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Query: UMLS:C0022116 (ischemia)
 91,303 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Effects of treatment with (+/-)-1-(3,4-dimethoxyphenyl)-2-(4- diphenylmethylpiperazinyl)ethanol dihydrochloride (NC-1100), a calcium entry blocker, on ischemic neuronal damage were investigated. Monkeys were subjected to temporary occlusion of eight (bilateral common carotid, internal and external carotid, and vertebral arteries) major arteries. Blood flow was restored after 5, 10, 13, and 15 min occlusion, and NC-1100 (1 mg/kg) was then immediately infused intravenously. Monkeys were killed by perfusion fixation 5 days after occlusion. All brain regions were then histologically investigated for ischemic neuronal changes. Physiological data of NC-1100-treated subjects were not significantly different than those of untreated subjects. Heart rate tended to decrease after ischemia in treated subjects. Occlusion of 8 arteries for 10 to 15 min produced ischemic neuronal damage confined exclusively to the CA1 subfield of the hippocampus. Treatment with NC-1100 markedly reduced ischemic neuronal damage in the CA1 subfield of the hippocampus. It is suggested that postischemic treatment with the calcium entry blocker, NC-1100, might protect the brain from the ischemic damage produced in patients suffering from transient ischemia.
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PMID:Calcium entry blocker ameliorates ischemic neuronal damage in monkey hippocampus. 139 25

The alterations of second-messenger ligand binding and cerebral blood flow (CBF) were evaluated in the gerbil brain after 2-h unilateral common carotid artery occlusion. [3H]Forskolin (FK) and [3H]phorbol-12,13-dibutyrate (PDBu) were used as specific ligands for adenylate cyclase (AC) and protein kinase C (PKC) activity estimation, respectively. CBF was determined at the end of the experiment by the [14C]iodoantipyrine method. A quantitative autoradiographic method permitted simultaneous measurement of the three parameters in the same brain. The levels in the caudate-putamen, globus pallidus, and hippocampus were analyzed. The animals were divided into three groups: Group 1 with severe ischemia (CBF in the lateral nuclei of the thalamus (CBFt) less than 50 ml/100 g/min), Group 2 with mild ischemia (CBFt greater than or equal to 50 ml/100 g/min), and the Sham Group. The PDBu binding revealed a statistically significant increase in the caudate-putamen, lateral nuclei of the thalamus and hippocampus (CA1 and CA3 regions and dentate gyrus) on the ischemic side in Group 1 as compared to that in Group 2 and the Sham Group. In contrast, the FK binding did not show any significant changes in any of the regions. These data and our previous findings for 6-h ischemia suggest that (1) PKC translocation to the cell membrane may occur at the early ischemic phase in particular regions including the caudate-putamen, lateral nuclei of the thalamus and hippocampus, with the translocated PKC gradually diminishing during the subsequent ischemic period; and (2) the suppression of the AC system observed in 6-h ischemia may not appear in the early ischemic phase.
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PMID:Alteration of second-messenger ligand binding following 2-hr hemispheric ischemia in the gerbil brain. 139 61

Effect of indomethacin on post-ischemic changes of CA1 neurons was studied in the hippocampus of the Mongolian gerbil. The gerbil was employed because due to poor development of posterior communicating artery ischemia could be easily induced in the forebrain simply by occluding bilateral common carotid arteries. Indomethacin (5 mg/kg, i.p.) was administered 30 min before the occlusion. The occlusion lasted for 5 divided into four groups. In one group, the temperature was not controlled. In the remaining three groups, the temperature was kept at 35.5 degrees C, 37.5 degrees C, and 39.5 degrees C, respectively. Seven days after the occlusion neuronal density was assessed on histological sections stained with hematoxylin eosin. It was found that in all groups indomethacin was effective in preventing delayed neuronal death regardless of the difference in the cranial temperature. However, delayed neuronal death was the least in the lowest temperature group. The drug also prevented the post-ischemic hyperthermia observed in the temperature non-controlled group. These results indicate that indomethacin has its own pharmacological action to prevent delayed neuronal death.
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PMID:[Effect of indomethacin on delayed neuronal death of hippocampal CA1 sector in gerbil under different levels of controlled cranial temperatures]. 140 Sep 7

We examined whether MK-801, an N-methyl-D-aspartate (NMDA)-receptor antagonist, or anisomycin, a reversible protein synthesis inhibitor, inhibits the induction of ischemic tolerance following preconditioning with sublethal ischemia in gerbil hippocampus. Preconditioning with 2 min of ischemia, which induced heat shock protein-72 immunoreactivity, prevented hippocampal CA1 neuronal damage following 3 min of ischemia produced 3 days later. MK-801, but not anisomycin, inhibited the induction of tolerance although the heat shock protein synthesis was reduced in both groups. The present result suggests that NMDA receptor activation, causing stress response, induces the ischemic tolerance.
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PMID:MK-801, but not anisomycin, inhibits the induction of tolerance to ischemia in the gerbil hippocampus. 140 77

Involvement of nerve growth factor (NGF) in the pathogenesis of delayed neuronal death (DND) of CA1 neurons in the hippocampus has been suggested. We measured regional changes in the content of tissue NGF of the hippocampus in the Mongolian gerbil after 5 min forebrain ischemia. The NGF content was found to decrease significantly in the CA3 and dentate regions by 32% two days after ischemia. By contrast in the CA1 region, the level of NGF became significantly elevated by 50% two weeks after ischemia or later. The early reduction of NGF content in the afferent area projecting to the CA1 sector might be primarily linked to the pathogenesis of DND, whereas the delayed increase within the CA1 sector might be a secondary local response mainly of reactive astroglia.
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PMID:Significance of nerve growth factor content levels after transient forebrain ischemia in gerbils. 140 81

GABAergic inhibitory mechanisms may offer protection to neurons after global ischemia. We tested the effects of gamma-vinyl GABA, a GABA-transaminase inhibitor, via continuous infusion in the third ventricle (Alza pumps) in a gerbil model of repetitive forebrain ischemia. We used two episodes of 3 min duration with a 'reperfusion' interval of 1 h between the insults. Histological analysis was done with silver staining 5 days after the insult. Our results show that there is significant protection of the hippocampus CA1 region and substantia nigra reticulata in treated animals compared to controls. An increase in GABA levels, decrease in glutamate, or mild hypothermia, may be potential mechanisms for this protection. GABAergic agents may prove useful agents in repetitive ischemia.
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PMID:Gamma-vinyl GABA prevents hippocampal and substantia nigra reticulata damage in repetitive transient forebrain ischemia. 142 28

To clarify the role of serotonin in cerebral ischemia, we examined the effects of selective serotonin reuptake inhibitors, citalopram and clomipramine, on ischemic neuronal damage in the gerbil. Pretreatment with citalopram (40 mg/kg i.p.) and clomipramine (20 mg/kg i.p.) protected against neuronal destruction of hippocampal CA1 pyramidal cells following 5 min of forebrain ischemia. Furthermore, microdialysis assays showed that a striking increase in extracellular excitatory amino acid levels during ischemia was significantly inhibited by pretreatment with citalopram and clomipramine. However, citalopram (40 mg/kg i.p.) did not alter the extracellular amino acid concentrations in normal gerbils. Thus, serotonin reuptake inhibitors have a protective effect against ischemic neuronal damage. Furthermore, the present result suggests that the protective effect is mediated through prevention of the accumulation of extracellular excitatory amino acids during and after ischemia.
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PMID:Protective effects of serotonin reuptake inhibitors, citalopram and clomipramine, against hippocampal CA1 neuronal damage following transient ischemia in the gerbil. 142 46

The effects of dizocilipine maleate (MK-801), a noncompetitive N-methyl-D-aspartate (NMDA) receptor/channel antagonist, were tested on the dysfunction of neurotransmitter and signal transduction systems and morphological damage 7 days after transient forebrain ischemia in gerbils. Neurotransmitter system (adenosine A1, muscarinic cholinergic receptor) and signal transduction system (inositol 1,4,5-trisphosphate receptor: IP3, protein kinase C: PKC, L-type calcium channels) binding sites were mapped by in vitro quantitative receptor autoradiography. All ligands used in the present study decreased significantly in the CA1 subfield 7 days after ischemia. In normothermic animals, pretreatment with MK-801 failed to protect against decreased receptor binding in the hippocampus 7 days after ischemia. Moreover, in a morphological study, pre- and posttreatment of MK-801 failed to show protective effects against ischemic neuronal damage. On the other hand, pretreatment of MK-801, without maintaining body temperature, prevented the neuronal death of CA1 subfield 7 days after ischemia. These results weaken the hypothesis that NMDA receptor/channel may play a pivotal role in the pathogenesis of neuronal damage after transient forebrain ischemia.
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PMID:Effects of hyperthermia on the effectiveness of MK-801 treatment in the gerbil hippocampus following transient forebrain ischemia. 142 62

To investigate cerebral injury in the monkey due to transient ischemia, monkeys were each subjected to temporary occlusion of eight (bilateral common carotid, internal and external carotid, and vertebral) major arteries. After 0 (control), 5, 10, 13, 15, and 18 min occlusion, blood flow was restored. The monkeys were sacrificed by perfusion fixation 5 days after the operation, and all brain regions were then histologically examined for ischemic neuronal changes induced by the occlusion. The amplitude of EEG signals from skull and scalp became almost isoelectric within 1-6 min after the onset of occlusion. The EEG signals from the hippocampus were markedly attenuated within 1-4 min, although they did not become completely isoelectric. Blood pressure was significantly increased after 10-min ischemia. Five-min occlusion produced no ischemic neuronal changes except a slight increment of glial cells in the striatum and III, V, and VI layers of the neocortices. After 10- to 15-min occlusion, there were ischemic cell changes restricted exclusively to the CA1 subfield of the hippocampus. Eighteen-min occlusion produced more prominent ischemic neuronal damage in the CA1 subfield of the hippocampus, but ischemic neuronal damage was no longer confined to the hippocampus. These results suggest that only the CA1 subfield of the monkey hippocampus could be damaged by mild ischemic insult. We demonstrate that the limited lesion of the hippocampus, especially the CA1 subfield, after 10- to 15-min occlusion of eight arteries in the monkey, produces a model equivalent to human amnesia caused by transient ischemic insult.
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PMID:Hippocampal neuronal damage after transient forebrain ischemia in monkeys. 142 66

In rodents damage from repetitive transient cerebral ischemia is more severe than that seen with a single ischemic insult of similar duration. Mild hypothermia has been shown to be very effective in protecting the brain during single ischemic insults. We tested the protective effects of hypothermia in repetitive ischemic insults. We used the gerbil model of repetitive ischemia (three minutes ischemia repeated at one hourly intervals three times) and histological evaluation was done using the silver staining technique. Our study reveals that a decrease in body and scalp temperature by 1-2 degrees Celsius can significantly reduce neuronal damage in the cerebral cortex, CA1 region of the hippocampus and substantia nigra reticulata during repetitive ischemia. As the hypothermia was induced after the initial insult, we believe this offers an opportunity for intervention in the clinical settings.
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PMID:During repetitive forebrain ischemia, post-ischemic hypothermia protects neurons from damage. 142 40


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