Citalopram attenuated neurobehavioral, biochemical, and metabolic alterations in transient middle cerebral artery occlusion model of stroke in male Wistar rats

Abstract

Oxidative stress and inflammation are implicated as cardinal mechanisms of neuronal death following stroke. In the present study citalopram (Cit) was investigated in a 2 h middle cerebral artery occlusion (MCAo) model of stroke in male Wistar rats. Pretreatment, posttreatment (Post Cit) and pre plus posttreatment (Pre + Post Cit) with Cit were evaluated for its neuroprotective effect. In pretreatment protocol, effect of Cit at three doses (2, 4, and 8 mg/kg) administered i.p., 1 h prior to MCAo was evaluated using neurological deficit score (NDS), motor deficit paradigms, and cerebral infarction 24 h post-MCAo. In posttreatment and pre plus posttreatment protocol, the effective dose of Cit (4 mg/kg) was administered i.p., 0.5 h post-reperfusion (Post Cit) only, and 1 h prior to MCAo and again at 0.5 h post-reperfusion (Pre + Post Cit), respectively. These two groups were assessed for NDS and cerebral infarction. Though NDS was significantly reduced in both Post Cit and Pre + Post Cit groups, significant reduction in cerebral infarction was evident only in Pre + Post Cit group. Infarct volume assessed by magnetic resonance imaging was significantly attenuated in Pre + Post Cit group (10.6 ± 1.1%) compared to MCAo control group (18.5 ± 3.0%). Further, Pre + Post Cit treatment significantly altered 17 metabolites along with attenuation of malondialdehyde, reduced glutathione, matrix metalloproteinases, and apoptotic markers as compared to MCAo control. These results support the neuroprotective effect of Cit, mediated through amelioration of oxidative stress, inflammation, apoptosis, and altered metabolic profile.

Neuroprotective effects of Olea europaea L. fruit extract against cigarette smoke‐induced depressive‐like behaviors in Sprague–Dawley rats

“…These outcomes are supported by the findings of Gupta et al. (2018). They expounded the neuroprotective role of citalopram (2, 4, and 8 mg/kg) in Wistar rats and observed the antioxidant mechanism behind the neuroprotective action of citalopram.…”

Post Stroke Depression to be Expected

“…Furthermore, Fluoxetine injections in rat models enhanced neurogenesis and prevented a pathological increase in stem cell recruitment in the hippocampus [228]. Similarly, Citalopram demonstrates neuroprotective effects by decreasing oxidative stress, inflammation and apoptosis [229]. Additionally, the natural antidepressant hyperforin also improves post-stroke depression and post-stroke isolation in rat models by inhibiting TGF-β resulting in the promotion of hippocampal neurogenesis [230,231].…”

Therapeutic potential of serotonin in ischemic stroke

“…Citalopram exerted anti-inflammatory and antioxidant activities in a rat model of focal cerebral ischemia. Pre, post and pre and post administration of it reduced cerebral infarct volume, grip test score and neurological deficit score in a 2 h MCAO model of ischemia [55]. Another study showed that citalopram protected CA1 pyramidal cells after transient cerebral ischemia in gerbil through prevention of excitatory amino acids, glutamate and aspartate, accumulation during and after forebrain ischemia [56] and also decreased glutamate release from lipopolysaccharideactivated microglia which in turn increased the survival of oxygen-glucose deprivation injured neurons [57].…”

“…Citalopram alleviates the activity of the apoptotic markers, caspase-3, caspase-9, MMP-2 and MMP-9 and reduces the levels of MDA and NO. It reduces the release of the inflammatory mediators; TNF-α and IL-1β which ameliorate the ischemia-induced cell death and inflammation [55][56][57]. As fluoxetine and paroxetine, escitalopram overexpresses BDNF and reduces ischemiainduced oxidative stress.…”