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Query: UMLS:C0038454 (stroke)
 147,016 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The pathophysiology of stroke in humans is much more complex than what is typically studied in animal models. Embolic stroke models are more complex than pure ischemia models, but are more representative of human disease and may be particularly useful in the study of new therapeutic strategies. Vascular damage is a prominent feature of embolic stroke, and may be a useful therapeutic target. Serotonin antagonists, adenosine-regulating agents, free radical scavengers, matrix metalloproteinase inhibitors, and HMG-CoA reductase inhibitors are all potentially valuable agents in treating vascular damage after stroke. These agents facilitate decreased infarction volume, hemorrhage, and improved cerebral bloodflow.
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PMID:Endothelium-targeted pharmacotherapeutics for the treatment of stroke. 1213 9

The involvement of nitric oxide (NO) in the branchial circulation and cardiac performance of the Antarctic hemoglobinless icefish Chionodraco hamatus was investigated using isolated and perfused head and working heart preparations. In the branchial vasculature under basal (i.e. unstimulated conditions), the nitric oxide synthase (NOS) inhibitor L-NIO (L-N(5)-(1-iminoethyl) ornithine, 10(-5) and 10(-4) M), caused a marked vasoconstriction (20%), indicating a basal nitrergic vasodilator tone, while the dose-response curve of the NO donor SIN-1 (3-morpholinosydnonimine) showed a dose-dependent vasodilator effect. Acetylcholine induced a dose-dependent branchial vasoconstriction mediated by muscarinic receptors, since the effects were abolished by pre-treatment with atropine (10(-4) M). Serotonin (5-HT) induced a dose-dependent branchial methysergide-sensitive vasoconstriction which was abolished by pre-treatment with L-NIO, indicating a NO-dependent mechanism. On the isolated heart, the NOS inhibitor L-NMMA (N(G)-monomethyl-L-arginine) 10(-4) M produced a small, but significant decrease of heart rate and, as a consequence, a decrease of power output, while the NO donor sodium nitroprusside (SNP) 10(-4) M elicited increases of stroke volume, stroke work and power output, suggesting an exogenous NO-dependent positive inotropism. Exposure of the bulbus arteriosus to L-NMMA was without any appreciable effect. In contrast, SNP produced a notable relaxation of the bulbus wall with a marked increase of its stiffness, as indicated by the increase of systolic and diastolic dP/dt max (23 and 104%, respectively).
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PMID:Control of cardiovascular function in the icefish Chionodraco hamatus: involvement of serotonin and nitric oxide. 1254 77

A transient forebrain ischemia produced a delayed neuronal death of the hippocampus pyramidal cells in stroke-prone spontaneously hypertensive rats (SHRSP). Long term exposure of rats to stress has been reported to induce deleterious effects on the brain including morphological neuronal degeneration in the hippocampus. The present study was designed to examine the effects of psychological and physical stress on the ischemia-related neuronal death and the effects of 5-hydroxytryptamine(4) (5-HT(4)) receptor antagonist. SHRSP were exposed to the psychological or physical stress for 60 min in the communication box once or repeatedly for 3 days and occluded. SB204070, a 5-HT(4) receptor antagonist was injected before the occlusion. Seven days after the occlusion, the number of the neurons damaged morphologically was examined. A transient bilateral carotid occlusion produced a neuronal death of the CA1 subfield of the hippocampus in a time-dependent manner between 3 and 10 min. A 4 min occlusion induced very little morphological damage and a 5 min one produced a significant neuronal death. Exposure of rats to the psychological stress during 60 min for 3 days before the ischemic insults damaged the pyramidal cells by 4 min ischemia much more than without stress. Physical stress daily for 3 times also increased the damaged neurons. Pretreatment of SB204070 0.1 mg/kg after the stress exposure for 3 days significantly decreased the neuronal damage exacerbated by the stress exposure; however, it did not alter the damage induced by 4 or 10 min occlusion without stress. These results suggest that the repeated exposure of animals to the stress dramatically exacerbates the neuronal death by a transient ischemia and the 5-HT(4) receptor may be involved in the stress-induced exacerbating mechanism of the neuronal damage.
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PMID:Involvement of 5-hydroxytryptamine4 receptor in the exacerbation of neuronal loss by psychological stress in the hippocampus of SHRSP with a transient ischemia. 1272 57

Housing rats in an enriched environment improves functional outcome after ischemic stroke, this may reflect neuronal plasticity in brain regions outside the lesion. Which components of the enriched environment that are of greatest importance for recovery after brain ischemia is uncertain. We have previously found that enriched environment and social interaction alone both improve functional recovery after focal cerebral ischemia, compared with isolated housing with voluntary wheel-running. In this study, the aim was to separate components of the enriched environment and investigate the effects on some potential mediators of improved functional recovery; such as the inducible transcription factors nerve growth factor-induced gene A (NGFI-A) and NGFI-B, and the glucocorticoid and serotonin systems. After permanent middle cerebral artery occlusion, rats were divided into four groups: individually housed with no equipment (deprived group), individually housed with free access to a running wheel (running group), housed together in a large cage with no equipment (social group) or in a large cage furnished with exchangeable bars, chains and other objects (enriched group). mRNA expression of inducible transcription factors, serotonin and glucocorticoid receptors was determined with in situ hybridisation 1 month after cerebral ischemia. Rats housed in enriched or social environments showed significantly higher mRNA expression of NGFI-A and NGFI-B in cortical regions outside the lesion and in the CA1 (cornu ammonis region of the hippocampus), compared with isolated rats with or without a running wheel. NGFI-A and NGFI-B mRNA expression in cortex and in CA1 was significantly correlated to functional outcome. 5-Hydroxytryptamine receptor 1A (5-HT(1A)) mRNA expression and binding, as well as 5-HT(2A) receptor mRNA expression were decreased in the hippocampus (CA4 region) of the running wheel rats. Mineralocorticoid receptor gene expression was increased in the dentate gyrus amongst wheel-running rats. No group differences were found in plasma corticosterone levels or mRNA levels of glucocorticoid receptor, corticotropin-releasing hormone, 5-HT(2C) or c-fos. In conclusion, we have found that social interaction is a major component of the enriched environment regarding the effects on NGFI-A and NGFI-B expression. These transcription factors may be important mediators of improved functional recovery after brain infarctions, induced by environmental enrichment.
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PMID:Effects of postischemic environment on transcription factor and serotonin receptor expression after permanent focal cortical ischemia in rats. 1280 85

Statins inhibit cholesterol biosynthesis and protect against ischaemic stroke. It has become increasingly apparent that the beneficial effects of statin therapy may extend beyond lowering of serum cholesterol. The present study was done to explore possible pleiotropic statin effects at the level of the cerebral vascular smooth muscle. Lovastatin, lovastatin acid, simvastatin and pravastatin, were added to segments of the rat basilar artery and effects on contraction and Ca2+ handling were examined. Pravastatin had no effect on contraction. Simvastatin, lovastatin, and, to a lesser degree, lovastatin acid, caused relaxation (IC50=0.8, 1.9 and 22 micromol/l) of both intact and denuded arteries precontracted with 5-HT or high-K+. This effect was not reversed by mevalonate, suggesting that it was not related to cholesterol or isoprenoid metabolism. Relaxation was associated with a reduction of the intracellular Ca2+ concentration measured with Fura 2 and with a reduced Mn2+ quench rate, suggesting a direct effect on ion channels in the smooth muscle cell membrane. Current measurements in isolated and voltage clamped basilar artery muscle cells demonstrated that both lovastatin and lovastatin acid inhibit L-type Ca2+ current. We propose that lipophilicity is an important factor behind the effects of statins on vascular tone and that Ca2+ current inhibition is the likely mechanism of action.
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PMID:Lovastatin induces relaxation and inhibits L-type Ca(2+) current in the rat basilar artery. 1296 37

Differences of alcohol drinking behavior, brain dopamine (DA) and serotonin (5-HT) levels and releases in the striatum were investigated in stroke-prone spontaneously hypertensive rats (SHRSP) and age-matched stroke-resistant spontaneously hypertensive rats (SHRSR). Voluntary alcohol (EtOH) consumption in SHRSP rats increased at 1 and 2 hours in the 4 hour time access. In the DA level, SHRSP showed decreases in the caudate-putamen (C/P) and dorsal raphe nucleus (DRN) compared with in SHRSR. 5-HT levels in the C/P, ventral tegmental area-subtantia nigra (V/S) and DRN of the SHRSP were decreased compared with that in SHRSR. The basal extracellular levels of 5-HT release in the C/P were increased in SHRSP as compared with those in SHRSR. K(+)- or EtOH-induced DA and 5-HT releases in the C/P of the SHRSP were a lower magnitude than those in SHRSR. Increased basal extracellular 5-HT releases showing low levels of 5-HT in the C/P of SHRSP mean an abnormality of serotonergic neuronal functions in a normal physiological condition. Higher voluntary alcohol drinking behavior, so called lower susceptibility to EtOH, in the SHRSP may be associated with the degenerated rewarding system including the DRN. These results suggest that the hypertensive state causes the dysfunction in the striatum of the brain rewarding system and induces the risk for increasing alcohol consumption to compensate for the alteration of serotonergic neurons.
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PMID:Pharmacological studies of alcohol susceptibility and brain monoamine function in stroke-prone spontaneously hypertensive rats (SHRSP) and stroke-resistant spontaneously hypertensive rats (SHRSR). 1460 56

In our pilot study, the depressive-like behaviors of mice exposed to cerebral ischemia reperfusion (CIR) were observed and the antidepressant effects of radix puerariae (RP; root of the Pueraria plant) extract in CIR mice were assessed because it was speculated that the neuronal damage caused by CIR played an important role in the development of poststroke depression (a common and severe complication after stroke) and the RP extract was reported to exhibit effect of neuronal protection from cerebral ischemia damage. Our studies above indicated that the RP extract markedly shortened the increased immobility time induced by CIR of male mice in the forced swimming test (FST) and tail suspension test (TST), indicating a possible antidepressant activity. Thus, the aim of the present study was to confirm the putative antidepressant effect of RP extract (75, 150, and 300 mg/kg, administered orally 24 h after the CIR) on reserpine-induced symptoms. To get further insight into the mode of antidepressant action of RP extract, biochemical examination was conducted concomitantly to examine possible involvement of the brain monoamine systems in the behavioral syndromes observed. In CIR mice, pronounced low levels of norepinephrine (NE) and 4-dihydroxyphenylacetic acid (DOPAC, a metabolite of dopamine) in the hippocampus or striatum were detected, which were reversed by RP extract, whereas no significant change of serotonin (5-HT) was detected in either CIR or RP extract-treated mice. The data suggested that the disturbance of NE and DA systems in hippocampus and striatum played more important roles in the development of depressive-like behavior of CIR mice than 5-HT system did, and RP extract ameliorated the abnormal symptoms caused by CIR, which may throw new lights on the treatment of poststroke depression.
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PMID:The antidepressant effect of ethanol extract of radix puerariae in mice exposed to cerebral ischemia reperfusion. 1521 73

Weight gain is associated with the use of many psychotropic medications, including antidepressants, mood stabilizers, antipsychotic drugs, and may have serious long term consequences: it can increase health risks, specifically from overweight (BMI = 25-29.9 kg/m2) to obesity (BMI > or =30 kg/m2), according to Body Mass Index (BMI), and the morbidity associated therewith in a substantial part of patients (hypertension, coronary heart desease, ischemic stroke, impaired glucose tolerance, diabetes mellitus, dyslipidemia, respiratory problems, osteoarthritis, cancer); according to patients, psychosocial consequences such as a sense of demoralization, physical discomfort and being the target of substantial social stigma are so intolerable that they may discontinue the treatment even if it is effective. The paper reviews actual epidemiological data concerning drug induced weight gain and associated health problems in psychiatric patients : there is a high risk of overweight, obesity, impaired glucose tolerance, diabetes mellitus, premature death, in patients with schizophrenia or bipolar disorder; and the effects of specific drugs on body weight: Tricyclic Antidepressants (TCA) induced weight gain correlated positively with dosage and duration of treatment, more pronounced with amitriptyline ; Selective Serotonin Reuptake Inhibitors (SSRI) decrease transiently bodyweight during the first few weeks of treatment and may then increase bodyweight; weight gain appears to be most prominent with some mood stabilizers (lithium, valproate); atypical antipsychotics tend to cause more weight gain than conventional ones and weight gain, diabetes, dyslipidemia, seem to be most severe with clozapine and olanzapine. Conceming the underlying mechanisms of drug induced weight gain, medications might interfere with central nervous functions regulating energy balance; patients report about: increase of appetite for sweet and fatty foods or "food craving" (antidepressants, mood stabilizers, antipsychotic drugs) and weight gain despite reduced appetite which can be explained by an altered resting metabolic rate (TCA, SSRI, Monoaminoxidase Inhibitors MAO I). According to current concepts, appetite and feeding are regulated by a complex of neurotransmitters, neuromodulators, cytokines and hormones interacting with the hypothalamus, including the leptin and the tumor necrosis factor system. The pharmacologic mechanisms underlying weight gain are presently poorly understood: maybe the different activities at some receptor systems may induce it, but also genetic predisposition. Understanding of the metabolic consequences of psychotropic drugs (weight gain, diabetes, dyslipidemia) is essential: the insulin-like effect of lithium is known; treatment with antipsychotic medications increases the risk of impaired glucose tolerance and diabetes mellitus. Several management options of weight gain are available from choosing or switching to another drug, dietary advices, increasing physical activities, behavioural treatment, but the best approach seems to attempt to prevent the weight gain : patients beginning maintenance therapy should be informed of that risk, and nutritional assessment and counselling should be a routine part of treatment management, associated with monitoring of weight, BMI, blood pressure, biological parameters (baseline and three months monitoring of fasting glucose level, fasting cholesterol and triglyceride levels, glycosylated haemoglobin). Psychiatrics must pay attention to concomitant medications and individual factors underlying overweight and obesity. Weight gain has been described since the discovery and the use of the firstpsychotropic drugs, but seems to intensify with especially some of the second generation antipsychotic medications ; understanding of the side effects of psychotropic drugs, including their metabolic consequences (weight gain, diabetes, dyslipidemia) is essential for the psychiatrics to avoid on the one hand a risk of lack of compliance, a discontinuation of the pharmacological medication and also a risk of relapse and rehospitalization, and on the other hand to avoid acute life threatening events (diabetic ketoacidocetosis and non ketotic hyperosmolar coma, long term risk complications of diabetes and overweight).
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PMID:[Psychotropic drugs induced weight gain: a review of the literature concerning epidemiological data, mechanisms and management]. 1638 18

Receptors have a prominent role in brain function, as they are the effector sites of neurotransmission at the postsynaptic membrane, have a regulatory role on presynaptic sites for transmitter reuptake and feedback, and are modulating various functions on the cell membrane. Distribution, density, and activity of receptors in the brain can be visualized by radioligands labeled for SPECT and PET, and the receptor binding can be quantified by appropriate tracer kinetic models, which can be modified and simplified for particular application. Selective radioligands are available for the various transmitter systems, by which the distribution of these receptors in the normal brain and changes in receptor binding during various physiologic activities or resulting from pathologic conditions can be visualized. The quantitative imaging for several receptors has gained clinical importance-for example, dopamine (D2)) receptors for differential diagnosis of movement disorders and for assessment of receptor occupancy by neuroleptics drugs; serotonin (5-hydroxytryptamine, 5-HT) receptors and the 5-HT transporter in affective disorders and for assessment of activity of antidepressants; nicotinic receptors and acetylcholinesterase as markers of cognitive and memory impairment; central benzodiazepine-binding sites at the gamma-aminobutyric acid A (GABAA) receptor complex as markers of neuronal integrity in neurodegenerative disorders, epilepsy, and stroke and as the site of action of benzodiazepines; peripheral benzodiazepine receptors as indicators of inflammatory changes; opioid receptors detecting increased cortical excitability in focal epilepsy but also affected in perception of and emotional response to pain; and several receptor systems affected in drug abuse and craving. Further studies of the various transmitter/receptor systems and their balance and infraction will improve our understanding of complex brain functions and will provide more insight into the pathophysiology of neurologic and psychiatric disease interaction.
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PMID:Brain receptor imaging. 1645 37

The lobster Homarus americanus inhabits ocean waters that vary in temperature over a 25 degrees C range, depending on the season and water depth. To investigate whether the lobster heart functions effectively over a wide range of temperatures we examine the temperature dependence of cardiac performance of isolated lobster hearts in vitro. In addition, we examined whether modulation of the heart by serotonin depends on temperature. The strength of the heartbeat strongly depends on temperature, as isolated hearts are warmed from 2 to 22 degrees C the contraction amplitude decreases by greater than 60%. The rates of contraction and relaxation of the heart are most strongly temperature dependent in the range from 2 to 4 degrees C but become temperature independent at warmer temperatures. Heart rates increase as a function of temperature both in isolated hearts and in intact animals, however hearts in intact animals beat faster in the temperature range of 12-20 degrees C. Interestingly, acute Q10 values for heart rate are similar in vivo and in vitro over most of the temperature range, suggesting that temperature dependence of heart rate arises mainly from the temperature effects on the cardiac ganglion. In contrast to earlier reports suggesting that the strength and the frequency of the lobster heartbeat are positively correlated, we observe no consistent relationship between these parameters as they change as a function of temperature. Stroke volume decreases as a function of temperature. However, the opposing temperature-dependent increase in heart rate partially compensates to produce a relationship between cardiac output and temperature in which cardiac output is maximal at 10 degrees C and significantly decreases above 20 degrees C. Serotonin potentiates contraction amplitude and heart rate in a temperature-independent manner. Overall, our results show that although the parameters underlying cardiac performance show different patterns of temperature dependence, cardiac output remains relatively constant over most of the wide range of environmental temperatures the lobster inhabits in the wild.
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PMID:Temperature dependence of cardiac performance in the lobster Homarus americanus. 1651 28


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