Lower isoflurane concentration affects spatial learning and neurodegeneration in adult mice compared with higher concentrations.
BACKGROUND
Volatile anesthetics such as isoflurane are widely used in clinical and research contexts. Concerns have been raised that the effects of these drugs on the central nervous system may result in long-term impairment after surgery or general anesthesia. Hence, this study aimed to detect how different isoflurane concentrations influence spatial learning and cell death in adult mice.


METHODS
Fifty-two C57BL/6 mice were randomly divided in four groups. Mice in three groups were exposed to different concentrations of isoflurane (1, 1.5, and 2%) for 1 h; the control group was not exposed to anesthesia. Five mice per group were killed 3 h after anesthesia to perform histopathologic and immunohistochemical analyses (hematoxylin-eosin staining; caspase-3 activation). Eight mice per group were used for behavioral tests (open field, T-maze spontaneous alternation, and water maze) on subsequent days.


RESULTS
There were no differences between groups in the T-maze spontaneous alternation test or in the open field (no confounding effects of stress or locomotion). The group anesthetized with 1% isoflurane performed worse in the water maze task on day 1 (550.4 ±162.78 cm) compared with the control group (400.1 ± 112.88 cm), 1.5% isoflurane (351.9 ± 150.67 cm), and 2% isoflurane (364.5 ± 113.70 cm; P ≤ 0.05) and on day 3 (305.0 ± 81.75 cm) compared with control group (175.13 ± 77.00 cm) and 2% isoflurane (204.11 ± 85.75 cm; P ≤ 0.038). In the pyramidal cell layer of the region cornu ammonis 1 of the hippocampus, 1% isoflurane showed a tendency to cause more neurodegeneration (apoptosis) (61.4 ± 26.40, profiles/mm) than the group with 2% of isoflurane (20.6 ± 17.77, profiles/mm; P = 0.051).


CONCLUSIONS
Low isoflurane concentration (1%) caused spatial learning impairment and more neurodegeneration compared with higher isoflurane concentrations. Results for mice receiving the latter concentrations were similar to those of control mice.
Valentim
Ana M
AM
Instituto de Biologia Molecular e Celular, Universidade do Porto, Porto, Portugal. amaria@ibmc.up.pt
Di Giminiani
Pierpaolo
P
Ribeiro
Patrícia O
PO
Rodrigues
Paula
P
Olsson
I Anna S
IA
Antunes
Luís M
LM
D000367:Age Factors; D018685:Anesthetics, Inhalation / Q000008:administration & dosage; D000818:Animals; D004305:Dose-Response Relationship, Drug; D007530:Isoflurane / Q000008:administration & dosage* / Q000009:adverse effects*; D008297:Male; D018782:Maze Learning / Q000187:drug effects* / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D009410:Nerve Degeneration / Q000139:chemically induced* / Q000473:pathology; D011897:Random Allocation; D013037:Spatial Behavior / Q000187:drug effects* / Q000502:physiology
D018685:Anesthetics, Inhalation; D007530:Isoflurane