Neurodegenerative Stroke Models

Models for Stroke Pathophysiology

A description of ischemic models offered, the area of expected damage, and the relevant cognitive/behavior tests. 

• MCAo - Focal Ischemia

  The focal cerebral ischemic model (MCAO) of stroke is commonly used to assess ischemic injury in the brain. Occlusion of the middle cerebral artery leads to a reduction of cerebral blood flow in both the striatum and the cortex, but the degree largely depends on the duration and site of occlusion. It is a highly reproducible model that results in focal brain damages similar to those occurring in human stroke. Model options include permanent occlusion, which produces massive damage, or transient occlusion where the artery is occluded for a period of time before reperfusion.

  Ischemic MCAo models for stroke:

  Occlusion:	Permanent	Transient
  Expected Area of Damage:	Cortex Striatum/Globus Pallidus, Thalamic Nucleus, Hippocampus	Mainly Cortex
  Cognitive/Behavior Tests:	Spatial memory, contralateral motor function and coordination (Staircase, Adhesion removal test, water maze, grip test)	Contralateral motor function and coordination (Staircase, adhesion removal test, grip test)
  Histology Assessment:	Thionine/H&E/TTC for infarct size & assessment	Thionine/H&E/TTC for infarct size & assessment

   

  Thionine Staining of Coronal Sections of Rat Brain Tissue

  

  Figures A & C. Normal Rat Brain Tissue. Figures B. & D. Rat brain 72 hours post-MCAo, demonstrating clear damage due to infarct in the right hemisphere.  

• 4VO - Global Ischemia

  The Global Ischemia model involves permanent occlusion of vertebral arteries and transient occlusion of carotid arteries. Brain injury in the hippocampus is caused by lack of cerebral blood flow. This model mimics cardiac arrest and coronary bypass surgery.

  The 4VO model can be used to evaluate lack of blood flow to the brain, as found in cardiac arrest and coronary bypass surgery. It is also used to evaluate neurodegeneration, dementia and oxygen stress.

  Options:

  • Permanent 4VO
  • Transient 4VO

  Common Assessments:

  • Histology
  • Water maze
  • Grip Test

  Example Data:

  

  Rats were given 8 trials to find the platform in the water maze test. Sham vs vehicle and test treated groups were evaluated. The animals that received the test item were able to find the platform in the water maze test in a similar fashion to sham animals. The vehicle treated animals were unable to find the platform after 8 trials.