Huperzine A attenuates cognitive deficits and brain injury in neonatal rats after hypoxia–ischemia

Wang, Lai Shuan; Zhou, Jin; Shao, Xiao M.; Tang, Xi

doi:10.1016/s0006-8993(02)02977-3

Cited by 59 publications

(35 citation statements)

References 23 publications

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“…Rats treated with HupA at doses of 0.05 or 0.1 mg/kg ip for 5 weeks after HI injury performed better than saline-treated HI rats, and neuronal damage in the ipsilateral hemisphere was attenuated ( Figure 7). These findings suggest that HupA might be beneficial in the treatment of HI encephalopathy in adults and neonates [83] .…”

Section: It Is Well-documented That N-methyl-d-aspartatementioning

confidence: 72%

Progress in studies of huperzine A, a natural cholinesterase inhibitor from Chinese herbal medicine1

Rui

Yan

Tang

2006

Acta Pharmacologica Sinica

411

223

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Huperzine A (HupA), a novel alkaloid isolated from the Chinese herb Huperzia serrata, is a potent, highly specific and reversible inhibitor of acetylcholinesterase (AChE). Compared with tacrine, donepezil, and rivastigmine, HupA has better penetration through the blood-brain barrier, higher oral bioavailability, and longer duration of AChE inhibitory action. HupA has been found to improve cognitive deficits in a broad range of animal models. HupA possesses the ability to protect cells against hydrogen peroxide, β-amyloid protein (or peptide), glutamate, ischemia and staurosporine-induced cytotoxicity and apoptosis. These protective effects are related to its ability to attenuate oxidative stress, regulate the expression of apoptotic proteins Bcl-2, Bax, P53, and caspase-3, protect mitochondria, upregulate nerve growth factor and its receptors, and interfere with amyloid precursor protein metabolism. Antagonizing effects of HupA on N-methyl-D-aspartate receptors and potassium currents may also contribute to its neuroprotection as well. Pharmacokinetic studies in rodents, canines, and healthy human volunteers indicated that HupA was absorbed rapidly, distributed widely in the body, and eliminated at a moderate rate with the property of slow and prolonged release after oral administration. Animal and clinical safety tests showed that HupA had no unexpected toxicity, particularly the dose-limiting hepatotoxicity induced by tacrine. The phase IV clinical trials in China have demonstrated that HupA significantly improved memory deficits in elderly people with benign senescent forgetfulness, and patients with Alzheimer disease and vascular dementia, with minimal peripheral cholinergic side effects and no unexpected toxicity. HupA can also be used as a protective agent against organophosphate intoxication.

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Section: It Is Well-documented That N-methyl-d-aspartatementioning

confidence: 72%

Progress in studies of huperzine A, a natural cholinesterase inhibitor from Chinese herbal medicine1

Rui

Yan

Tang

2006

Acta Pharmacologica Sinica

411

223

View full text Add to dashboard Cite

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“…Similarly, in a gerbil model of transient global ischemia, huperzine A administration significantly reduced memory impairment and neuronal degeneration in the CA1 region of the hippocampus and partially restored hippocampal ChAT activity [83] . Moreover, huperzine A treatment showed significant protection from neuropathology damage and associated behavior in the hypoxic-ischemic neonatal rat model [84] , the transient cerebral ischemia and reperfusion mice model [85] , and the MCAO rat model [48] .…”

Section: Acetylcholinesterase Inhibitorsmentioning

confidence: 97%

Cholinergic deficiency involved in vascular dementia: possible mechanism and strategy of treatment

2009

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Vascular dementia (VaD) is a progressive neurodegenerative disease with a high prevalence. Several studies have recently reported that VaD patients present cholinergic deficits in the brain and cerebrospinal fluid (CSF) that may be closely related to the pathophysiology of cognitive impairment. Moreover, cholinergic therapies have shown promising effects on cognitive improvement in VaD patients. The precise mechanisms of these cholinergic agents are currently not fully understood; however, accumulating evidence indicates that these drugs may act through the cholinergic anti-inflammatory pathway, in which the efferent vagus nerve signals suppress pro-inflammatory cytokine release and inhibit inflammation, although regulation of oxidative stress and energy metabolism, alleviation of apoptosis may also be involved. In this paper, we provide a brief overview of the cholinergic treatment strategy for VaD and its relevant mechanisms of anti-inflammation.

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“…In models of hypoxia-ischemia, unilateral ligature of the carotid artery in postnatal day (P) 7 rats followed by hypoxia induced delayed appearance and development of neurological reflexes, as well as motor and memory disorders by up to 5 weeks [13,14]. Maternal hypoxia during pregnancy has been shown to delay the development of motor reflexes in newborn mice [15].…”

Section: Introductionmentioning

confidence: 99%

Maternal Exposure to Lipopolysaccharide Leads to Transient Motor Dysfunction in Neonatal Rats

Rousset

Kassem²,

Aubert³

et al. 2013

Dev Neurosci

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Epidemiological and experimental data implicate maternal infection and inflammation in the etiology of brain white matter injury, which may lead to cerebral palsy in preterm newborns. Our aim was to investigate motor development of the offspring after maternal administration of lipopolysaccharide (LPS). Wistar rats were intraperitoneally injected with Escherichia coli LPS or saline on gestational days 19 and 20. From birth to 3 weeks, pups were tested for neurobehavioral development, neurological signs and reflexes. From 3 to 6 weeks, motor coordination was investigated. At 4 months, animals were tested for locomotion. Brain myelination was assessed by myelin basic protein immunohistochemistry. Days of appearance of several neurological reflexes were significantly delayed, and neonate LPS pups displayed retarded performance in righting, gait and negative geotaxis. At the juvenile stage, LPS animals showed important impairment in coordination. However, although the LPS group performed worse in most tests, they reached vehicle levels by 5 weeks. At 4 months, LPS animals did not show variations in locomotion performances compared to vehicle. No myelination differences have been observed in the brains at adulthood. Maternal LPS administration results in delayed motor development even though these alterations fade to reach control level by 5 weeks. Motor impairments observed at the early stage in this study could be linked to previously reported hypomyelination of the white matter induced by maternal LPS challenge in the neonates. Finally, the normal myelination shown here at adulthood may explain the functional recovery of the animals and suggest either a potential remyelination of the brain or a delayed myelination in LPS pups.

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Huperzine A attenuates cognitive deficits and brain injury in neonatal rats after hypoxia–ischemia

Cited by 59 publications

References 23 publications

Progress in studies of huperzine A, a natural cholinesterase inhibitor from Chinese herbal medicine1

Progress in studies of huperzine A, a natural cholinesterase inhibitor from Chinese herbal medicine1

Cholinergic deficiency involved in vascular dementia: possible mechanism and strategy of treatment

Maternal Exposure to Lipopolysaccharide Leads to Transient Motor Dysfunction in Neonatal Rats

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