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Background: Sleep deprivation (SD) is commonplace in modern society and there are large individual differences in the vulnerability to SD. We aim to identify the structural network differences based on diffusion tensor imaging (DTI) that contribute to the individual different vulnerability to SD. Methods: The number of psychomotor vigilance task (PVT) lapses was used to classify 49 healthy subjects on the basis of whether they were vulnerable or resistant to SD. DTI and graph theory approaches were used to investigate the topologic organization differences of the brain structural connectome between SD‐vulnerable and ‐resistant individuals. We measured the level of global efficiency and clustering in rich club and non‐rich club organizations. Results: We demonstrated that participants vulnerable to SD had less global efficiency, network strength, and local efficiency but longer shortest path length compared with participants resistant to SD. Lower efficiency was mainly distributed in the right insula, bilateral thalamus, bilateral frontal, temporal, and temporal lobes. Furthermore, a disrupted subnetwork was observed that consisted of widespread connections. Moreover, the vulnerable group showed significantly decreased strength of the rich club compared with the resistant group. The strength of rich club connectivity was found to be correlated negatively with PVT performance (r = −0.395, p = 0.005). We further tested the reliability of the results. Conclusion: The findings revealed that individual differences in resistance to SD are related to disrupted topologic efficiency connectome pattern, and our study may provide potential connectome‐based biomarkers for the early detection of the vulnerable degree to SD. [ABSTRACT FROM AUTHOR]

Aims: The blood‐brain barrier (BBB) is a specialized and indispensable structure in brain blood vessels that is damaged during Alzheimer's disease (AD). CD147 is expressed on the BBB and deeply engaged in the AD pathological process. In this study, we aimed to provide a better understanding of the roles of CD147 in BBB function in health and neurodegenerative disease. Methods and Results: We measured CD147 expression in mouse brains and demonstrated that CD147 is exclusively expressed in brain endothelial cells (BECs), and its expression decreases with age. After constructing endothelial‐specific CD147 knockout mice, we performed RNA‐sequencing on BECs isolated from mice of different ages as well as a range of database analyses. We found that endothelial CD147 is essential for the dual functions of the BBB, including barrier maintenance and transporter regulation. This study also shows that CD147 plays a pivotal role in neurodegenerative diseases, particularly in AD. Conclusions: Our findings suggested that targeting CD147 in BECs may represent a novel therapeutic strategy, which promoted the design of future experimental investigations and the mechanistic understanding of neurodegenerative diseases. [ABSTRACT FROM AUTHOR]

Aims: To explore large‐scale brain network alterations and examine their clinical and neuropsychological relevance in patients with anti‐N‐methyl‐D‐aspartate receptor (NMDAR) encephalitis. Methods: Twenty‐four patients with anti‐NMDAR encephalitis and 26 matched healthy controls (HCs) were enrolled in our study. Based on the multimodal MRI dataset, individual morphological, structural, and functional brain networks were constructed and compared between the two groups at multiple levels. The associations with clinical/neuropsychological variables and the discriminant ability of significant alterations were further studied. Results: Multimodal network analysis revealed that anti‐NMDAR encephalitis mainly affected morphological and structural networks, but subtle alterations were observed in functional networks. Intriguingly, decreased network local efficiency was observed for both morphological and structural networks and increased nodal centrality in the lateral orbital gyrus was convergently observed among the three types of networks in the patients. Moreover, the alterations, particularly those from structural networks, accounted largely for cognitive deficits of the patients and could distinguish the diseased individuals from the HCs with excellent performance (area under the curve =0.933). Conclusions: The current study provides a comprehensive view of characteristic multimodal network dysfunction in anti‐NMDAR encephalitis, which is crucial to establish new diagnostic biomarkers and promising therapeutic targets for the disease. [ABSTRACT FROM AUTHOR]

Summary: Background: We intended to compare and rank all the immunotherapies including immunosuppressant agents or monoclonal antibodies for myasthenia gravis (MG). Methods: A network meta‐analysis was performed to synthesize the direct evidence and indirect evidence. Quantitative MG score (QMGS) was defined as the primary outcome. The secondary outcomes included the glucocorticoid reduction and hazard ratios (HR) from the counts of adverse events (AEs). Results: We identified 14 studies including 808 MG patients. For the primary outcome, cyclosporine A (CsA) was hierarchically the best with statistical significances of −1.18 (−1.81, −0.59) vs placebo (PLA), −0.98 (−1.72, −0.23) vs mycophenolate mofetil, and −0.77 (−1.57, −0.032) vs tacrolimus (TAC). When the intervention periods were controlled, both eculizumab (ECZ) of −1.50 (−2.81, −0.18) and CsA of −1.23 (−1.81, −0.64) vs PLA reached a statistical significance. Belimumab and ECZ ranked the most tolerable therapies while CsA of 2.41 (0.58, 10.01) ranked the last vs PLA. Conclusion: These findings demonstrated that ECZ represented the most effective and tolerable therapeutic alternative to be recommended for refractory MG. TAC may be a beneficial therapy to treat MG extensively while the efficacy of CsA and cyclophosphamide may be limited by their multiple or severe AEs. [ABSTRACT FROM AUTHOR]

Aims Pseudoginsenoside-F11 ( PF11), an ocotillol-type ginsenoside, has been reported to exert wide-ranging neuroprotective properties. The aim of this study was to investigate the effect and potential mechanisms of PF11 on the autophagic/lysosomal pathway following ischemic stroke. Methods Male Sprague-Dawley rats underwent permanent middle cerebral artery occlusion ( pMCAO). Cerebral ischemia outcome, TUNEL staining, Fluoro-Jade B staining were carried out 24 hours poststroke. The autophagic/lysosomal-related proteins were measured. Results A single administration of PF11 significantly decreased the infarct area, reduced the brain water content, and improved neurological functions, even 4 hours after the onset of pMCAO. Meanwhile, PF11 lessened the ischemic insult-mediated loss of neurons and activation of astrocytes and microglia. Furthermore, PF11 attenuated pMCAO-induced accumulations of autophagosomes and apoptosis. We further observed a remarkable effect of PF11 in reversing the ischemic insult-induced accumulation of autophagosomes ( LC3- II) and abnormal aggregation of autophagic proteins ( SQSTM1 and ubiquitin). Furthermore, PF11 was capable of improving lysosomal function and lysosome/autophagosome fusion following pMCAO, and this change was reversed by the lysosomal inhibitor chloroquine. Also, the improvement of ischemic outcome and the antiapoptotic effect induced by PF11 was reversed by CQ. Conclusion These findings indicate that the autophagic flux is impaired in a rat model of pMCAO, and that PF11 exerts an excellent protective effect against ischemic stroke by alleviating autophagic/lysosomal defects. [ABSTRACT FROM AUTHOR]

Aims Sildenafil, a phosphodiesterase type 5 inhibitor, has been found to produce functional recovery in ischemic rats by increasing the c GMP level and triggering neurogenesis. The aim of this study was to investigate further sildenafil mechanisms. Methods Male Sprague- Dawley rats underwent middle cerebral artery occlusion and reperfusion, followed by intraperitoneal or intravenous treatment of sildenafil starting 2 h later. Behavioral tests were performed on day 1 or day 7 after reperfusion, while cerebral infarction, edema, Nissl staining, Fluoro- Jade B staining, and electron microscopy studies were carried out 24 h poststroke. The c GMP-dependent Nogo-66 receptor ( Nogo- R) pathway, synaptophysin, PSD-95/neuronal nitric oxide synthases (n NOS), brain-derived neurotrophic factor ( BDNF)/tropomyosin-related kinase B ( Trk B), and nerve growth factor ( NGF)/tropomyosin-related kinase A ( Trk A) were measured. Results Sildenafil enhanced neurological recovery and inhibited infarction, even following delayed administration 4 h after stroke onset. Furthermore, sildenafil reduced the loss of neurons and modulated the expressions of the c GMP-dependent Nogo- R pathway. Moreover, sildenafil protected the structure of synapses and mediated the expressions of synaptophysin, PSD-95/n NOS, BDNF/ Trk B, and NGF/ Trk A. Conclusions Sildenafil produces significant neuroprotective effects on injured neurons in acute stroke, and these are mediated by the c GMP-dependent Nogo- R pathway, NGF/ Trk A, and BDNF/ Trk B. [ABSTRACT FROM AUTHOR]

Aims It has been well documented that angiotensin II type 1 ( AT1) receptor blockers ( ARBs) are known to attenuate neural damage and the c-Jun N-terminal protein kinase 3 ( JNK3) pathway and caspase-3 signal are involved in neuronal cell death following cerebral ischemia/reperfusion ( I/ R). In this study, we first showed that losartan could protect neurons against cerebral I/ R-induced injury. Methods Cerebral ischemia model was induced by four-vessel occlusion. Antisense oligodeoxynucleotides ( ODNs) against AT1 receptor and losartan were used to detect whether the AT1 receptor implicated in cerebral I/ R. Immunoprecipitation ( IP) and immunoblotting ( IB) were used to detect the interactions between β-arrestin-2 and AT1/apoptosis signal-regulating kinase 1 ( ASK1)/ MAP kinase kinase 4 ( MKK4) signaling module following cerebral I/ R. Results First, losartan decreased cerebral I/ R-induced neuronal death. Second, losartan depressed the β-arrestin-2-assembled AT1/ ASK1/ MKK4 signaling module. Third, losartan depressed the activation of c-jun, JNK3, Bcl-2, caspase-3 and the release of cytochrome c from mitochondria to cytoplasm. Conclusion Taken together, losartan could attenuate neural damage following the cerebral I/R via inhibiting the β-arrestin-2-assembled AT1/ ASK1/ MKK4 signaling module and depressing the activation of c-jun, JNK3, and caspase-3 and the release of cytochrome c. [ABSTRACT FROM AUTHOR]