Pathological Comparisons of the Hippocampal Changes in the Transient and Permanent Middle Cerebral Artery Occlusion Rat Models

Frontiers in Neurology

卷:10

Fang Liu¹  Shupeng Li¹  Phil Ok Koh²  Yuhua Jiang³  Gongping Liu⁴  Lina Tariq Al Kury⁵  Shehla Khatoon⁶  Tao Li⁷  Arif-Ullah Khan⁹  Alam Zeb⁹  Fawad Ali Shah⁹  Xifei Yang¹¹  Huo Yao¹² 

[1] 0Centre for Addiction and Mental Health, Campbell Research Institute, Toronto, ON, Canada;

[2] 1Department of Anatomy, College of Veterinary Medicine, Research Institute of Life Science, Gyeongsang National University, Jinju-si, South Korea;

[3] 2Cancer Centre, The Second Hospital of Shandong University, Jinan, China;

[4] Co-innovation Center of Neuroregeneration, Nantong University, Nantong, China;

[5] College of Natural and Health Sciences, Zayed University Abu Dhabi, Abu Dhabi, United Arab Emirates;

[6] Department of Anatomy, Khyber Medical College, Khyber Medical University, Peshawar, Pakistan;

[7] Department of Forensic Medicine, School of Medicine, Xi'an Jiaotong University, Xi'an, China;

[8] Department of Pathophysiology, School of Basic Medicine and the Collaborative Innovation Center for Brain Science, Key Laboratory of Ministry of Education of China and Hubei Province for Neurological Disorders, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China;

[9] Department of Pharmacology, Riphah Institute of Pharmaceutical Sciences, International University, Islamabad, Pakistan;

[10] Department of Psychiatry, University of Toronto, Toronto, ON, Canada;

[11] Key Laboratory of Modern Toxicology of Shenzhen, Shenzhen Center for Disease Control and Prevention, Shenzhen, China;

[12] State Key Laboratory of Oncogenomics, School of Chemical Biology and Biotechnology, Peking University Shenzhen Graduate School, Shenzhen, China;

关键词: ischemic stroke;    hippocampus;    diabetes;    transient and permanent cerebral ischemia;    neurodegeneration;    glutamate receptor;   

DOI  :  10.3389/fneur.2019.01178

来源: DOAJ

【 摘 要 】

Ischemic strokes are categorized by permanent or transient obstruction of blood flow, which impedes delivery of oxygen and essential nutrients to brain. In the last decade, the therapeutic window for tPA has increased from 3 to 5–6 h, and a new technique, involving the mechanical removal of the clot (endovascular thrombectomy) to allow reperfusion of the injured area, is being used more often. This last therapeutic approach can be done until 24 h after stroke onset. Due to this fact, more acute ischemic stroke patients are now being recanalized, and so tMCAO is probably the “best” model to address these patients that have a potential good outcome in terms of survival and functional recovery. However, permanent occlusion patients are also important, not only to increase survival rate but also to improve functional outcomes, although these are more difficult to achieve. So, both models are important, and which target different stroke patients in the clinical scenario. Hippocampus has a vital role in memory and cognition, is prone to ischemic induced neurodegeneration. This study was designed to delineate the molecular, pathological, and neurological changes in rat models of t-MCAO, permanent MCAO (pMCAO), and pMCAO with diabetic conditions in hippocampal tissue. Our results showed that these three models showed distinct discrepancies at numerous pathological process, including key signaling molecules involved in neuronal apoptosis, glutamate induced excitotoxicity, neuroinflammation, oxidative stress, and neurotrophic changes. Our result suggests that the two commonly used MCAO models exhibited tremendous differences in terms of neuronal cell loss, glutamate excitotoxic related signaling, synaptic transmission markers, neuron inflammatory and oxidative stress molecules. These differences may reflect the variations in different models, which may provide valuable information for mechanistic and therapeutic inconsistences as experienced in both preclinical models and clinical trials.

【 授权许可】

Unknown