Oleuropein Improved Post Cerebral Stroke Cognitive Function by Promoting Histone Acetylation and Phosphorylation of cAMP Response Element-Binding Protein in MCAO Rats

Abstract

Background: Post-stroke cognitive impairment (PSCI) is commonest clinical disorder in which peripheral cholinergic activity is important. Oleuropein (OLP) is polyphenol is present in olive oil. Here we evaluated the effect of OLP in cognitive dysfunction rats in post cerebral stroke model. Methods: The post cerebral stroke cognitive dysfunction PSD rat model was created by occlusion of transient middle cerebral artery. The rats were divided into 6 groups named, Sham + Vehicle, Sham + OLP (50 mg/kg), PSD rats + Vehicle, PSD rats + OLP (20, 50 or 100 mg/kg). The spatial learning was assessed by Morris water maze (MWM). The expression of choline acetyltransferase (ChAT), acetylcholine (ACH), extent of histone acetylation and phosphorylation of cAMP response element-binding protein (CREB) were evaluated by Western blot assay and immunofluorescence staining. Results: Treatment of OLP at various doses showed higher number of spontaneous and rewarded alterations and lesser percentage bias compared to vehicle treated PSD rats. OLP resulted in decreased levels of ChAT and ACH, whereas the degree of histone acetylation and phosphorylation of CREB improved in dose dependent pattern. Conclusion: treatment of OLP improved PSCI via increasing the phosphorylation of CREB and histone acetylation, thus attenuating cholinergic activity.

Oleuropein Inhibits Astrocyte Damage Induced by Oxygen-Glucose Deprivation

“…According to the reports, oleuropein can ameliorate the enhancement of LDH and MDA and the reduction of SOD activity in the cerebral tissues of infarcted rats in a stroke rat model, providing neuroprotective effects on ischemic stroke through its antioxidant and antithrombotic activities [30] . Oleuropein improves cognitive function after stroke by promoting histone acetylation and phosphorylation of cyclic Adenosine 3′,5′-Monophosphate (cAMP) responsive element binding protein in middle cerebral artery occlusion rats [31] . In a rat intracerebral hemorrhage model established by collagenase injection, oleuropein treatment has shown to have overall relief of neurologic deficits and cerebral edema associated with intracerebral hemorrhage in a dose-dependent manner [32] .…”

Multivariate logistic regression analysis of clinical characteristics and risk factors of cognitive impairment after cerebral ischemic stroke: implications for clinical treatment

“…The risk of PSCI in patients with recurrent stroke is 2.7 times higher than that in patients with first stroke. The probability of developing dementia after the first stroke is 10%, while that after recurrent stroke is more than one-third ( 27 ).…”

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“…OP (100 mg/kg) was administered intraperitoneally (i.p.) [18]-every other day for four weeks after BDL. The BDL surgery group received saline (i.p.)…”