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Oedema and glial cell involvement in the aged mouse brain after permanent focal ischaemia
A P Fotheringham1, C A Davies, I Davies
1The University of Manchester, Schools of Medicine and Biological Sciences, Manchester, UK.
Abstract:
This study examines the effect of age on oedema and brain swelling, and associated glial cell involvement on the size of the lesion in two models of permanent, focal cerebral ischaemia. Ischaemia was induced in male C57BL/Icrfat mice (4-6 and 26-31-month-old) by middle cerebral artery (MCA) occlusion using either electrocoagulation after craniotomy (MCA/craniotomy), or by an intraluminal filament through the carotid artery (MCA/icf). Twenty-four hours after inducing ischaemia, brain swelling and lesion size were measured in young and aged mice, and cerebral oedema by wet/dry brain weights. Histopathology and immunocytochemistry were performed on a separate set of perfusion fixed brains. The MCA/icf technique produced a significantly larger lesion than MCA/craniotomy in both age groups. The percentage of water taken into the brain was significantly greater after MCA/icf, with aged mice showing the greatest increase. When lesion size was corrected for brain swelling there was no age-related increase in the size of the lesion. The numbers of microglia and astroglia increased significantly in the parietal cortex of aged control animals, and there were qualitative differences in the glial response between the two stroke models. This study emphasizes the importance of age in models of permanent focal ischaemia, with oedema clearly being a significant factor. Differ-ences in the responsiveness of the glial cell population with age may be of fundamental importance in the progress of ischaemic brain damage.
Insights
Age significantly impacts brain swelling and oedema in stroke models, with aged mice showing greater water uptake. Lesion size, when corrected for swelling, revealed no age-related increase, highlighting oedema
Area of Science:
- Neuroscience
- Pathology
- Gerontology
Background:
- Age is a critical factor in stroke outcomes.
- Understanding age-related changes in brain injury models is essential.
- Cerebral oedema and glial responses are key components of ischemic brain damage.
Purpose of the Study:
- To investigate the influence of age on cerebral oedema, brain swelling, and glial cell responses in permanent focal cerebral ischemia models.
- To compare two distinct surgical methods for inducing ischemia (MCA/craniotomy vs. MCA/icf) regarding their impact on lesion size and oedema in young versus aged mice.
- To determine if age-related differences in lesion size persist after accounting for brain swelling.
Main Methods:
- Induction of permanent, focal cerebral ischemia in young (4-6 months) and aged (26-31 months) male C57BL/Icrfat mice using middle cerebral artery (MCA) occlusion via electrocoagulation (MCA/craniotomy) or an intraluminal filament (MCA/icf).
- Measurement of brain swelling and lesion size 24 hours post-ischemia.
- Assessment of cerebral oedema using wet/dry brain weights.
- Histopathological and immunocytochemical analysis of glial cell (microglia, astroglia) populations.
Main Results:
- The MCA/icf method resulted in significantly larger lesions and greater brain water content compared to MCA/craniotomy in both age groups.
- Aged mice exhibited the most significant increase in brain water content, indicating greater oedema.
- When lesion size was adjusted for brain swelling, no age-related increase was observed.
- Aged mice showed increased numbers of microglia and astroglia in the parietal cortex, with distinct glial responses between the two ischemia models.
Conclusions:
- Age significantly influences oedema and brain swelling in focal cerebral ischemia models, playing a crucial role in lesion development.
- The observed lack of age-related increase in corrected lesion size suggests that oedema is a primary driver of apparent size differences.
- Age-related alterations in glial cell responsiveness may be fundamentally important in modulating the progression of ischemic brain damage.