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

The importance of spinal cord amino acid receptors in the regulation of blood pressure was investigated in normotensive (Wistar Kyoto, WKY), spontaneously hypertensive (SHR), and stroke-prone spontaneously hypertensive (SPR) rats. Also investigated was the possible role of these spinal cord receptors in mediating pressor changes evoked by electrical stimulation of two separate areas of the rostral ventrolateral medulla (RVLM) containing different neuronal populations, either the adrenaline-containing C1 area or the serotonin-containing B3 area. Intrathecal administration of the amino acid receptor antagonist kynurenate (KYN), or the selective N-methyl-D-aspartate (NMDA) receptor antagonist 2-amino-5-phosphonovalerate (2APV), reduced basal blood pressure in anesthetized SHR and SPR in a dose-dependent manner, but were ineffective or elicited only small decreases in WKY. In all three strains, electrical stimulation in RVLM, in either the C1 or B3 area, evoked frequency-dependent pressor responses. Administration of 2APV or KYN was effective in attenuating these pressor responses in all three strains of rats. The effects of stimulation in the RVLM-B3 area were virtually abolished by administration of 2APV followed by the serotonin receptor antagonist methysergide. The results suggest that spinal cord excitatory amino acid receptors are important in blood pressure regulation in rats. Amino acid receptors, perhaps of the NMDA subtype, appeared to mediate pressor responses to stimulation of the RVLM-C1 and RVLM-B3 regions in both normotensive and hypertensive animals. On the other hand, excitatory amino acid receptor antagonists reduced basal blood pressure only in the hypertensive rats.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effect of intrathecal amino acid receptor antagonists on basal blood pressure and pressor responses to brainstem stimulation in normotensive and hypertensive rats. 169 9

Previous investigations by our group and others have demonstrated that poststroke depressions are not fully explained by the severity of associated impairment. We have consistently found, however, a strong association between development of major depression and left anterior brain injury. Recent studies have demonstrated that either left anterior cortical or subcortical lesions may lead to the development of major depression and that preexisting subcortical atrophy may play an important permissive role in the development of major depression. Patients with a mild degree of ventricular enlargement perhaps related to perinatal damage may be more likely to develop poststroke major depression following a lesion of the left frontal cortex or left basal ganglia than a patient without preexisting atrophy. Poststroke mania, on the other hand, is strongly associated with right hemisphere lesions as well as a preexisting subcortical atrophy and sometimes a family history of affective disorder. Thus, mania following brain injury may require the convergence of two factors: a right hemisphere brain injury and either a preexisting subcortical atrophy or a genetic vulnerability. PET scan findings have suggested that the biochemical response of the two hemispheres to stroke may be different. Right hemisphere stroke produces an increase in serotonin receptor binding, which is not found following comparable left hemisphere strokes. Within the left hemisphere, the lower the serotonin binding, the more severe the depression. This suggests that the right but not the left hemisphere may have an ability to increase serotonin binding in noninjured regions, producing a biochemical "compensation" for damage. This differential biochemical response to injury between the right and left hemisphere may partially explain why left hemisphere injury leads to depression and right hemisphere injury (in special circumstances) lead to mania. There remain, however, numerous unanswered questions and many important areas for future research. Although this area of neuropsychiatry is just beginning to develop, it is hoped that insights gained from studying mood disorders in brain-injured patients may also help to illuminate mechanisms involved in affective disorder in patients without brain injury.
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PMID:Mood disorders following stroke: new findings and future directions. 260 85

Patients with right-hemisphere strokes (N = 9) more than 1 year after injury had greater cortical binding of (3-N-[11C]methyl)spiperone than a similar group of patients with left-hemisphere strokes (N = 8) or normal control subjects (N = 17). The higher S2 serotonin receptor binding occurred in uninjured regions of the right parietal and temporal cortex. The ratio of binding in the ipsilateral to contralateral cortex showed a significant negative correlation with severity of depression scores in the left temporal cortex. These findings suggest that the biochemical response of the brain may be different depending on which hemisphere is injured and that some depressions may be a consequence of the failure to upregulate serotonin receptors after stroke.
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PMID:PET imaging of cortical S2 serotonin receptors after stroke: lateralized changes and relationship to depression. 339 77

A patient with post-stroke depression following infarction of the left basal ganglia is described. The patient's depression remitted during a 6-week double-blind treatment trial while receiving placebo medication. Cortical S2-receptor binding that was measured using 11C-N methyl spiperone and positron emission tomography (PET), increased in the left temporal cortex by more than 25% during the treatment trial. The change in serotonin receptor binding and its relationship to the improvement in mood observed in this patient are consistent with previously published data demonstrating a correlation between serotonin receptor binding in the left temporal cortex and severity of symptoms of depression.
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PMID:Spontaneous remission of post-stroke depression and temporal changes in cortical S2-serotonin receptors. 758 Jan 80

Ketanserin, a selective S2-serotonin receptor blocker with alpha 1-adrenergic blocking effects, may be a suitable antihypertensive medication after coronary artery surgery and lacks side effects seen with other vasodilators. Fifty patients with systolic blood pressures greater than 150 mmHg after coronary artery surgery were given, in a randomized double-blind fashion, either ketanserin (K) or saline (S). Each patient received six successive boluses of 1 mL of S or 1 mL of K (5 mg) at 2-minute intervals. After the last injection, sodium nitroprusside was started whenever the systolic blood pressure exceeded 150 mmHg. In the K group, the following significant (P < 0.05) changes occurred: systolic and diastolic arterial pressure -12% and -11%, respectively; heart rate -3%; systolic and diastolic pulmonary artery pressure -5% and -6%; central venous pressure -5%; pulmonary capillary wedge pressure -5%; systemic vascular resistance -16%; pulmonary vascular resistance -8%; stroke index +6%. None of these parameters changed significantly in the S group. There was no change in pulmonary shunt fraction in either group. In the K group, five patients did not require any further antihypertensive therapy during the 120 minutes following the last bolus injection. Twenty patients needed sodium nitroprusside during this period. This occurred 37 minutes (+/- 17 min) after the last bolus. In conclusion, after coronary artery bypass surgery, K is an effective antihypertensive medication, which does not cause reflex tachycardia or an increase in pulmonary shunt fraction. Exceeding the recommended dose of 10 (or 20) mg, as done in this study, does not seem to improve effectiveness or prolong the duration of action.
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PMID:Use of ketanserin in the treatment of hypertension following coronary artery surgery. 806 Dec 66

Cortical serotonin receptor binding was measured with positron-emission tomography (PET) in uninjured regions of cortex in 26 stroke patients. Cognitive function was assessed with the Mini-Mental State Exam (MMSE) and a neuropsychological test battery. Left frontal cortex serotonin binding was correlated positively with MMSE total score (r = 0.50, P = 0.01) and with the MMSE concentration, writing, and copying tasks (r = 0.42, 0.56, 0.53, respectively; P < 0.05). Tests of orientation and repetition of difficult phrases were significantly correlated with serotonin binding (r = 0.53 and 0.52, respectively; P < 0.05). These findings suggest that cognitive performance after stroke may be influenced by alterations in the serotonergic system.
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PMID:A preliminary study of cortical S2 serotonin receptors and cognitive performance following stroke. 828 37

The European Neuroscience--Seventh Biennial FENS Forum, held in Amsterdam, included topics covering new therapeutic developments in the field of neuroscience. This conference report highlights selected presentations on sodium channel inhibitors, ionotropic glutamate receptor antagonists, serotonin receptor modulators, and novel therapies for depression, pain and stroke. Investigational drugs discussed include ST-1936 (Sigma-Tau Industrie Farmaceutiche Riunite SpA), LY-392098 (Eli Lilly & Co) and Lu-AA21004 (H Lundbeck A/S/Takeda Pharmaceutical Co Ltd).
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PMID:European Neuroscience--Seventh Biennial FENS Forum. 2079 40

Since its discovery as a src kinase substrate more than three decades ago, appreciation for the physiologic functions of annexin A2 and its associated proteins has increased dramatically. With its binding partner S100A10 (p11), A2 forms a cell surface complex that regulates generation of the primary fibrinolytic protease, plasmin, and is dynamically regulated in settings of hemostasis and thrombosis. In addition, the complex is transcriptionally upregulated in hypoxia and promotes pathologic neoangiogenesis in the tissues such as the retina. Dysregulation of both A2 and p11 has been reported in examples of rodent and human cancer. Intracellularly, A2 plays a critical role in endosomal repair in postarthroplastic osteolysis, and intracellular p11 regulates serotonin receptor activity in psychiatric mood disorders. In human studies, the A2 system contributes to the coagulopathy of acute promyelocytic leukemia, and is a target of high-titer autoantibodies in patients with antiphospholipid syndrome, cerebral thrombosis, and possibly preeclampsia. Polymorphisms in the human ANXA2 gene have been associated with stroke and avascular osteonecrosis of bone, two severe complications of sickle cell disease. Together, these new findings suggest that manipulation of the annexin A2/S100A10 system may offer promising new avenues for treatment of a spectrum of human disorders.
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PMID:The annexin A2/S100A10 system in health and disease: emerging paradigms. 2319 60

Despite the fact that a high proportion of elderly stroke patients develop mood disorders, the mechanisms underlying late-onset neuropsychiatric and neurocognitive symptoms have so far received little attention in the field of neurobiology. In rodents, aged animals display depressive symptoms following stroke, whereas young animals recover fairly well. This finding has prompted us to investigate the expression of serotonin receptors 2A and 2B, which are directly linked to depression, in the brains of aged and young rats following stroke. Although the development of the infarct was more rapid in aged rats in the first 3 days after stroke, by day 14 the cortical infarcts were similar in size in both age groups i.e. 45% of total cortical volume in young rats and 55.7% in aged rats. We also found that the expression of serotonin receptor type B mRNA was markedly increased in the perilesional area of aged rats as compared to the younger counterparts. Furthermore, histologically, HTR2B protein expression in degenerating neurons was closely associated with activated microglia both in aged rats and human subjects. Treatment with fluoxetine attenuated the expression of Htr2B mRNA, stimulated post-stroke neurogenesis in the subventricular zone and was associated with an improved anhedonic behavior and an increased activity in the forced swim test in aged animals. We hypothesize that HTR2B expression in the infarcted territory may render degenerating neurons susceptible to attack by activated microglia and thus aggravate the consequences of stroke.
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PMID:Up-regulation of serotonin receptor 2B mRNA and protein in the peri-infarcted area of aged rats and stroke patients. 2701 93

In addition to maintaining immune tolerance, FOXP3+ regulatory T (Treg) cells perform specialized functions in tissue homeostasis and remodelling1,2. However, the characteristics and functions of brain Treg cells are not well understood because there is a low number of Treg cells in the brain under normal conditions. Here we show that there is massive accumulation of Treg cells in the mouse brain after ischaemic stroke, and this potentiates neurological recovery during the chronic phase of ischaemic brain injury. Although brain Treg cells are similar to Treg cells in other tissues such as visceral adipose tissue and muscle3-5, they are apparently distinct and express unique genes related to the nervous system including Htr7, which encodes the serotonin receptor 5-HT7. The amplification of brain Treg cells is dependent on interleukin (IL)-2, IL-33, serotonin and T cell receptor recognition, and infiltration into the brain is driven by the chemokines CCL1 and CCL20. Brain Treg cells suppress neurotoxic astrogliosis by producing amphiregulin, a low-affinity epidermal growth factor receptor (EGFR) ligand. Stroke is a leading cause of neurological disability, and there are currently few effective recovery methods other than rehabilitation during the chronic phase. Our findings suggest that Treg cells and their products may provide therapeutic opportunities for neuronal protection against stroke and neuroinflammatory diseases.
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PMID:Brain regulatory T cells suppress astrogliosis and potentiate neurological recovery. 3060 86


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