Neuroscience Letters 397 (2006) 135–139 Neurochemical effects of exercise and neuromuscular electrical stimulation on brain after stroke: A microdialysis study using rat model Lai-Yee Leung a , Kai-Yu Tong a,∗ , Shao-Min Zhang b , Xiang-Hui Zeng b , Ke-Pin Zhang b , Xiao-Xiang Zheng b a Department of Health Technology and Informatics, The Hong Kong Polytechnic University, Hung Hom, Kowloon, Hong Kong b College of Biomedical Engineering and Instrument Science, Zhejiang University, Hangzhou, China Received 30 September 2005; received in revised form 3 December 2005; accepted 4 December 2005 Abstract Treadmill exercise and neuromuscular electrical stimulation are common clinical approaches for stroke rehabilitation. Both animal and clinical studies have shown the functional improvements after these interventions. However, the neurochemical effects on the ischemic brain had not been well studied. This study aimed at evaluating the effects of treadmill exercise and neuromuscular electrical stimulation (NMES), and studying their effects during a 2-week training, on the levels of common neurotransmitters (aspartate, glutamate, taurine and gamma-aminobutyric acid (GABA)) in the hippocampus following transient focal cerebral ischemia. Either treadmill exercise or neuromuscular electrical stimulation was prescribed to the rats 24 h after cerebral ischemia whereas Control group remained in cages for 2 weeks. Microdialysis technique was used to collect dialysates from ipsilesional hippocampus in vivo. It was found that the glutamate level was increased significantly during treadmill exercise and then returned to baseline level. Both interventions did not trigger significant effects on aspartate and glutamate basal levels during the 2 weeks. The relatively high taurine level in Control groups may suggest that the interventions might suppress the taurine release in hippocampus. GABA and aspartate levels did not showed significant changes over the 2 weeks in all groups. These results provide insights to explain the neurochemical effects on the ischemic injured brain during the course of rehabilitation. © 2005 Elsevier Ireland Ltd. All rights reserved. Keywords: Exercise; Electrical stimulation; Rehabilitation; Microdialysis; Cerebral stroke Stroke is a leading cause of long-term disabilities. Efficacy of treadmill exercise in stroke rehabilitation had been revealed in many clinical studies [1,21]. Recent animal studies have shown the benefits of exercise after stroke. It was found that brain infarc- tion volume was reduced in the rats with early treadmill exercise after ischemic stroke [22,32,33]. Some studies indicated early intensive physical training after stroke may exacerbate the brain damage [14,19]. Risedal et al. suggested that the increased tis- sue loss might be due to a motor activity-induced increase of excitatory transmitters in the presence of excitatory and toxic substances from the ischemic tissue [28]. Certain neurotransmit- ters such as glutamate and taurine might play a role in recovery of motor function after brain injury [3]. Neuromuscular elec- trical stimulation (NMES) is also widely used in post-stroke rehabilitation strategy. Clinical studies had been conducted to ∗ Corresponding author. Tel.: +852 27667662; fax: +852 23624365. E-mail address: k.y.tong@polyu.edu.hk (K.-Y. Tong). show the beneficial effects of NMES on hemiplegic or para- plegic subjects [11,27]. Functional magnetic resonance imaging (fMRI) revealed that brain activation in specific neural regions was observed when applying neuromuscular electrical stimula- tion in both healthy and stroke subjects [18,30]. Kido and Stein used transcranial magnetic stimulation to measure motor-evoked potential in tibialis anterior to evaluate the cortical excitability in healthy adult walking with or without NMES. The results sug- gested that NMES might effectively facilitate plastic changes in the central nervous system [17]. Limited studies investigated neurochemical change in the brain in the course of time follow- ing the exercise and NMES interventions after focal cerebral ischemia. The varying levels of the neurotransmitters over the time of intervention may provide important implications to the motor recovery mechanism. The objective of this study was to investigate the effects of exercise and NMES during a 2-week training, on the levels of common neurotransmitters (aspartate, glutamate, taurine and GABA) in the hippocampus following focal cerebral ischemia. 0304-3940/$ – see front matter © 2005 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.neulet.2005.12.006