Ruiqi Chen

The cyclophilin D/Drp1 axis regulates mitochondrial fission contributing to oxidative stress-induced mitochondrial dysfunctions in SH-SY5Y cells

Oxidative stress plays a central role in the pathogenesis of various neurodegenerative diseases. Increasing evidences have demonstrated that structural abnormalities in mitochondria are involved in oxidative stress related nerve cell damage. And Drp1 plays a critical role in mitochondrial dynamic imbalance insulted by oxidative stress-derived mitochondria. However, the status of mitochondrial fusion and fission pathway and its relationship with mitochondrial properties such as mitochondrial membrane permeability transition pore (mPTP) have not been fully elucidated. Here, we demonstrated for the first time the role of Cyclophilin D (CypD), a crucial component for mPTP formation, in the regulation of mitochondrial dynamics in oxidative stress treated nerve cell. We observed that CypD-mediated phosphorylation of Drp1 and subsequently augmented Drp1 recruitment to mitochondria and shifts mitochondrial dynamics toward excessive fission, which contributes to the mitochondrial structural and functional dysfunctions in oxidative stress-treated nerve cells. CypD depletion or over expression accompanies mitochondrial dynamics/functions recovery or aggravation separately. We also demonstrated first time the link between the CypD to mitochondrial dynamics. Our data offer new insights into the mechanism of mitochondrial dynamics which contribute to the mitochondrial dysfunctions, specifically the role of CypD in Drp1-mediated mitochondrial fission. The protective effect of CsA, or other molecules affecting the function of CypD hold promise as a potential novel therapeutic strategy for governing oxidative stress pathology via mitochondrial pathways.

Neuroprotection of nalmefene for postoperative patients with spontaneous intracerebral hemorrhage

Background: Endogenous opiates play an important role in the secondary injury of brain tissue after central nervous system injury. It was confirmed that nalmefene, an opiates receptor antagonist, has neuroprotective efficacy in animal models. However, evidence of nalmefene treatment for surgical patients with spontaneous intracerebral hemorrhage is insufficient. Methods: Outcomes of patients treated with nalmefene were retrospectively compared with that of patients without any anti-opiate treatment. The primary outcome was functional outcome at 6 months post ictus, which was assessed using modified Rankin Scales (mRSs). Secondary outcomes included mortality in 30 d post ictus, state of consciousness evaluated using Glasgow Coma Scale (GCS) at 1, 3, 7 d post operation and complications. Results: Of 79 patients in the nalmefene treatment group, 22 (27.85%) had a favorable functional outcome at 6 months, while in the control group, 12 of 72 (16.67%) had the same result (p = 0.273). A significantly better outcome was observed in the treatment group during only one subgroup analyses which was GCS between 3 and 8 (32.26% vs. 6.45%, p = 0.006). Conclusions: Nalmefene treatment was safe for patients with spontaneous intracerebral hemorrhage but could not improve the outcome of either short-term consciousness or long-term functional outcome.

Radiologic Characteristics and High Risk of Seizures in Infants with Ruptured Intracranial Aneurysms: Case Report and Review of the Literature

OBJECTIVE To evaluate the parameters related to the high risk of preoperative seizures in infants (1 year or younger) with ruptured intracranial aneurysms. METHODS Infants with ruptured intracranial aneurysms treated at our institution from January 2012 to January 2018 were retrospectively analyzed. Seventeen similar cases of infant patients with seizures reported in published studies were reviewed. RESULTS The mean age of the 7 infant patients treated at our institution was 4.1 ± 3.3 months (range, 28 days to 11 months), with 2 male and 5 female subjects. One patient (14.3%) had an internal carotid artery aneurysm with subarachnoid hemorrhage, and the remaining 6 patients (85.7%) had middle cerebral artery (MCA) aneurysms in the distal arterial region with lobe hemorrhage. Five of the 7 infants (71.4%) had seizures, 4 of whom (4/5, 80.0%) had MCA distal arterial aneurysms with lobe hemorrhage. Management was successful for all patients with aneurysm clipping or resection surgery, and one patient experienced postoperative seizures. Of the 17 reviewed cases of infant patients with seizures, 10 patients (58.8%) exhibited the typical distal arterial aneurysm with lobe hemorrhaging, and 6 (60%) of them had aneurysms in MCA. CONCLUSIONS Infant patients with ruptured intracranial aneurysms have a high risk of preoperative seizures. The typical radiologic finding of distal arterial aneurysm with lobe hemorrhage was frequently observed in the MCA, and it might be related to the high risk of preoperative seizures in this population. Microsurgical techniques effectively control postoperative seizures in infants with ruptured intracranial aneurysms.

Elevated hemoglobin is associated with cerebral infarction in Tibetan patients with primary hemorrhagic neurovascular diseases

OBJECTIVES Although many studies have focused on primary hemorrhagic neurovascular diseases (PHNVDs) in different races, studies of PHNVDs in the plateau area of China are still insufficient. Chinese Tibetan people are the largest population living in the plateau area. Previous studies have shown that Tibetan PHNVD patients have a significantly higher incidence of cerebral infarction, but the mechanism remains uncertain. This study aimed to develop a better understanding on the mechanism of their high risk of cerebral infarction. PATIENTS AND METHODS In this retrospective case control study, we used a hospital information system to search for consecutive Tibetan patients with PHNVDs from January 2012 to June 2016. Intra-hospital data including baseline information and complications were recorded, and the risk factors for cerebral infarction were analyzed. RESULTS Univariate analysis and cox proportional hazard multivariate regression analysis revealed that elevated hemoglobin (HGB) concentration was positively associated with an increased incidence of cerebral infarction (P<0.001). The cutoff value that maximized the ability to predict in-hospital infarction in Tibetans with PHNVDs was 15.2g/dL. Tibetan PHNVD patients with an increased HGB concentration were more likely to present with cerebral infarction within the first 5days after onset of PHNVDs, and the probability was highest on the 3rd day. CONCLUSIONS HGB levels could be used to predict in-hospital cerebral infarction in Tibetan patients with PHNVDs. These patients are more likely to develop in-hospital infarction when the HGB concentration is higher than 15.2g/dL. For Tibetan PHNVD patients with an elevated HGB concentration, most cerebral infarctions occurred within the first five days after onset, with more incidents occurring on the third day.

Blood blister-like aneurysms in Tibetans: A retrospective observational study

OBJECT Although research on blood blister-like aneurysms (BLAs) in different population is well documented, studies of that in the plateau area remain elusive. This study aimed to develop a better understanding of BLAs in Tibetan population, which is a typical representation of people in plateau area. METHODS In this retrospective observational study, the hospital information system (HIS) was used to search for consecutive patients with BLAs by using the discharge diagnoses. A total of 19 Tibetan patients and 34 Han patients were recruited from January 2012 to January 2016. Intra-hospital and follow-up data were collected and compared between two races. RESULTS Compared with Han group, Tibetan group got significantly higher ratio of BLAs among aneurysmal subarachnoid hemorrhages (aSAHs) (19.6% (19/97) vs 3.2% (34/1071), p<0.001), higher Incidence of atypical located BLAs (26.3% vs 2.9%, p=0.034), higher risk of cerebral infarction (63.2% vs 11.8%, p<0.001), and greater number of patients with unfavorable outcomes at 6 months after ictus (57.9% vs 23.5%, p=0.028). In Tibetan group, patients underwent endovascular treatment presented with significantly lower cerebral infarction rate (p=0.019) and better neurological functional recovery outcome (p=0.048) compared with surgical group. CONCLUSIONS Compared with Han patients, Tibetan BLA patients presented with high risk of occurrence with atypical locations and high incidence of cerebral infarctions with poor prognoses. Endovascular treatment benefits more for Tibetan BLA patients in reducing cerebral infarctions and improving neurological functional recovery prognosis.