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Originally Posted by JTH
I'm going to just take an educated guess here since it wasn't explained.
Donnie wasn't affected by the serum splashing on here at first, it only started when The Creep came to be. Which clearly means The Creep had something to do with it. The Creep when in the lab absorbed the brain serum in the beaker, and which like in the premiere with being able to harness mutagen from Raph, Creep became able to extract the serum as well. Meaning that since Donnie had traces of the serum within him, The Creep was able to draw the serum from Donnie and extract his intellect in the process. Immediately afterwards, Donnie began to show signs of effects during the sparring session as well as in the lab. Then like when Creep started glowing during the second Dojo fight, that's to be believed as Creep drawing more knowledge from Donnie, after that The Creep gained more fighting ability and defeated Raph & Mikey when he countered their attacks, (Which if you remember, Donnie lost his knowledge to counter when sparring Raph) and soon after that fight and Creep disappeared. Donnie showed more signs of fading intellect.
I did begin to doubt that theory when I thought Creep was destroyed after the Shellraiser explosion and Donnie was still getting worse after it; but when they showed Creepweed, it meant he was still alive so the extraction was still happening.
Again, that's just a guess, but there doesn't seem to be any other logical reasoning. 
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I could see that being answered in a later episode. That observation made my Leo was too relevant to ignore. Maybe Donnie will theorize on it for a later episode.
That aside, great theory.