Time-dependent effects of platelet-rich plasma on the memory and hippocampal synaptic plasticity impairment in vascular dementia induced by chronic cerebral hypoperfusion

Chronic cerebral hypoperfusion (CCH) is a common pathophysiological mechanism that underlies cognitive decline and degenerative processes in dementia and other neurodegenerative diseases. Low cerebral blood flow (CBF) during CCH leads to disturbances in the homeostasis of hemodynamics and energy metabolism, which in turn results in oxidative stress, astroglia overactivation, and synaptic protein downregulation. These events contribute to synaptic plasticity and cognitive dysfunction after CCH. Tripchlorolide (TRC) is an herbal compound with potent neuroprotective effects. The potential of TRC to improve CCH-induced cognitive impairment has not yet been determined. In the current study, we employed behavioral techniques, electrophysiology, Western blotting, immunofluorescence, and Golgi staining to investigate the effect of TRC on spatial learning and memory impairment and on synaptic plasticity changes in rats after CCH. Our findings showed that TRC could rescue CCH-induced spatial learning and memory dysfunction and improve long-term potentiation (LTP) disorders. We also found that TRC could prevent CCH-induced reductions in N-methyl-D-aspartic acid receptor 2B, synapsin I, and postsynaptic density protein 95 levels. Moreover, TRC upregulated cAMP-response element binding protein, which is an important transcription factor for synaptic proteins. TRC also prevented the reduction in dendritic spine density that is caused by CCH. However, sham rats treated with TRC did not show any improvement in cognition. Because CCH causes disturbances in brain energy homeostasis, TRC therapy may resolve this instability by correcting a variety of cognitive-related signaling pathways. However, for the normal brain, TRC treatment led to neither disturbance nor improvement in neural plasticity. Additionally, this treatment neither impaired nor further improved cognition. In conclusion, we found that TRC can improve spatial learning and memory, enhance synaptic plasticity, upregulate the expression of some synaptic proteins, and increase the density of dendritic spines. Our findings suggest that TRC may be beneficial in the treatment of cognitive impairment induced by CCH.

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Embelin Improves the Spatial Memory and Hippocampal Long-Term Potentiation in a Rat Model of Chronic Cerebral Hypoperfusion

Scientific Reports ◽

10.1038/s41598-019-50954-y ◽

2019 ◽

Vol 9 (1) ◽

Cited By ~ 6

Author(s):

Saatheeyavaane Bhuvanendran ◽

Siti Najmi Syuhadaa Bakar ◽

Yatinesh Kumari ◽

Iekhsan Othman ◽

Mohd. Farooq Shaikh ◽

...

Keyword(s):

Synaptic Plasticity ◽

Spatial Memory ◽

Rat Model ◽

Long Term Potentiation ◽

Chronic Cerebral Hypoperfusion ◽

Cerebral Hypoperfusion ◽

Mrna Levels ◽

Post Surgery ◽

Term Potentiation

Abstract Alzheimer’s disease (AD) is the second most occurring neurological disorder after stroke and is associated with cerebral hypoperfusion, possibly contributing to cognitive impairment. In the present study, neuroprotective and anti-AD effects of embelin were evaluated in chronic cerebral hypoperfusion (CCH) rat model using permanent bilateral common carotid artery occlusion (BCCAO) method. Rats were administered with embelin at doses of 0.3, 0.6 or 1.2 mg/kg (i.p) on day 14 post-surgery and tested in Morris water maze (MWM) followed by electrophysiological recordings to access cognitive abilities and synaptic plasticity. The hippocampal brain regions were extracted for gene expression and neurotransmitters analysis. Treatment with embelin at the doses of 0.3 and 0.6 mg/kg significantly reversed the spatial memory impairment induced by CCH in rats. Embelin treatment has significantly protected synaptic plasticity impairment as assessed by hippocampal long-term potentiation (LTP) test. The mechanism of this study demonstrated that embelin treatment alleviated the decreased expression of BDNF, CREB1, APP, Mapt, SOD1 and NFκB mRNA levels caused by CCH rats. Furthermore, treatment with embelin demonstrated neuromodulatory activity by its ability to restore hippocampal neurotransmitters. Overall these data suggest that embelin improve memory and synaptic plasticity impairment in CCH rats and can be a potential drug candidate for neurodegenerative disease-related cognitive disorders.

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HCN Channels: From the Role in Chronic Cerebral Hypoperfusion-Induced Cognitive Impairments to a New Therapeutic Target for Vascular Dementia

Journal of Neurology & Neurophysiology ◽

10.4172/2155-9562.1000308 ◽

2015 ◽

Vol 06 (04) ◽

Author(s):

Pan Luo Lianjun Guo

Keyword(s):

Vascular Dementia ◽

Therapeutic Target ◽

Cognitive Impairments ◽

Chronic Cerebral Hypoperfusion ◽

Cerebral Hypoperfusion ◽

Hcn Channels

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Deletion of B-cell translocation gene 2 (BTG2) alters the responses of glial cells in white matter to chronic cerebral hypoperfusion

Journal of Neuroinflammation ◽

10.1186/s12974-021-02135-w ◽

2021 ◽

Vol 18 (1) ◽

Author(s):

Kaoru Suzuki ◽

Mitsuru Shinohara ◽

Yoshihiro Uno ◽

Yoshitaka Tashiro ◽

Ghupurjan Gheni ◽

...

Keyword(s):

White Matter ◽

B Cell ◽

Vascular Dementia ◽

Glial Cells ◽

White Matter Lesions ◽

Chronic Cerebral Hypoperfusion ◽

Cerebral Hypoperfusion ◽

Brdu Incorporation ◽

Wild Type

Abstract Background Subcortical ischemic vascular dementia, one of the major subtypes of vascular dementia, is characterized by lacunar infarcts and white matter lesions caused by chronic cerebral hypoperfusion. In this study, we used a mouse model of bilateral common carotid artery stenosis (BCAS) to investigate the role of B-cell translocation gene 2 (BTG2), an antiproliferation gene, in the white matter glial response to chronic cerebral hypoperfusion. Methods Btg2−/− mice and littermate wild-type control mice underwent BCAS or sham operation. Behavior phenotypes were assessed by open-field test and Morris water maze test. Brain tissues were analyzed for the degree of white matter lesions and glial changes. To further confirm the effects of Btg2 deletion on proliferation of glial cells in vitro, BrdU incorporation was investigated in mixed glial cells derived from wild-type and Btg2−/− mice. Results Relative to wild-type mice with or without BCAS, BCAS-treated Btg2−/− mice exhibited elevated spontaneous locomotor activity and poorer spatial learning ability. Although the severities of white matter lesions did not significantly differ between wild-type and Btg2−/− mice after BCAS, the immunoreactivities of GFAP, a marker of astrocytes, and Mac2, a marker of activated microglia and macrophages, in the white matter of the optic tract were higher in BCAS-treated Btg2−/− mice than in BCAS-treated wild-type mice. The expression level of Gfap was also significantly elevated in BCAS-treated Btg2−/− mice. In vitro analysis showed that BrdU incorporation in mixed glial cells in response to inflammatory stimulation associated with cerebral hypoperfusion was higher in Btg2−/− mice than in wild-type mice. Conclusion BTG2 negatively regulates glial cell proliferation in response to cerebral hypoperfusion, resulting in behavioral changes.

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