Look into LCM (Laser Capture Microdissection). I believe that it is currently the best way to isolate a particular cell type from a specific region.

https://www.nature.com/articles/nprot.2006.85

It can be hard to find a lab equipped for such an experiment, so maybe try to find a collaborator to help.

Hi Matthew L Neal , thankyou for your answer . This technique can be applied only with collaboration as you said. Do you know if any protocol exists to dissect out the tissue with a lesion and isolate a particular cell type (for instance Microglia) in my case with MACS (Magnetic assorted cell sorting) (using cd11b beads)?

It CAN be done, but from my experience you will need to pool at least 2-3 animals depending on how much brain tissue you want to examine.

Miltenyi kits have high death and low yields, so I would recommend using either a percoll gradient or Opti-Prep gradient to isolate the microglia, such as this paper:

https://academic.oup.com/brain/article/141/6/1753/4944716

You can use a percoll gradient to get to a population of cells, and then use MACS for CD11b to further purify if you want to. But like I said, yields will be low so I would anticipate you needing to pool brains.

The lesions created by lysolecithine are focal and in corpus callosum. I agree that a lot of lesioned animals will have to be pooled in order to get a decent amount of cells only from lesions. We have used Miltenyi MACS beads to isolate cells from the whole brain but have never tried mACS for a localised isolation. So u find Percoll gradient or opti Prep much more suitable in this case ? Matthew L Neal

or any other method/protocol which you might know other then these two ?