Effects Of J147 On Post‐Operative Cognitive Dysfunction

Abstract

BackgroundPostoperative cognitive dysfunction (POCD) is a major complication in patients undergoing surgery. The inflammatory response necessary for wound healing seems derailed and is reflected in the brain as neuroinflammation and consequently cognitive decline. J147 has anti‐dementia and anti‐aging effects that may be attributed to anti‐inflammatory properties.Aiminvestigate effects of J147 treatment in an animal model for POCD.Materials and MethodsMale Wistar rats (n=60; ±350g) were randomly divided over 1. non‐surgery; 2. control surgery; 3. surgery + acute J147 (20 mg/kg) and 4. surgery + chronic J147 (30 mg/kg/day). Acutely treated rats received one single oral administration of J147 before surgery, chronically treated rats received oral J147 through their food during the whole experiment. Behavioral testing consisted of an Open Field test (OF), Novel Object and Novel Location Recognition test (NOR/NLR) and the Morris Water Maze (MWM) to assess exploratory behavior, object memory, spatial learning and memory, and cognitive flexibility, resp. Two weeks after surgery, rats were sacrificed, and blood and brain tissue is collected for later analyses of (neuro)inflammation.ResultsAll rats survived surgery and were subjected to behavioral testing. The OF showed that chronic treated animals payed significant more visits to the center (12.6±1.5 vs 9.7±1.4 in control surgery), at similar distance moved. No difference in spatial learning capacity, reflected in the learning curve of the MWM test, was seen between the groups. Platform crossings in the MWM indicated that chronic treatment can restore the spatial memory deficits caused by surgery (1.6±0.2 vs 1.0±0.1). NOR test did not discriminate between groups. In NLR, control surgery rats performed at chance level (60±5 vs 50%), whereas performance in chronic treated rats significantly increased above chance level; 70±6%. For the acute treated group no significant differences were seen compared to the control surgery group in all the tests.ConclusionOur data indicate that chronic J147, but not acute J147 prevents cognitive impairment following abdominal surgery in our POCD model. Therefore, chronic J147 treatment could provide a promising novel therapeutic approach in POCD in patients. To study the underlying mechanism of (neuro) inflammation, plasma cytokines levels and microglia activation in the brain will be determined.Support or Funding InformationThe study is supported by funding from ABREXA