If made correctly, it is highly unlikely that a brush handle would rot from the inside -- the knot will be set in ample epoxy, and the entire inner wood surface will be coated with/impregnated by epoxy.
Rot is much more probable from the outside, In my opinion, a wood handle should be finished in a good classic varnish (like a marine spar varnish). This will give it a high-gloss finish which may not be the most classy looking, but certainly the most durable. Alternative would be a matte outdoor or floor acrylic resin, classier looks, but slightly less durable. Or a reactive finish, although I haven't been able to source on in consumer-size quantities...