Physiological Ischemic Training Promotes Brain Collateral Formation and Improves Functions in Patients with Acute Cerebral Infarction

Front Neurol. 2016 Dec 22:7:235. doi: 10.3389/fneur.2016.00235. eCollection 2016.

Abstract

Objectives: To observe the effectiveness and mechanisms of physiological ischemic training (PIT) on brain cerebral collateral formation and functional recovery in patients with acute cerebral infarction.

Methods: 20 eligible patients with acute cerebral infarction were randomly assigned to either PIT group (n = 10) or Control group (n = 10). Both groups received 4 weeks of routine rehabilitation therapy, while an additional session of PIT, which consisted of 10 times of maximal voluntary isometric handgrip for 1 min followed by 1 min rest, was prescribed for patients in the PIT groups. Each patient was trained with four sections a day and 5 days a week for 4 weeks. The Fugl-Meyer Assessment (FMA), the Modified Barthel Index (MBI), and the short-form 36-item health survey questionnaire (SF-36) were applied for the evaluation of motor impairment, activity of daily living, and quality of life at the baseline and endpoint. MRI was applied to detect the collateral formation in the brain. The concentration of vascular endothelial growth factor (VEGF) and endothelial progenitor cells (EPCs) number in plasma were also tested at the endpoint.

Results: Demographic data were consistent between experimental groups. At the endpoint, the scores of the FMA, MBI, and SF-36 were significantly higher than that at baseline. As compared to the Control group, the score of FMA and SF-36 in PIT group was significantly higher, while no significant difference was detected between groups in terms of MBI. Both groups had significantly higher cerebral blood flow (CBF) level at endpoint as compared to that at baseline. Moreover, the CBF level was even higher in the PIT group as compared to that in the Control group after 4 weeks of training. The same situations were also found in the plasma VEGF and EPCs assessment. In addition, positive correlations were found between FMA score and CBF level (r = 0.686, p < 0.01), CBF level and VEGF concentration (r = 0.675, p < 0.01), and VEGF concentration and EPC number (r = 0.722, p < 0.01).

Conclusion: PIT may be effective in increasing the expression of VEGF and recruitment of EPCs and in turn promote the formation of brain collateral circulation. The positive correlations may demonstrate a potential association between biological and functional parameters, and PIT may be able to improve the motor function, activity of daily living, and quality of life in patients with stroke.

Keywords: cerebral blood flow; endothelial progenitor cells; physiological ischemic training; stroke; vascular endothelial growth factor.