Intensive treadmill training promotes cognitive recovery after cerebral ischemia-reperfusion in juvenile rats

Behav Brain Res. 2021 Mar 5:401:113085. doi: 10.1016/j.bbr.2020.113085. Epub 2020 Dec 28.

Abstract

Rehabilitation training is routine for children who experience stroke, but its protective mechanism remains unclear. To study the effect of treadmill training intensity on hippocampal synaptic plasticity after cerebral ischemia, a model of middle cerebral artery occlusion (MCAO)/reperfusion was established in young rats to simulate childhood ischemic stroke. The rats were randomly allocated into five groups: sham operation, MCAO, low-intensity exercise and MCAO (5 m/min), medium-intensity exercise and MCAO (10 m/min), and high-intensity exercise and MCAO (15 m/min). Intervention was continued for 14 days, and a series of experimental tests were conducted. After MCAO, the juvenile rats exhibited a series of morphological and functional alterations, including changes in their neurobehavior and cerebral infarct volumes. Compared with control rats, MCAO rats had a longer escape latency and crossed fewer platforms in the water maze test and exhibited decreased hippocampal neuron density and Synapsin I and PSD95 expression. Furthermore, MCAO rats exhibited synapse morphology changes and abnormal serum levels of lactic acid and corticosterone. Treadmill training effectively reduced the neurobehavioral scores and cerebral infarction volumes, with medium-intensity training showing the best effect. Treadmill training shortened the escape latency, increased the number of platform crossings, and improved the spatial cognitive abilities of the rats, with the medium intensity training having the best effect on spatial learning/memory efficiency. Treadmill training increased the neuron density in the hippocampus, with the medium-intensity training resulting in the highest density. Treadmill training had a positive effect on the expression of Synapsin I and PSD95, with the medium-intensity training showing the strongest effect. Treadmill training improved the sub-microstructure synapse morphology, with the medium-intensity training demonstrating the best effect. Treadmill training increased the plasma levels of lactic acid and corticosterone, with the high-intensity training having the most obvious effect. Treadmill training can provide neuroprotection by promoting hippocampal synaptic plasticity, with medium-intensity training showing the most optimal effects.

Keywords: Childhood stroke; Hippocampal synaptic plasticity; Intensive treadmill training; PSD95; Synapsin I.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Age Factors
  • Animals
  • Behavior, Animal / physiology
  • Cognitive Dysfunction / etiology
  • Cognitive Dysfunction / rehabilitation*
  • Disease Models, Animal
  • Disks Large Homolog 4 Protein / metabolism*
  • Hippocampus / physiopathology*
  • Infarction, Middle Cerebral Artery / complications
  • Infarction, Middle Cerebral Artery / pathology
  • Infarction, Middle Cerebral Artery / rehabilitation*
  • Ischemic Stroke / etiology
  • Ischemic Stroke / rehabilitation*
  • Neuronal Plasticity / physiology*
  • Physical Conditioning, Animal*
  • Rats
  • Reperfusion Injury / complications
  • Spatial Learning / physiology
  • Synapsins / metabolism*

Substances

  • Disks Large Homolog 4 Protein
  • Dlg4 protein, rat
  • Synapsins