(vascular lesions measuring 0.05 -3mm in diameter) can lead to functional
deficits that are larger than expected and could last for much longer than
- Decline of
cognitive function has been found to be linked to cerebrovascular diseases
such as atherosclerosis and cerebral amyloid angiopathy.
- Studies have
shown that occurrence of microinfarcts is markedly higher in patients with
dementia and cognitive decline.
- Mechanism by
which these microinfarcts lead to cognitive impairment has not been well
- This study aims
to determine how microinfarcts may contribute to dementia and cognitive
In effect these
observations might possibly enhance the occurrence of dementia and cognitive
decline, according to recent research conducted at the Medical
University of South Carolina (MUSC).
Aim of the Study
The study wished to determine how mini-strokes
could cause dementia and cognitive impairment, the mechanisms of which remain
‘Small infarcts in the brain that are caused by mini-strokes may contribute to dementia and cognitive decline.’
This assessment was made more difficult
by the fact that microinfarcts are difficult to diagnose by standard available
neuroimaging techniques. In addition, there has been poor correlation between
clinical functional deficit and post-mortem microscopic evidence making it
extremely difficult to link microinfarcts to the timeline of cognitive
and intellectual impairment.
"These infarcts are so small and
unpredictable, we just haven't had good tools to detect them while the person
was still alive," said Andy Shih, Ph.D., Assistant Professor of
Neurosciences and senior author on the article. "So, until now, we
basically just had post-mortem snapshots of these infarcts at the end of the
battle as well as measures of the
person's cognitive decline, which might have been taken years before the brain
became available for study."
Hypothesis of the Study
The research team embarked their study based on the hypothesis that the extent
of functional deficit caused by the microinfarcts could actually be larger than
the evidence offered
by microscopy or radiological imaging such as magnetic resonance
"Even though a person may experience
hundreds of thousands of microinfarcts in their lifetime, each event is
extremely small and thought to resolve in a matter of days," said Shih.
"It's been estimated that, overall, microinfarcts affect less than 2% of
the entire human brain. But those estimates of tissue loss are based only on
the 'core' of the microinfarct, the area of dead or dying tissue that we can
see in routine, post-mortem, histological stains."
Details of the Study
The research team developed a mouse model to assess the effects of individual cortical
microinfarcts on brain function over several weeks
following the occurrence
of the microinfarct. This would enable creation of lesions that could be followed
up over a period of time and to obtain printouts of brain activity that were
well-defined over a period.
, the team occluded a single vessel in the barrel
cortex of mice that were fitted with cranial windows. The resultant functional
deficit was measured by sensory evoked brain activity measured by
activity-related c-Fos expression or in vivo two-photon imaging of single
vessel hemodynamic responses and correlated with the location and size of the
core of the microinfarct.
Results of the Study
- Post-mortem c-Fos immunostaining
indicated that the area affected by the microinfarct was least 12 times
greater in volume than the microinfarct core.
- In vivo, two-photon imaging of
single vessel hemodynamic response elicited by sensory stimulation,
estimated that neuronal activity in the affected region was depressed for
up to 14 to 17 days after the microinfarct.
Together, the results show that functional deficits caused by a single
microinfarct involves a much larger area around the lesion than was previously
thought and that the resulting deficits last much longer
"The MRI signal increased and then
went away as we'd expected, but we were surprised on autopsy to see that there
was still lots going on --tissue damage and neuroinflammation,"
Shih explained. "Even after three weeks the neurally evoked blood flow
responses had only partially recovered. So, that means a microinfarct can come
and go and you can see it briefly with MRI but it leaves a lasting impression
on brain function-possibly for months."
According to Shih, the cumulative effects
of multiple microinfarcts suffered over a period of time could actually equal
the impact of a single large infarct.
Takeaway from the Study
authors feel that standard available methods employed do not reveal the
true extent of the damage caused by microinfarcts.
Dr Shih hopes that the findings of
their study would help clinicians in the interpretation of MRI and help
researchers better correlate their findings in studies conducted.
findings of the study could lead to the establishment of newer preventive
"On a clinical level, maybe it's a
situation where therapeutics can play a bigger role. Maybe drugs that we
already have can mitigate the cumulative damage of microinfarcts," speculated
Shih. "The neuro-protective idea hasn't flown very far for acute stroke,
in part, because the window of time for protecting the brain from stroke damage
is very narrow. But, for microinfarcts, you don't have to know exactly when
they occur. If an MRI shows a person is at high risk for microinfarcts, maybe
one day we can put them on a drug for a while to reduce the impacts of these