Src inhibition rescues FUNDC1-mediated neuronal mitophagy in ischaemic stroke.

BACKGROUND: Ischaemic stroke triggers neuronal mitophagy, while the involvement of mitophagy receptors in ischaemia/reperfusion (I/R) injury-induced neuronal mitophagy remain not fully elucidated. Here, we aimed to investigate the involvement of mitophagy receptor FUN14 domain-containing 1 (FUNDC1) and its modulation in neuronal mitophagy induced by I/R injury. METHODS: Wild-type and FUNDC1 knockout mice were generated to establish models of neuronal I/R injury, including transient middle cerebral artery occlusion (tMCAO) in vivo and oxygen glucose deprivation/reperfusion in vitro. Stroke outcomes of mice with two genotypes were assessed. Neuronal mitophagy was analysed both in vivo and in vitro. Activities of FUNDC1 and its regulator Src were evaluated. The impact of Src on FUNDC1-mediated mitophagy was assessed through administration of Src antagonist PP1. RESULTS: To our surprise, FUNDC1 knockout mice subjected to tMCAO showed stroke outcomes comparable to those of their wild-type littermates. Although neuronal mitophagy could be activated by I/R injury, FUNDC1 deletion did not disrupt neuronal mitophagy. Transient activation of FUNDC1, represented by dephosphorylation of Tyr18, was detected in the early stages (within 3 hours) of neuronal I/R injury; however, phosphorylated Tyr18 reappeared and even surpassed baseline levels in later stages (after 6 hours), accompanied by a decrease in FUNDC1-light chain 3 interactions. Spontaneous inactivation of FUNDC1 was associated with Src activation, represented by phosphorylation of Tyr416, which changed in parallel with the level of phosphorylated FUNDC1 (Tyr18) during neuronal I/R injury. Finally, FUNDC1-mediated mitophagy in neurons under I/R conditions can be rescued by pharmacological inhibition of Src. CONCLUSIONS: FUNDC1 is inactivated by Src during the later stage (after 6 hours) of neuronal I/R injury, and rescue of FUNDC1-mediated mitophagy may serve as a potential therapeutic strategy for treating ischaemic stroke.

Bloody fluids located between the temporal muscle and targeted cerebral cortex affect the establishment of indirect collaterals in Moyamoya disease with surgical bypass: A case-control study.

Objective: Bypass yields favorable outcomes in the treatment of Moyamoya disease (MMD). Bloody fluids accumulate between the targeted cortex and the temporal muscle after surgical bypass. These fluids are handled empirically via subcutaneous tubes or conservative treatments. However, substances located in certain positions may adversely affect the establishment of indirect collaterals (ICs) from muscular grafts. Methods: Patients in our hospital from January 2014 to December 2019 were eligible for inclusion. Digital subtraction angiography (DSA) and radiological examinations were used during the perioperative and follow-up periods. Bloody fluid volumes were calculated using computed tomography- (CT-) based 3D Slicer software. The characteristics of bloody fluids, patient demographics, and clinical data were retrospectively analyzed. Results: In total, 110 patients underwent indirect or combined bypass with follow-up DSA. The mean age of the enrolled patients was 42.4 ± 11.8 years. Previous ischemia (p = 0.001), previous hemorrhage (p = 0.013), bloody fluid volume (p = 0.049), and the time of imaging (p = 0.081) were associated with indirect outcomes. Ordinal regression analysis confirmed that good indirect outcomes were associated with previous ischemia (p < 0.001) and a large bloody fluid volume (p = 0.013). Further subgroups based on fluid volume were significantly correlated with IC establishment (p = 0.030). Conclusions: A large bloody fluid volume and previous ischemic history were associated with good indirect outcomes. The presence of bloody fluids may reflect impaired degrees of muscular donors due to bipolar electrocoagulation, thus highlighting the importance of appropriate application of bipolar forceps.

Wall Imaging for Unilateral Intracranial Vertebral Artery Hypoplasia with Three-dimensional High-isotropic Resolution Magnetic Resonance Images.

BACKGROUND: There are few studies for evaluating wall characteristics of intracranial vertebral artery hypoplasia (VAH). The aim of this study was to determine wall characteristics of VAH with three-dimensional volumetric isotropic turbo spin echo acquisition (3D VISTA) images and differentiate between acquired atherosclerotic stenosis and VAH. METHODS: Thirty patients with suspicious VAH by luminograms were retrospectively enrolled between January 2014 and February 2015. The patients were classified as "acquired atherosclerotic stenosis" or "VAH" based on 3D VISTA images. The wall characteristics of VAH were assessed to determine the presence of atherosclerotic lesions, and the patients were classified into two subgroups (VAH with atherosclerosis and VAH with normal wall). Wall characteristics of basilar arteries and vertebral arteries were also assessed. The clinical and wall characteristics were compared between the two groups. RESULTS: Five of 30 patients with suspicious VAH were finally diagnosed as acquired atherosclerotic stenosis by 3D VISTA images. 25 patients were finally diagnosed as VAH including 16 (64.00%) patients with atherosclerosis and 9 (36.00%) patients with normal wall. In the 16 patients with atherosclerosis, plaque was found in 9 patients, slight wall thickening in 6 patients, and thrombus and wall thickening in 1 patient. Compared with VAH patients with normal wall, VAH patients with atherosclerosis showed atherosclerotic basilar arteries and dominant vertebral arteries more frequently (P = 0.000). CONCLUSIONS: Three-dimensional VISTA images enable differentiation between the acquired atherosclerotic stenosis and VAH. VAH was also prone to atherosclerotic processes.

Plaques of Nonstenotic Basilar Arteries with Isolated Pontine Infarction on Three-dimensional High Isotropic Resolution Magnetic Resonance Imaging.

BACKGROUND: There are few studies for evaluating plaque characteristics of nonstenotic basilar arteries (BA). Our aim was to determine entire BA plaques with a three-dimensional volumetric isotropic turbo spin-echo acquisition (VISTA) and investigate the differences between the patients with and without isolated pontine infarction (IPI). METHODS: Twenty-four consecutive symptomatic patients with nonstenotic BA on time of flight magnetic resonance angiography (TOF MRA) were enrolled from China-Japan Friendship Hospital between January 2014 and December 2014. BA was classified as "normal" or "irregular" based on TOF MRA, and "normal wall", "slight wall-thickening", and "plaque" based on three-dimensional VISTA images. Outcomes from MRA and VISTA were compared. Patients were categorized as IPI and non-IPI groups based on the diffusion-weighted imaging. Clinical and plaque characteristics were compared between the two groups. RESULTS: A total of 1024 image slices including 311 (30.37%) plaque slices, 427 (41.70%) slight wall-thickening slices, and 286 (27.93%) normal wall slices for the entire BA from 23 patients were finally included for analysis. VISTA images detected plaques in all the 9 (100%) irregular MRA patients and 7 of 14 (50%) normal MRA patients. IPI was found in 11 (47.83%) patients. Compared to non-IPI group, the IPI group had a higher percentage of plaque slices (P = 0.001) and lower percentage of normal wall slices (P = 0.014) than non-IPI group. CONCLUSIONS: Three-dimensional VISTA images enable detection of BA plaques not visualized by MRA. BA plaques could be found in both the IPI and non-IPI group. However, IPI group showed plaques more extensively in BA than the non-IPI group.

[Medical rescue of China National Earthquake Disaster Emergency Search and Rescue Team in Lushan earthquake].

OBJECTIVE: To summarize and analyze the medical mission of China National Earthquake Disaster Emergency Search and Rescue Team (CNESAR) in Lushan earthquake, to promote the medical rescue effectiveness incorporated with search and rescue. METHODS: Retrospective analysis of medical work data by CNESAR from April 21th, 2013 to April 27th during Lushan earthquake rescue, including the medical staff dispatch and the wounded case been treated. RESULTS: The reasonable medical corps was composed by 22 members, including 2 administrators, 11 doctors [covering emergency medicine, orthopedics (joints and limbs, spinal), obstetrics and gynecology, gastroenterology, cardiology, ophthalmology, anesthesiology, medical rescue, health epidemic prevention, clinical laboratory of 11 specialties], 1 ultrasound technician, 5 nurses, 1 pharmacist, 1 medical instrument engineer and 1 office worker for propaganda. There were two members having psychological consultants qualifications. The medical work were carried out in seven aspects, including medical care assurance for the CNESAR members, first aid cooperation with search and rescue on site, clinical work in refugees' camp, medical round service for scattered village people, evacuation for the wounded, mental intervention, and the sanitary and anti-epidemic work. The medical work covered 24 small towns, and medical staff established 3 medical clinics at Taiping Town, Shuangshi Town of Lushan County and Baoxing County. Medical rescue, mental intervention for the old and kids, and sanitary and anti-epidemic were performed at the above sites. The medical corps had successful evacuated 2 severe wounded patients and treated the wounded over thousands. Most of the wounded were soft tissue injuries, external injury, respiratory tract infections, diarrhea, and heat stroke. CONCLUSIONS: Compared with the rescue action in 2008 Wenchuan earthquake, the aggregation and departure of rescue team in Lushan earthquake, the traffic control order in disaster area, the self-aid and buddy aid are better, which give rise to the casualties to the lowest. The medical mission incorporated with search and rescue work showed that the medical performance manner altered with stages, the medical staff match changed with the mission, and the focus related with rescue time.

[Discussion about health assessment and epidemic prevention mode for China National Earthquake Disaster Emergency Search and Rescue Team in Lushan earthquake].

OBJECTIVE: To discuss health assessment and epidemic prevention in earthquake rescue, to establish emergency health and epidemic prevention mode for the national earthquake emergency medical rescue team scientifically, and to provide references and consultations for emergency hygiene and epidemic prevention measures in disaster medicine. METHODS AND RESULTS: China National Earthquake Disaster Emergency Search and Rescue Team gathered and evaluated environment, food, drinking water and other health related information around more than 2000 earthquake victims in Baoxing County, Shuangshi Town and Qingren Township from 20th April 2013 to 27th by using methods such as field epidemiological investigations. The national earthquake emergency medical rescue team spread comprehensive evaluation focusing on the local epidemics, find out the starting point of epidemic prevention, and then built reporting system in disaster area. The team also formulated the emergency detection system of food and drinking water and carried out health education. CONCLUSION: After the golden 72 hours, by comprehensive evaluation the establishment of early response in disaster area and spreading epidemic prevention, this team achieved the full coverage of three in the earthquake area, the resettlement of residents and families in that area and gradually formed a disaster medical rescue hygiene and epidemic prevention mode.