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Ischaemic preconditioning in the rat brain: a longitudinal magnetic resonance imaging (MRI) study
P G Mullins1, D G Reid, P D Hockings
1Safety Assessment, GlaxoSmithKline, The Frythe, Welwyn, Herts AL6 9AR, UK.
Abstract:
Ischaemic preconditioning in rats was studied using MRI. Ischaemic preconditioning was induced, using an intraluminal filament method, by 30 min middle cerebral artery occlusion (MCAO), and imaged 24 h later. The secondary insult of 100 min MCAO was induced 3 days following preconditioning and imaged 24 and 72 h later. Twenty-four hours following ischaemic preconditioning most rats showed small sub-cortical hyperintense regions not seen in sham-preconditioned rats. Twenty-four hours and 72 h following the secondary insult preconditioned animals showed significantly smaller lesions (24 h = 112 +/- 31 mm(3), mean +/- standard error; 72 h = 80 +/- 35 mm(3)), which were confined to the striatum, than controls (24 h = 234 +/- 32 mm(3), p = 0.026; 72 h = 275 +/- 37 mm(3), p = 0.003). In addition during lesion maturation from 24 to 72 h post-secondary MCAO, preconditioned rats displayed an average reduction in lesion size as measured by MRI whereas sham-preconditioned rats displayed increases in lesion size; this is the first report of such differential lesion volume evolution in cerebral ischaemic preconditioning.
Insights
Ischaemic preconditioning significantly reduced brain lesion size in rats after middle cerebral artery occlusion (MCAO). Preconditioned rats showed smaller, striatum-confined lesions compared to controls, with unique lesion volume evolution.
Area of Science:
- Neuroscience
- Cerebrovascular Research
- Medical Imaging
Background:
- Ischaemic preconditioning is a phenomenon where brief periods of ischemia protect against subsequent longer ischemic insults.
- Understanding the protective mechanisms and efficacy of preconditioning is crucial for developing neuroprotective strategies.
- Magnetic Resonance Imaging (MRI) offers non-invasive in vivo monitoring of brain tissue changes during ischemic events.
Purpose of the Study:
- To investigate the neuroprotective effects of ischaemic preconditioning on brain lesion development and evolution following middle cerebral artery occlusion (MCAO) in a rat model.
- To quantify lesion volumes and characterize lesion evolution using MRI.
- To explore the temporal dynamics of lesion maturation in preconditioned versus control subjects.
Main Methods:
- Induction of ischaemic preconditioning in rats via a 30-minute middle cerebral artery occlusion (MCAO).
- Administration of a secondary, prolonged MCAO (100 minutes) insult three days after preconditioning.
- Serial MRI scans were performed 24 hours and 72 hours post-secondary MCAO to assess lesion volume and location.
- Comparison of lesion sizes between preconditioned rats and sham-preconditioned control rats.
Main Results:
- Ischaemic preconditioning induced small sub-cortical hyperintense regions on MRI 24 hours post-preconditioning.
- Preconditioned rats exhibited significantly smaller infarct volumes (24h: 112 ± 31 mm³, 72h: 80 ± 35 mm³) compared to controls (24h: 234 ± 32 mm³, 72h: 275 ± 37 mm³).
- Lesions in preconditioned rats were confined to the striatum, and demonstrated a reduction in size from 24 to 72 hours, unlike controls which showed lesion expansion.
Conclusions:
- Ischaemic preconditioning provides significant neuroprotection against MCAO-induced brain injury in rats.
- MRI is effective in quantifying lesion size and monitoring lesion evolution following cerebral ischemia.
- This study presents the first evidence of differential lesion volume evolution in cerebral ischaemic preconditioning, highlighting a unique protective mechanism.