Integrated analysis of differentially expressed lncRNAs in Medial Temporal Lobe Epilepsy.

BACKGROUND: Medial temporal lobe epilepsy (MTLE) is the most frequent type of epilepsy. In recent years, the important roles of lncRNAs in regulating human diseases progression had been implicated, including in epilepsy. However, comprehensive analysis of differentially expressed lncRNAs in Medial Temporal Lobe Epilepsy was still lacking. OBJECTIVES: The aim of this study was to explore relevant lncRNAs in MTLE. METHODS: In present study, we analyzed a public dataset GSE25453 to identify differentially expressed lncRNAs and mRNAs in the MTLE. RESULTS: A total of 16 lncRNAs (C6orf176, NCRNA00259, PRO1768, TTTY11, LOC149620, GDEP, LOC400891, HLA-DRB6, TTTY21, TTTY3, NBR2, TTTY1, FAM183B, C15orf51, FAM74A3, and MALAT1) were identified. LncRNA co-expression network analysis showed these lncRNAs were mainly enriched in regulating transcription, inflammatory response, DNA binding, Jak Stat Signaling Pathway, and Mapk Signaling Pathway. Meanwhile, lncRNA-mRNA-biological processes networks were also performed to evaluate the potential roles of key lncRNAs in MTLE. CONCLUSIONS: This study will be useful to explore the potential candidate biomarkers for diagnosis, prognosis, and drug targets of MTLE.

Computational fluid dynamics (CFD) analysis in a ruptured vertebral artery dissecting aneurysm implanted by Pipeline when recurrent after LVIS-assisted coiling treatment: Case report and review of the literatures.

BACKGROUNDS: Hemodynamics plays an important role in the natural history of the process of rupture and recurrence of intracranial aneurysms. This study aimed to investigate the role of hemodynamics for recurrence in a vertebral artery dissecting aneurysm (VADA). METHODS: A patient with a ruptured VADA firstly treated by low-profile visualized intraluminal support (LVIS)-assisted coiling, and was implanted with a Pipeline Embolization Device (PED) after aneurysm recurrence. Finite element analysis and computational fluid dynamics simulations were conducted in 6 serial imaging procedures, and the calculated hemodynamics was correlated with aneurysm recurrence. RESULTS: Wall shear stress (WSS) was not effectively suppressed, resulting in aneurysm recurrence with initial entry tear to occur above the protuberance after 7 months of LVIS stent-assisted coiling. With the implantation of PED, WSS, inflow stream and velocity at the aneurysm neck significantly decreased. During the 3-month follow-up after PED deployment, there was significant shrinkage of the sac and the blood flow in the sac was reduced considerably. The 27-month follow-up after PED deployment indicated the aneurysm was stable. CONCLUSIONS: The present case study suggests that insufficient suppression of high WSS and high inflow velocity at the neck of the parent artery, especially near the posterior inferior cerebellar artery, might be associated with aneurysm recurrence.

Fatal intracranial hemorrhage after carotid artery stenting: Three case reports and a literature review.

INTRODUCTION: We herein describe three patients who developed fatal intracranial hemorrhage (ICH) after carotid artery stenting (CAS).Case Presentation: We retrospectively reviewed 126 patients who underwent CAS from January 2016 to December 2018 and identified 3 patients (2.4%) (all male, mean age of 59 years) who developed ICH after CAS. Two of them developed left basal ganglia hemorrhage with extension into the ventricle and subarachnoid space, and the third patient developed primary ventricular bleeding. One hemorrhage occurred immediately after CAS, whereas the other two occurred 3 hours and 8 hours after the procedure, respectively. The mean stenosis of the treated carotid arteries was 91%. All three hemorrhages were fatal, and the mean time from hemorrhage to death was 50 hours. CONCLUSION: ICH is a potentially fatal complication of CAS and often occurs several hours after the procedure. Headache, vomiting, and consciousness disorders are the most common symptoms of ICH. Careful screening to identify high-risk patients and strict management of perioperative blood pressure are important to prevent this complication.

The Enterprise2 Stent for Endovascular Treatment of Intracranial Aneurysms: Short-Term Results From a Single Center Experience.

Background: Self-expanding devices, such as the Enterprise VRD (EP-VRD) have widely used for stent-assisted coiling treatment in wided-necked aneuryms while some thromboembolic complications were reported due to its incomplete stent apposition (ISA). We report our experiences on the novel Enterprise2 (EP-VRD2) stent in vivo in the treatment of intracranial and cranial cervical junction aneurysms. Methods: Twenty-five consecutive patients with intracranial or cranial cervical junction aneurysms were treated with EP-VRD2 stents retrospectively collected in our institution. We use the 'jailing' technique in all cases and deployed the stent by using pushing over the outer curve technique. The 3- or 6-monthS follow-up was done regularly by DSA. Results: Twenty-five EP-VRD2 stents were implanted to treat 21 aneurysms at the siphon segment of internal carotid artery (ICA), one at the petrous segment, two at the cervical segment, one at the verteral artery with five accompanied with stenosis. Two patients had kinking during the procedure and were solved by microwire or microcatheter massaging. Four patients with a larger arc angle and a smaller radius of the parent vessel was detected ISA. No patient underwent the ischemic event after the operation. Twenty-three of 25 patients were evaluated after 3- or 6-months by DSA, 22 showed complete occlusion (RROC1), one slight re-stenosis in the follow-up within those five patients with stenosis. A length of 23 mm seemed associated with ISA (p < 0.01). Conclusion: The EP-VRD2 performed well in our small patient series; however, ISA could still occur with a sharp angle of the parent vessel.

Co-expression Network Analysis Revealing the Potential Regulatory Roles of lncRNAs in Alzheimer's Disease.

Alzheimer's disease (AD) is one of the most common types of dementia among the elderly. Previous studies had revealed that the dysregulation of lncRNAs played important roles in human diseases, including AD. However, there is still a lack of comprehensive analysis of differently expressed long non-coding RNAs (lncRNAs) in different distinct regions related to AD. In present study, we identified a total of 678, 593, 941, 1445, 1179, 466 differently expressed lncRNAs that were found in entorhinal cortex (EC), middle temporal gyrus(MTG), hippocampus (HIP), superior frontal gyrus (SFG), posterior cingulate (PC), cortex and primary visual cortex (VCX) AD samples, respectively. Furthermore, we constructed lncRNA-mRNA co-expression networks in AD to explore the potential roles of these lncRNAs. Differentially expressed (DE) lncRNAs were involved in regulating metabolic process, respiratory electron transport chain and ATP metabolic process showed by GO analysis. Interestingly, KEGG analysis revealed these lncRNAs were associated with neurodegenerative disorders such as Alzheimer's disease, Huntington's disease and Parkinson's disease. Four lncRNAs (LOC100507557, LOC101929787, NEAT1, and JAZF1-AS1) were identified as key lncRNAs in AD progression and dysregulated in different distinct regions related to AD. Our study has uncovered several key lncRNAs in AD, which would give novel underlying therapeutic and prognostic targets for AD.

Lentivirus-Mediated Overexpression of MicroRNA-210 Improves Long-Term Outcomes after Focal Cerebral Ischemia in Mice.

AIMS: MicroRNAs play an important role in the pathogenesis of ischemic brain injury and in the repair process during postischemic condition. However, the key miRNAs and their function in these processes remain unclear. METHODS: Circulating blood MicroRNAs profiles were examined in the ischemic stroke patients. The predicted network of difference was analyzed by ingenuity pathway analysis. The key MicroRNAs were selected, and the function was further studied in a mouse ischemia model. The predicted downstream target was confirmed. RESULTS: We found that 24 MicroRNAs were differently expressed in stroke patients compared to the control (P < 0.05). Bioinformatic analysis showed a MicroRNAs regulated network with the highest score in the stroke cascade, which was consisted of 10 MicroRNAs including key hypoxia-related miR-210 and its predicted downstream target brain derived neurotrophic factor (BDNF). Lentivirus-mediated miR-210 overexpression enhanced the microvessel density and the number of neural progenitor cells in the ischemic mouse brain (P < 0.05) and improved neurobehavioral outcomes in the ischemic mouse (P < 0.05). MiR-210 upregulation increased mBDNF/proBDNF protein expression in the normal and ischemic mouse brain. The dual-luciferase reporter assay identified that BDNF was the direct target of miR-210. CONCLUSION: MiR-210 is a crucial ischemic stroke-associated MicroRNAs and a potential target for the stroke therapy.

Granulocyte colony-stimulating factor regulates JNK pathway to alleviate damage after cerebral ischemia reperfusion.

BACKGROUND: Granulocyte-macrophage colony-stimulating factor (GM-CSF) is a potent hematopoietic growth factor that both enhances the survival and drives the differentiation and proliferation of myeloid lineage cells. Recent studies have suggested that GM-CSF has a neuroprotective effect against cerebral ischemia injury, but the molecular mechanisms have been unclear. This study aimed to investigate the influences of a short-acting (half-life 3.5 hours) G-CSF and a long-acting (half-life 40 hours) pegylated G-CSF on the JNK signaling pathway after cerebral ischemia reperfusion. METHODS: A total of 52 Sprague-Dawley rats were randomly divided into four groups: a sham group (n = 4), a vehicle with saline (n = 16), a short-acting G-CSF treatment group (n = 16) and a long-acting G-CSF treatment group (n = 16). The cerebral ischemia reperfusion model was established for the sham group and G-CSF treatment groups by middle cerebral artery occlusion (MCAO). Five days post reperfusion, rats were sacrificed and the brains were removed. Changes in neurological function after cerebral ischemia reperfusion was evaluated according to Neurological Severity Score (NSS) and the lesion volume and infarct size were measured by 2,3,5-triphenyltetrazolium chloride staining. The numbers of apoptotic neurons in these ischemic areas: left cerebral cortex, striatum and hippocampus were calculated by TUNEL assay, and expression of JNK/P-JNK, c-jun/P-c-jun in these areas was detected by Western blotting. RESULTS: Compared with the saline vehicle group ((249.68±23.36) mm(3), (19.27±3.37)%), G-CSF-treated rats revealed a significant reduction in lesion volume (long-acting: (10.89±1.90)%, P < 0.01; short-acting G-CSF: (11.69±1.41)%, P < 0.01) and infarct size (long-acting: (170.53±18.47) mm3, P < 0.01; short-acting G-CSF: (180.74±16.93) mm3, P < 0.01) as well as less neuron functional damage (P < 0.01) and a smaller number of apoptotic neurons in ischemic areas (P < 0.01). The activity of P-JNK and P-c-jun in the cerebral ischemia reperfusion-damaged cortex and hippocampus was significantly decreased in all G-CSF-treated rats (P < 0.05). However, between the long-acting and short-acting G-CSF sets, there were no significant differences found in the activity of P-JNK and P-c-jun in the cortex, hippocampus and striate body (P > 0.05). CONCLUSIONS: Hypodermic injection of 50 µg/kg G-CSF attenuated the damage caused by cerebral ischemia reperfusion in rats, which might be associated with down-regulated activation of the P-JNK and P-c-jun pathway after cerebral ischemia reperfusion. Long-acting G-CSF may be a novel choice for both clinical and basic research in treating cerebral ischemia.

NAD(+) administration decreases ischemic brain damage partially by blocking autophagy in a mouse model of brain ischemia.

Nicotinamide adenine dinuleotide (NAD(+)) plays critical roles in multiple biological functions. Previous studies have indicated that NAD(+) treatment decreases oxidative stress-induced death of primary neurons and astrocytes. Intranasal administration of NAD(+) also reduces brain damage in a rat model of transient focal brain ischemia. However, the mechanisms underlying this protective effect remain unknown. In this study, we used a mouse model of brain ischemia to test our hypothesis that NAD(+) decreases ischemic brain damage partially by preventing autophagy. Adult male mice were subjected to transient middle cerebral artery occlusion (tMCAO) for 90min, and NAD(+) was administered intraperitoneally (i.p.) immediately after reperfusion started. We found that administration with 50mg/kg NAD(+) led to significant decreases in infarct size, edema formation, and neurological deficits at 48h after ischemia. NAD(+) administration also significantly decreased brain ischemia-induced autophagy in the cortex and hippocampus. We further found that prevention of autophagy by 3-methyladenine (3-MA), a selective autophagy inhibitor, significantly reduced ischemic brain damage, suggesting an important role of autophagy in the ischemic brain injury in our animal model. Collectively, our findings have suggested that NAD(+) administration decreases ischemic brain damage at least partially by blocking autophagy. This is the first suggested mechanism regarding the protective effects of NAD(+) in cerebral ischemia, which further highlights the promise of NAD(+) for treating brain ischemia.

Roles of oxidative stress in synchrotron radiation X-ray-induced testicular damage of rodents.

Synchrotron radiation (SR) X-ray has characteristic properties such as coherence and high photon flux, which has excellent potential for its applications in medical imaging and cancer treatment. However, there is little information regarding the mechanisms underlying the damaging effects of SR X-ray on biological tissues. Oxidative stress plays an important role in the tissue damage induced by conventional X-ray, while the role of oxidative stress in the tissue injury induced by SR X-ray remains unknown. In this study we used the male gonads of rats as a model to study the roles of oxidative stress in SR X-ray-induced tissue damage. Exposures of the testes to SR X-ray at various radiation doses did not significantly increase the lipid peroxidation of the tissues, assessed at one day after the irradiation. No significant decreases in the levels of GSH or total antioxidation capacity were found in the SR X-ray-irradiated testes. However, the SR X-ray at 40 Gy induced a marked increase in phosphorylated H2AX - a marker of double-strand DNA damage, which was significantly decreased by the antioxidant N-acetyl cysteine (NAC). NAC also attenuated the SR X-ray-induced decreases in the cell layer number of seminiferous tubules. Collectively, our observations have provided the first characterization of SR X-ray-induced oxidative damage of biological tissues: SR X-ray at high doses can induce DNA damage and certain tissue damage during the acute phase of the irradiation, at least partially by generating oxidative stress. However, SR X-ray of various radiation doses did not increase lipid peroxidation.

MicroRNA-210 as a novel blood biomarker in acute cerebral ischemia.

MicroRNA-210 (miR-210), a master and pleiotropic hypoxia-microRNA, plays multiple roles in brain ischemia. However, miR-210 expression and its function in humans have not been explored. The aim of our study is to evaluate the correlation of blood miR-210 with clinical findings in acute ischemic stroke. Blood samples were obtained from stroke patients (n=112) and healthy controls (n= 60). MiR-210 was measured at within 3, 7 and 14 days after stroke using a quantitative PCR technique. Stroke severity and clinical outcome were evaluated by NIHSS and modified Rankin Score. Both blood and brain miR-210 in ischemic mice was examined and the correlation was investigated. Compared to healthy controls, blood miRNA-210 was significantly decreased in stroke patients (0.93 vs. 1.36; P=0.001), especially at 7 days (0.56 vs. 1.36; P=0.001) and 14 days of stroke onset (0.50 vs. 1.36; P=0.001). The cut off point of miR-210 in diagnosis was 0.505 with 88.3 per cent sensitivity. MiR-210 level in stroke patients with good outcome was significantly higher than patients with poor outcome (1.2 vs. 0.44; P=0.012). The correlation between blood and brain miR-210 in ischemic mice was positive (R2=0.57, P=0.001). Blood miR-210 is a novel sensitive biomarker for clinical diagnosis and prognosis in acute cerebral ischemia.