共查询到20条相似文献,搜索用时 31 毫秒
1.
T. Mainprize A. Shuaib MD FRCPC S. Ijaz R. Kanthan H. Miyashita J. Kalra 《Neurochemical research》1995,20(8):957-961
GABAergic neurons in the striatum are very sensitive to the effects of ischemia. The progressive decline in striatal GABA following transient forebrain ischemia in gerbils may be secondary to either a decreased production or an increase in reuptake mechanisms or both. The current experiment was designed to evaluate release of GABA by stimulation with K+ or inhibition of its uptake with nipecotic acid or their combination (K+ nipecotic) after repetitive forebrain ischemia in gerbils by in-vivo microdialysis on Days 1, 3, 5, and 14 following the insult. Infusion of nipecotic acid or potassium chloride, resulted in a significant increase in extracellular GABA. This response was significantly decreased in the post-ischemic animals. The synergistic effect of increased GABA concentrations by the infusion of nipecotic acid+potassium chloride seen in the controls was not evident in the post-ischemic animals. In conclusion, though there is a reduction in the extracellular GABA concentrations in the first week following an ischemic insult, restorative mechanisms are operative in the second week as seen by the increasing GABA concentrations. 相似文献
2.
Prevention of kidney ischemia/reperfusion-induced functional injury and JNK, p38, and MAPK kinase activation by remote ischemic pretreatment 总被引:7,自引:0,他引:7
MAPK activities, including JNK, p38, and ERK, are markedly enhanced after ischemia in vivo and chemical anoxia in vitro. The relative extent of JNK, p38, or ERK activation has been proposed to determine cell fate after injury. A mouse model was established in which prior exposure to ischemia protected against a second ischemic insult imposed 8 or 15 days later. In contrast to what was observed after 30 min of bilateral ischemia, when a second period of ischemia of 30- or 35-min duration was imposed 8 days later, there was no subsequent increase in plasma creatinine, decrease in glomerular filtration rate, or increase in fractional excretion of sodium. A shorter period of prior ischemia (15 min) was partially protective against subsequent ischemic injury 8 days later. Unilateral ischemia was also protective against a subsequent ischemic insult to the same kidney, revealing that systemic uremia is not necessary for protection. The ischemia-related activation of JNK and p38 and outer medullary vascular congestion were markedly mitigated by prior exposure to ischemia, whereas preconditioning had no effect on post-ischemic activation of ERK1/2. The phosphorylation of MKK7, MKK4, and MKK3/6, upstream activators of JNK and p38, was markedly reduced by ischemic preconditioning, whereas the post-ischemic phosphorylation of MEK1/2, the upstream activator of ERK1/2, was unaffected by preconditioning. Pre- and post-ischemic HSP-25 levels were much higher in the preconditioned kidney. In summary, post-ischemic JNK and p38 (but not ERK1/2) activation was markedly reduced in a model of kidney ischemic preconditioning that was established in the mouse. The reduction in JNK and p38 activation can be accounted for by reduced activation of upstream MAPK kinases. The post-ischemic activation patterns of MAPKs may explain the remarkable protection against ischemic injury observed in this model. 相似文献
3.
The changes in acetylcholine (ACh), monoamine and monoamine metabolite levels following cerebral ischemia in Mongolian gerbils were examined. In addition, the effects of Sho-saiko-to-go-keishi-ka-shakuyaku-to (TJ-960), which is a spray-dried mixture of 9 herbal drugs, on these changes were also examined. The dramatic decrement of ACh levels in ischemic gerbils was significantly inhibited by p.o. administration of TJ-960 at a daily dose of 3.5 g/kg or 700 mg/kg for one month. Norepinephrine (NE) was also reduced in all ischemic brain regions, and TJ-960 also recovered the level of NE. In ischemic gerbil brains, the dopamine (DA) levels decreased and its metabolites increased in the striatum, but DA and its metabolites in the thalamus+midbrain region increased. The serotonin (5HT) level was reduced in the cerebral cortex and hippocampus. TJ-960 inhibited these monoaminergic changes in ischemic gerbils. This suggests that TJ-960 may provide anti-ischemic action and beneficial effects on various symptoms induced by ischemia. 相似文献
4.
Noradrenaline and dopamine injected into the lateral brain ventricle exerted a significant effect on the behavior of rats. Both amines caused a slight rise in the basic locomotor activity which was significantly increased in the animals with inhibited monoamine oxidase activity. Besides that, they suppressed the behavior of rats in the open-field test, inhibited the conditioned avoidance response, decreased body temperature and increased amphetamine-induced motor hyperactivity. Noradrenaline, in contrast to dopamine, changed the intensity of amphetamine-induced stereotypy and prolonged the action of hypnotics. The central action of both catecholamines (in higher doses especially) seemed to have a biphasic course: in the first phase after administration depression was observed which was more pronounced after noradrenaline administration, in the second phase a stimulating effect b 相似文献
5.
Kwon YS Ann HS Nabeshima T Shin EJ Kim WK Jhoo JH Jhoo WK Wie MB Kim YS Jang KJ Kim HC 《Neurochemistry international》2004,45(1):157-170
We evaluated whether combined treatment with selegiline, a selective MAO-B inhibitor, and EGb 761, a standard extract of Ginkgo biloba, has synergistic effects against ischemic reperfusion injury (IRI) in gerbils. Interestingly, we observed that pretreatment with EGb 761 significantly attenuated selegiline-induced hyperactivity. This finding paralleled striatal fos-related antigen immunoreactivity (FRA-IR) in mice. Four minutes of bilateral carotid artery occlusion caused substantial cell loss in the CA1 of the hippocampus 5 days post-ischemic insult. Pretreatment with EGb 761, with or without selegiline, significantly attenuated this neuronal loss. Combined treatment with EGb 761 plus selegiline was more efficacious in preventing this loss. Synaptosomal formations of protein carbonyl, lipid peroxidation (malondialdehyde (MDA) + 4-hydroxyalkenal (4-HDA)), and reactive oxygen species (ROS) in the hippocampus remained elevated 5 days post-ischemic insult. The antioxidant effects appeared to be most significant in the group treated with EGb 761 plus selegiline. This combined treatment produced more significant attenuation of IRI-induced alterations in intramitochondrial calcium accumulation, the mitochondrial transmembrane potential, and mitochondrial Mn-superoxide dismutase-like immunoreactivity (Mn-SOD-IR) than either treatment alone. Our results suggest that co-administration of EGb 761 and selegiline produces significant neuroprotective effects via suppression of oxidative stress and mitochondrial dysfunction without affecting neurological function. 相似文献
6.
Isabella Zini Roberta Grimaldi Emilio Merlo Pich Michele Zoli Kjell Fuxe Luigi F. Agnati 《Neurochemistry international》1990,16(4):451-468
A morphological and functional characterization of the four-vessel occlusion model of transient (30 min) forebrain ischemia has been carried out. The rats were classified as fully ischemic when an isoelectric pattern of electroencephalographic activity was present within 5 min of the occlusion of carotid arteries. Otherwise they were considered as partially ischemic rats. The modifications of cerebral blood content during and after the ischemic insult were assessed by a histochemical method which visualizes red blood cells in cerebral vessels. The periods of increase and decrease of red blood cell content were found to correspond to previous reports of post-ischemic hyper- and hypoperfusion. Neuronal damage was assessed by a quantitative analysis of Nissl stained preparations of cingulate cortex, dorsal hippocampus and striatum. The signs of morphological damage were quantified by means of computer-assisted image analysis of Nissl preparations. The highest vulnerability to the ischemic insult was demonstrated in the pyramidal layer of the hippocampal CA1 field and in the lateral striatum. Arterial blood pressure measurements were performed during the ischemic and post-ischemic periods, demonstrating a peak increase of arterial blood pressure within 2 min after carotid artery occlusion, followed by a slow decrease towards basal levels during the ischemic period and a full recovery within 15 min of reperfusion. Ischemic rats were tested in a neurological test battery and in a passive avoidance task. While a full recovery of the relatively simple tasks of the neurological test battery was attained within 14 days of reperfusion, a highly significant impairment of passive avoidance behavior was still present 15 days after the ischemic insult. Finally, a discriminant analysis was applied to separate, on the basis of non-invasive techniques (neurological tests and hot plate), the group of completely ischemic rats from that of partially ischemic rats. 相似文献
7.
The relationship of cerebral neurotransmitters acetylcholine (ACh), noradrenaline (NA), dopamine (DA), 5-hydroxytryptamine (5HT) to the energy state of the brain was examined in mice at various times following complete ischemia produced by decapitation, in gerbils submitted to transient global ischemia (10 min bilateral carotid artery occlusion, 5 or 30 min recirculation), and in rats 24 hr after irreversible microembolism. Ischemia caused significant reductions in brain monoamine concentrations. The alterations in NA, DA, and 5HT levels persisted during recirculation and were unrelated to energy restoration. They were accompanied by an increase in the concentrations of related metabolites, suggesting that synthesis was unable to compensate for the release of the transmitters at early post-ischemic time periods. As described for the catecholamines and 5HT, ischemia resulted in a significant decrease in ACh level, but recirculation was associated with a rapid increase in ACh concentration. Impaired synthesis and/or increased release of ACh can be responsible for the decrease in ACh concentration during ischemia. Early post-ischemic elevation of ACh may be related to the large increase in brain choline brought about by ischemia. 相似文献
8.
Renal ischemia was produced in anesthetized rats by a bilateral ligation of the renal artery, vein, and ureter. Pretreatment with hydralazine (0.3-10.0 mg/kg i.v.) resulted in a dose dependent reduction in elevated plasma creatinine levels 24 hr after a 60 min ischemic episode, indicating a protective effect on post-ischemic renal function. Hydralazine (3.0 mg/kg, i.v.) produced a fall in arterial blood pressure and exaggerated and/or extended post-ischemic depressions in renal blood flow, renal transport activity (in vitro para-aminohippurate uptake) and renal ATP levels. These results indicate that the hypotensive activity of hydralazine may have indirectly benefited the post-ischemic kidney by prolonging a relative anoxic condition which possibly allowed renal cells to recover under conditions where minimal tubular activity was present. 相似文献
9.
Lee CH Yoo KY Choi JH Park JH Kim DH Park JH Hwang IK Cho JH Kim YM Won MH 《Cellular and molecular neurobiology》2011,31(3):449-457
In this study, the authors examined the difference of phosphorylated extracellular signal-regulated kinase 1/2 (pERK1/2) in
the hippocampal CA1 region (CA1) between adult and aged gerbils after 5 min of transient cerebral ischemia. Delayed neuronal
death in the CA1 of the aged group was much slower than that in the adult group after ischemia/reperfusion (I/R). pERK1/2
immunoreaction was observed in the CA1 region of the sham-operated adult gerbil. pERK1/2 immunoreactivity and protein levels
in the ischemic CA1 region of the adult group were markedly increased 4 days after I/R, and then reduced up to 10 days after
I/R. In contrast, pERK1/2 immunoreaction was hardly detected in the CA1 region of sham-operated aged gerbils, and the immunoreactivity
increased from 1 day after the ischemic insult, and still observed until 10 days post-ischemia. In addition, pERK1/2-immunoreaction
was expressed in astrocytes in the ischemic CA1 region: The expression in the ischemia-operated aged gerbils was later than
that in the ischemia-operated adult gerbils. These results indicate that different patterns of ERK1/2 immunoreactivity may
be associated with different processes of delayed neuronal death in adult and aged animals. 相似文献
10.
ALTERATIONS OF CYCLIC NUCLEOTIDE-RELATED ENZYMES AND ATPase DURING UNILATERAL ISCHEMIA AND RECIRCULATION IN GERBIL CEREBRAL CORTEX 总被引:5,自引:5,他引:0
Joan P. Schwartz B. B. Mrsulja B. J. Mrsulja Janet V. Passonneau I. Klatzo 《Journal of neurochemistry》1976,27(1):101-107
Abstract— Several enzyme activities were determined in gerbil cerebral cortex during unilateral ischemia or in the post-ischemic period following 1 h of ischemia. Adenylate cyclase and Na + -K + -activated ATPase showed essentially the same pattern. Neither enzyme changed during ischemia but the activities decreased on recirculation to 40–60% of right side control by 5 h. The ATPase had returned to control level by 20h; the adenylate cyclase by 7 days of recirculation. Particulate cyclic AMP-dependent protein kinase in the ischemic left hemisphere decreased throughout the 6h of ischemia. It remained depressed in the first 5 h of the post-ischemic period but returned to control by 20 h. The soluble protein kinase activity, the soluble cyclic AMP and cyclic GMP phosphodiesterase and the Mg2+ dependent ATPase did not change significantly during the ischemic or post-ischemic periods. The results suggest that ischemia and/or recirculation may affect cellular membranes and membrane-bound enzymes, in particular. Furthermore, the results imply that despite apparent metabolite recovery during the post-ischemic period, enzymatic changes are occurring that may be important for both the quality of recovery and the response to further ischemic insult. 相似文献
11.
Cho JH Hwang IK Yoo KY Kim SY Kim DW Kwon YG Choi SY Won MH 《Neurochemistry international》2008,52(4-5):659-668
We examined the intracellular delivery of Pep-1-cargo protein against transient ischemic damage in the hippocampal CA1 region in gerbils. For this study, we introduced green fluorescent protein (GFP) and constructed Pep-1-GFP protein. At 12h after Pep-1-GFP treatment, GFP fluorescence was shown in almost CA1 pyramidal neurons in ischemic animals; in the sham-operated group, GFP fluorescence was shown in a few pyramidal neurons. Next, we confirmed the long-term effects of Pep-1-Cu,Zn-superoxide dismutase 1 (SOD1) against ischemic damage. In behavioral test, locomotor activity was significantly increased in Pep-1- and Pep-1-SOD1-treated groups 1 day after ischemia/reperfusion; the locomotor activity in the Pep-1-treated group was higher than that of the Pep-1-SOD1-treated group. Thereafter, the locomotor activity in both groups was decreased with time. Four days after ischemia/reperfusion, the locomotor activity in the Pep-1-SOD1-treated group was similar to that of the sham group; in the Pep-1-treated group, the activity was lower than that of the sham group. In the histochemical study, the cresyl violet positive neurons in the Pep-1-SOD1-treated group were abundantly detected in the hippocampal CA1 region 5 days after ischemia/reperfusion. In biochemical study, SOD1 protein level and activity in all Pep-1-treated ischemic groups were significantly lower than that of the Pep-1-SOD1-treated group. Our results indicate that Pep-1-cargo fusion proteins can be efficiently delivered into neurons in the ischemic hippocampus, and that Pep-1-SOD1 treatment in ischemic animals show a neuroprotection in the ischemic hippocampus for a long time. 相似文献
12.
Kucharova K Lukacova N Pavel J Radonak J Hefferan MP Kolesar D Kolesarova M Marsala M Marsala J 《Cellular and molecular neurobiology》2006,26(7-8):1293-1308
1. Brief interruption of spinal cord blood flow resulting from transient abdominal aortic occlusion may lead to degeneration of specific spinal cord neurons and to irreversible loss of neurological function. The alteration of nitric oxide/nitric oxide synthase (NO/NOS) pool occurring after ischemic insult may play a protective or destructive role in neuronal survival of affected spinal cord segments.2. In the present study, the spatiotemporal changes of NOS following transient ischemia were evaluated by investigating neuronal NOS immunoreactivity (nNOS-IR), reduced nicotinamide adenine dinucleotide phosphate diaphorase (NADPHd) histochemistry, and calcium-dependent NOS (cNOS) conversion of [3H] l-arginine to [3H] l-citrulline.3. The greatest levels of these enzymes and activities were detected in the dorsal horn, which appeared to be most resistant to ischemia. In that area, the first significant increase in NADPHd staining and cNOS catalytic activity was found immediately after a 15-min ischemic insult.4. Increases in the ventral horn were observed later (i.e., after a 24-h reperfusion period). While the most intense increase in nNOS-IR was detected in surviving motoneurons of animals with a shorter ischemic insult (13 min), the greatest increase of cNOS catalytic activity and NADPHd staining of the endothelial cells was found after stronger insult (15 min).5. Given that the highest levels of nNOS, NADPHd, and cNOS were found in the ischemia-resistant dorsal horn, and nNOS-IR in surviving motoneurons, it is possible that NO production may play a neuroprotective role in ischemic/reperfusion injury. 相似文献
13.
Bilateral ischemia has been shown to alter the net brain levels of energy metabolites such as ATP, phosphocreatine, glucose, and glycogen. The amino acid neurotransmitter gamma-aminobutyric acid (GABA) exerts a tonic inhibitory influence on neural activity. The present studies were designed to evaluate the influence of elevated GABA levels on the metabolic sequelae of ischemia. The GABA transaminase inhibitor gamma-vinyl-GABA (GVG; vigabatrin) was administered to Mongolian gerbils before the production of a bilateral ischemic incident. GABA levels were elevated in all regions assayed. Levels of energy metabolites were also increased, an indication of reduced energy utilization. In control animals, in the absence of GVG, 1 min of bilateral ischemia produced decreases in the levels of all metabolites. In animals pretreated with GVG, the effects of 1 min of bilateral ischemia were attenuated. These data suggest that the level of ongoing activity may affect the response to an ischemic insult. Furthermore, GVG may have a clinical indication in reducing the effect of minor ischemic incidents. 相似文献
14.
Osamu Kai Shin-ichi Inoue Tomoko Kobayashi Tohru Moribayashi Tsuyoshi Wakita Miwa Irie 《Experimental Animals》2002,51(2):163-166
The levels of total and 2-mercaptoethanol (2-ME)-resistant antibodies in male Mongolian gerbils (Meriones unguiculatus) to sheep red blood cells (SRBC) were higher than those in male C57BL/6 mice after the first and second immunizations. On the other hand, the total antibody level to Brucella abortus (BA) in gerbils was comparable to that in mice, whereas 2-ME-resistant antibody titers were lower after the first and second immunizations than in mice. After injection of 8 x 10(4) SRBC, male gerbils did not produce either total or 2-ME-resistant antibodies after the first immunization, but they produced total and 2-ME-resistant antibodies after the first to the fourth immunizations with different dilutions of BA, and both types of antibody titers significantly increased with the repeated immunizations. There were no sex differences in total and 2-ME-resistant antibody production to SRBC. 相似文献
15.
Carnosine Protects the Brain of Rats and Mongolian Gerbils against Ischemic Injury: After-Stroke-Effect 总被引:3,自引:0,他引:3
Dobrota D Fedorova T Stvolinsky S Babusikova E Likavcanova K Drgova A Strapkova A Boldyrev A 《Neurochemical research》2005,30(10):1283-1288
Carnosine, a specific constituent of excitable tissues of vertebrates, exhibits a significant antioxidant protecting effect
on the brain damaged by ischemic-reperfusion injury when it was administered to the animals before ischemic episode. In this
study, the therapeutic effect of carnosine was estimated on animals when this drug was administered intraperitoneally (100 mg/kg
body weight) after ischemic episode induced by experimental global brain ischemia. Treatment of the animals with carnosine
after ischemic episode under long-term (7–14 days) reperfusion demonstrated its pronounced protective effect on neurological
symptoms and animal mortality. Carnosine also prevented higher lipid peroxidation of brain membrane structures and increased
a resistance of neuronal membranes to the in vitro induced oxidation. Measurements of malonyl dialdehyde (MDA) in brain homogenates showed its increase in the after brain stroke
animals and decreased MDA level in the after brain stroke animals treated with carnosine. We concluded that carnosine compensates
deficit in antioxidant defense system of brain damaged by ischemic injury. The data presented demonstrate that carnosine is
effective in protecting the brain in the post-ischemic period.
Special issue dedicated to Dr. Bernd Hamprecht 相似文献
16.
Brain temperature is an important variable in determining the outcome of cerebral ischemia; increases in core temperature escalate neural damage whereas decreases in core temperature reduce damage. Fever induction often occurs in patients prior to or as a direct or indirect result of the ischemic insult, with a worsened stroke outcome, compared with non-febrile ischemic patients. Most importantly, post-ischemic hypothermia reduces long term neural damage and associated behavioral deficits in animals studied for up to a year after the ischemic insult. This review discusses the importance of monitoring the brain temperature of stroke patients and implemention of therapeutic thermoregulatory strategies to reduce the temperature of ischemic patients. 相似文献
17.
G. Damsma D. P. Boisvert L. A. Mudrick D. Wenkstern H. C. Fibiger 《Journal of neurochemistry》1990,54(3):801-808
Striatal microdialysis was performed in rats subjected to 20 min of transient forebrain ischemia produced by occlusion of the carotid arteries during hemorrhagic hypotension. Extracellular changes of dopamine, serotonin, and their metabolites were monitored before, during, and after the ischemic insult at 10-min intervals by on-line HPLC analysis. During ischemia, extracellular dopamine increased dramatically (156 times baseline), as did 3-methoxytyramine (3-MT), whereas 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) decreased (15-25% of baseline). Upon reperfusion, dopamine was cleared from the extracellular fluid within 40 min and reached a stable level (70% of baseline). DOPAC and HVA increased (250-330%) transiently and reached their maximum 1 h following reperfusion, whereas 3-MT decreased to undetectable levels within 20 min. Although baseline levels of serotonin were not detectable, serotonin and 5-hydroxyindoleacetic acid showed a qualitatively similar temporal pattern to dopamine and its acid metabolites. Killing rats by cervical dislocation produced changes in extracellular dopamine, serotonin, and their metabolites that were almost identical to those seen during ischemia. Pargyline pretreatment 2 h before ischemia had marginal effects on the postischemic clearing of dopamine. The pargyline pretreatment, however, did increase the survival rate of rats subjected to ischemia, and this protective effect might be due to the pargyline-induced blockade of the post-ischemic monoamine oxidase-mediated increase in dopamine metabolism and the concurrent production of the potentially neurotoxic molecule, hydrogen peroxide. 相似文献
18.
AimsDiabetes increases the chances of stroke and the stroke itself is thought to induce hyperglycemia and diabetes. However, this latter contention remains uncorroborated. We investigated whether ischemic hippocampal neuronal cell death induces glucose dysregualtion by modulating insulin resistance, glucose-stimulated insulin secretion, and β-cell mass in Mongolian gerbils fed either a high fat or low fat diet.Main methodsGerbils were subjected to either an occlusion of the bilateral common carotid arteries for 8 mins to render them ischemic, or a sham operation. Ischemic gerbils were fed either an 11% fat diet (LFD) or a 40% fat diet (HFD) for 7, 14 or 28 days.Key findingsArtery occlusion resulted in a 70% or greater initial reduction in hippocampal CA1 neurons and only HFD decreased the percentage of CA1 neurons as the ischemic periods became longer. Oral glucose tolerance test (OGTT) results revealed that ischemia induced glucose intolerance, and longer ischemic periods and HFD exacerbated this glucose intolerance in ischemic gerbils. Insulin secretion during the OGTT was lower in ischemic gerbils than sham gerbils and the decrease was greatest in the 28 day-HFD among all the groups. Insulin resistance was elevated the most in 28 day-HFD ischemic gerbils. There was a progressive loss of pancreatic β-cell mass as the post-ischemic time period increased as consequence of HFD; the decrease being caused by increased apoptosis. This increase in apoptosis was partly associated with increased serum levels of IL-1β, TNF-α and non-esterified fatty acids.SignificanceHippoccampal neuronal cell death deteriorates glucose homeostasis initially through the modulation of insulin secretion and also causes a decrease in β-cell mass while HFD negatively impacts glucose regulation. 相似文献
19.
20.
Energy metabolism was studied in the cerebral cortex of gerbils during and following ischemia induced by 1 h of unilateral carotid artery occlusion. An aneurysm clip was applied to the right common carotid artery of 50-70 g gerbils under brief halothane anesthesia, and the clip was removed 1 h later. Clinical state (gait, responsiveness, seizures) was evaluated during carotid occlusion, and 40% of the animals showed clinical evidence of stroke. Cortical energy stores (2 ATP + ADP + P-creatine) were more than half depleted in the ipsilateral cortex of clinically-affected gerbils, and glucose fell by 75%; lactate rose over 7-fold in the same specimens. After release of the carotid clip, clinical state improved, and biochemical abnormalities partially resolved. However, even after 24 h, the concentration of ATP and the total pool of adenine nucleotides remained subnormal. Metabolic activity in the ischemic cortex, assessed as the utilization of high-energy phosphates following decapitation, was normal after 1 h of recovery and decreased (-50%) after 24 h but was increased by more than 50% after 4 h. Cerebral glucose utilization, evaluated from autoradiographs prepared after intravenous administration of 2-[1-14C]deoxyglucose, was also increased in the cortex, hippocampus, and thalamus after 4 h of recovery. This post-ischemic hypermetabolism in tissue damaged by ischemia may identify a critical period for cell repair, when therapy could be decisive. 相似文献