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

Prior epileptic episodes have been shown to decrease markedly the neuronal damage induced by a second epileptic episode, similar to the tolerance following an episode of mild ischemia. Endogenous neuroprotective effects mediated by various mechanisms have been put forward. This study investigated whether neuroprotection against the excitotoxic damage induced by re-exposure to an epileptic challenge can reflect a change in epileptic susceptibility. Tolerance was elicited in rats by a preconditioning session using intrahippocampal kainic acid (KA) administration followed at 1, 7 and 15-day intervals by a subsequent intraventricular KA injection. The degree of pyramidal cell loss in the vulnerable CA3 subfield contralateral to the KA-injected hippocampus was extensively reduced in animals experiencing KA ventricular administration. This neuroprotection was highly significant 1 and 7 days after injection, but not 15 days after injection. In preconditioned animals, the after-discharge threshold was assessed as an index of epileptic susceptibility. It increased significantly from 1 to 15 days after intrahippocampal KA administration. Finally, an enhancement of neuropeptide Y expression in both non-principal cells and mossy fibers was detected, occurring at the same time as the decrease in epileptic susceptibility. These results provide further evidence of an 'epileptic tolerance' as shown by the substantial neuroprotective effect of a prior episode of epileptic activity upon subsequent epileptic insult and suggest that the prevention of excitotoxic damage after preconditioning results from an endogenous neuroprotective mechanism against hyperexcitability and seizures.
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PMID:Decreased epileptic susceptibility correlates with neuropeptide Y overexpression in a model of tolerance to excitotoxicity. 1125 Nov 94

Neuronal nitric oxide-I is constitutively expressed in approximately 2% of cortical interneurons and is co-localized with gamma-amino butric acid, somatostatin or neuropeptide Y. These interneurons additionally express high amounts of glutamate receptors which mediate the glutamate-induced hyperexcitation following cerebral injury, under these conditions nitric oxide production increases contributing to a potentiation of oxidative stress. However, perilesional nitric oxide synthase-I containing neurons are known to be resistant to ischemic and excitotoxic injury. In vitro studies show that nitrosonium and nitroxyl ions inactivate N-methyl-D-aspartate receptors, resulting in neuroprotection. The question remains of how these cells are protected against their own high intracellular nitric oxide production after activation. In this study, we investigated immunocytochemically nitric oxide synthase-I containing cortical neurons in rats after unilateral, cortical photothrombosis. In this model of focal ischemia, perilesional, constitutively nitric oxide synthase-I containing neurons survived and co-expressed antioxidative enzymes, such as manganese- and copper-zinc-dependent superoxide dismutases, heme oxygenase-2 and cytosolic glutathione peroxidase. This enhanced antioxidant expression was accompanied by a strong perinuclear presence of the antiapoptotic Bcl-2 protein. No colocalization was detectable with upregulated heme oxygenase-1 in glia and the superoxide and prostaglandin G(2)-producing cyclooxygenase-2 in neurons. These results suggest that nitric oxide synthase-I containing interneurons are protected against intracellular oxidative damage and apoptosis by Bcl-2 and several potent antioxidative enzymes. Since nitric oxide synthase-I positive neurons do not express superoxide-producing enzymes such as cyclooxygenase-1, xanthine oxidase and cyclooxygenase-2 in response to injury, this may additionally contribute to their resistance by reducing their internal peroxynitrite, H(2)O(2)-formation and caspase activation.
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PMID:Nitric oxide synthase-I containing cortical interneurons co-express antioxidative enzymes and anti-apoptotic Bcl-2 following focal ischemia: evidence for direct and indirect mechanisms towards their resistance to neuropathology. 1152 39

Detailed quantitative analysis of the vulnerability of different hippocampal and striatal neurons to global forebrain ischemia has not previously been performed. Here we have studied the survival of immunocytochemically identified neurons using an unbiased stereological method in rats subjected to global forebrain ischemia for 30 min and sacrificed 48 h, 1 week or 4 weeks thereafter. Within the hippocampal formation, there was extensive, progressive loss of CA1 pyramidal neurons and dentate hilar neuropeptide Y (NPY)-positive interneurons. In contrast, no reduction of the number of CA3 and CA4 pyramidal neurons or hilar parvalbumin-positive interneurons was detected. In the dorsolateral striatum, the insult caused a major loss of projection neurons immunoreactive to dopamine- and adenosine 3':5'-monophosphate-regulated phosphoprotein with a molecular weight of 32 kilodalton (DARPP-32). The number of parvalbumin-positive striatal interneurons was significantly reduced, while NPY-positive interneurons were resistant. All striatal cholinergic interneurons survived the ischemic insult. At 48 h following the ischemia, the cholinergic interneurons within the lesioned striatum transiently expressed the p75 neurotrophin receptor (p75(NTR)), as shown by double-label immunocytochemistry. Furthermore, there was a significant increase in the number of choline acetyltransferase (ChAT)- and TrkA-immunoreactive interneurons at 4 weeks after the insult. Injections with the cell mitotic division marker BrdU provided no evidence that the elevated cholinergic cell number was due to neurogenesis. Probably, the higher number of ChAT- and TrkA-positive interneurons reflected increased intracellular levels of the corresponding proteins leading to more cells detectable with immunocytochemistry. This study gives the first quantitative description of the vulnerability of defined hippocampal and striatal neurons after global forebrain ischemia. The ischemia-induced increases of p75(NTR), TrkA and ChAT in cholinergic striatal interneurons at various time points after the insult suggest that neurotrophin signaling might be important for the survival and function of these cells in the post-ischemic phase.
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PMID:Stereological assessment of vulnerability of immunocytochemically identified striatal and hippocampal neurons after global cerebral ischemia in rats. 1154 75

Recent studies have shown increased immunoreactivity for neuropeptide Y (NPY) within the perilesional cortex following experimental middle cerebral artery occlusion (MCAO) or focal excitotoxic damage. Downregulation of the NPY Y1 receptor gene using an antisense oligodeoxynucleotide produced a doubling of the infarct volume, implying that NPY may mediate neuroprotection against focal ischemia. The effects of treatment with NPY on infarct volume and hemodynamic parameters were investigated in the present study. Adult male Sprague-Dawley rats were anesthetized with sodium pentobarbital to undergo right-sided endovascular MCAO for 2 h. A single dose of NPY was given via intracarotid injection (10 microg/kg) at the beginning of reperfusion, intracisternal injection (10 or 30 microg/kg) at 30 min of ischemia, or intracerebroventricular (i.c.v.) injection (10 or 70 microg/kg) at 30 min of ischemia. Control groups received the vehicle only via the same route. Body temperature was maintained constant, and hemodynamic parameters were monitored during anesthesia. Laser Doppler flowmetry was used to monitor the regional cerebral blood flow (rCBF) during ischemia and reperfusion in some rats. The rats were decapitated on day 3, and their brains were cut into 2-mm thick coronal slices before reaction with a 2% solution of 2,3,5-triphenyltetrazolium chloride to reveal the infarct. Compared to the respective control groups, NPY treatment via any method of administration increased the relative infarct volume. Suppression of rCBF was observed during reperfusion. These results indicate that peripheral or central administration of NPY impairs reperfusion following experimental MCAO and worsens the outcome of focal cerebral ischemia.
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PMID:Peripheral and central administration of neuropeptide Y in a rat middle cerebral artery occlusion stroke model reduces cerebral blood flow and increases infarct volume. 1182 Oct 7

In a rat endovascular middle cerebral artery occlusion (MCAO) stroke model, we previously showed that intracerebroventricular (ICV) injection of neuropeptide Y (NPY) or an Y1 receptor agonist, [Leu(31),Pro(34)]-NPY, increased the infarct volume, that an Y1 receptor antagonist, BIBP3226, reduced the infarct volume, and that an Y2 receptor agonist, NPY3-36, had no effect. In this study, we used electron paramagnetic resonance (EPR) spectroscopy to measure nitric oxide (NO) and examined how ICV administration of NPY or its receptor analogs would modulate the brain NO level between the bregma levels +2 and -4 mm during MCAO, since excessive NO mediates ischemic damage. The relative brain NO concentration was increased to 131.94 +/- 7.99% (mean +/- SEM; n = 8) at 15 min of MCAO. NPY treatment further increased the relative brain NO concentration to 250.94 +/- 50.48% (n = 8), whereas BIBP3226 significantly reduced the brain NO concentration to 69.63 +/- 8.84% (n = 8). [Leu(31),Pro(34)]-NPY (137.61 +/- 14.54%; n = 7) or NPY3-36 (129.23 +/- 21.77%; n = 8) did not affect the brain NO concentration at 15 min of MCAO. Our results suggest that the NPY-Y1 receptor activation mediates ischemic injury via NO overproduction and that inhibition of the Y1 receptor may confer protection via suppression of excessive NO production during ischemia.
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PMID:Neuropeptide Y-Y1 receptor modulates nitric oxide level during stroke in the rat. 1193 3

Recent studies using middle cerebral artery occlusion in the rat have suggested a role of neuropeptide Y in ischemic pathophysiology. In this study, we investigated the effects of an i.c.v. injection of a neuropeptide Y-Y2 receptor agonist, neuropeptide Y 3-36, a Y1 receptor agonist, [Leu(31),Pro(34)]-neuropeptide Y, or a Y1 receptor antagonist, BIBP3226, on infarct volume and hemodynamic parameters following middle cerebral artery occlusion. Adult male Sprague-Dawley rats were subjected to transient middle cerebral artery occlusion for 2 h. A single i.c.v. injection of neuropeptide Y 3-36 (15 microg/kg), [Leu(31),Pro(34)]-neuropeptide Y (30 microg/kg), or BIBP3226 (5, 15, or 45 microg/kg) was given at 30 min of ischemia. Blood pressure, heart rate, and regional cerebral perfusion were monitored during ischemia and reperfusion. The rats were decapitated after 70 h of reperfusion, and their brains were cut into 2-mm-thick coronal slices before reaction with a 2% solution of 2,3,5-triphenyltetrazolium chloride to reveal the infarct. When compared with an infarct volume of 17.4+/-4.4% of the ipsilateral hemisphere following injection of neuropeptide Y 3-36, administration of the Y1 receptor analogs significantly modified the infarct volume (ordinary one-way analysis of variance (ANOVA), P<0.0001). [Leu(31),Pro(34)]-neuropeptide Y increased the infarct volume to 32.0+/-4.1% (Student-Newman-Keuls post-test, P<0.01), whereas BIBP3226 at 15 microg/kg decreased the infarct volume to 6.5+/-1.0% (post-test P<0.05). Although there was no major difference in the hemodynamic parameters among the groups, injection of [Leu(31),Pro(34)]-neuropeptide Y tended to further reduce cerebral perfusion during ischemia, while injection of BIBP3226 at 15 microg/kg appeared to have the opposite effect. In addition to glutamate, calcium ion and nitric oxide, activation of the neuropeptide Y-Y1 receptors may mediate cerebral damage during focal ischemia. Conversely, inhibiting the Y1 receptors may protect the brain against ischemic injury. Further studies are warranted to confirm the neuroprotective potential of neuropeptide Y-Y1 receptor inhibition.
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PMID:Intracerebroventricular injection of a neuropeptide Y-Y1 receptor agonist increases while BIBP3226, a Y1 antagonist, reduces the infarct volume following transient middle cerebral artery occlusion in rats. 1253 45

We conducted a study of the influence of the vasoactive peptides atrial natriuretic peptide (ANP) and neuropeptide Y (NPY) on survival of patients on hemodialysis and their association and relative importance with cardiac and clinical variables. Thirty-three hemodialysis patients were characterized by age, sex, diagnosis, blood pressure, serum (S)-albumin, serum (S)-urea, hemoglobin, dialysis dose, weight gain, duration of dialysis, cardiac hypertrophy, volume, failure, and ischemia and plasma levels of ANP and NPY. The outcomes were analyzed for early deaths (< 1 year) and for all deaths. The association of the variables to early deaths and all deaths, respectively, was studied in Cox proportional hazard analyses. The variables were also studied in three hierarchical steps: clinical variables only, clinical and cardiac variables, and all variables. For all deaths, the independent variables were plasma NPY (pmol/L) (hazard ratio [HR] = 1.035, p = 0.004), heart volume (ml/m2) (HR = 1.009, p = 0.001), and S-albumin (g/L) (HR = 0.750, p = 0.034). For early deaths, the independent variables were predialysis ANP (pmol/L) (HR = 1.008, p = 0.034) and NPY (pmol/L) (HR = 1.031, p = 0.026). In the hierarchical study, excluding the vasoactive peptides, heart volume, heart failure and S-albumin were independently associated with all deaths, and mean arterial blood pressure was associated with early death. When also excluding the cardiac parameters, S-albumin was associated with all deaths and mean arterial blood pressure with early death. In conclusion, plasma levels of the vasoactive peptides ANP and NPY are the most important group in a hierarchy of variables that predict imminent death in hemodialysis patients, and NPY is associated with late death. ANP and NPY apparently sum up the detrimental influence of many factors in hemodialysis patients.
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PMID:Neuropeptide-Y and atrial natriuretic peptide as prognostic markers in patients on hemodialysis. 1255 11

Previously we showed that neuropeptide Y (NPY), a sympathetic vasoconstrictor neurotransmitter, stimulates endothelial cell migration, proliferation, and differentiation in vitro. Here, we report on NPY's actions, receptors, and mediators in ischemic angiogenesis. In rats, hindlimb ischemia stimulates sympathetic NPY release (attenuated by lumbar sympathectomy) and upregulates NPY-Y2 (Y2) receptor and a peptidase forming Y2/Y5-selective agonist. Exogenous NPY at physiological concentrations also induces Y5 receptor, stimulates neovascularization, and restores ischemic muscle blood flow and performance. NPY-mediated ischemic angiogenesis is not prevented by a selective Y1 receptor antagonist but is reduced in Y2(-/-) mice. Nonischemic muscle vascularity is also lower in Y2(-/-) mice, whereas it is increased in NPY-overexpressing rats compared with their WT controls. Ex vivo, NPY-induced aortic sprouting is markedly reduced in Y2(-/-) aortas and spontaneous sprouting is severely impaired in NPY(-/-) mice. NPY-mediated aortic sprouting, but not cell migration/proliferation, is blocked by an antifetal liver kinase 1 antibody and abolished in mice null for eNOS. Thus, NPY mediates neurogenic ischemic angiogenesis at physiological concentrations by activating Y2/Y5 receptors and eNOS, in part due to release of VEGF. NPY's effectiveness in revascularization and restoring function of ischemic tissue suggests its therapeutic potential in ischemic conditions.
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PMID:Neuropeptide Y induces ischemic angiogenesis and restores function of ischemic skeletal muscles. 1281 21

Panic disorder serves as a clinical model for testing whether mental stress can cause heart disease. Our own cardiologic management of panic disorder provides case material of recurrent emergency room attendances with angina and electrocardiogram ischemia, triggered arrhythmias (atrial fibrillation, ventricular fibrillation), and documented coronary artery spasm, in some cases with coronary spasm being complicated by coronary thrombosis. Application of radiotracer catecholamine kinetics and clinical microneurography methodology suggests there is a genetic predisposition to panic disorder that involves faulty neuronal norepinephrine uptake, possibly sensitizing the heart to symptom generation. During panic attacks there are large sympathetic bursts, recorded by clinical microneurography in the muscle sympathetic nerve neurogram, and large increases in cardiac norepinephrine spillover, accompanied by surges of adrenal medullary epinephrine secretion. In other conditions such as heart failure and presumably here also, a high level of sympathetic nervous activation can mediate increased cardiac risk. The sympathetic nerve cotransmitter, neuropeptide Y (NPY), is released from the cardiac sympathetics during panic attacks, an intriguing finding given that NPY can cause coronary artery spasm. There is ongoing, continuous release of epinephrine from the heart in panic sufferers, perhaps attributable to epinephrine loading of cardiac sympathetic nerves by uptake from plasma during panic attacks, or possibly to in situ synthesis of epinephrine through the action of intracardiac phenylethanolamine-N-methytransferase (PNMT) activated by repeated cortisol responses. We have used internal jugular venous sampling and measurement of overflowing lipophilic brain monoamine metabolites to quantify brain norepinephrine and serotonin turnover in untreated patients with panic disorder. We find normal norepinephrine turnover but a marked increase in brain serotonin turnover in patients with panic disorder, in the absence of a panic attack, which presumably represents an underlying neurotransmitter substrate for the condition.
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PMID:Cardiac sympathetic nerve biology and brain monoamine turnover in panic disorder. 1524 Apr 8

In this in vitro study, we investigated the influence of neuropeptide Y (NPY) Y1 receptor activation or inhibition on the viability of cultured neuronal or glial cells following oxygen glucose deprivation (OGD). Viability of cultured cells was assessed using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide. When compared to the vehicle-treated control group, treatment with NPY or [Leu31,Pro34]-NPY (Y1 agonist) reduced viability of cultured SK-N-MC (Y1-expressing) human neuronal cells at 24 h after 1 h of OGD, while BIBP3226 (Y1 antagonist) improved viability. Except at the highest concentration of NPY used in the study, treatment with NPY or NPY3-36 (Y2 agonist) did not influence viability of cultured SH-SY5Y (Y2-expressing) human neuronal cells at 24 h after 1 h of OGD. In addition, treatment with NPY, [Leu31,Pro34]-NPY, NPY3-36, or BIBP3226 did not affect viability of cultured primary astrocytes at 24 h after 4 h of OGD. The present results agree with those of a recent in vivo study. Activation of NPY-Y1 receptors may mediate ischemic pathophysiological processes, and inhibiting the Y1 receptors may be protective. The combination of OGD and cultured neuronal cells may be useful in future studies on the neuroprotective and harmful mechanisms of NPY-Y1 receptor inhibition and activation during ischemia, respectively.
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PMID:Neuropeptide Y-Y1 receptor agonist worsens while antagonist improves survival of cultured Y1-expressing neuronal cells following oxygen and glucose deprivation. 1559 75


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