Bibliographic Details
| Title: |
Alleviated cerebral infarction in male mice lacking all nitric oxide synthase isoforms after middle cerebral artery occlusion. |
| Authors: |
Kubota, Haruaki, Tsutsui, Masato, Kuniyoshi, Kanako, Yamashita, Hirotaka, Shimokawa, Hiroaki, Sugahara, Kazuhiro, Kakinohana, Manabu |
| Source: |
Journal of Anesthesia; Feb2024, Vol. 38 Issue 1, p44-56, 13p |
| Subject Terms: |
NITRIC-oxide synthases, CEREBRAL infarction, ARTERIAL occlusions, CEREBRAL arteries, GENE expression |
| Abstract: |
Purpose: The role of the nitric oxide synthases (NOSs) system in cerebral infarction has been examined in pharmacological studies with non-selective NOSs inhibitors. However, due to the non-specificity of the non-selective NOSs inhibitors, its role remains to be fully elucidated. We addressed this issue in mice in which neuronal, inducible, and endothelial NOS isoforms were completely disrupted. Methods and results: We newly generated mice lacking all three NOSs by crossbreeding each single NOS−/− mouse. In the male, cerebral infarct size at 24 h after middle cerebral artery occlusion (MCAO) was significantly smaller in the triple n/i/eNOSs−/− genotype as compared with wild-type genotype. Neurological deficit score and mortality rate were also significantly lower in the triple n/i/eNOSs−/− than in the WT genotype. In contrast, in the female, there was no significant difference in the cerebral infarct size in the two genotypes. In the male triple n/i/eNOSs−/− genotype, orchiectomy significantly increased the cerebral infarct size, and in the orchiectomized male triple n/i/eNOSs−/− genotype, treatment with testosterone significantly reduced it. Cyclopaedic and quantitative comparisons of mRNA expression levels in cerebral infarct lesions between the male wild-type and triple n/i/eNOSs−/− genotypes at 1 h after MCAO revealed significant involvements of decreased oxidative stress and mitigated mitochondrial dysfunction in the alleviated cerebral infarction in the male triple n/i/eNOSs−/− genotype. Conclusions: These results provide the first evidence that the NOSs system exerts a deleterious effect against acute ischemic brain injury in the male. [ABSTRACT FROM AUTHOR] |
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| Database: |
Complementary Index |
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