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.)Â 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)Â
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.
As always, I appreciate your information. So, will this cerebral cavitation show up grossly upon autopsy? Can you see it on a MRI? Is the area filled with anything?
So, is it safe to say that most necrosis that occurs will be coagulation necrosis. However, in the CNS, where we lack the sturdy ecm, the area liquefies instead?
Thanks,
Leslie
Hi Leslie –
Yes – depending on how big the cavitation is, you should be able to see it at autopsy and on MRI. The cavity may be empty, if the blood has been resorbed, or sometimes there will be old hemorrhagic material inside. It just depends on how well the macrophages clean up things (and how big the cavity was to start with).
Yes: most of the time, when we see necrosis in an organ, it is coagulative necrosis (because much of the time, it’s due to a lack of blood supply). And yes: in the CNS, the area liquefies instead!
Hello! I’m a bit stuck on something, I was hoping maybe you could help…Rubin’s pathology text mentions that “coagulative necrosis of the brain may occur after cerebral artery occlusion and is followed by rapid dissolution— liquefactive necrosis…” Is this (temporary?) coagulative necrosis related to the first 12-24 hours after an infarct you mentioned here?
And thanks as always for all these amazing posts 😉
Hi Stephanie – Hmm…I think there is a discrepancy between Rubin’s and Robbins on this point. Robbins maintains that the type of necrosis you see in the brain is liquefactive, not coagulative. On page 43 of the new (9th) edition, it says, “Ischemia caused by obstruction in a vessel may lead to coagulative necrosis of the supplied tissue in all organs except the brain” and, farther down the same page, “For unknown reasons, hypoxic death of cells within the central nervous system often manifests as liquefactive necrosis.” I haven’t heard of coagulative necrosis occurring in the brain – so I’d have to side with Robbins on this point. Hope that helps!
Hi Kristine ,
Can you tell the difference between chromatin clumping and Nuclear pyknosis after cell ischemia.Apparently one is reversible and the latter is not but arent they the same thing?
Thanks
Good question. Chromatin clumping can be seen in lots of different situations. It is just what it sounds like: some areas of the chromatin are darker and more clumpy than others. It’s kind of an unevenness in the appearance of the chromatin. Neutrophils, for example, normally have very clumped chromatin, whereas monocytes don’t. Pyknosis is a sign of irreversible cell injury. In pyknosis, the entire nucleus is a uniform, solid, dark dot. There’s no variation – it’s just all dark and solid.
Wow! We never think of this. I’m an RN. However– I had a very serious CVA (in that order). My infarct was between the sizes of a golf ball and tennis ball. It’s absolutely insane to think that a human is missing such a large piece of their brain and still functioning and taking care of other patients!!!
I had a stroke when I was 24. Here is my Swiss cheese brain.