Transient middle cerebral artery occlusion induces microglial priming in the lumbar spinal cord: a novel model of neuroinflammation

Katie Moisse¹^,2 , Ian Welch²^,3 , Tracy Hill³ , Kathryn Volkening¹ and Michael J Strong¹^,2^,4

¹Cell Biology Research Group, Robarts Research Institute, London, Ontario, Canada

²Department of Pathology, University of Western Ontario, London, Ontario, Canada

³Department of Animal Care and Veterinary Services, University of Western Ontario, London, Ontario, Canada

⁴Department of Clinical Neurological Sciences, the University of Western Ontario, London, Ontario, Canada

author email corresponding author email

Journal of Neuroinflammation 2008, 5:29doi:10.1186/1742-2094-5-29


Published:	7 July 2008

Abstract

Background

Middle cerebral artery occlusion (MCAo) in mice results in a brain infarct, the volume of which depends on the length of occlusion. Following permanent occlusion, neuropathological changes – including a robust glial inflammatory response – also occur downstream of the infarct in the spinal cord.

Methods

We have performed short, transient MCAo in mice to induce penumbral damage spanning the motor cortex. A 30 minute MCAo using a poly-L-lysine-coated intraluminal suture introduced through a common carotid artery incision was performed in 17 female C57BL/6 mice. Five sham-operated mice received common carotid artery ligation without insertion of the suture. Neurobehavioural assessments were performed during occlusion, immediately following reperfusion, and at 24 and 72 hours post-reperfusion. Routine histological and immunohistochemical studies were performed at 24 and 72 hours.

Results

In 11 of the surviving 16 mice subjected to MCAo, we observed a focal, subcortical necrotic lesion and a reproducible, diffuse cortical lesion with accompanying upper motor neuron involvement. This was associated with contralateral ventral spinal cord microglial priming without significant reactive astrocytosis or lower motor neuron degeneration.

Conclusion

The advantages to this method are that it yields a reproducible cortical lesion, the extent of which is predictable using behavioural testing during the period of ischemia, with upper motor neuron involvement and downstream priming, but not full activation, of microglia in the lumbar spinal cord. In addition, survival is excellent following the 30 minutes of occlusion, rendering this a novel and useful model for examining the effects of microglial priming in the spinal motor neuron pool.