The effects of early exercise on brain damage and recovery after focal cerebral infarction in rats

Abstract

AimExercise can be used to enhance neuroplasticity and facilitate motor recovery after a stroke in rats. We investigated whether treadmill running could reduce brain damage and enhance the expression of midkine (MK) and nerve growth factor (NGF), increase angiogenesis and decrease the expression of caspase-3.MethodsSeventy-seven Wistar rats were split into three experimental groups (ischaemia-control: 36, ischaemia-exercise: 36, sham-exercise: 5). Stroke was induced by 90-min left middle cerebral artery occlusion using an intraluminal filament. Beginning on the following day, the rats were made to run on a treadmill for 20 min once a day for a maximum of 28 consecutive days. Functional recovery after ischaemia was assessed using the beam-walking test and a neurological evaluation scale in all rats. Infarct volume, and the expression of MK, NGF, anti-platelet-endothelial cell adhesion molecule (PECAM-1), and caspase-3 were evaluated at 1, 3, 5, 7, 14 and 28 days after the induction of ischaemia.ResultsOver time motor coordination and neurological deficits improved more in the exercised group than in the non-exercised group. The infarct volume in the exercised group (12.4 ± 0.8%) subjected to treadmill running for 28 days was significantly decreased compared with that in the control group (19.8 ± 4.2%, P < 0.01). The cellular expression levels of MK, NGF and PECAM-1 were significantly increased while that of caspase-3 was decreased in the peri-infarct area of the exercised rats.ConclusionsOur findings show that treadmill exercise improves motor behaviour and reduces neurological deficits and infarct volume, suggesting that it may aid recovery from central nervous system injury.

PECAM‐1‐targeted micron‐sized particles of iron oxide as MRI contrast agent for detection of vascular remodeling after cerebral ischemia

“…Augmented PECAM-1 immunoreactivity in and around ischemic lesions, reflective of higher blood vessel density, has been found particularly between 2 and 14 days after stroke in different rodent models (21,22,24). Furthermore, PECAM-1 expression in post-stroke brain tissue has been shown to increase in response to angiogenesis-stimulating exercise (22), and to decrease after administration of an angiogenesis inhibitor (23)…”

“…PECAM-1 has been frequently applied as an endothelial marker in tissues, including assessments of changes in vascularization after experimental stroke (22)(23)(24)(25). Augmented PECAM-1 immunoreactivity in and around ischemic lesions, reflective of higher blood vessel density, has been found particularly between 2 and 14 days after stroke in different rodent models (21,22,24).…”

“…PECAM-1 is found on the surface of platelets, neutrophils and monocytes and constitutively expressed on endothelial cells. A marked increase after cerebral ischemia has been observed in post-stroke brain tissue in experimental setting (21,22), suggestive of increased vascular density, for example, through angiogenesis. In this study we explored the potential of MRI of PECAM-1-targeted micron-sized particles of iron oxide (MPIO) to detect vascular remodeling at 3 and 7 days after experimental stroke in mice.…”

Treadmill Exercise Facilitates Functional Recovery and Neuroprotection in Subacute Stroke Rat

“…Treadmill exercise is a forced exercise in animal studies which may induce stress, and stress may have negative effect on rats' recovery, since stress has been found to affect structural plasticity of the hippocampus in two forms [11]: repeated stress causes atrophy of dendrites in the CA3 region, and both acute and chronic stress suppresses neurogenesis of dentate gyrus granule neurons. On the contrary, other researchers believed treadmill exercise training can protect neurons [12], [13]. For example, Hayes' study showed that treadmill exercise assisted neuroprotection and it was proposed that there is something else brought by treadmill training but not the stress inducing such neuroprotection result [14].…”

“…They found that early treadmill training (started 24h post MCAo/r surgery, 30min per day, 5 days a week with a speed of 20m/min and 0° slope, and rats experienced one-week training and another one-week resting, and then were sacrificed) had significant effects in reducing brain infarct volume compared with spontaneous recovery. In Matsuda's study [13], researchers found that treadmill exercise starting from 24h after MCAo/r surgery for 28 consecutive days reduced neurological deficits and infarct volume in Wister rats weighing 220-260g. Even though the protocols (one-week training plus one-week resting, 4-week training, and this one-week consecutive training), the species (SD rats or Wister rats) or weights are different between theirs and ours, all results supported that treadmill training can facilitate post-stroke motor function recovery and provide neuroprotection in rats.…”