Objective: To investigate the ameliorative effect of curcumin pretreatment against impaired spatial working memory on global cerebral ischemia-reperfusion rats and to explore its mechanism.
Methods: After trained on a modified T-maze, 120 adult SD rats were randomly divided into 5 groups: sham group (S group), cerebral ischemia-reperfusion group (IR group), curcumin group (C group), LPS group (L group) and curcumin+LPS group (C+L group). Rats were treated with drugs or vehicles 1 h before 10 min global cerebral ischemia. Six rats in each group 7 days after reperfusion were tested in T-maze. Six rats in each group were sacrificed at 2 h, 1, 3 and 7 d after reperfusion and their serum or brains were harvested. Brain sections were stained with HE or toluidine blue and neuronal damage was quantified by the average neuronal density of CA1 area. Immunohistochemical staining for hippocampal IL-1β and TNF-α was carried out, levels of serum IL-1β and TNF-α was detected using ELISA procedure.
Results: Compared with S group, percentage of T-maze correct responses was decreased (88% ± 12% vs 69% ± 8%, P < 0.05), an extensive pyramidal neurons loss in CA1 area was observed, level of IL-1β (0.26 ± 0.04 vs 0.53 ± 0.06, P < 0.05;48 ± 13 vs 161 ± 31, P < 0.05) and TNF-α (40.244 ± 0.025 vs 0.418 ± 0.036, P < 0.05; 33 ± 4 vs 85 ± 15, P < 0.05) in hippocampi or serum was increased in IR group. Compared with IR group, percentage of T-maze correct responses was increased (78% ± 13%) and average pyramidal neuronal density in CA1 area was increased with an decrease in hippocampi or serum IL-1β (0.44 ± 0.09, 72 ± 19) and TNF-α (0.307 ± 0.047, 57 ± 14) in C group(P < 0.05). Compared with IR group, percentage of T-maze correct responses (61% ± 6%) was decreased with IL-1β (0.86 ± 0.13, 331 ± 51), TNF-α (0.735 ± 0.059, 185 ± 20) in hippocampi and serum was increased in L group (P < 0.05). Compared with L group, percentage of T-maze correct responses (69% ± 12%) and average pyramidal neuronal density in CA1 area was increased with IL-1β (0.69 ± 0.09, 246 ± 24), TNF-α(0.586 ± 0.047, 105 ± 25) in hippocampi and serum was decreased in C+L group (P < 0.05).
Conclusion: Curcumin pretreatment improves the impaired spatial working memory in global cerebral ischemia-reperfusion rats by inhibiting proinflammatory cytokines.