabetes, atrial fibrillation, acute NIHSS, and last known well time from stroke to CT perfusion acquisition between the two groups. The core growth rate in the IVT group was lower than that in the non-IVT group, which was statistically significant after multivariate adjustment (coefficient: -5.20, 95% CI= [-9.85, -0.56], p = 0.028). There was a significant interaction between the IVT and the collateral index in predicting the core growth rate. The analysis was then stratified according to the collateral index, and the results suggested that IVT reduced the core growth rate more significantly after the worsening of collateral circulation (coefficient: 15.38, 95% CI= [-26.25, -4.40], p = 0.007). The 3-month modified Rankin score and 24 h-ASPECTS were not statistically significant between the two groups. Conclusion: Intravenous thrombolysis reduces the core growth rate in patients with AIS, especially those with poor collateral status.

Clinical and laboratory factors related to acute isolated vertigo or dizziness and cerebral infarction.

OBJECTIVE: To clarify the relationship of clinical factors with isolated vertigo or dizziness of cerebrovascular origin. METHODS: Clinical data of patients admitted in East Hospital from Jan. 2015 to Apr. 2016, whose complaint were acute vertigo or dizziness were retrospectively collected. All patients arrived at the emergency department within 24 hr of symptom onset, had no acute ischemic lesion first CT and NIHSS score of 0. Patients were divided into cerebral infarction group and noncerebral infarction group according to subsequent cerebral imaging results and clinical and laboratory factors related to cerebral infarction were analyzed. RESULT: 51.6% of patients were female (n = 141). 46 patients (16.8%) were diagnosed with acute cerebral infarction. Baseline demographic data of the two groups was not significantly different. Univariate analysis found that history of smoking (p = 0.009), headache (p = 0.028), unsteadiness (p = 0.009), neuron specific enolase (p = 0.001), and vertebral artery abnormalities found on imaging (p = 0.009) were the significant difference between two groups. Increased neuron specific enolase (p = 0.005) and an abnormal vertebral artery (p = 0.044) were significant on multivariate analysis. CONCLUSIONS: 16.8% of acute isolated vertigo or dizziness presentations were diagnosed with acute cerebral infarction. Increased serum neuron specific enolase and vertebral artery abnormalities were the strongest indicators of acute cerebral infarction.