Prostaglandin E1 Alleviates Cognitive Dysfunction in Chronic Cerebral Hypoperfusion Rats by Improving Hemodynamics

Abstract

Compensatory vascular mechanisms can restore cerebral blood flow (CBF) but fail to protect against chronic cerebral hypoperfusion (CCH)-mediated neuronal damage and cognitive impairment. Prostaglandin E1 (PGE1) is known as a vasodilator to protect against ischemic injury in animal models, but its protective role in CCH remains unclear. To determine the effect of PGE1 on cerebral hemodynamics and cognitive functions in CCH, bilateral common carotid artery occlusion (BCCAO) was used to mimic CCH in rats, which were subsequently intravenously injected with PGE1 daily for 2 weeks. Magnetic resonance imaging, immunofluorescence staining and Morris water maze (MWM) were used to evaluate CBF, angiogenesis, and cognitive functions, respectively. We found that PGE1 treatment significantly restored CBF by enhancing vertebral artery dilation. In addition, PGE1 treatment increased the number of microvascular endothelial cells and neuronal cells in the hippocampus, and decreased the numbers of astrocyte and apoptotic cells. In the MWM test, we further showed that the escape latency of CCH rats was significantly reduced after PGE1 treatment. Our results suggest that PGE1 ameliorates cognitive dysfunction in CCH rats by enhancing CBF recovery, sustaining angiogenesis, and reducing astrocyte activation and neuronal loss.

Selective neurodegeneration of the hippocampus caused by chronic cerebral hypoperfusion: F-18 FDG PET study in rats

“…Another previous F-18 FDG PET study in a CCH mouse model revealed that glucose metabolism in the hippocampus, as well as in the cortex, decreased for up to 6 months after applying microcoils to bilateral CCA, but selective vulnerability to ischemia was not detected in the hippocampus [ 33 ]. This may be because the compensation mechanisms for the recovery of CBF were not more extensive in mice than in rats, and the sustained decrease in CBF in the cortex affected the decrease in cerebral glucose metabolism [ 36 , 37 ].…”

PGE1 triggers Nrf2/HO-1 signal pathway to resist hemin-induced toxicity in mouse cortical neurons

“…The effect of PGE1 on cytoprotection has been widely reported in preclinical models, but the underlying molecular mechanism needs to be clarified (42,43). Combined with lithium, PGE1 exerted significant roles in a rat cerebral ischemia model (12). Moreover, PGE1 is also reported to prevent neuronal apoptosis in the superficial dorsal horn following chronic constriction of the sciatic nerve in rats (17).…”

“…For the therapy of patients with peripheral arterial occlusive disease, PGE1 has played broad roles in clinical practices (9,10). Clinical and pre-clinical evidence showed the benefits of PGE1 on curing ischemic heart disease and cerebral ischemia (8,(11)(12)(13). We have previously tried to use PGE1 to treat ICH patients in the clinic and have achieved positive protective results (14).…”

Effects of cerebral hypoperfusion on the cerebral white matter: a meta‑analysis

“…In the other nine cases, the most common carotid arteries (CCAs) were operated for inducing cerebral hypoperfusion (9/13). Five studies conducted suture ligation, (Ouchi et al, 1998;Ohmori et al, 2011;Kitamura et al, 2012;Park et al, 2019;Xie et al, 2019) and four studies used micro-coils with an inner diameter of 0.18 mm (Shibata et al, 2004;Nishio et al, 2010;Patel et al, 2017;Dominguez et al, 2018). One study used facial vein ligation with sutures for inducing cerebral hypoperfusion (Chen et al, 2009).…”