Sevoflurane Postconditioning Protects From an Early Neurological Deficit After Subarachnoid Hemorrhage: Results of a Randomized Laboratory Study in Rats.

ABSTRACT

BACKGROUND: Subarachnoid hemorrhage (SAH) is associated with neurocognitive impairment. Recent data suggest that sevoflurane attenuates edema formation after SAH in rats. However, so far, no information is available about the long-term repair phase, nor if sevoflurane impacts functionality by increasing vascularity. This study tested whether sevoflurane postconditioning would improve long-term neurologic deficit through increased formation of new vessels close to the hemorrhage area. METHODS: Fifty-three animals were subjected to SAH or sham surgery with or without a 2-hour sevoflurane postconditioning (versus propofol anesthesia). Animal survival, including dropout animals due to death or reaching termination criteria, as well as neurologic deficit, defined by the Garcia score, were assessed 2 hours after recovery until postoperative day 14. On day 14, blood samples and brain tissue were harvested. Vessel density was determined by the number of cluster of differentiation 31 (CD31)-positive vessels, and activated glial cells by glial fibrillary acidic protein (GFAP)-positive astrocytes per field of view. RESULTS: The survival rate for sham animals was 100%, 69% in the SAH-propofol and 92% in the SAH-sevoflurane groups. According to the log-rank Mantel-Cox test, survival curves were significantly different (P = .024). The short-term neurologic deficit was higher in SAH-propofol versus SAH-sevoflurane animals 2 hours after recovery and on postoperative day 1 (propofol versus sevoflurane 14. 6 ± 3.4 vs 15. 9 ± 2.7 points, P = .034, and 16. 2 ± 3.5 vs 17. 8 ± 0.9 points, P = .015). Overall complete recovery from neurologic deficit was observed on day 7 in both SAH groups (18. 0 ± 0.0 vs 18. 0 ± 0.0 points, P = 1.000). Cortical vascular density increased to 80. 6 ± 15.0 vessels per field of view in SAH-propofol animals (vs 71. 4 ± 10.1 in SAH-sevoflurane, P < .001). Activation of glial cells, an indicator of neuroinflammation, was assessed by GFAP-positive astrocytes GFAP per field of view. Hippocampal GFAP-positive cells were 201 ± 68 vs 179 ± 84 cells per field of view in SAH-propofol versus SAH-sevoflurane animals (P < .001). CONCLUSIONS: Sevoflurane postconditioning improves survival by 23% (SAH-sevoflurane versus SAH-propofol). The sevoflurane intervention could attenuate the early neurologic deficit, while the long-term outcome was similar across the groups. A higher vascular density close to the SAH area in the propofol group was not associated with improved outcomes.