Neuroprotective effects of zafirlukast, piracetam and their combination on L‐Methionine‐induced vascular dementia in rats

Abstract

Vascular dementia is considered a vascular cognitive impairment disease caused by neuronal degeneration in the brain. Several studies have supported the hypothesis that oxidative stress and endothelial dysfunction are the main pathogenic factors in vascular dementia. This current study aims to determine the possible neuroprotective effects of zafirlukast, piracetam and the combination of piracetam and zafirlukast on L‐methionine‐induced vascular dementia in rats. Male Wistar albino rats were divided into five groups. Group I was the normal control, and group II received L‐methionine (1700 mg/kg, P.O.) for 32 days. The remaining groups received zafirlukast (20 mg/kg, P.O.), piracetam (600 mg/kg, P.O.) or their combination (zafirlukast 20 mg/kg + piracetam 600 mg/kg, P.O.) for 32 days after L‐methionine administration. Afterwards, the cognitive and memory performances of the rats were investigated using the novel object recognition (NOR) test; rats were then sacrificed for histopathological and biochemical analyses. L‐methionine‐induced vascular dementia altered rats’ behaviours and the brain contents of different neurotransmitters and acetylcholinesterase activity while increasing levels of oxidative stress and causing notable histopathological alterations in brain tissues. The treatment of vascular dementia with zafirlukast and the combination improved neurochemical, behavioural and histological alterations to a comparable level to those of piracetam. Thus, zafirlukast, piracetam and the combination of both drugs can be considered as potential therapeutic strategies for the treatment of vascular dementia induced by L‐methionine. To the best of our knowledge, this study is the first to explore the neuroprotective effects of zafirlukast and piracetam on L‐methionine‐induced vascular dementia.

Sitagliptin Attenuates the Cognitive Deficits in L-Methionine-Induced Vascular Dementia in Rats

“…Novel object recognition (NOR) of the VaD group revealed a lack of curiosity in investigating novel objects, indicating reduced recognition function and memory performance. This agrees with previous reported results [ 19 ]. During the Y-maze test, the VaD group showed a lower percentage of alternation.…”

“…There was a significant elevation of serums TNF- α and IL-6 and a significant decrease in IL-10 in the VaD group compared with the values of the control group. This agrees with previous reported results [ 19 ]. TNF- α triggers the inflammatory response by activating a cascade of cytokines, chemokines, and growth factors.…”

“…The current study's findings back up this claim, with increased MDA, a lipid peroxidation marker, and a decrease in SOD concentration in the VaD group compared with the control group. This agrees with previous studies [ 9 , 19 ]. Oxidative stress caused by excessive ROS production is a major contributor to tissue damage or an enhanced inflammatory response [ 42 ].…”

“…Group II (L-methionine-induced VaD group) [VaD]: L-methionine (purchased from Sigma, St Louis, MO, USA, in the form of powder) was administered at a dose of 1700 mg/kg, dissolved in distilled water, and given once daily by oral gavage for 32 days to induce VaD [ 19 ].…”

Observation on the clinical efficacy of external ventricular drain combined with intraventricular urokinase injection and intravenous piracetam in the treatment of intraventricular hemorrhage

“… 15 Consequently, the key to the treatment of IVH is to relieve the compression of intracerebral parenchyma by intraventricular hematoma and protect the brain tissue from further injury to the maximum extent. 16 It has been shown in recent studies 17 that in the case of intracerebral hemorrhage combined with IVH, EVD may be a promising method to improve blood clearance rate, boasting advantages such as less damage to brain tissue, simple operation, short duration and so on. However, adverse effects such as cerebral ventricle easily blocked by blood clots, poor drainage, reduced intraventricular hematocele clearance will also follow.…”