Exercise preconditioning exhibits neuroprotective effects on hippocampal CA1 neuronal damage after cerebral ischemia

Abstract

Recent evidence has suggested the neuroprotective effects of physical exercise on cerebral ischemic injury. However, the role of physical exercise in cerebral ischemia-induced hippocampal damage remains controversial. The aim of the present study was to evaluate the effects of pre-ischemia treadmill training on hippocampal CA1 neuronal damage after cerebral ischemia. Male adult rats were randomly divided into control, ischemia and exercise + ischemia groups. In the exercise + ischemia group, rats were subjected to running on a treadmill in a designated time schedule (5 days per week for 4 weeks). Then rats underwent cerebral ischemia induction through occlusion of common carotids followed by reperfusion. At 4 days after cerebral ischemia, rat learning and memory abilities were evaluated using passive avoidance memory test and rat hippocampal neuronal damage was detected using Nissl and TUNEL staining. Pre-ischemic exercise significantly reduced the number of TUNEL-positive cells and necrotic cell death in the hippocampal CA1 region as compared to the ischemia group. Moreover, pre-ischemic exercise significantly prevented ischemia-induced memory dysfunction. Pre-ischemic exercise mighct prevent memory deficits after cerebral ischemia through rescuing hippocampal CA1 neurons from ischemia-induced degeneration.

Keywords: Nissl staining; TUNEL; apoptosis; cerebral ischemia; hippocampus; memory; nerve regeneration; neural regeneration; physical exercise.

Figure 1

The effects of pre-ischemic exercise on memory function of rats with cerebral ischemia (passive avoidance memory test). (A) Step-through latency. (B) Total time that the rats spent in the dark chamber during the retention session (n = 7 rats per group, 3 sections per rat). The results are shown as the mean ± SD. *P < 0.05, vs. sham group. #P < 0.05, vs. ischemia group (analysis of variance with Dunnett's T3 post-hoc test).

Figure 2

Nissl staining of hippocampal CA1 region after induction of transient global cerebral ischemia. (A) The CA1 region of the hippocampus; (B) sham group; (C) ischemia group; (D) exercise + ischemia group. Damaged cells were sparsely arranged and their shapes were fuzzy (arrows indicate the necrotic cells; B–D are higher magnification (400×) of the boxed area in A). (E) Effects of pre-ischemic exercise on ischemia-induced necrosis in the hippocampal CA1 neurons (n = 7 rats per group, 3 sections per rat). The results are shown as the mean ± SD. *P < 0.001, vs. sham group; #P < 0.001, vs. ischemia group (analysis of variance with Scheffe's post-hoc test).

Figure 3

TUNEL staining of hippocampal CA1 region after induction of transient global cerebral ischemia. (A) The CA1 region of the hippocampus; (B) sham group; (C) ischemia group; (D) exercise + ischemia group (arrows indicate TUNEL-positive cells; B, C and D are higher magnification (400×) of the boxed area in A). (E) Effect of pre-ischemic exercise on the number of TUNEL-positive cells in the hippocampal CA1 region after cerebral ischemia (n = 7 rats per group, 3 sections per rat). The results are shown as the mean ± SD. *P < 0.001, vs. sham group; #P < 0.05, vs. ischemia group; analysis of variance with Scheffe's post-hoc test).