title: Whole-scale neurobehavioral assessments of photothrombotic ischemia in freely moving mice.
abstract: BACKGROUND
  Neurobehavioral assessments have been considered as an essential component of preclinical research in ischemic stroke. However, real-time neurobehavioral evaluation is seldom applied during ischemia induction as it is usually accompanied with anesthesia.
  
  
  METHODS
  We induced photothrombosis in freely moving mice after one-week recovery from cannula implantation surgeries. After rose bengal (RB) injection (100 mg/kg, i.p.), photothrombosis was induced in freely moving mice by 473 nm laser irradiation through the cannulas implanted into unilateral primary motor cortex beforehand. Mice received nimodipine (15 mg/kg, i.p.), a widely used anti-ischemic agent, or vehicle before irradiation. Motor coordination and equilibrium were evaluated by rotarod and rung walk tests throughout the whole process of ischemia. Endurance capacity was assessed by treadmill at 1 day and 7 days after irradiation. Mice were decapitated at different time points post irradiation for TTC (2,3,5-triphenyltetrazolium chloride) staining.
  
  
  RESULTS
  Consistent with the results of TTC staining, motor deficits firstly occurred at 15-min post irradiation and aggravated 1-day later, while the capacity improved 3-days later and partially recovered 7-days post irradiation. And, the recovery process was accelerated by nimodipine application.
  
  
  METHODS
  This method established a precise linkage between focal brain ischemia development and neurobehavioral deficits throughout a full scale of photothrombosis, which avoided the confounding factors of anesthetics and surgeries on neurobehavioral assessments, as infarct was induced in freely moving mice.
  
  
  CONCLUSIONS
  This method with high temporal and spatial resolution will be an optimal model for neurobehavioral evaluation in preclinical anti-ischemic drug screening.
authors.affiliation: School of Life Sciences, University of Science and Technology of China, Hefei 230027, China; Key Laboratory of Animal Models and Human Disease Mechanisms, and KIZ/CUHK Joint Laboratory of Bioresources and Molecular Research in Common Disease, and Laboratory of Learning and Memory, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650223, China.
authors.forename: Cheng-Long
authors.initials: CL
authors.lastname: Yu
authors.affiliation: School of Life Sciences, University of Science and Technology of China, Hefei 230027, China; Key Laboratory of Animal Models and Human Disease Mechanisms, and KIZ/CUHK Joint Laboratory of Bioresources and Molecular Research in Common Disease, and Laboratory of Learning and Memory, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650223, China.
authors.forename: Heng
authors.initials: H
authors.lastname: Zhou
authors.affiliation: Key Laboratory of Animal Models and Human Disease Mechanisms, and KIZ/CUHK Joint Laboratory of Bioresources and Molecular Research in Common Disease, and Laboratory of Learning and Memory, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650223, China.
authors.forename: An-Ping
authors.initials: AP
authors.lastname: Chai
authors.affiliation: Key Laboratory of Animal Models and Human Disease Mechanisms, and KIZ/CUHK Joint Laboratory of Bioresources and Molecular Research in Common Disease, and Laboratory of Learning and Memory, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650223, China.
authors.forename: Yue-Xiong
authors.initials: YX
authors.lastname: Yang
authors.affiliation: Key Laboratory of Animal Models and Human Disease Mechanisms, and KIZ/CUHK Joint Laboratory of Bioresources and Molecular Research in Common Disease, and Laboratory of Learning and Memory, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650223, China. Electronic address: talktomaomao@163.com.
authors.forename: Rong-Rong
authors.initials: RR
authors.lastname: Mao
authors.affiliation: School of Life Sciences, University of Science and Technology of China, Hefei 230027, China; Key Laboratory of Animal Models and Human Disease Mechanisms, and KIZ/CUHK Joint Laboratory of Bioresources and Molecular Research in Common Disease, and Laboratory of Learning and Memory, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650223, China. Electronic address: lxu@vip.163.com.
authors.forename: Lin
authors.initials: L
authors.lastname: Xu
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols; D020520:Brain Infarction / Q000175:diagnosis / Q000209:etiology; D002545:Brain Ischemia / Q000175:diagnosis* / Q000209:etiology*; D004195:Disease Models, Animal; D005047:Etoposide; D005080:Exercise Test; D007069:Ifosfamide; D020767:Intracranial Thrombosis / Q000150:complications* / Q000209:etiology; D007834:Lasers / Q000009:adverse effects*; D008124:Locomotion / Q000502:physiology; D008297:Male; D008727:Methotrexate; D051379:Mice; D008815:Mice, Inbred Strains; D009069:Movement Disorders / Q000175:diagnosis / Q000209:etiology*; D045442:Rotarod Performance Test; D014851:Wakefulness
chemical_list: D005047:Etoposide; D007069:Ifosfamide; D008727:Methotrexate
keywords: Freely moving mice; Neurobehavioral assessments; Nimodipine; Photothrombotic ischemia