New research suggests that ministrokes affect a wider area of the brain than previously thought, and that their effects last longer.
Transient ischemic attacks, or "ministrokes," occur when an artery becomes briefly blocked by a blood clot. A ministroke is the same as a regular stroke - the only difference is that they last for a shorter period of time.
Ministrokes - also called cortical microinfarcts - cause minuscule lesions of approximately 0.05-3 millimeters in diameter, but an increasing amount of research seems to link ministrokes with cognitive decline and dementia.
Analyzing ministroke effects in mice
Motivated by the existing evidence, researchers from the Medical University of South Carolina (MUSC) hypothesized that ministrokes might affect brain function on a greater scale than what is usually shown by histological evidence or MRI scans.
The team was led by Andy Shih, Ph.D., an assistant professor of Neurosciences at MUSC, and the findings were published in the Journal of Cerebral Blood Flow and Metabolism.
Shih and team designed a mouse model so that they could study the effects of individual microinfarcts on the cortical tissue over several weeks following the ministroke.
Researchers used photothrombosis - an experimental stroke technique developed in 1985 to induce cerebral infarction in rats - to close up a single arteriole in the so-called barrel cortex of mice. The barrel cortex is part of the somatosensory cortex of mice, marsupials, and other rodents, and it has a specific structure that mirrors the whiskers on the snout.
For this experiment, researchers implanted cranial windows in the barrel cortex, and then compared functional readouts of brain activity with the location of the ministroke core.
They performed both in vivo and post-mortem brain analyses. The team used c-Fos expression and in vivo, two-photon imaging of single vessel hemodynamic responses in order to measure the precise scale of sensory-evoked neural activity.
Ministrokes have wider, longer-lasting impact than previously thought
The data revealed by the study suggests that a single ministroke affects a much larger area and has longer-lasting effects than previously understood.
The post-mortem c-Fos immunostaining showed that the ministroke had affected an area 12 times greater in volume than the microinfarct core.
Additionally, the single vessel two-photon imaging revealed that the neuronal activity across this affected area was depressed for 14-17 days after the ministroke.
The results were deemed "surprising" by the researchers.
"I knew larger strokes could have distant effects, but I was surprised that something of this scale could have such a large effect. The MRI signal increased and then went away as we had expected, but we were surprised on autopsy to see that there was still lots going on - tissue damage and neuroinflammation. Even after 3 weeks, the neurally evoked blood flow responses had only partially recovered. This 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."
Andy Shih, Ph.D.
Significance of the findings
Shih explains the significance of the study both in terms of the methodology typically used to assess the impact of ministrokes, and the implications for preventive care.
"These infarcts are so small and unpredictable, we just have not had good tools to detect them while the person was still alive," he says. "Until now, we just had post-mortem snapshots of these infarcts at the end of the dementia battle as well as measures of the person's cognitive decline, which might have been taken years before the brain became available for study."
Most ministrokes are difficult to detect with conventional neuroimaging techniques, as often the in vivo data does not match the post-mortem histological evidence. This makes it difficult for researchers to connect the ministrokes with the development of cognitive decline over time.
However, the research conducted by Shih and team bypassed these difficulties by creating a model allowing them to follow the effects of individual cortical ministrokes over several weeks.
Furthermore, Shih suggests that the findings might also shape future preventive practices. Given that microinfarcts have such a long-lasting impact over a wide area, several microinfarcts may cause "enough accumulated damage in the brain's circuitry to equal the impact of a larger event."
"On a clinical level, maybe [...] therapeutics can play a bigger role. Maybe drugs that we already have can mitigate the cumulative damage of microinfarcts [...] 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 lesions."