Tat-NR2B9c attenuates oxidative stress via inhibition of PSD95-NR2B-nNOS complex after subarachnoid hemorrhage in rats

  • Neuropharmacology. 2024 Mar 21:109905. doi: 10.1016/j.neuropharm.2024.109905.
Haocheng Zhang  1 ,  Longbiao Xu  2 ,  Yezhao He  1 ,  Zeyu Zhang  3 ,  Jiahao Zhang  1 ,  Qian Yu  1 ,  Yibo Liu  1 ,  Xiaoyu Wang  1 ,  Anke Zhang  1 ,  Kaikai Wang  1 ,  Yuanjian Fang  4 ,  Sheng Chen  5
Affiliations
  • 1. Department of Neurosurgery, School of Medicine, The Second Affiliated Hospital, Zhejiang University, Zhejiang Province, Hangzhou, China; Key Laboratory of Precise Treatment and Clinical Translational Research of Neurological Diseases, Hangzhou, Zhejiang, China.
  • 2. Department of Neurosurgery, The Third Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, China.
  • 3. Department of Neurosurgery, Renji Hospital, Shanghai Jiao Tong University School of Medicine, China.
  • 4. Department of Neurosurgery, School of Medicine, The Second Affiliated Hospital, Zhejiang University, Zhejiang Province, Hangzhou, China; Key Laboratory of Precise Treatment and Clinical Translational Research of Neurological Diseases, Hangzhou, Zhejiang, China. Electronic address: [email protected].
  • 5. Department of Neurosurgery, School of Medicine, The Second Affiliated Hospital, Zhejiang University, Zhejiang Province, Hangzhou, China; Key Laboratory of Precise Treatment and Clinical Translational Research of Neurological Diseases, Hangzhou, Zhejiang, China. Electronic address: [email protected].
PMID: 38521229 DOI: 10.1016/j.neuropharm.2024.109905
Abstract

Oxidative stress plays important roles in the pathogenesis of early brain injury (EBI) after subarachnoid hemorrhage (SAH). Tat-NR2B9c has shown efficacy as a neuroprotective agent in several studies. Here, we identified the neuroprotective role of Tat-NR2B9c after SAH and its related mechanisms. The results showed that Tat-NR2B9c treatment attenuated oxidative stress, therefore alleviated neuronal Apoptosis and neurological deficits after SAH. Tat-NR2B9c treatment could alleviate mitochondrial vacuolization induced by SAH. Compared to SAH + vehicle group, Tat-NR2B9c resulted in the decrease of Acetylated superoxide dismutase2 (Ac-SOD2), Bcl-2-associated X protein (Bax) and cleaved-caspase3 (CC3) protein expression, and the up-regulation of Sirtunin 3 (SIRT3) and Bcl-2 protein level. Moreover, Tat-NR2B9c attenuated excitotoxicity by inhibiting the interaction of PSD95-NR2B-nNOS. Our results demonstrated that Tat-NR2B9c inhibited oxidative stress via inhibition of PSD95-NR2B-nNOS complex formation after SAH. Tat-NR2B9c may serve as a potential treatment for SAH induced brain injury.

Keywords
Oxidative stress; Postsynaptic density protein-95; Subarachnoid hemorrhage; Tat-NR2B9c.
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