The association between human cytomegalovirus (HCMV) and glioblastoma multiforme (GBM) is becoming a new concept. However, information on the geographic variability of HCMV prevalence in GBM remains scarce. Moreover, the potential roles of various viruses, such as polyomaviruses and oncogenic viruses, in gliomagenesis remain unclear. Our aim was to investigate the prevalence of HCMV in GBM among Japanese patients. Furthermore, this was the first study that evaluated infection with four new human polyomaviruses in GBMs. This study also provided the first data on the detection of human papillomavirus (HPV) in GBM in the Eastern world.

Microglia, the resident immune cells of the central nervous system, can display a pro-inflammatory M1 phenotype or an anti-inflammatory M2 phenotype. Arginase (Arg)-1 expressed in interleukin-4 (IL-4)-induced M2 microglia reduces nitric oxide (NO) production by competing with inducible NO synthase for L-arginine, which contributes to the attenuation of brain inflammation. Although previous studies have indicated that brain zinc promotes M1 activation, the effect of zinc on M2 microglial activation remains to be determined. In the present study, murine primary microglia treated with 10 ng mL⁻¹ IL-4 exhibited increased Arg-1 mRNA expression and levels of intracellular free zinc. Chelation of this increased intracellular free zinc by the cell permeable zinc chelator N,N,N′,N′-tetrakis-(2-pyridylmethyl)ethylenediamine (TPEN) aggravated the IL-4-induced mRNA expression and enzymatic activity of Arg-1. However, the cell impermeable zinc chelator CaEDTA had no effect on Arg-1 expression or cytosolic levels of free zinc in IL-4-induced M2-polarized microglia. Furthermore, treatment with IL-4 resulted in upregulation of phagocytic activity in microglia, while administration of TPEN abolished IL-4-induced phagocytic activity. Moreover, this effect was reversed viaL-arginine supplementation. These findings suggest that IL-4 induces an increase in intracellular free zinc in microglia, which may act as a negative regulator of IL-4-induced Arg-1 expression, and that such negative regulation is essential for microglial phagocytic activity.

Background/Objectives: Non-saccular aneurysms are a rare subtype of intracranial aneurysms with complex morphologies. Although treatment strategies for ruptured non-saccular and saccular aneurysms differ significantly, large-scale comparisons of the outcomes between the two types remain limited. We aimed to compare the clinical characteristics, procedure-related complications, and functional outcomes between patients with subarachnoid hemorrhage (SAH) caused by non-saccular or saccular aneurysms. Methods: We retrospectively analyzed 1176 consecutive patients with aneurysmal SAH from a population-based stroke registry in Kochi Prefecture, Japan. Aneurysms were classified as saccular or non-saccular based on the morphology, and clinical variables, radiological features, and treatment modalities were compared. Additionally, 840 patients who underwent intervention for their aneurysms within 3 days of onset were further investigated to evaluate the impact of the non-saccular aneurysm shape on poor functional outcomes, defined as a modified Rankin Scale score ≥ 3 at discharge. Results: Non-saccular aneurysms were more common in younger patients and located in the posterior circulation. Procedure-related ischemic complications were more likely to occur in non-saccular aneurysms than in saccular aneurysms (odds ratio [OR]: 2.57, 95% confidence interval [CI]: 1.56–4.97, p < 0.001). In a multivariable logistic regression analysis, a non-saccular morphology was an independent risk factor of poor outcomes (OR: 2.92, 95% CI: 1.34–6.32, p = 0.007) after adjustment for potential confounders. Interaction and subgroup analyses revealed that the negative effects of non-saccular aneurysms on functional outcomes were more prominent in younger patients aged ≤ 60 years. Conclusions: Non-saccular aneurysms are independently associated with ischemic complications and poor outcomes after SAH, particularly in younger patients.