(-)-SCR1693 Protects against Memory Impairment and Hippocampal Damage in a Chronic Cerebral Hypoperfusion Rat Model

Abstract

Chronic cerebral hypoperfusion (CCH) is one of the most common causes of vascular dementia (VaD) and is recognised as an etiological factor in the development of Alzheimer’s disease (AD). CCH can induce severe cognitive deficits, as assessed by the water maze task, along with neuronal loss in the hippocampus. However, there are currently no effective, approved pharmacological treatments available for VaD. In the present study, we created a rat model of CCH using bilateral common carotid artery occlusion and found that (-)-SCR1693, a novel compound, prevented rats from developing memory deficits and neuronal damage in the hippocampus by rectifying cholinergic dysfunction and decreasing the accumulation of the phospho-tau protein. These results strongly suggest that (-)-SCR1693 has therapeutic potential for the treatment of CCH-induced VaD.

Methanolic extract of Tamarix Gallica attenuates hyperhomocysteinemia induced AD-like pathology and cognitive impairments in rats

“…Moreover, TG antagonized tau hyperphosphorylation, decreased Aβ production, attenuated synaptic impairments and neuroinflammation induced by HHcy. In a similar setting with our study, SCR1693, a synthesized hybrid compound composed of an acetylcholinesterase inhibitor (AChEI) and a calcium channel blocker (CCB) was previously found to improve memory impairments [53,54], cell death and hippocampal neuron loss [55], inhibited Aβ production and induced tau dephosphorylation [35]. Therefore, we used this compound as a positive control.…”

Clinical and Pathological Benefit of Twendee X in Alzheimer's Disease Transgenic Mice with Chronic Cerebral Hypoperfusion

“…CCH is one major cause of vascular dementia, but is also an important risk factor of AD progression. 13 Our previous studies suggested that CCH enhanced neurodegenerative processes by promoting oxidative stress and neuroinflammation. [7][8] Since hippocampal neurons are critically important for memory function, 14 the positive effect on working memory (Fig.…”

Combination of isoflurane and propofol, a means for general anesthesia in the orthopedic surgery of perioperative cerebral hypoperfusion rats to avoid cognitive impairment Anesthesia of perioperative cerebral hypoperfusion

“…We speculate that although neurons are still alive, some cognitive-related functional structures may have changed, which in turn affects behavioral outcomes. As it has been described that, under chronic cerebral hypoperfusion, synaptic connectivity failure in the hippocampus could result in less efficient learning or memory [28]. Or perhaps some of the damage has already occurred during anesthesia, but it needs time to accumulate enough to kill the neurons.…”