The Journal of neuroscience : the official journal of the Society for Neuroscience
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Multicenter Study
Circular RNA TLK1 Aggravates Neuronal Injury and Neurological Deficits after Ischemic Stroke via miR-335-3p/TIPARP.
Circular RNAs (circRNAs) are expressed at high levels in the brain and are involved in various CNS diseases. However, the potential role of circRNAs in ischemic stroke-associated neuronal injury remains largely unknown. Here, we investigated the important functions of circRNA TLK1 (circTLK1) in this process. ⋯ The levels of circTLK1 were significantly increased in the brain tissue and plasma isolated from animal models of ischemic stroke and patients. Knockdown of circTLK1 significantly decreased infarct volumes, attenuated neuronal injury, and improved subsequent long-term neurological deficits. To our knowledge, these results provide the first definitive evidence that circTLK1 is detrimental in ischemic stroke.
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Multicenter Study
Morphological Abnormalities of Thalamic Subnuclei in Migraine: A Multicenter MRI Study at 3 Tesla.
The thalamus contains third-order relay neurons of the trigeminal system, and animal models as well as preliminary imaging studies in small cohorts of migraine patients have suggested a role of the thalamus in headache pathophysiology. However, larger studies using advanced imaging techniques in substantial patient populations are lacking. In the present study, we investigated changes of thalamic volume and shape in a large multicenter cohort of patients with migraine. High-resolution T1-weighted MRI data acquired at 3 tesla in 131 patients with migraine (38 with aura; 30.8 ± 9 years old; 109 women; monthly attack frequency: 3.2 ± 2.5; disease duration: 14 ± 8.4 years) and 115 matched healthy subjects (29 ± 7 years old; 81 women) from four international tertiary headache centers were analyzed. The thalamus and thalamic subnuclei, striatum, and globus pallidus were segmented using a fully automated multiatlas approach. Deformation-based shape analysis was performed to localize surface abnormalities. Differences between patients with migraine and healthy subjects were assessed using an ANCOVA model. After correction for multiple comparisons, performed using the false discovery rate approach (p < 0.05 corrected), significant volume reductions of the following thalamic nuclei were observed in migraineurs: central nuclear complex (F(1,233) = 6.79), anterior nucleus (F(1,237) = 7.38), and lateral dorsal nucleus (F(1,238) = 6.79). Moreover, reduced striatal volume (F(1,238) = 6.9) was observed in patients. This large-scale study indicates structural thalamic abnormalities in patients with migraine. The thalamic nuclei with abnormal volumes are densely connected to the limbic system. The data hence lend support to the view that higher-order integration systems are altered in migraine. ⋯ This multicenter imaging study shows morphological thalamic abnormalities in a large cohort of patients with episodic migraine compared with healthy subjects using state-of-the-art MRI and advanced, fully automated multiatlas segmentation techniques. The results stress that migraine is a disorder of the CNS in which not only is brain function abnormal, but also brain structure is undergoing significant remodeling.