Propofol protects rats against intra-cerebroventricular streptozotocin-induced cognitive dysfunction and neuronal damage.

Abstract

Cognitive dysfunction is a severe issue of Alzheimer's disease. Thus, the present study was conducted to enumerate the protective effect of propofol (PPL) in rats against intra-cerebroventricular streptozotocin (STZ)-induced cognitive dysfunction and neuronal damage. The effect of PPL was investigated to evaluate behavioural changes in STZ-induced cognitive dysfunction in Wistar rats using Object Recognition Task (ORT) for nonspatial, Morris Water Maze (MWM) for spatial and locomotor activity. The effect of PPL was also investigated on acetylcholine (ACh) esterase (AChE) activity and oxidative stress markers, e.g., nitrite, malonaldehyde (MDA), superoxide dismutase (SOD), and glutathione (GSH). The level of pro-inflammatory cytokines, e.g., tumour necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-6, was also studied in the PPL-treated group. The effect of PPL on the level of neurotransmitters, e.g., dopamine (DA), serotonin (5-HT), and norepinephrine (NE) and their metabolites 3,4-dihydroxyphenylacetic acid (DOPAC), 5-hydroxyindoleacetic acid (5-HIAA), and homovanillic acid (HVA) levels were also estimated in frozen hippocampal tissues by high-performance liquid chromatography. Histopathology analysis of neurons in the hippocampus of rats was performed using haematoxylin and eosin (H&E) staining. Propofol showed significant improvement in the spatial and nonspatial memory deficit of rats in the MWM test and ORT in rats. It also causes improvement in locomotor activity of rats by preserving ACh via inhibition of AChE. It also potentiates the expression of DA, 5-HT, and NE with a simultaneous reduction in the level of metabolites (DOPAC, HVA, and 5-HIAA). PPL showed a reduction of oxidative stress in rats by restoring the level of nitrite, SOD, MDA, and GSH near to normal. In the PPL-treated group, the level of TNF-α, IL-1β, and IL-6 was found reduced in a dose-dependent manner. In histopathology analysis of neurons in the hippocampus of the STZ rats, PPL causes dose-dependent reduction of pyknosis in the nucleus, which confirmed the protective effect of PPL. The present study demonstrated that PPL could significantly attenuate cognitive dysfunction and neuronal damage in STZ-induced rats.