ROS assay was conducted based on the instructions of ROS assay kit (Jiancheng, China).ĭata were showed as mean ± standard deviation (SD). Western blot analysis, immunofluorescence, and Golgi staining techniques were performed to assess the changes of protein levels. Long-term neurologic functions (rotarod test in the 1st, 2nd, and 3rd week and Morris water maze on days 21–25 following SAH) were also evaluated. Mortality rate and short-term neurological functions (modified Garcia scoring system and beam balance test) were assessed at 24 h after SAH. The degree of SAH was assessed with a new grading system as previously described ( Xu et al., 2019). We performed endovascular perforation SAH model ( Xu et al., 2019) for this study. All experiments in this study were conducted according to the protocols proposed by the local Institutional Animal Care and Use Committee (IACUC). The data that support the findings of this study are available from the corresponding author upon reasonable request. In this study, we hypothesized that peroxisomal dysfunction contributes greatly to WMI following SAH. However, the roles of peroxisomes in SAH have not been reported yet. Peroxisomal dysfunction in the white matter may result in devastating damages to the myelin, including delayed myelination, hypomyelination, demyelination, and dysmyelination ( Trompier et al., 2014).
In the brain, peroxisomes are important for detoxification of reactive oxidative species (ROS) and metabolism of myelin lipids in oligodendrocytes ( Kassmann, 2014).
Peroxisome is a type of organelle widely found in eukaryotic cells. However, the underlying mechanisms of WMI following SAH are still unclear. In our previous study, we found that WMI occurred in the early stage of SAH, which is characterized by amyloid precursor protein (APP) accumulation, myelin basic protein (MBP) degradation, and white matter edema ( Peng et al., 2019). More than half of the central nervous system is composed of white matter, which is more vulnerable to ischemia/hemorrhagic stroke than gray matter ( Pang et al., 2019). Previous studies have mainly focused on studying the injuries of the cortex or hippocampus following SAH however, white matter injury (WMI) after SAH has not been well addressed. Subarachnoid hemorrhage (SAH) is one of the most severe cerebrovascular diseases with a high rate of death and disability. The use of thioredoxin-interacting protein (TXNIP) shRNA significantly offset the effects of CAT shRNA, and the use of glycerone phosphate acyl transferase (GNPAT) shRNA significantly reversed the effects of CAT CRISPR by decreasing the levels of plasmalogens and reactive oxidative species (ROS).Ĭonclusion: Peroxisomal dysfunction induced by SAH reversely exacerbated cerebral WMI following SAH, which was at least partly mediated by TXNIP and GNPAT pathways. Results: Catalase (CAT) CRISPR treatment significantly attenuated neurological deficits and reduced long-term spatial learning and memory impairments after SAH by increasing the level of myelin basic protein (MBP) while decreasing the levels of amyloid precursor protein (APP), interleukin 6 (IL-6), and tumor necrosis factor (TNF)-α.
Western blotting, immunofluorescence, and Golgi staining techniques were performed to assess the changes in protein levels. We evaluated short- and long-term neurobehavior after SAH. Methods: We utilized short hairpin RNA (shRNA) and clustered regularly interspaced short palindromic repeats (CRISPR) to verify the role of peroxisomes in WMI following SAH. 5Department of Emergency Medicine, Bursa City Hospital, Bursa, Turkeyīackground and Purpose: White matter injury (WMI) exists in the early stage of subarachnoid hemorrhage (SAH) and has not been well addressed so far.4Department of Emergency Medicine, Bursa Yuksek Ihtisas Training and Research Hospital, University of Health Sciences, Bursa, Turkey.3Department of Neurosurgical Intensive Care Unit, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.2Department of Neurosurgery, Affiliated Tumor Hospital of Guangxi Medical University, Nanning, China.1Department of Neurosurgery, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.Weilin Xu 1*† Jun Yan 2† Shuda Chen 3† Umut Ocak 4,5 Anwen Shao 1 Jianmin Zhang 1
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