ABSTRACT
To study the cognitive effects of diterpene ginkgolides (DG), transient middle cerebral artery occlusion (tMCAO)-induced rats were established. tMCAO-rats induced by suture method were divided into sham operation group, solvent control group, NBP group, DG group. The animal experiments in the present study were performed in accordance with the Ethical Guidelines of the Laboratory Animal Welfare Ethical Committee of Peking Union Medical College (00000646, 00000635). The effects of DG on tMCAO rats were evaluated by neurological severity score, cerebral infarction volume measurement, step-down and Morris water maze test. In the acute tMCAO rat model, 100 mg·kg-1 DG improved the neural score and infarction volume. In the chronic tMCAO rat model, DG 100 mg·kg-1 significantly improved the survival rate of tMCAO-induced rats. The Morris water maze results showed 100 mg·kg-1 DG decreased the latency of tMCAO-induced rats to find the platform, while the effect was weaker than the NBP. However, DG 30 mg·kg-1 did not show a significant effect. In conclusion, DG exerted a therapeutic effect on transient middle cerebral artery occlusion.
ABSTRACT
To compare the neuroprotective and anti-dementia pharmacological effects of chiral oxiracetam, glutamate and calcium ions were used to establish neuronal injury models in vitro, and the protective effects of chiral oxiracetam on primary neurons were assayed by MTT. Permanent bilateral common carotid artery occlusion (2-VO)-induced rats were randomly divided into sham group, model group, galantamine 3 mg‧kg-1 group, oxiracetam groups (30, 100 and 200 mg‧kg-1), S-oxiracetam groups (30, 100 and 200 mg‧kg-1) and R-oxiracetam 200 mg‧kg-1 group. The animal experiments in the present study were performed in accordance with the Ethical Guidelines of the Laboratory Animal Welfare Ethical Committee of Peking Union Medical College. Morris water maze and step-down test were applied to evaluate the cognitive dysfunction induced by cerebral hypoperfusion in rats. Oxiracetam, S-oxiracetam and R-oxiracetam exerted protective effects on primary neuronal damage caused by various stimuli, and oxiracetam and S-oxiracetam showed better neuro-protective effects. Morris water maze and step-down results showed that oxiracetam, S-oxiracetam and R-oxiracetam improved the cognition of 2-VO rats. In summary, S-oxiracetam exerted a better neuro-protective effect than oxiracetam and R-oxiracetam.
ABSTRACT
The rat models of focal cerebral ischemic reperfusion and subarachnoid hemorrhage were used to evaluate the therapeutic effects of artificial musk to provide support for its clinical application. All animal experiments were performed following the regulations of the Animal Ethics Committee of Peking Union Medical College. The results showed that oral administration of artificial musk had significant protective effects on acute ischemic and hemorrhagic stroke. In the dose range of 10-200 mg·kg-1, the mortality, neurobehavioral and cerebral infarction volume of rats in model group indicated a clear dose dependent relationship. The effective dose of artificial musk is 10 mg·kg-1 in ischemic stroke and 200 mg·kg-1 in hemorrhagic stroke. These findings suggest that the treatments of artificial musk in ischemic stroke and in hemorrhagic stroke are different, and such differences should be noted for its clinical use.
ABSTRACT
Gastrodin, parishin and parishin C were purified from a water extract of GE (rhizome of Gastrodia elata, an herb medicine for treatment of neuronal disorders). In order to compare the pharmacological effects of gastrodin, parishin and parishin C on improving cognition deficits, we tested them in an animal model of cognition disorders induced by scopolamine and in a study of in vivo long-term potentiation (LTP) recordings. In the Morris water maze task, parishin C (15 and 50 mg·kg-1, P -1, P -1. In vivo LTP recordings showed that parishin C at 5, 10 and 20 mg·kg-1, parishin at 10, 30 and 100 mg·kg-1 reversed the suppression of LTP by scopolamine in rats in a dose-dependent manner. However, gastrodin at 100 mg·kg-1 showed only a modest effect. In summary, the action of parishin C in the improvement of dementia induced by scopolamine was more potent than parishin and gastrodin.
ABSTRACT
<p><b>OBJECTIVE</b>To investigate the effect of specific blockage of mutant p53 gene by individualized antisense RNA in vitro.</p><p><b>METHODS</b>Mutation status of p53 in human breast cancer cell lines was determined by immunocytochemical staining, PCR-SSCP and sequencing. Single strand antisense transcription system targeting specific p53 mutation site (mt-p53) was constructed, and corresponding antisense RNA was prepared. The hybridization of antisense RNA with its corresponding mt-p53 gene was confirmed by in-situ hybridization. Human breast cancer cells were transfected with antisense RNA by cationic liposome-mediated method. Time course of effects of antisense RNA was investigated by immunocytochemical staining and cell growth inhibiting assay. Expression of mt-p53 protein was examined by Western blot. Cell proliferation was evaluated by MTT assay and cell cycle distribution was determined by flow cytometry (FCM). Apoptosis was determined by TUNEL assay.</p><p><b>RESULTS</b>Mutation of p53 exon 8 was found in MDA-MB-231 cells and antisense transcription system (pGEM3zf (+/-) p53exon8) was then constructed successfully. In transfected MDA-MB-231 cells, hybridization signals were observed in cytoplasm. Fourth-eight hours after transfection, the antisense RNA (ASp53exon8'RNA) had a significant retarding effect on p53 related proliferation inhibition, along with a decrease of p53 protein expression.</p><p><b>CONCLUSIONS</b>ASp53exon8'RNA specifically blocks mt-p53 gene expression, resulting in an inhibition of MDA-MB-231 cell proliferation. Such an approach may be used as a therapeutic option against human malignancy.</p>
Subject(s)
Female , Humans , Apoptosis , Base Sequence , Breast Neoplasms , Metabolism , Pathology , Cell Line, Tumor , Cell Proliferation , Codon , Gene Expression Regulation, Neoplastic , Molecular Sequence Data , Mutation , Plasmids , RNA, Antisense , Recombinant Proteins , Metabolism , Transfection , Tumor Suppressor Protein p53 , Genetics , MetabolismABSTRACT
<p><b>AIM</b>To study the effects of tacrine on IK and IA potassium current in primary cultured rat hippocampal neurons.</p><p><b>METHODS</b>Whole cell patch clamp and primary rat hippocampal neuron cultures were used.</p><p><b>RESULTS</b>Tacrine was shown to reduce the amplitude of IK and IA, in concentration-dependent manners. The IC50s at +40 mV for reduction of IK and IA were 23 and 52.6 mumol.L-1, respectively. Tacrine (30 mumol.L-1) shifted the steady state activation of IK and IA to negative potentials by 12 and 15 mV, respectively. The V1/2 of activation curves for IK current before and after the application of tacrine were (6.7 +/- 1.4) mV and (-5.4 +/- 1.3) mV, respectively. The k of activation curves for IK current was 13.4 + 1.3 and 12.5 + 1.4 without and with tacrine, respectively. The V1/2 of activation curve for IA current were (-9.9 +/- 2.6) mV and (-24 +/- 5) mV in the absence and presence of tacrine, respectively, and the k value was not changed.</p><p><b>CONCLUSION</b>Tacrine inhibited IK and IA currents in rat hippocampal neurons and it is more potent for blocking IK.</p>
Subject(s)
Animals , Female , Male , Rats , Animals, Newborn , Cells, Cultured , Cholinesterase Inhibitors , Pharmacology , Hippocampus , Cell Biology , Physiology , Neurons , Cell Biology , Physiology , Patch-Clamp Techniques , Potassium Channels , Potassium Channels, Inwardly Rectifying , Rats, Wistar , Tacrine , PharmacologyABSTRACT
<p><b>AIM</b>To study the effects of 17beta-estradiol on Kv2.1 potassium channel current and delayed rectifier potassium current (IK) in cultured rat hippocampal neurons.</p><p><b>METHODS</b>The effects of 17beta-estradiol on Kv2.1 channel current and IK in cultured rat hippocampal neurons were observed using the whole cell patch clamp techniques.</p><p><b>RESULTS</b>17beta-Estradiol was shown to reduce the amplitude of Kv2.1 current and IK in concentration-dependent manners. The IC50s of 17beta-estradiol blocking Kv2.1 and IK were 2.4 and 4.0 micromol x L(-1), respectively. 17beta-Estradiol (3 micromol x l(-1)) significantly shifted the steady-state activation and inactivation curves of Kv2.1 current to negative potentials. However, it only produced the shift of the steady-state activation curve of IK to the negative potential without effect on the steady-state inactivation of IK.</p><p><b>CONCLUSION</b>17beta-Estradiol inhibits Kv2.1 and IK of hippocampus at similar level. The inhibition of 17beta-estradiol on IK current may be partially via blocking Kv2.1 current.</p>