I may be wrong, but there may be issues of pentration of RNA later in a whole mose brain - you may have to cut it into smaller pieces to ensure adeqate penetration. yes the tissue does seem to get a bit harder, but you usuallly need to remove the RNA later and soak in an RNAse free liquid to rehydrate the tissue. brain tissue is pretty soft compared to other tissues - gut etc so it is relatively easy to homogenise in Trisol.You should get quite a lot of RNA from a whole brain.

Ian

Whenever using RNAlater, I place the tissue (usually liver, in my case) and incubate at 4 degrees Celsius for about 24 hours. After this I always remove the RNAlater before storing the tissue at -80 (or -20) degrees Celsius in order to prevent salt crystal formation - if you don't follow this protocol, I've found that the tissue becomes similar to the consistency of frozen chewing gum, which does become difficult to homogenize.

I usually prefer snap freezing with liquid nitrogen for long term storage of any tissue though...