Wasps' Andrea Masi and La Rochelle's Gonzalo Canale have been ruled out of the entire RBS 6 Nations tournament.
Azzurri boss Brunel admitted it will be a challenge without as many as seven frontline stars.
Italy open their Six Nations with a trip to Wales on Saturday, February 1, with Brunel aware a host of youngsters must climb quickly to international class.
"We must be ambitious, we won twice last year against Ireland and France," said Brunel.
"It's a problem when you take out key men like Canale, Masi, because in terms of depth we do not have a pool of 40 or 50 players to choose from.
"Their experience is vital, but what we must do now is usher in young players as quickly as possible.
"We have to integrate them very quickly to the level of competition: the speed of the game, the choices, the decisions, the reactions and how you can adapt to what happens.
"What we need to do is trust them, show them they can do what they need to do.
"We have to integrate them quickly, and that's when the older and more experienced players come in."
Captain Sergio Parisse said Italy must rediscover the form showed in last season's Six Nations after disappointing summer and autumn schedules.
Intent on pushing the attacking envelope again, the world-class Stade Francais number eight said Italy must not revert to tight-game type.
"Back in 2008 the questions were all about us having a good scrum, but I think we are more complete as a team now," said Parisse.
"We can play in our backs and play a good kind of rugby, it's not just dominating the scrum.
"We beat Ireland and France, and our objective is to continue this way, we lost it slightly in June and November, and we've got to bring that back now.
"We've got to stick to that attacking style, we've got to go at it, and there are some risks you've just got to take, rather than just kicking ball away and defending the line."