Cerebroprotective effects of ibuprofen on diabetic encephalopathy in rats

Diabetic encephalopathy is characterised by cognitive impairment, neurochemical and structural abnormalities. The aim of the study was to investigate the effects of ibuprofen on diabetic encephalopathy and potential mechanisms.

Diabetes was induced through a single intraperitoneal injection of streptozotocin (60 mg/kg). Diabetic rats were treated with ibuprofen (40 mg/kg) by gavage for 8 weeks. Cognitive performances were evaluated using Morris water maze. The temporal cortex and hippocampus were obtained to evaluate the levels of advanced glycation endproducts (AGEs) and their receptor (RAGE), the activity, protein expression, and mRNA levels of β-amyloid precursor protein cleaving enzyme 1 (BACE1), the protein and mRNA expression of peroxisome proliferator-activated receptor γ (PPARγ), and the protein expression of cyclooxygenase 2 (COX-2) and inducible nitric oxide synthase (iNOS). Blood was obtained for the evaluation of interleukin 1β level.

Chronic ibuprofen treatment significantly prevented the decline in learning and memory ability of diabetic rats and loss of neurons in the CA1 and CA3 areas of the hippocampus. Moreover, ibuprofen treatment markedly reduced the activity, protein, and mRNA levels of BACE1, AGE level, protein expression of RAGE, COX-2, and iNOS in the brain, and interleukin 1β level in serum, while increasing the protein and mRNA expression of PPARγ in the brain of diabetic rats. However, ibuprofen had no effects on the hyperglycaemia and the body weight of diabetic rats.

These findings demonstrated that ibuprofen markedly ameliorated diabetic encephalopathy, potentially reflecting the down-regulation of BACE1, the suppression of the AGE/RAGE axis, and the anti-inflammation in diabetic rat brain.