TNF and Brain atrophy: Despite encouraging results obtained with an engineered inactive form of TNF-α injected intracerebroventricularly in R6/2 transgenic mice [224], systemic delivery of etanercept, a TNF-α-inhibiting drug, failed to improve cognitive and motor deficits in R6/2 mice and only partially reduced brain atrophy [225], an effect possibly related to the poor blood-brain barrier penetrance of the drug.