Neuroprotective Agents

PURPOSE: The aim of this study was to investigate the potential effects of mild hypoxia in the mature and immature brain. METHODS: We prepared organotypic slice cultures of the hippocampus and used hippocampal tissue cultures at 7 and 14 days in vitro (DIV) to represent the immature and mature brain, respectively. Tissue cultures were exposed to 10% oxygen for 60 minutes. Twenty-four hours after this hypoxic insult, propidium iodide fluorescence images were obtained, and the damaged areas in the cornu ammonis 1 (CA1), CA3, and dentate gyrus (DG) were measured using image analysis. RESULTS: In the 7-DIV group compared to control tissue, hypoxia-exposed tissue showed decreased damage in two regions (CA1: 5.59%+/-2.99% vs. 4.80%+/-1.37%, P=0.900; DG: 33.88%+/-12.53% vs. 15.98%+/-2.37%, P=0.166), but this decrease was not statistically significant. In the 14-DIV group, hypoxia-exposed tissue showed decreased damage compared to control tissues; this decrease was not significant in the CA3 (24.51%+/-6.05% vs. 18.31%+/-3.28%, P=0.373) or DG (15.72%+/-3.47% vs. 9.91%+/-2.11%, P=0.134), but was significant in the CA1 (50.91%+/-5.90% vs. 32.30%+/-3.34%, P=0.004). CONCLUSION: Although only CA1 tissues cultured for 14 DIV showed significantly less damage after exposure to hypoxia, the other tissues examined in this study showed a tendency towards less damage after hypoxic exposure. Therefore, mild hypoxia might play a protective role in the brain.
Anoxia* ; Brain ; Dentate Gyrus ; Fluorescence ; Hippocampus ; Neuroprotective Agents* ; Oxygen ; Propidium

The function of erythropoietin (EPO) is recognized as a stimulator for proliferation of red blood cell (RBC), however,recent studies have showed that EPO and EPO-R are widely distributed in nervous system, which indicates that it may also have important functions in nervous system. Studies proved its neuroprotective effects, especially in ischemic-hypoxic nerve tissues. These effects are mainly activated through several signal transduction pathway downstream and multiple mechanisms are involved. As a neuroprotective factor, EPO has been investigated in the clinical studies, which may lead to the clinical application in the future.
Erythropoietin ; metabolism ; physiology ; Humans ; Neurophysiology ; Neuroprotective Agents ; Signal Transduction

BACKGROUND: The present study was performed in order to evaluate the duration-dependent neuroprotective effect of post-ischemic mild hypothermia against delayed neuronal damage following transient global ischemia and to estimate the optimal duration of brief post-ischemic mild hypothermia. METHODS: Post-ischemic mild hypothermia of different duration(1 hour, 3 hours, and 6 hours) was performed immediately after 10-minute global ischemia in gerbils, and the hippocampal CA1 cell loss after 3 days was evaluated. The duration-dependent neuroprotective effect of post-ischemic mild(33-34degrees C) hypothermia of each duration was compared to the normothermic control by using histopathological methods. RESULTS: 1, 3 and 6 hours of mild hypothermia immediately following reperfusion resulted in progressively increased protection from ischemic damage, 10.0+/-8.2%, 33.7+/-21.9%, and 75.9+/-13.4%, respectively. The 3-hour and the 6-hour post-ischemic mild hypothermia groups revealed significant decreases in hippocampal CA1 area cell loss compared to the normothermic control group(9.0+/-7.7%, p<0.05), and the 6-hour group had a greater preservation than the 3-hour group(p<0.05). CONCLUSION: The results suggest that post-ischemic mild hypothermia protects against delayed neuronal damage in the hippocampal CA1 area following 10-minute transient global ischemia: 3-hour post-ischemic mild hypothermia provides a potential reduction of neuronal damage, but a 6-hour treatment is more effective in preventing neuronal damage than a 3-hour one.
Brain Ischemia ; Gerbillinae* ; Hypothermia* ; Ischemia ; Neurons ; Neuroprotective Agents* ; Reperfusion

To elucidate the neurotoxic mechanism of methylmercury on cultured bovine oligodendrocytes, neurotoxic effect was estimated by MTT assay after cultures were exposed to various concentrations of methylmercuric chloride (MMC). In addition, neuroprotective effect of antioxidant, allopurinol agonist MMC-induced neurotoxicity was examined on these cultures. Exposure of cultured bovine oligodendrocytes to MMC showed less than 50% of the cell viability 24 hours after treatment with 35µM of MMC. And also, allopurinol blocked the neurotoxicity induced by MMC on these cultures. These results suggest that oxygen radicals involve in MMC-mediated neurotoxicity, and also seletive antioxidants such as allopurinol are effective in blocking the neurotoxicity induced by MMC on cultured bovine oligodendrocytes.
Allopurinol* ; Antioxidants ; Cell Survival ; Neuroprotective Agents ; Oligodendroglia ; Reactive Oxygen Species

OBJECTIVE: To explore the effect and mechanism of surround needling combined with acupoint injection on acute herpetic neuralgia (AHN). METHODS: Ninety-nine patients with T-T segment AHN were randomly divided into 3 groups, 33 cases in each group, including 2 cases dropped off in the surround needling group, 4 cases dropped off in the acupoint injection group, and 3 cases dropped off in the combined group. Oral valacyclovir was given in each group, 0.3 g each time, 2 times a day for 10 days. Oblique insertion of needle used at points around the herpes in the surround needling group, and continuous wave was stimulated to tolerance for 20 min; the same acupoints were selected as the surround needling group, stimulated with the mixture injection of mecobalamin and lidocaine in the acupoint injection group; After the surround needling, acupoint injection was performed in the combined group. The treatment was given once a day, 14 times for a course, and one course was needed in all groups. The skin healing conditions (blistering, crusting, and dislocation time) of each group were compared after treatment. The pain scores, pain area and quality of life scores in each group were observed before and after treatment. The levels of neuron specific enolase (NSE), substance P (SP) and calcitonin gene-related peptide (CGRP) in the local blister fluid were measured before and after treatment in all groups. RESULTS: The blistering, crusting and dislocation time in the combined group were earlier than the other two groups (all <0.05). The pain score and pain area in the each group were significantly lower than those before treatment, and the quality of life score was significantly higher than that before treatment (all <0.05). The improvements of pain score and quality of life score in the combined group were more obvious than the other two groups (all <0.05). After treatment, the levels of NSE, SP and CGRP in the local blister fluid in each groups were significantly lower than those before treatment (all <0.05). The indexes in the combined group were significantly lower than those in the other two groups (all <0.05). CONCLUSION Both surround needling and acupoint injection have an adjuvant effect on AHN. The combination of the two is better, the skin is healed quickly, the analgesia is significant, and the contents of local NSE, SP and CGRP are significantly decreased. The mechanism of action is to exert neuroprotective effects.
Acupuncture Points ; Humans ; Neuralgia ; therapy ; Neuroprotective Agents ; Quality of Life

We examined the neuroprotective and neurotrophic effects of Tremella fuciformis. The neurotrophic effects of the hot water extract of T. fuciformis was evaluated by microscopically monitoring its potency to induce neurite outgrowth in PC12h cells. The hot water extract of T. fuciformis promoted neurite outgrowth in PC12h cells in this study, superior to other natural substances which was reported previously. When cells were treated with the hot water extract of T. fuciformis prior to beta-amyloid peptide treatment (active domain of A peptide 25~35 treated), toxicity was significantly diminished (p<0.01). These results suggest that T. fuciformis might potentially be used as a precautionary agent in neurodegenerative disease, such as Alzheimer's disease, etc.
Alzheimer Disease ; Neurites ; Neurodegenerative Diseases ; Neuroprotective Agents ; Water

One new and two known dammarane-type saponins were isolated from the leaves of Gynostemma pentaphyllum using various chromatographic methods. Their structures were identified by HR-ESI-MS,~( 1)H-NMR, ~(13)C-NMR, 2 D-NMR spectra as 2α,3β,12β,20,24(S)-tetrahdroxydammar-25-en-3-O-[β-D-glucopyranosyl(1→2)-β-D-glucopyranosyl]-20-O-β-D-xylopyranosyl(1→6)-β-D-glucopyranoside(1, a new compound, namely gypenoside J5) and 2α,3β,12β,20,24(R)-tetrahdroxydammar-25-en-3-O-[β-D-glucopyranosyl(1→2)-β-D-glucopyranosyl]-20-O-β-D-xylopyranosyl(1→6)-β-D-glucopyranoside(2) and 2α,3β,12β,20-tetrahydroxy-25-hydroperoxy-dammar-23-en-3-O-[β-D-glucopyranosyl(1→2)][β-D-glucopyranosyl]-20-O-[β-D-xylopyranosyl(1→6)]-β-D-glucopy-ranoside(3), respectively. Compounds 1 and 2 were a pair of C-24 epimers. All compounds showed weak cytotoxicity agxinst H1299, HepG2, PC-3, SH-SY5 Y cancer cell lines. However, they exerted protective effect against SH-SY5 Y cellular damage induced by H_2O_2 dose-dependently, of which compound 1 displayed the strongest antioxidant effect. The present study suggested that G. pentaphyllum has antioxidative potential and the saponins from G. pentaphyllum are considered as the active compounds with neuroprotecitve effect.
Gynostemma ; Molecular Structure ; Neuroprotective Agents/pharmacology* ; Saponins/pharmacology* ; Triterpenes/pharmacology*

In central neurons, an excessive or sustained rise in the concentration of free cytoplasmic Ca2+ ions([Ca2+]i) after hypoxia may promote rapid neurodegeneration both in vitro and in vivo. Treating cells with Ca2+ chelating agents may prevent or delay a loss of cellular Ca2+ homeostasis after hypoxic injury and thus constitute an effective strategy for minimizing neuronal damage. Cell-permeant Ca2+ chelators such as 1,2-bis-(2-aminophenoxy) ethrane -N,N,N',N' -tetraacetic acid acetoxymethyl ester(BAPTA-AM) have shown evidence of neuroprotective effect against hypoxic neuronal injury. This study was designed to examine dose response and to estimate therapeutic window of BAPTA-AM for the recovery from hypoxia in vitro. Electrophysiological studies were made in CA1 neurons in rat hippocampal slices which were superfused with artificial cerebrospinal fluid(ASCF) in tissue chamber. Hypoxia was induced by replacement of 95% N2+5% CO2 from 95% O2+5% CO2 for 20min. Recovery from hypoxic injury was evaluated by using a percentage recovery of population spike. BAPTA-AM in concentration of 1, 10 and 50micrometer were administered to the artificial cerebrospinal fluid(ASCF) for 2 hours prior to hypoxia, simultaneous with hypoxia and after hypoxia. The experimental specimens were divided to seven groups and each group was compared to control ASCF group. Recovery of population spike after hypoxia was about 70% in control ASCF group, which was mild type hypoxic injury. BAPTA-AM in 10 micrometer concentration, when given just prior to hypoxia, enhanced recovery of poppulation spikes at 15 and 30min following reoxygenation(p<0.05), in comparison with control ASCF. BAPTA-AM had no neuroprotective acitvity when given after the onset of hypoxia. Also, BAPTA-AM in 1 and 50 micrometer concentration did not accentuate recovery of population spike after hypoxia. Dose response curve was inverted U-shape and the response was maximun in 10 micrometer concentration of BAPTA-AM.
Animals ; Anoxia ; Chelating Agents ; Cytoplasm ; Enflurane ; Homeostasis ; Neurons ; Neuroprotective Agents* ; Rats

BACKGROUND AND OBJECTIVES: The neuroprotective effect of Ginkgo biloba has been demonstrated in several in vivo and in vitro models. The effect of Ginkgo biloba on vestibular compensation following unilateral labyrinthectomy (UL) was investigated. Material and Methods: Spontaneous nystagmus and c-Fos protein expression were measured following UL in Sprague-Dawley rats with pretreatment of Ginkgo biloba (50 mg/kg, i.p.). RESULTS: After pretreatment with Ginkgo biloba (50 mg/kg, i.p.) expression of c-Fos protein in the vestibular nuclear complex and frequency of spontaneous nystagmus were measured till 24 hours after UL. UL produced spontaneous nystagmus with frequency of 124+/-.2 beats/min at post-op 2 hrs and 70+/-.1 beats/min at post-op 24 hrs. Pretreatment with Ginkgo biloba significantly decreased the frequency of spontaneous nystagmus till post-op 24 hrs compared to control group (p<0.05). UL produced marked expression of c-Fos protein in bilateral medial vestibular nucleus, inferior vestibular nucleus, and superior vestibular nucleus, and the number of expression was significantly higher in contralateral vestibular nuclei to the lesion than ipsilateral vestibular nuclei at post-op 2 hrs (p<0.01). The number of c-Fos protein expression was decreased with time and significantly higher in ipsilateral vestibular nuclei than contralateral ones at post-op 24 hrs (p<0.01). Pretreatment with Ginkgo biloba significantly decreased the number of c-Fos protein expression following UL (p<0.01) and abolished the asymmetry of c-Fos protein expression in bilateral vestibular nuclei at post-op 24 hrs. CONCLUSION: These results suggest that Ginkgo biloba may facilitate vestibular compensation following UL through modulation of neurotransmitters and neuroprotective effects.
Animals ; Compensation and Redress ; Ginkgo biloba* ; Neuroprotective Agents ; Neurotransmitter Agents ; Rats* ; Rats, Sprague-Dawley ; Vestibular Nuclei