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Mini-Literature Review
Mini-Literature Review
Mini-Literature Review
I had the opportunity to work in a lab which studies rodent models of stroke recovery.
More specifically, the project I was involved in looked at the impact of cerebral microinfarctions
on the behaviour of mice. The first article in this review describes the mouse model of diffuse
microinfarction used in this project and the second article examines a clinical study looking at
the relationship between microvascular brain pathology and late-life motor impairment.
necrosis; they can be considered like a microscopic stroke. These lesions are not visible on
in the aging brain, present in 30% of people aged over 65 years old. Furthermore, current data
suggests that microinfarcts can cause clinical symptoms, notably cognitive impairment. [1]
predominantly done post-mortem. Gergely Silasi et al. conducted a study to find a reliable
animal model for small-vessel disease described in the article “A mouse model of small-vessel
injury”. [2] Although rodent models already exist for the purpose of looking at the impact of
microocclusions, they have their flaws. For example, laser light can be used to induce thrombosis
or microhemorrhage in the neocortex of mice or rats to disrupt blood flow in single vessels.
carotid artery producing many clots, mimicking microinfarcts in humans. However, it can be
very challenging to locate these crystals histologically thus making it difficult to know how
were injected unilaterally into the common carotid artery (CCA) to produce microocclusions.
the need to perform additional labeling to visualize neurons afterwards. In order to see the
obstruction in the blood flow of mice, Texas red-conjugated dextran was injected an hour before
the perfusion fixation. The dextran is mostly retained in arterioles that are blocked by lodged
microspheres while the rest of the vessels are cleared, making it possible to locate the
microocclusions. Following the sacrifice of the mice, structural damage was assessed by
confocal imaging in GFP-labeled cells in thin histologic sections for sequential neuronal
analysis.
After quantification of the distribution of the microspheres, it can be seen that 423±218
microspheres lodged in each brain. Majority of the microspheres were lodged in the cortex or the
thalamus. In addition, the average diameter of the blocked vessels corresponds to the
measurement of penetrating arteriole diameter in vivo of 10-20μM. The researchers also found
that 16.4% of the lodged microspheres produced noticeable damage to neuronal structure, mostly
in the hippocampus and white matter compared to the neocortex. Additionally, neuronal damage
in the hippocampus was more severe than the cortex, striatum or thalamus. Lastly, microglial
activation was only present in 21% of occlusion sites, indicating that only a subset of occlusions
These findings demonstrate that this mouse model produces structural damage similar to
the disruption seen in patients with small-vessel disease. The model also partially reflects the
distribution of lesions in patients. This study is of great significance as it shows that injection of
microspheres in mice can be used as an effective animal model to study the effects of
In the aging population, impaired motor function is common, however the root of these
impairments is uncertain. In the clinical study “Microvascular brain pathology and late-life
motor impairment” Buchman et al. aim to see if microvascular brain pathology is associated with
late-life motor impairment. Although multiple studies have linked microvascular brain
pathologies to cognitive decline, this angle focusing on motor function had not been looked at
before. [3]
This study was completed on a large scale with more than 2500 elderly people
undergoing motor assessment tasks, with the brain of 850 deceased participants evaluated for
microvascular pathologies. Motor performance tests included finger strength, pinch and grip
strength, gait and balance. The results of these examinations were then converted into a global
motor score (GMS). Certain regions of the brains were assessed post-mortem after being fixed
and examined for microscopic cerebral infarcts, CAA and cerebral arteriolosclerosis as well as
other cerebrovascular pathologies. The data collected was analyzed using Spearman correlations.
was present in 60% of the cases. These microinfarcts were discreetly associated with
arteriolosclerosis and showed a trend with CAA. The total number of microinfarcts could be
related to reduced GMS proximate to death, more specifically subcortical microinfarcts had an
impact on the GMS, whereas cortical microinfarcts did not. Further breakdown of the results
show that multiple microinfarcts are associated to lower GMS as a oppose to single
microinfarcts. The analysis was repeated to see if any of the pathologies were more strongly
associated with an individual motor task. It was found that microinfarcts caused a subtle, yet
These findings suggest that there is indeed motor impairments due to microvascular brain
pathology, notably post-microinfarction, although the effects are discreet. Moreover, this gives
us a better clue of the severity of the motor impairments and their impact on people.
Microvascular brain pathology could possibly explain the weakening in strength seen in older
people as it has been shown that loss of muscle mass does not account for this decline. This
study is important as it brings to light an independent cause of late-life motor impairment that is
currently under-studied. Ultimately, this article provides an important basis for other studies of
this kind, crucial to expanding our knowledge on cerebral disease and its consequences.
References
[1] Buchman, A. S., Yu, L., Boyle, P. A., Levine, S. R., Nag, S., Schneider, J. A., & Bennett, D.
A. (2013). Microvascular brain pathology and late-life motor impairment. Neurology, 80(8),
712–718. https://doi.org/10.1212/WNL.0b013e3182825116
[2] Silasi, G., She, J., Boyd, J. D., Xue, S., & Murphy, T. H. (2015). A mouse model of small-
vessel disease that produces brain-wide-identified microocclusions and regionally selective
neuronal injury. Journal of cerebral blood flow and metabolism : official journal of the
International Society of Cerebral Blood Flow and Metabolism, 35(5), 734–738.
https://doi.org/10.1038/jcbfm.2015.8
[3] Buchman, A. S., Yu, L., Boyle, P. A., Levine, S. R., Nag, S., Schneider, J. A., & Bennett, D.
A. (2013). Microvascular brain pathology and late-life motor impairment. Neurology, 80(8),
712–718. https://doi.org/10.1212/WNL.0b013e3182825116