[Frontiers in Bioscience E4, 2476-2489, June 1, 2012]

Very early-initiated physical rehabilitation protects against ischemic brain injury

Pengyue Zhang1, Qi Zhang1, Hongjian Pu1, Yi Wu1, Yulong Bai1, Peter S. Vosler2, Jun Chen1, 2, Hong Shi1, Yanqin Gao1,Yongshan Hu1

1Department of Rehabilitation of Huashan Hospital, State Key Laboratory of Medical Neurobiology, Department of Sports Medicine and Rehabilitation, The Yonghe Branch of Huashan Hospital, and Institute of Brain Sciences, Fudan University, Shanghai 200032, China, 2Department of Neurology, University of Pittsburgh School of Medicine, Pittsburgh, PA15261, USA

TABLE OF CONTENTS

1. Abstract
2. Introduction
3. Materials and methods
3.1. Animal model of transient focal cerebral ischemia
3.2. Treadmill training
3.3. Tissue section preparation
3.4. Measurement of infarct volume
3.5. Immunofluorescence staining and image analysis
3.6. Tissue processing and total RNA extraction
3.7. Reverse transcription and semi-quantitative real-time RT-PCR
3.8. Blood-brain barrier permeability evaluation
3.9. Brain water content determine
3.10. Behavioral training and evaluations
3.11. Statistical analysis
4. Results
4.1. Physiological Variables
4.2. VEIPR reduced infarct volume
4.3. VEIPR inhibited the activation of astrocytes and microglia cells
4.4. VEIPR suppressed proinflammatory cytokine and cell adhesion molecule mRNA expression after tFCI
4.5. VEIPR improves BBB integrity and decreases brain edema after tFCI
4.6. VEIPR promotes functional recovery
4.6.1. Neurological deficits
4.6.2. Motor function
4.6.3. Spatial learning and memory
5. Discussion
6. Acknowledgements
7. References

1. ABSTRACT

Recent clinical data suggest that very early initiated physical rehabilitation (VEIPR) within 24 hours after stroke may reduce morbidity. However, there is limited evidence to support the beneficial effects of VEIPR and the underlying mechanisms are yet unknown. The present study investigated the effect of VEIPR on brain damage, inflammation, and neurobehavioral outcomes following cerebral ischemia. Rats that underwent transient focal cerebral ischemia (tFCI) were randomly assigned to VEIPR or non-exercise (NE) groups. VEIPR was induced 24 hours after the insult by initiating treadmill training for a maximum of 14 days while the NE group remained sedentary in their cages during this period. The results indicated that VEIPR significantly improved recovery of functional behavior as measured by neurological score, foot fault test, and Morris water maze performance. We also demonstrated that VEIPR significantly reduced infarct volume, brain water content, BBB damage, and acute inflammatory response. In summary, our results provide novel evidence that VEIPR confers marked neuroprotection against experimental stroke by attenuating pro-inflammatory reactions, brain edema, BBB damage, and cognitive and behavioral deficits.