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(S)-Oxiracetam is the Active Ingredient in Oxiracetam that Alleviates the Cognitive Impairment Induced by Chronic Cerebral Hypoperfusion in Rats.

ABSTRACT: Chronic cerebral hypoperfusion is a pathological state that is associated with the cognitive impairments in vascular dementia. Oxiracetam is a nootropic drug that is commonly used to treat cognitive deficits of cerebrovascular origins. However, oxiracetam is currently used as a racemic mixture whose effective ingredient has not been identified to date. In this study, we first identified that (S)-oxiracetam, but not (R)-oxiracetam, was the effective ingredient that alleviated the impairments of spatial learning and memory by ameliorating neuron damage and white matter lesions, increasing the cerebral blood flow, and inhibiting astrocyte activation in chronic cerebral hypoperfused rats. Furthermore, using MALDI-MSI and LC-MS/MS, we demonstrated that (S)-oxiracetam regulated ATP metabolism, glutamine-glutamate and anti-oxidants in the cortex region of hypoperfused rats. Altogether, our results strongly suggest that (S)-oxiracetam alone could be a nootropic drug for the treatment of cognitive impairments caused by cerebral hypoperfusion.

SUBMITTER: Li W

PROVIDER: S-EPMC5577264 | biostudies-literature | 2017 Aug

REPOSITORIES: biostudies-literature

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(S)-Oxiracetam is the Active Ingredient in Oxiracetam that Alleviates the Cognitive Impairment Induced by Chronic Cerebral Hypoperfusion in Rats.

Li Wan W Liu Huihui H Jiang Hanjie H Wang Chen C Guo Yongfei Y Sun Yi Y Zhao Xin X Xiong Xin X Zhang Xianhua X Zhang Ke K Nie Zongxiu Z Pu Xiaoping X

Scientific reports 20170830 1

Chronic cerebral hypoperfusion is a pathological state that is associated with the cognitive impairments in vascular dementia. Oxiracetam is a nootropic drug that is commonly used to treat cognitive deficits of cerebrovascular origins. However, oxiracetam is currently used as a racemic mixture whose effective ingredient has not been identified to date. In this study, we first identified that (S)-oxiracetam, but not (R)-oxiracetam, was the effective ingredient that alleviated the impairments of s ...[more]

PMID: 28855592

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Project description:Objective:Currently, most models of vascular cognitive impairment are established by occluding the carotid arteries uni- or bilaterally to reduce the cerebral blood flow mimicking chronic cerebral hypoxia. Due to the sudden blood flow interruption, a gradual narrowing of the carotid artery cannot be completely imitated. This paper aims to establish a bilateral carotid stenosis model with mild cognitive dysfunction and mild white matter changes to simulate patients with vascular predementia. Methods:Aged Wistar rats (18 months old) underwent either bilateral common carotid artery stenosis (BCAS) or occlusion (BCAO) surgery or a sham operation (control group). The cerebral blood flow in the frontal cortex was measured using Doppler flowmetry. Thirty days after surgery, cognitive function impairments were determined with the Morris water maze; cerebral magnetic resonance imaging was performed to detect changes in fractional anisotropy to assess white matter injuries, and histological studies were performed. Results:The aged rats in the BCAS group showed a more gradual cerebral blood flow reduction and a lower mortality rate (11%) compared to rats in the BCAO group. The water maze test revealed a more marginal impairment affecting spatial learning and memory in rats with BCAS than in rats with BCAO. Diffusion tensor imaging detected white matter injuries in the hippocampus and cerebral cortex of BCAS rats. Particularly, a small portion of nerve fibers of the lateral somatosensory cortex was significantly different between rats of the BCAO and BCAS groups. In the BCAS group, the microscopic structure of the hippocampal CA1 region changed slightly after 30 days and sustained a slight mitochondrial crista crack. Fluorescence staining indicated that the number of GFAP-positive cells was increased in rat brains of the BCAS group, and this phenomenon was even more pronounced in the BCAO group. The hnRNPA2/B1 and GABAAR-?1 expression levels were significantly decreased in the hippocampus of rats with BCAS compared to those of controls. Conclusion:Severe bilateral carotid stenosis induced mild cognitive dysfunction and slight structural changes in the brains of aged rats. Thus, a chronic cerebral hypoperfusion model was successfully established.

Dataset Information

(S)-Oxiracetam is the Active Ingredient in Oxiracetam that Alleviates the Cognitive Impairment Induced by Chronic Cerebral Hypoperfusion in Rats.

Publications

(S)-Oxiracetam is the Active Ingredient in Oxiracetam that Alleviates the Cognitive Impairment Induced by Chronic Cerebral Hypoperfusion in Rats.

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