Conflicting results regarding SOX17 genes and the risk of intracranial aneurysms (IA) exist in the Korean population, although significant positive correlations were noted in genome-wide association studies in European and Japanese populations. Therefore, we aimed to investigate an association between SOX17 gene variants and IA using exome sequencing data. This study included 26 age-gender matched IA patients and 26 control subjects. The SOX17 gene variants identified from whole-exome sequencing data were examined. Genetic associations to estimate odds ratio (OR) and 95% confidence interval (CI) were performed using the software EPACTS. The mean age of the IA and control groups were 51.0±9.3 years and 49.4±14.3 years, respectively (p=0.623). Seven variants of SOX17, including six single nucleotide polymorphisms and one insertion and deletion, were observed. Among these variants, rs12544958 (A>G) showed the most association with IA, but the association was not statistically significant (OR, 1.97; 95% CI, 0.81-4.74; p=0.125). Minor allele frequencies of the IA patients and controls were 0.788 and 0.653, respectively. None of the remaining variants were significantly associated with IA formation. No significant association between SOX17 gene variants and IA were noted in the Korean population. A large-scale exome sequencing study is necessary to investigate any Korean-specific genetic susceptibility to IA.

Objective : The influence of moderate-to-severe traumatic brain injury (TBI) on acute pulmonary injury is well established, but the association between acute pulmonary injury and mild TBI has not been well studied. Here, we evaluated the histological changes and fluctuations in inflammatory markers in the lungs to determine whether an acute pulmonary inflammatory response occurred after mild TBI.Methods : Mouse models of mild TBI (n=24) were induced via open-head injuries using a stereotaxic impactor. The brain and lungs were examined 6, 24, and 72 hours after injury and compared to sham-operated controls (n=24). Fluoro-Jade B staining and Astra blue and hematoxylin staining were performed to assess cerebral neuronal degeneration and pulmonary histological architecture. Quantitative real-time polymerase chain reaction analysis was done to measure inflammatory cytokines.Results : Increased neuronal degeneration and the mRNA expression of interleukin (IL)-6, tumor necrosis factor (TNF)-α, IL-10, and transforming growth factor (TGF)-β were observed after mild TBI. The IL-6, TNF-α, and TGF-β levels in mice with mild TBI were significantly different compared to those of sham-operated mice 24 hours after injury, and this was more pronounced at 72 hours. Mild TBI induced acute pulmonary interstitial edema with cell infiltration and alveolar morphological changes. In particular, a significant infiltration of mast cells was observed. Among the inflammatory cytokines, TNF-α was significantly increased in the lungs at 6 hours, but there was no significant difference 24 and 72 hours after injury.Conclusion : Mild TBI induced acute pulmonary interstitial inflammation and alveolar structural changes, which are likely to worsen the patient’s prognosis.

Kim BJ, et al. J Clin Neurol. 2022 Mar;18(2):163-170. https://doi.org/10.3988/jcn.2022.18.2.163

Objective : To evaluate the interactions among differentially expressed autophagy and mitophagy markers in subarachnoid hemorrhage (SAH) patients with delayed cerebral ischemia (DCI).Methods : The expression data of autophagy and mitophagy-related makers in the cerebrospinal fluid (CSF) cells was analyzed by real-time reverse transcription-polymerase chain reaction and Western blotting. The markers included death-associated protein kinase (DAPK)-1, BCL2 interacting protein 3 like (BNIP3L), Bcl-1 antagonist X, phosphatase and tensin homolog-induced kinase (PINK), Unc-51 like autophagy activating kinase 1, nuclear dot protein 52, and p62. In silico functional analyses including gene ontology enrichment and the protein-protein interaction network were performed.Results : A total of 56 SAH patients were included and 22 (38.6%) of them experienced DCI. The DCI patients had significantly increased mRNA levels of DAPK1, BNIP3L, and PINK1, and increased expression of BECN1 compared to the non-DCI patients. The most enriched biological process was the positive regulation of autophagy, followed by the response to mitochondrial depolarization. The molecular functions ubiquitin-like protein ligase binding and ubiquitin-protein ligase binding were enriched. In the cluster of cellular components, Lewy bodies and the phagophore assembly site were enriched. BECN1 was the most connected gene among the differentially expressed markers related to autophagy and mitophagy in the development of DCI.Conclusion : Our study may provide novel insight into mitochondrial dysfunction in DCI pathogenesis.

Objective : To perform a comparative analysis of therapeutic effects associated with two different shapes of ceria nanoparticles, ceria nanorods (Ceria NRs) and ceria nanospheres (Ceria NSs), in an in vitro model of traumatic brain injury (TBI).Methods : In vitro TBI was induced using six-well confluent plates by manually scratching with a sterile pipette tip in a 6×6-square grid. The cells were then incubated and classified into cells with scratch injury without nanoparticles and cells with scratch injury, which were treated separately with 1.16 mM of Ceria NSs and Ceria NRs. Antioxidant activities and anti-inflammatory effects were analyzed.Results : Ceria NRs and Ceria NSs significantly reduced the level of reactive oxygen species compared with the control group of SH-SY5Y cells treated with Dulbecco’s phosphate-buffered saline. The mRNA expression of superoxide dismutases was also reduced in nanoparticle-treated SH-SY5Y cells, but apparently the degree of mRNA expression decrease was not dependent on the nanoparticle shape. Exposure to ceria nanoparticles also decreased the cyclooxygenase-2 expression, especially prominent in Ceria NR-treated group than that in Ceria NS-treated group.Conclusion : Ceria nanoparticles exhibit antioxidant and anti-inflammatory effects in TBI models in vitro. Ceria NRs had better antiinflammatory effect than Ceria NSs, but showed similar antioxidant activity.

Although technological advances and clinical studies on stem cells have been increasingly reported in stroke, research targeting hemorrhagic stroke is still lacking compared to that targeting ischemic stroke. Studies on hemorrhagic stroke are also being conducted, mainly in the USA and China. However, little research has been conducted in Korea. In reality, stem cell research or treatment is unfamiliar to many domestic neurosurgeons. Nevertheless, given the increased interest in regenerative medicine and the increase of life expectancy, attention should be paid to this topic. In this paper, we summarized pre-clinical rodent studies and clinical trials using stem cells for hemorrhagic stroke. In addition, we discussed results of domestic investigations and future perspectives on stem cell research for a better understanding.