The hypothalamus may mediate migraine and ictal photophobia: evidence from Granger causality analysis.

BACKGROUND: The hypothalamus plays a central role in the pathophysiology of migraine and is considered to be the "migraine generator." It participates in initiating a migraine attack through its connectivity to regions of the brain involved in processing and modulating pain. However, the underlying mechanisms of hypothalamic effective functional connectivity that bring about migraines remain unclear. This study investigated the hypothalamus-based directional effective connectivity in migraine without aura patients and assessed associations among the clinical characteristics. METHODS: Seven patients with migraine without aura during the attack (MWoA-DA) (four with photophobia (MWoA-DAWP) and three without photophobia (MWoA-DAWoP)), twenty-seven patients with migraine without aura during the interictal period (MWoA-DI), and twenty-nine healthy controls (HC) were included in this study. Granger causality analysis (GCA) was used to investigate the directional effective connectivity between the hypothalamus and other brain regions. RESULTS: MWoA-DA patients exhibited decreased outflow from the bilateral hypothalamus to the visual cortex compared with the MWoA-DI patients and HCs. The MWoA-DAWP group primarily contributed to this result. The MWoA-DA patients showed decreased outflow from the bilateral hypothalamus to the right inferior parietal gyrus compared with the HCs. The visual analogue scale (VAS) was negatively correlated with abnormal effective functional connectivity from the right hypothalamus to the right inferior parietal gyrus in the MWoA-DA group. CONCLUSIONS: These data provide evidence that the hypothalamus might serve as a central component of a multisystem network implicated in migraine and ictal photophobia, which includes hypothalamus and the visual and trigeminovascular systems.

Contrast-induced encephalopathy mimicking stroke after a second cerebral DSA: an unusual case report.

BACKGROUND: Contrast-induced encephalopathy (CIE) is a rare complication of the angiography process. CIE may mimic stroke symptoms clinically and subarachnoid hemorrhage radiologically. Previous CIE cases occurred after the initial digital subtraction angiography (DSA) scan. Here, we encountered an unusual case of CIE mimicking a stroke with an internal carotid artery (ICA) aneurysm and ipsilateral ICA stenosis that occurred after a second DSA procedure. CASE PRESENTATION: A 77-year-old female with a history of hypertension and coronary heart disease underwent two cerebral DSA procedures over 1 week. She was given the same nonionic and iso-osmolar Visipaque agent (smaller than 200 ml) for both procedures. However, neurological complications only occurred after the second DSA procedure. On the first diagnostic cerebral DSA, she was diagnosed with an intracranial aneurysm of the left ICA with moderate stenosis (approximately 50%) in the initial part of the ipsilateral ICA. However, after the second aneurysm embolization procedure by DSA, she developed right hemiplegia, aphasia, and epilepsy, mimicking left middle cerebral artery occlusion. An emergency CT showed a diffuse hyperdensity in the left subarachnoid space, mimicking SAH. MRI demonstrated that the lesion was hyperintense on T2WI, FLAIR imaging, and DWI but was normal on ADC mapping. On postoperative Day 6, her neurologic deficits had completely resolved after initial fluid restriction, corticosteroid treatment, and rehydration. CONCLUSION: This case indicates that clinicians should consider the occurrence of CIE following any angiography procedure, even if the initial cerebral DSA procedure is successful and without complications.

The potential effect of salvianolic acid B against rat ischemic brain injury in combination with mesenchymal stem cells.

BACKGROUND: Mesenchymal stem cells (MSCs) and Salvianolic acid B (SAB) are known to exert potent anti-inflammatory and anti-oxidative properties. But the effect of SAB and MSCs combination treatment on the cerebral ischemia/reperfusion injury (CI/RI) is not clear. METHODS: After the CI/RI animal model established, rats were administered with MSCs and SAB individually or combination treatment. To evaluate the therapeutic potential, behavioral tests, TTC staining, Hematoxylin-eosin (HE) staining, and immunofluorescence assays were performed to evaluate the neuroprotection and endogenous neurogenesis. Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining and enzyme linked immunosorbent assay (ELISA) were performed to evaluate the anti-apoptosis and anti-inflammatory effect. Meanwhile, the expression of the TLR4/NF-ĸB/MYD88 signal pathway-related proteins was evaluated by Western blot. RESULTS: MSCs and SAB individually or combination treatment have protective effect in CI/RI rats. More importantly, the rats with the combination treatment showed a better behavioral recovery, neurogenesis and smaller infarct size compared with the rats administered with MSCs or SAB individually. Further research showed that the combination treatment decreased CI/RI induced inflammatory cytokines and oxidative stress, including inhibiting the production of IL-1ß, IL-6, TNF-α, decreasing the levels of malondialdehyde (MDA), and increased the activity of superoxide dismutase (SOD). In addition, the neuroprotection effect of SAB and MSCs combination was achieved through the regulation of TLR4/NF-κB/MyD88 signaling pathway related proteins, including inhibition the protein levels of TLR4, MYD88, p-NF-κB p65, TRAF6-and action of SIRT1 in brain tissues. CONCLUSION: The present study indicated that the MSCs and SAB combination treatment had better protective effect against rat ischemic brain injury. The combination of SAB and MSCs may provide a potent and promising strategy for the treatment of ischemic stroke and is worthy for further development.

Integrated Analysis of miRNA and mRNA Expression Profiles Reveals the Molecular Mechanism of Posttraumatic Stress Disorder and Therapeutic Drugs.

Purpose: Post-traumatic stress disorder (PTSD) is a result of trauma exposure and is related to psychological suffering as a long-lasting health issue. Further analysis of the networks and genes involved in PTSD are critical to the molecular mechanisms of PTSD. Methods: In this study, we aimed to identify key genes and molecular interaction networks involved in the pathogenesis of PTSD by integrating mRNA and miRNA data. Results: By integrating three high-throughput datasets, 5606 differentially expressed genes (DEGs) were detected, including five differentially expressed miRNAs (DEmiRNAs) and 5525 differentially expressed mRNAs (DEmRNAs). Nineteen upregulated and 46 downregulated DEmRNAs were identified in both GSE64813 and GSE89866 datasets, while five upregulated DEmiRNAs were found in the GSE87768 dataset. Functional annotations of these DEmRNAs indicated that they were mainly enriched in blood coagulation, cell adhesion, platelet activation, and extracellular matrix (ECM)-receptor interaction. Integrated protein-protein and miRNA-protein interaction networks among the DEGs were established with the help of 65 nodes and 121 interactions. Finally, 286 small molecules were obtained based on the Drug-Gene Interaction database (DGIdb). Three genes, prostaglandin-endoperoxide synthase 1 (PTGS1), beta-tubulin gene (TUBB1), and cyclin-dependent kinase inhibitor 1A (CDKN1A), were the most promising targets for PTSD therapy. Additionally, the present study also provided a higher performance diagnostic model for PTSD based on 17 DEmRNAs, which was validated in two independent datasets, GSE109409 and GSE63878. Conclusion: Our data provides a new molecular aspect that ECM-receptor interaction and the platelet activation process could be the potential molecular mechanism of PTSD, and the genes involved in this process may be promising therapeutic targets. A higher-performance diagnostic model for PTSD has also been identified.

Role of the endolysosomal pathway and exosome release in tau propagation.

The progressive deposition of misfolded and aggregated forms of Tau protein in the brain is a pathological hallmark of tauopathies, such as Alzheimer's disease (AD) and frontotemporal degeneration (FTD). The misfolded Tau can be released into the extracellular space and internalized by neighboring cells, acting as seeds to trigger the robust conversion of soluble Tau into insoluble filamentous aggregates in a prion-like manner, ultimately contributing to the progression of the disease. However, molecular mechanisms accountable for the propagation of Tau pathology are poorly defined. We reviewed the Tau processing imbalance in endosomal, lysosomal, and exosomal pathways in AD. Increased exosome release counteracts the endosomal-lysosomal dysfunction of Tau processing but increases the number of aggregates and the propagation of Tau. This review summarizes our current understanding of the underlying tauopathy mechanisms with an emphasis on the emerging role of the endosomal-lysosomal-exosome pathways in this process. The components CHMP6, TSG101, and other components of the ESCRT complex, as well as Rab GTPase such as Rab35 and Rab7A, regulate vesicle cargoes routing from endosome to lysosome and affect Tau traffic, degradation, or secretion. Thus, the significant molecular pathways that should be potential therapeutic targets for treating tauopathies are determined.

Isolated Medial Longitudinal Fasciculus Midbrain Infarction Mimicking Medial Rectus Paralysis.

INTRODUCTION: Medial longitudinal fasciculus infarction is rare in clinical practice and generally accompanied by brain tissue damage around the medial longitudinal fasciculus. Isolated medial longitudinal fasciculus midbrain infarction was seldom reported. CASE REPORT: An 81-year-old man with hypertension was admitted to our hospital because of sudden onset diplopia. A neurological examination revealed right adduction paresis without abducting nystagmus in the left eye, whereas the convergence reflex was normal. Diffusion-weighted magnetic resonance imaging demonstrated a small acute lacunar medial longitudinal fasciculus infarction in the right midbrain at the level of the inferior colliculus. Diffusion-tensor imaging showed a reduction of the right medial longitudinal fasciculus. Medial longitudinal fasciculus infarction is rare and occurs most commonly in the pons. The authors report on a case of isolated medial longitudinal fasciculus infarction that was diagnosed because of sudden diplopia and manifested as simple internal rectus paralysis with no abducting nystagmus on the contralateral side of the lesion. CONCLUSION: Isolated midbrain-medial longitudinal fasciculus infarction without contralateral abducting nystagmus is a rare occurrence. It can be differentiated from partial oculomotor palsy by assessing the convergence reflex, primary gaze, and diffusion-tensor imaging.