Microscopic effect after stroke

We talk a lot about strokes in a clinical way in medical school. We discuss which areas of the brain are involved, and we correlate the areas damaged with the patient’s symptoms.

But what actually happens in the affected brain regions after a stroke? Injuries in the brain don’t heal like they do in other organs (you don’t form a scab and a scar in your brain). Let’s take a look at the steps the body takes to heal itself following an ischemic event in the brain.

There are basically four stages of healing following an infarct, and they usually happen in a predictable timeframe.

1. The first day (12-24 hours)

• After brain tissue dies, it takes a while before you can see any real changes in the cells. The first changes occur in neurons. Somewhere around 12 hours following an infarct, neuronal cytoplasm develops tiny holes (microvacuoles) and takes on a deep pink-red color (the neurons are actually called red neurons at this point – you can see why in the image above). 
• Later the nucleus undergoes pyknosis (in which it becomes small and dark) and karyorrhexis (in which it fragments into little bits, like cookie crumbs. Pathologists love food analogies and use them whenever possible.) Cells in general (but especially endothelial cells and astrocytes) tend to swell up and become more faded in color. Myelinated fibers disintegrate.

2. The second day (24-48 hours)

• Somewhere around the end of the first day, neutrophils swarm into the area, staying until about the end of the second day, at which point they take off and are replaced by  macrophages (which come in from the blood as monocytes). Microglia (the resident phagocytic cells of the brain) become activated too. 
• The tissue begins to undergo liquefactive necrosis from all those nasty enzymes released by the neutrophils. 
• Macrophages are like little moms going around and cleaning up the seemingly never-ending mess. 
• Astrocytes start to react, becoming large and getting ready to divide.

3. The next few weeks (2-3 weeks) 

• Macrophages continue to clean stuff up. They become stuffed with debris, and you can still see some of them hanging around months or even years later. 
• Astrocytes multiply and develop prominent, arborizing cytoplasmic extensions.

4. After several months

• Eventually, the astrocytes calm down, and what’s left is a cavity surrounded by a dense network of glial fibers and new blood vessels. There’s no collagen formation like there is in many other organs (like skin) – so there’s no filling in of the lost tissue space.

This whole process takes place from the outside of the lesion moving inward. Which is kind of cool because you’ll often see several stages of healing going on in the same lesion.

Ref.: Pathology Student