Paired associative stimulation improves synaptic plasticity and functional outcomes after cerebral ischemia

• Published in: Neural regeneration research Vol. 14; no. 11; pp. 1968 - 1976
• Main Authors: Hu, Yan, Guo, Tie-Cheng, Zhang, Xiang-Yu, Tian, Jun, Lu, Yin-Shan
• Format: Journal Article
• Language: English
• Published: India Wolters Kluwer India Pvt. Ltd 01.11.2019; Medknow Publications and Media Pvt. Ltd; Medknow Publications & Media Pvt. Ltd; Department of Rehabilitation Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science & Technology, Wuhan, Hubei Province, China; Department of Rehabilitation Medicine, Zhongnan Hospital of Wuhan University, Wuhan, Hubei Province, China%Department of Rehabilitation Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science & Technology, Wuhan, Hubei Province, China%Department of Rehabilitation Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science & Technology, Wuhan, Hubei Province, China; Department of Rehabilitation Medicine, the Fifth Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan Province, China%Department of Rehabilitation Medicine, Zhongnan Hospital of Wuhan University, Wuhan, Hubei Province, China; Wolters Kluwer - Medknow; Wolters Kluwer Medknow Publications
• Subjects: Brain; Care and treatment; Cerebral ischemia; cerebral ischemia; paired associative stimulation; cognitive function; long-term potentiation; synaptic plasticity; Morris water maze; synaptic structure; N-methyl-D-aspartic acid receptor; brain-derived neurotrophic factor; multi-electrode array; neural regeneration; Experiments; Ischemia; Laboratory animals; Medical research; Memory; Neural stimulation; Neuroplasticity; Stroke; Beijing China; China; cognitive function; Morris water maze; neural regeneration; cerebral ischemia; synaptic structure; paired associative stimulation; brain-derived neurotrophic factor; synaptic plasticity; N-methyl-D-aspartic acid receptor; long-term potentiation; multi-electrode array; neural regenerati
• ISSN: 1673-5374; 1876-7958
• DOI: 10.4103/1673-5374.259618

Paired associative stimulation is a relatively new non-invasive brain stimulation technique that combines transcranial magnetic stimulation and peripheral nerve stimulation. The effects of paired associative stimulation on the excitability of the cerebral cortex can vary according to the time interval between the transcranial magnetic stimulation and peripheral nerve stimulation. We established a model of cerebral ischemia in rats via transient middle cerebral artery occlusion. We administered paired associative stimulation with a frequency of 0.05 Hz 90 times over 4 weeks. We then evaluated spatial learning and memory using the Morris water maze. Changes in the cerebral ultra-structure and synaptic plasticity were assessed via transmission electron microscopy and a 64-channel multi-electrode array. We measured mRNA and protein expression levels of brain-derived neurotrophic factor and N-methyl-D-aspartate receptor 1 in the hippocampus using a real-time polymerase chain reaction and western blot assay. Paired associative stimulation treatment significantly improved learning and memory in rats subjected to cerebral ischemia. The ultra-structures of synapses in the CA1 area of the hippocampus in rats subjected to cerebral ischemia were restored by paired associative stimulation. Long-term potentiation at synapses in the CA3 and CA1 regions of the hippocampus was enhanced as well. The protein and mRNA expression of brain-derived neurotrophic factor and N-methyl-D-aspartate receptor 1 increased after paired associative stimulation treatment. These data indicate that paired associative stimulation can protect cognition after cerebral ischemia. The observed effect may be mediated by increases in the mRNA and protein expression of brain-derived neurotrophic factor and N-methyl-D-aspartate receptor 1, and by enhanced synaptic plasticity in the CA1 area of the hippocampus. The animal experiments were approved by the Animal Ethics Committee of Tongji Medical College, Huazhong University of Science & Technology, China (approval No. TJ-A20151102) on July 11, 2015.