Effects of long-term infusion of sedatives on the cognitive function and expression level of RAGE in hippocampus of rats.
This study aims to investigate the effects of long-term infusion of midazolam, propofol, and lytic cocktail on the rat cognitive ability and expression of receptor for advanced glycation end products (RAGE) in the hippocampus. The correlation between cognitive function and RAGE protein expression level could provide basis for clinical application.



Adult male Wistar rats were first treated with midazolam, propofol, lytic cocktail, and saline solution for 5 consecutive days, respectively, and then their behavioral performance in a Morris water maze was monitored to determine the effects of these sedatives on the cognition of spatial learning and memory. After the behavioral tests, the expression level of RAGE protein in the hippocampus of each rat was determined by ELISA and immunohistochemistry.



Compared with the control rats, the sedative-treated rats showed impaired performance in the Morris water maze. These three sedatives rendered similar extents of impairment of learning and memory at the first day after the treatment (p < 0.05, vs. control). However, the impairment by propofol and lytic cocktail gradually reduced in the following days (p < 0.05), while the impairment by midazolam did not show a significant reduction (p > 0.05). In addition, midazolam and propofol, but not lytic cocktail, caused significant upregulation of RAGE expression in the hippocampus. The upregulation of RAGE protein was further corroborated by the increment of RAGE-positive cells in the CA1 region of hippocampus from midazolam- and propofol-treated rats.



The long-term treatment of propofol, midazolam, and lytic cocktail could impair cognition. The upregulation of RAGE protein in hippocampus might play a role in the midazolam- and propofol-caused cognitive dysfunction.
Department of ICU, Baotou Central Hospital, Baotou, 014040, Inner Mongolia, China.
Junyan
J
Wang
Department of ICU, Baotou Central Hospital, Baotou, 014040, Inner Mongolia, China.
Mengxuan
M
Niu
Department of ICU, Baotou Central Hospital, Baotou, 014040, Inner Mongolia, China. shuanchengbai@sina.com.
Shuancheng
S
Bai
D000818:Animals; D003071:Cognition / Q000187:drug effects*; D003072:Cognition Disorders / Q000139:chemically induced; D006624:Hippocampus / Q000187:drug effects; D006993:Hypnotics and Sedatives / Q000633:toxicity*; D007858:Learning / Q000187:drug effects*; D008297:Male; D008568:Memory / Q000187:drug effects*; D008569:Memory Disorders / Q000139:chemically induced; D008874:Midazolam / Q000008:administration & dosage; D015742:Propofol / Q000008:administration & dosage; D051381:Rats; D017208:Rats, Wistar
D006993:Hypnotics and Sedatives; D008874:Midazolam; D015742:Propofol
Cognitive dysfunction; Lytic cocktail; Midazolam; Propofol; RAGE protein