Abstract Details

Title Amantadine Improves Cognitive Outcome after Fluid Percussion Traumatic Brain Injury in Rats

Topic Critical Care/Emergency Neurology/Trauma

Presentation(s) P05 - (-)

Poster/Presentation
Number 209

Objective

Background BACKGROUND: Dopaminergic pathway dysfunction may contribute to the cognitive sequelae of TBI. Amantadine can enhance arousal and cognition after human TBI, while only modest cognitive improvement is reported with low dose amantadine in experimental TBI. Here, the effect of clinically relevant doses of amantadine is evaluated in experimental TBI.

Design/Methods DESIGN/METHODS: Rats were subjected to moderate fluid percussion injury and treated with amantadine (AMT) at 15, 45, or 135 mg/kg/day. Based on pharmacokinetic data, doses of 45 and 145 mg/kg/day are projected to be comparable to doses used for the treatment of Parkinson's disease in humans. Drug administration was initiated one hour post-TBI, and continued for 16 days. Spatial learning/memory performance was evaluated with the Morris water maze (MWM) on days 12-16 post-TBI. Rats were sacrificed on day 16, and CA3 pyramidal neurons quantified using unbiased stereology.

Results RESULTS: Treatment with AMT at 45 mg/kg/day or higher resulted in improved overall performance (latency to find the hidden platform on days 12-16) in the MWM compared to control (p=0.041). Similar results were obtained for the terminal performance (latency on days 15-16), where AMT treatment at 45 mg/kg/day or higher improved performance, with statistical significance being achieved at 135 mg/kg/day (p=0.028). To determine the effects of AMT on neuroprotection, the number of CA3 pyramidal neurons was quantitated. Differences in number of surviving neurons between the 135 mg/kg/day AMT and the control were significant (p=0.02). AMT at 15 mg/kg/day was not effective by any measure.

Conclusions CONCLUSIONS: Amantadine is the only drug with clinical evidence demonstrating a benefit for the treatment of TBI. We show that amantadine produced significant improvement in cognitive performance and neuroprotection after experimental TBI. These results demonstrate the therapeutic potential of amantadine for the post-injury treatment of TBI.

Authors/Disclosures
Jack Nguyen PRESENTER	No disclosure on file
Josep Gamez, MD, PhD (HOSPITAL UNIVERSITARI VALL D' HEBRON)	The institution of Dr. Gamez has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for CSL Behring. The institution of Dr. Gamez has received research support from Government of Spain (FIS FEDER).
	No disclosure on file
	No disclosure on file
Greg Went (Adamas)	No disclosure on file
	No disclosure on file

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