Citation

Zhao J, Hylin MJ, Kobori N, Hood KN, Moore AN, Dash PK. J. Neurotrauma 2018; 35(2): 362-374.

Affiliation

University of Texas Medical School, Neurobiology and Anatomy , PO Box 20708 , 6431 Fannin St, MSB 7.160 , Houston, Texas, United States , 77030 ; P.Dash@uth.tmc.edu.

Copyright

(Copyright © 2018, Mary Ann Liebert Publishers)

DOI

10.1089/neu.2017.5102

PMID

29088998

Abstract

Acetylcholine is an excitatory neurotransmitter in the central nervous system that plays a key role in cognitive function, including learning and memory. Previous studies have shown that experimental traumatic brain injury (TBI) reduces cholinergic neurotransmission, decreases evoked release of acetylcholine, and alters cholinergic receptor levels. Galantamine (FDA-approved for the treatment of vascular dementia and Alzheimer's disease) has been shown to inhibit acetylcholinesterase activity, and allosterically potentiate nicotinic receptor signaling. We investigated if acute administration of galantamine can reduce TBI pathology and improve cognitive function tested days after the termination of the drug treatment. Post-injury administration of galantamine was found to decrease TBI-triggered BBB permeability (tested 24 hr after injury), to attenuate the loss of both GABAergic and newborn neurons in the ipsilateral hippocampus, and to improve hippocampal function (tested 10 days after termination of the drug treatment). Specifically, significant improvements in the Morris water maze, novel object recognition, and context-specific fear memory tasks were observed in animals injured treated with galantamine. Although mRNAs for both M1 (Nos2, TLR4, IL-12ß) and M2 (Arg1, CCL17, Mcr1) microglial phenotypes were elevated after TBI, galantamine treatment did not alter microglial polarization tested 24 hr and 6 days after injury. Taken together, these findings support the further investigation of galantamine as a treatment for TBI.

Language: en

Keywords

COGNITIVE FUNCTION; LEARNING AND MEMORY; controlled cortical impact