Desflurane Post-treatment Reduces Hypoxic-ischemic Brain Injury via Reducing Transient Receptor Potential Ankyrin 1 in Neonatal Rats

• Published in: Neuroscience 2023-07, Vol.522, p.121-131
• Main Authors: Zhou, Ting, Li, Jun, Cheng, Aobing, Zuo, Zhiyi
• Format: Article
• Language: English
• Subjects: Animals; Animals, Newborn; Ankyrins - metabolism; Brain - metabolism; Brain Injuries - metabolism; Cytoskeletal Proteins - metabolism; Desflurane; Female; Hypoxia-Ischemia, Brain - drug therapy; Hypoxia-Ischemia, Brain - metabolism; hypoxia–ischemia; Male; neonatal rats; neuroprotection; Neuroprotective Agents - metabolism; Neuroprotective Agents - pharmacology; post-treatment; Pregnancy; Rats; Rats, Sprague-Dawley; TRPA1
• ISSN: 0306-4522; 1873-7544; 1873-7544
• DOI: 10.1016/j.neuroscience.2023.05.007

•Brain hypoxia–ischemia (HI) induces brain structural and functional injury.•Desflurane post-treatment reduces HI-induced brain injury.•Transient receptor potential ankyrin 1 contributes to HI-induced brain injury. Perinatal hypoxic-ischemic (HI) brain injury leads to mortality and morbidity in neonates and children. There are no effective and practical methods to attenuate this brain injury. This study determined whether desflurane, a volatile anesthetic with limited effect on the cardiovascular system, protected against HI-induced brain damage and the role of transient receptor potential ankyrin 1 (TRPA1), a mediator for simulated ischemia-induced myelin damage, in this protection. Seven-day-old male and female Sprague-Dawley rats had brain HI. They were exposed to 4.8%, 7.6% or 11.4% desflurane immediately or 4.8% desflurane at 0.5, 1 or 2 h after the HI. Brain tissue loss was evaluated 7 days later. Neurological functions and brain structures of rats with HI and 4.8% desflurane post-treatment were evaluated 4 weeks after the HI. TRPA1 expression was determined by Western blotting. HC-030031, a TRPA1 inhibitor, was used to determine the role of TRPA1 in the HI-induced brain injury. HI induced brain tissue and neuronal loss, which was attenuated by all tested concentrations of desflurane. Desflurane post-treatment also improved motor function, learning and memory in rats with brain HI. Brain HI increased the expression of TRPA1 and this increase was inhibited by desflurane. TRPA1 inhibition reduced HI-induced brain tissue loss and impairment of learning and memory. However, the combination of TRPA1 inhibition and desflurane post-treatment did not preserve brain tissues, learning and memory better than TRPA1 inhibition or desflurane post-treatment alone. Our results suggest that desflurane post-treatment induces neuroprotection against neonatal HI. This effect may be mediated by inhibiting TRPA1.