Chronic cerebral hypoperfusion-induced memory impairment and hippocampal long-term potentiation deficits are improved by cholinergic stimulation in rats

Damodaran, Thenmoly; Müller, Christian P.; Hassan, Zurina

doi:10.1016/j.pharep.2019.01.012

Cited by 37 publications

(20 citation statements)

References 42 publications

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“…3 Deficits in cholinergic neurotransmission have also been considered as a common pathogenic factor of AD and VaD. 4 Studies have reported that patients with VaD exhibit cholinergic deficiency, 5,6 including decreased levels of acetylcholine (ACh) and cholinergic markers, such as choline acetyltransferase (ChAT), acetylcholinesterase (AChE), and vesicular acetylcholine transporter (VAChT), in the brain. One study reported a loss of cholinergic neurons in 40% of VaD patients, which was accompanied by reduced ACh in the cortex, hippocampus, striatum, and cerebrospinal fluid.…”

Section: Introductionmentioning

confidence: 99%

Dl-3-n-butylphthalide regulates cholinergic dysfunction in chronic cerebral hypoperfusion rats

Sun

Zhao

et al. 2020

J Int Med Res

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Objectives To investigate whether dl-3-n-butylphthalide (NBP) affects cholinergic system function and ameliorates cognitive decline in a rat model of vascular dementia (VaD). Methods The VaD rat model was established by bilateral common carotid artery ligation (two-vessel occlusion, 2VO). Rats were divided into five groups: control, sham, 2VO, 2VO+NBP (80 mg/kg; intragastric), and 2VO+donepezil (1 mg/kg; intragastric). Treatments were administered once daily for 2 weeks from day 21 post-surgery. Spatial learning and memory were evaluated by Morris water maze performance. Hippocampal choline acetyltransferase (ChAT), acetylcholinesterase (AChE), vesicular acetylcholine transporter (VAChT), vascular endothelial growth factor (VEGF), and brain-derived neurotrophic factor (BDNF) expressions were detected using immunohistochemistry, immunofluorescence, and real-time polymerase chain reaction methods. Results The daily escape latency was significantly longer in 2VO rats than in the sham or control groups, while the time spent in the target quadrant was significantly shorter. The daily escape latency of the 2VO+NBP group was significantly shorter compared with the 2VO group. Following NBP treatment, ChAT, AChE, VAChT, and BDNF expressions were significantly upregulated in the hippocampus. Conclusions Central cholinergic dysfunction may be involved in VaD pathogenesis. NBP treatment significantly improved spatial learning and memory in VaD rats, and may enhance cholinergic system function via BDNF-mediated neuroprotection.

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Section: Introductionmentioning

confidence: 99%

Dl-3-n-butylphthalide regulates cholinergic dysfunction in chronic cerebral hypoperfusion rats

Sun

Zhao

et al. 2020

J Int Med Res

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“…[ 30 ] The 2VO model has been widely reported to exhibit spatial learning and reference memory impairment due to the poor performance in Morris water maze task. [ 6–8,18 ] In this study, the 2VO rats had impaired learning and memory as in MWM they showed slower learning compared to the sham‐operated group. Hippocampus is the key structure for spatial learning and memory, and it is also one of the most susceptible regions to hypoperfusion, particularly in CA1 area.…”

Section: Discussionmentioning

confidence: 63%

“…Furthermore, the increasing synaptic strength was not maintained in 2VO rats after TBS and fell gradually throughout 2 h. Similar findings were found in other studies. [ 8,18,44,45 ] The result suggested that proteins involved in the synaptic plasticity might be attenuated in 2VO hippocampus rats. Thus, it can be speculated that neuronal damage might cause low expression of BDNF in the hippocampus of 2VO as seen in Western blot experiments and develop weak synaptic transmission as shown in LTP results.…”

Section: Discussionmentioning

confidence: 99%

“…After the incision was sutured, wound gel octenilin (Schulke & Mayr UK Ltd, Sheffield, UK) was applied on the incision area to prevent wound infection and the rats were kept individually in a transparent small cage to allow monitoring and recovery period for 7 days before the rats were pooled into a big cage that housed 5–7 rats per cage. [ 6,8,18 ] About 10% of the total rats subjected to 2VO developed drastic reductions in body weight and eye infections were excluded from the study.…”

Section: Methodsmentioning

confidence: 99%

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Xanthone-enriched fraction of Garcinia mangostana and α-mangostin improve the spatial learning and memory of chronic cerebral hypoperfusion rats

Tiang

Ahad

Murugaiyah

et al. 2020

Journal of Pharmacy and Pharmacology

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Objectives Xanthones isolated from the pericarp of Garcinia mangostana has been reported to exhibit neuroprotective effect. Methods In this study, the effect of xanthone-enriched fraction of Garcinia mangostana (XEFGM) and a-mangostin (a-MG) were investigated on cognitive functions of the chronic cerebral hypoperfusion (CCH) rats. Key findings HPLC analysis revealed that XEFGM contained 55.84% of a-MG. Acute oral administration of XEFGM (25, 50 and 100 mg/kg) and a-MG (25 and 50 mg/kg) before locomotor activity and Morris water maze (MWM) tests showed no significant difference between the groups for locomotor activity. Conclusions However, a-MG (50 mg/kg) and XEFGM (100 mg/kg) reversed the cognitive impairment induced by CCH in MWM test. a-MG (50 mg/kg) was further tested upon sub-acute 14-day treatment in CCH rats. Cognitive improvement was shown in MWM test but not in long-term potentiation (LTP). BDNF but not CaMKII was found to be down-regulated in CCH rats; however, both parameters were not affected by a-MG. In conclusion, a-MG ameliorated learning and memory deficits in both acute and sub-acute treatments in CCH rats by improving the spatial learning but not hippocampal LTP. Hence, a-MG may be a promising lead compound for CCH-associated neurodegenerative diseases, including vascular dementia and Alzheimer's disease.

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“…Chronic cerebral hypoperfusion (CCH) is a pathological state that usually occurs in brain diseases, such as Alzheimer's disease and vascular Parkinsonism, leading to cognitive impairment (Saggu et al, 2016). Recent studies have highlighted two typical pathological features of the chronically hypo-perfused brain are white matter injury and neuronal loss in the cerebral cortex and hippocampus (Damodaran et al, 2019;Roman et al, 2002;Yao et al, 2019). Further research found that in bilateral common carotid artery surgery (BCAS) mice, inhibiting the microglial inflammatory activation or altering microglial polarization decreased white matter injury and improved cognitive function (Miyanohara et al, 2018;Qin et al, 2017;Yao et al, 2019).…”

Section: Introductionmentioning

confidence: 99%

The Chinese herb Fructus Broussonetiae aids learning and memory in chronic cerebral hypoperfusion by reducing proinflammatory microglia activation in rats

Liu

Wang

et al. 2020

J. Integr. Neurosci.

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The neuroprotective role of Fructus Broussonetiae in a model of chronic cerebral hypoperfusion with cognitive decline was focused on neural plasticity and microglia/macrophage polarization. Chronic cerebral hypoperfusion was induced by bilateral common carotid artery ligation. Fructus Broussonetiae shortened escape latency and added the number of platform crossings of rats, up-regulated the expression of synaptophysin in the gray matter and increased myelin basic protein expression in the white matter. Further mechanistic experiments were conducted to examine microglia activation and M1/M2 polarization. It was shown that Fructus Broussonetiae reduced the activation of microglia revealed by decreased expression of ionized calcium-binding adapter molecule-1, inhibited M1 polarization of microglia and improved microglial M2 polarization shown by down-regulated the expression of inducible nitric oxide synthase and Fc fragment of IgG receptor IIIa and up-regulated the expression of arginase-1. In conclusion, the Chinese herb Fructus Broussonetiae can improve cognitive function following chronic cerebral hypoperfusion by down-regulating the activation of microglia, inhibiting microglial M1 polarization, and improving neural plasticity.

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Chronic cerebral hypoperfusion-induced memory impairment and hippocampal long-term potentiation deficits are improved by cholinergic stimulation in rats

Cited by 37 publications

References 42 publications

Dl-3-n-butylphthalide regulates cholinergic dysfunction in chronic cerebral hypoperfusion rats

Dl-3-n-butylphthalide regulates cholinergic dysfunction in chronic cerebral hypoperfusion rats

Xanthone-enriched fraction of Garcinia mangostana and α-mangostin improve the spatial learning and memory of chronic cerebral hypoperfusion rats

The Chinese herb Fructus Broussonetiae aids learning and memory in chronic cerebral hypoperfusion by reducing proinflammatory microglia activation in rats

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