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

Moisse K, Welch I, Hill T, Volkening K, Strong MJ - J Neuroinflammation (2008)

Bottom Line: Routine histological and immunohistochemical studies were performed at 24 and 72 hours.This was associated with contralateral ventral spinal cord microglial priming without significant reactive astrocytosis or lower motor neuron degeneration.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.

View Article: PubMed Central - HTML - PubMed

Affiliation: Cell Biology Research Group, Robarts Research Institute, London, Ontario, Canada. kmoisse@uwo.ca

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.

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Neurobehavioural assessment (NBA) scores of mice using (a) the Belayev et al. [17] scale and (b) the Yang et al. scale [26], during occlusion (MCAo), following reperfusion (0), 24 hours post-reperfusion and 72 hours post-reperfusion. All sham-operated mice exhibited scores of 0 at all time points.
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Figure 2: Neurobehavioural assessment (NBA) scores of mice using (a) the Belayev et al. [17] scale and (b) the Yang et al. scale [26], during occlusion (MCAo), following reperfusion (0), 24 hours post-reperfusion and 72 hours post-reperfusion. All sham-operated mice exhibited scores of 0 at all time points.

Mentions: During occlusion, all mice exhibited head rotation, eyelid drooping and abnormal tongue holding consistent with the development of a cerebral infarct. Interestingly, mice were highly vocal throughout the course of the study. Animals were examined carefully for evidence of pain and were not in apparent distress. Analgesics were administered according to guidelines. Following reperfusion, behavioural deficits were sustained with 12 of 16 mice achieving scores above the inclusion cutoffs proposed by Belayev and colleagues [17] suggesting the presence of a lesion (Figure 2b). Eleven of these 12 mice had a marked region of infarct and cortical pathology. Twenty-four hours post-reperfusion most animals remained vocal with only a moderate head tilt and a mild postural reflex (Figure 2a–b). All animals survived 24 hours post-reperfusion and maintained good body weight. Eight of 9 animals survived 72 hours post reperfusion.


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

Moisse K, Welch I, Hill T, Volkening K, Strong MJ - J Neuroinflammation (2008)

Neurobehavioural assessment (NBA) scores of mice using (a) the Belayev et al. [17] scale and (b) the Yang et al. scale [26], during occlusion (MCAo), following reperfusion (0), 24 hours post-reperfusion and 72 hours post-reperfusion. All sham-operated mice exhibited scores of 0 at all time points.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2474603&req=5

Figure 2: Neurobehavioural assessment (NBA) scores of mice using (a) the Belayev et al. [17] scale and (b) the Yang et al. scale [26], during occlusion (MCAo), following reperfusion (0), 24 hours post-reperfusion and 72 hours post-reperfusion. All sham-operated mice exhibited scores of 0 at all time points.
Mentions: During occlusion, all mice exhibited head rotation, eyelid drooping and abnormal tongue holding consistent with the development of a cerebral infarct. Interestingly, mice were highly vocal throughout the course of the study. Animals were examined carefully for evidence of pain and were not in apparent distress. Analgesics were administered according to guidelines. Following reperfusion, behavioural deficits were sustained with 12 of 16 mice achieving scores above the inclusion cutoffs proposed by Belayev and colleagues [17] suggesting the presence of a lesion (Figure 2b). Eleven of these 12 mice had a marked region of infarct and cortical pathology. Twenty-four hours post-reperfusion most animals remained vocal with only a moderate head tilt and a mild postural reflex (Figure 2a–b). All animals survived 24 hours post-reperfusion and maintained good body weight. Eight of 9 animals survived 72 hours post reperfusion.

Bottom Line: Routine histological and immunohistochemical studies were performed at 24 and 72 hours.This was associated with contralateral ventral spinal cord microglial priming without significant reactive astrocytosis or lower motor neuron degeneration.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.

View Article: PubMed Central - HTML - PubMed

Affiliation: Cell Biology Research Group, Robarts Research Institute, London, Ontario, Canada. kmoisse@uwo.ca

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.

Show MeSH
Related in: MedlinePlus