Isoflurane-induced Neuroapoptosis in the Neonatal Rhesus Macaque Brain

Author:

Brambrink Ansgar M.1,Evers Alex S.2,Avidan Michael S.3,Farber Nuri B.4,Smith Derek J.5,Zhang Xuezhao6,Dissen Gregory A.7,Creeley Catherine E.8,Olney John W.9

Affiliation:

1. Professor, Department of Anesthesiology and Perioperative Medicine, Oregon Health and Science University, Portland, Oregon.

2. Professor and Chairman.

3. Associate Professor, Department of Anesthesiology.

4. Associate Professor.

5. Research Associate.

6. Post Doctoral Fellow.

7. Staff Scientist, Division of Neuroscience, Oregon National Primate Research Center, Oregon Health and Science University, Beaverton, Oregon.

8. Instructor.

9. Professor, Department of Psychiatry, Washington University School of Medicine, St. Louis, Missouri.

Abstract

Background Brief isoflurane anesthesia induces neuroapoptosis in the developing rodent brain, but susceptibility of non-human primates to the apoptogenic action of isoflurane has not been studied. Therefore, we exposed postnatal day 6 (P6) rhesus macaques to a surgical plane of isoflurane anesthesia for 5 h, and studied the brains 3 h later for histopathologic changes. Method With the same intensity of physiologic monitoring typical for human neonatal anesthesia, five P6 rhesus macaques were exposed for 5 h to isoflurane maintained between 0.7 and 1.5 end-tidal Vol% (endotracheally intubated and mechanically ventilated) and five controls were exposed for 5 h to room air without further intervention. Three hours later, the brains were harvested and serially sectioned across the entire forebrain and midbrain, and stained immunohistochemically with antibodies to activated caspase-3 for detection and quantification of apoptotic neurons. Results Quantitative evaluation of brain sections revealed a median of 32.5 (range, 18.0-48.2) apoptotic cells/mm of brain tissue in the isoflurane group and only 2.5 (range, 1.1-5.2) in the control group (difference significant at P = 0.008). Apoptotic neuronal profiles were largely confined to the cerebral cortex. In the control brains, they were sparse and randomly distributed, whereas in the isoflurane brains they were abundant and preferentially concentrated in specific cortical layers and regions. Conclusion The developing non-human primate brain is sensitive to the apoptogenic action of isoflurane and displays a 13-fold increase in neuroapoptosis after 5 h exposure to a surgical plane of isoflurane anesthesia.

Publisher

Ovid Technologies (Wolters Kluwer Health)

Subject

Anesthesiology and Pain Medicine

Reference34 articles.

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