pituitrin and Nervous-System-Diseases

Stroke is a life-threatening condition in which accurate diagnoses and timely treatment are critical for successful neurological recovery. The current acute treatment strategies, particularly non-invasive interventions, are limited, thus urging the need for novel therapeutical targets. Arginine vasopressin (AVP) receptor antagonists are emerging as potential targets to treat edema formation and subsequent elevation in intracranial pressure, both significant causes of mortality in acute stroke. Here, we summarize the current knowledge on the mechanisms leading to AVP hyperexcretion in acute stroke and the subsequent secondary neuropathological responses. Furthermore, we discuss the work supporting the predictive value of measuring copeptin, a surrogate marker of AVP in stroke patients, followed by a review of the experimental evidence suggesting AVP receptor antagonists in stroke therapy. As we highlight throughout the narrative, critical gaps in the literature exist and indicate the need for further research to understand better AVP mechanisms in stroke. Likewise, there are advantages and limitations in using copeptin as a prognostic tool, and the translation of findings from experimental animal models to clinical settings has its challenges. Still, monitoring AVP levels and using AVP receptor antagonists as an add-on therapeutic intervention are potential promises in clinical applications to alleviate stroke neurological consequences.

Topics: Animals; Antidiuretic Hormone Receptor Antagonists; Arginine; Arginine Vasopressin; Glycopeptides; Nervous System Diseases; Stroke; Vasopressins

Copeptin, arginine vasopressin (AVP)-associated 39 aminoacid glycopeptide, is a C-terminal part of pro-AVP. AVP acts through V1a, V1b, and V2 receptors. The effect on V1a receptors is connected with arterial vasoconstriction, on V2 with antidiuretic action, and on V1b with the secretion of ACTH, insulin, glucagon. Copeptin is found in the circulation in equimolar amounts with AVP. It is a very stable peptide and easy to estimate. Copeptin is a good diagnostic marker in many disorders in which vasopressinergic dysfunction plays a role in pathogenesis such as a polyuria-polydipsia syndrome, neurological disease (ischemic stroke, nontraumatic, intracerebral hemorrhage, aneurysmal subarachnoid hemorrhage and neurodegenerative disease (multiple sclerosis). Copeptin is a diagnostic and prognostic marker in cardiovascular diseases like heart failure (HF) and acute myocardial infarct (AMI). Copeptin is a sensitive diagnostic marker in the early stage of AMI especially in patients with non-ST segment elevation and post AMI complications. Copeptin is also an important diagnostic and prognostic marker in metabolic diseases (diabetes mellitus, metabolic syndrome, insulin resistance), connected with some neurological and cardiovascular diseases. In the future, these findings may have also therapeutic applications in conditions where the AVP receptor antagonist therapy is appropriate.

Topics: Biomarkers; Cardiovascular Diseases; Glycopeptides; Humans; Nervous System Diseases; Neurophysins; Predictive Value of Tests; Prognosis; Protein Precursors; Vasopressins

Hyponatremia is frequently associated with neurological disease, neurosurgical procedures, and use of psychoactive drugs. Arginine vasopressin (AVP), or antidiuretic hormone, is the principal physiological regulator of water and electrolyte balance, and disruption of the normal AVP response to osmotic stimuli is a common cause of dilutional hyponatremia in neurological disorders. The hyponatremia-induced shift in water from the extracellular to the intracellular compartment can lead to cerebral edema and serious neurological complications, especially if the decrease in serum sodium concentration ([Na+]) is large or rapid. Overly rapid correction of the serum [Na+] may lead to osmotic demyelination and irreversible brain injury. Fluid restriction is considered first-line treatment and pharmacological agents currently used in the treatment of hyponatremia are limited by inconsistent response and adverse side effects. AVP receptor antagonists represent a new approach to the treatment of hyponatremia by blocking tubular reabsorption of water by binding to V2 receptors in the renal collecting ducts, resulting in aquaresis. Initial clinical experience with AVP receptor antagonists for hyponatremia has shown that these agents augment free water clearance, decrease urine osmolality, and correct serum [Na+] and serum osmolality. Controlled clinical trials now underway will help elucidate the role of AVP receptor antagonism in the treatment of hyponatremia.

Topics: Animals; Antidiuretic Hormone Receptor Antagonists; Humans; Hyponatremia; Models, Biological; Nervous System Diseases; Osmolar Concentration; Receptors, Vasopressin; Sodium; Vasopressins; Water-Electrolyte Balance; Water-Electrolyte Imbalance

The neuropeptides vasopressin, adrenocorticotropin (ACTH), and beta-endorphin seem to have important effects on memory and learning. Animal studies attempting to demonstrate these effects are difficult to interpret because of the complexity of behavior that is described as "learning" and the impossibility of assessing verbal learning in animals. This article therefore reviews some of the animal literature on neuropeptides and learning, but focuses primarily upon studies in humans, both in normal volunteers and in patients with neurological disorders. Vasopressin enhances learning under some conditions. Intranasal administration has been associated with improvement on psychometric tests in patients with mild Alzheimer's disease and Korsakoff's psychosis, although these findings are not uniform. It improves performance on memory tests in normal volunteers, but does not seem to improve the memory deficit after head trauma. Cerebrospinal fluid levels are low in patients with Alzheimer's disease. ACTH and melanocyte-stimulating hormone (MSH) are two peptides the primary behavioral effect of which seems to be on attention or goal-motivated behavior rather than on memory processes themselves. Visual discrimination and the ability to continue repetitive tasks are enhanced; in mentally retarded subjects, the administration of ACTH or MSH improves performance on a variety of neuropsychological tests. It does not, however, improve cognitive function in the elderly. Endogenous opioids including beta-endorphin and met-enkephalin seem to have primarily an amnesic effect in animal studies. Their role in human learning is still uncertain, although naloxone, which antagonizes their effects, has been associated with improved cognitive performance in patients with Alzheimer's disease. These data underscore the complexity of the processes associated with human memory and the rudimentary state of our present knowledge. Whatever the mechanisms, however, vasopressin, ACTH, and endogenous opioids seem to have important effects upon memory.

Topics: Adrenocorticotropic Hormone; Animals; Endorphins; Forecasting; Humans; Learning; Melanocyte-Stimulating Hormones; Memory; Memory Disorders; Nerve Tissue Proteins; Nervous System Diseases; Oxytocin; Pituitary Gland, Posterior; Vasopressins

Neuropeptides are sufficiently stable to allow valid radioimmunoassay of peptide concentrations in post-mortem human nervous tissue and in human cerebrospinal fluid. Studies have now documented abnormalities of peptide concentrations in degenerative diseases of the brain. Somatostatin concentration is reduced in the hippocampus and neocortex of patients dying with Alzheimer's type dementia. In Huntington's disease, there are reduced concentrations of substance P, met-enkephalin and cholecystokinin in the basal ganglia; in contrast the concentrations of somatostatin and TRH are increased. Immunocytochemical and experimental lesion studies are underway in an attempt to localize the peptide-containing cells affected by these disorders; and the potential role of alterations in neuropeptide function in the pathogenesis, clinical manifestations and therapy of these illnesses is of great interest. Although alterations of CSF peptide concentrations have been reported in a variety of human diseases, interpretation of these results requires knowledge of the origin and disposition of CSF peptides. Future research into the pathology of peptidergic systems will depend on the development of specific peptide antagonists to probe dynamic aspects of peptide function and on the application of the tools of molecular biology, such as specific mRNA assays, to human material.

Topics: Alzheimer Disease; Animals; Brain; Cholecystokinin; Choline O-Acetyltransferase; Endorphins; Epilepsy; Forecasting; Histocytochemistry; Humans; Huntington Disease; Migraine Disorders; Nerve Tissue Proteins; Nervous System Diseases; Pain; Parkinson Disease; Radioimmunoassay; Somatostatin; Substance P; Thyrotropin-Releasing Hormone; Tissue Distribution; Vasopressins

This review highlights that essentially all of the recently discovered putative central nervous system (CNS) peptides and other peptide substances are measurable in human cerebrospinal fluid (CSF). Preliminary evidence also suggests that peptides in CSF may have an active regulatory role in relation to CNS function and behavior. Even if this is not the case, CSF peptides may prove to be a useful indirect marker of CNS peptide function and metabolism. Alterations in peptides have been reported in neurological and psychiatric illness, pain symptoms and their treatment, symptoms such as anxiety, and following treatment with CNS active drugs such as carbamazepine. CSF methodologies provide a strategy for the study of the interaction of classical neurotransmitters and peptide substances and their relationship to neural function and behavior in man. Assessment of peptides in CSF may supplement post mortem studies of peptide levels and receptor distribution and help lead to new diagnostic and treatment approaches in neuropsychiatric disorders.

Topics: Adrenocorticotropic Hormone; Angiotensins; beta-Endorphin; Calcitonin; Endorphins; Humans; Mental Disorders; Nervous System Diseases; Oxytocin; Peptides; Somatostatin; Substance P; Vasoactive Intestinal Peptide; Vasopressins; Vasotocin

Topics: Abdomen; Autonomic Nervous System; Axons; Constipation; Cranial Nerves; Depression; Diabetic Neuropathies; Drug Interactions; Hallucinations; Humans; Hyponatremia; Hypotension, Orthostatic; Intestinal Obstruction; Muscular Atrophy; Nervous System Diseases; Neural Conduction; Norepinephrine; Pain; Paresthesia; Parkinson Disease; Peripheral Nervous System Diseases; Seizures; Vasopressins; Vincristine

Topics: Achilles Tendon; Animals; Antineoplastic Agents; Autonomic Nervous System; Central Nervous System Diseases; Cranial Nerves; Gastrointestinal Diseases; Hodgkin Disease; Humans; Lymphoma; Motor Activity; Nervous System; Nervous System Diseases; Neurologic Manifestations; Nitrogen Mustard Compounds; Paresthesia; Peripheral Nervous System Diseases; Procarbazine; Reflex, Stretch; Seizures; Vasopressins; Vinblastine; Vincristine

Topics: Adrenal Cortex Hormones; Adult; Analgesics; Antifibrinolytic Agents; Blood Transfusion; Cardiovascular Diseases; Child; Contraceptives, Oral; Estrogens; Factor IX; Factor VIII; Gastrointestinal Diseases; Hemarthrosis; Hemophilia A; Hemophilia B; Hemorrhage; Home Nursing; Humans; Infections; Inhalation; Nervous System Diseases; Social Adjustment; Thyroxine; Triiodothyronine; Urologic Diseases; Vasopressins

Topics: Anencephaly; Cavernous Sinus; Cerebral Angiography; Diabetes Insipidus; Diabetic Retinopathy; Endocrine System Diseases; Feedback; Hemianopsia; Humans; Hypothalamo-Hypophyseal System; Nervous System Diseases; Neurosecretion; Phlebography; Pituitary Hormones, Posterior; Pituitary Neoplasms; Pneumoencephalography; Sella Turcica; Vasopressins; Water Deprivation

Sensitive biomarkers are needed to rapidly identify high-risk infants after hypoxia-ischemia for neuroprotective treatment. Hypotension is a key determinant of hypoxic-ischemic neural injury, and a potent stimulus of humoral pressors including angiotensin-II and arginine vasopressin. We therefore aimed to quantify the relationship between vasopressin and angiotensin-II levels in the latent phase after hypoxia-ischemia induced by umbilical cord occlusion (UCO) with both the severity of preceding hypotension and subsequent neuronal injury.. Chronically instrumented near-term fetal sheep underwent sham-UCO or UCO for either 15 min or until mean arterial pressure was <8 mmHg. Neuronal injury was assessed after 72 h recovery.. Umbilical cord occlusion was associated with severe hypotension that recovered after UCO; two fetuses developed profound secondary hypotension within 6 h and died. Vasopressin levels but not angiotensin-II were significantly elevated 1-3 h after UCO and were closely associated with the severity of hypotension during UCO and the subsequent severity of neuronal loss in the parasagittal and lateral cortex, caudate nucleus and putamen. The Youden cut-point for vasopressin at 1 h was 180.0 pmol/L, with sensitivity 100% and specificity 92.3% for severe neuronal injury or death.. Vasopressin levels shortly after moderate-severe hypoxia-ischemia may be a useful early biomarker to guide the timely implementation of neuroprotective treatment.. It can be difficuIt to rapidly identify infants who might benefit from therapeutic hypothermia. We investigated whether increases in plasma pressor hormones early after hypoxia-ischemia were biomarkers for neonatal hypoxic-ischemic encephalopathy using near-term fetal sheep. Arginine vasopressin levels were elevated at 1-3 h after hypoxia-ischemia and were predictive of the severity of preceding hypotension and subsequent risk of severe neuronal injury or death after hypoxia-ischemia. Arginine vasopressin may help identify neonates at high risk of hypoxic-ischemic encephalopathy early within the therapeutic window for hypothermia.

Topics: Angiotensin II; Animals; Arginine Vasopressin; Biomarkers; Blood Gas Analysis; Disease Models, Animal; Female; Fetal Hypoxia; Hydrogen-Ion Concentration; Hypotension; Hypoxia-Ischemia, Brain; Male; Nervous System Diseases; Neurons; Sheep; Umbilical Cord; Vasopressins

To study the effects of the combination of adrenaline (epinephrine) and vasopressin compared to adrenaline alone on initial resuscitation success, 24h survival, and neurological outcome in a swine model of asphyxial cardiac arrest (CA).. This prospective randomized experimental study was conducted at a laboratory research department. Twenty female Landrace/Large-White pigs, 12-15 weeks of age, were investigated. Asphyxial CA was induced by clamping of the endotracheal tube. After 4min of untreated CA, resuscitation was initiated by unclamping the endotracheal tube, mechanical ventilation, chest compressions and adrenaline (Group A) or a combination of adrenaline with vasopressin (Group A+V) administered intravenously. In case of restoration of spontaneous circulation (ROSC), the animals were monitored for 30min and then observed for 24h.. Hemodynamic variables were measured at baseline during CPR and in the post-resuscitation period. Statistically significant difference was observed in groups A and A+V regarding coronary perfusion pressure (CPP) during the first minute of CPR. In both groups, ROSC and survival rates were comparable (p=NS). Neurological deficit score (NDS) was significantly higher in the combination group 24h following CA (p<0.001). Brain histological damage score (HDS) was also better in the combination group (p<0.001). Total HDS and NDS showed a statistical significant correlation (p<0.001).. In this porcine model of asphyxial CA, adrenaline alone as well as the combined administration of adrenaline and vasopressin resulted in similar ROSC and survival rates, but the combination of adrenaline and vasopressin resulted in improved neurological and cerebral histopathological outcomes.

Topics: Analysis of Variance; Animals; Asphyxia; Cardiopulmonary Resuscitation; Cerebrovascular Circulation; Combined Modality Therapy; Disease Models, Animal; Dose-Response Relationship, Drug; Drug Therapy, Combination; Epinephrine; Female; Heart Arrest; Hemodynamics; Infusions, Intravenous; Nervous System Diseases; Random Allocation; Recovery of Function; Reference Values; Risk Assessment; Survival Rate; Sus scrofa; Swine; Time Factors; Vasopressins

Topics: Central Nervous System Diseases; Child; Histiocytosis, Langerhans-Cell; Humans; Nervous System Diseases; Prognosis; Vasopressins

Topics: Animals; Genetic Diseases, Inborn; Genetics, Behavioral; Humans; Nervous System Diseases; Oxytocin; Vasopressins

We sought to determine the effects of a combination of vasopressin and epinephrine on neurologic recovery in comparison with epinephrine alone and saline placebo alone in an established porcine model of prolonged cardiopulmonary resuscitation (CPR). After 4 min of cardiac arrest, followed by 3 min of basic life support CPR, 17 animals were randomly assigned to receive, every 5 min, either a combination of vasopressin and epinephrine (vasopressin [IU/kg]/epinephrine [ micro g/kg]: 0.4/45, 0.4/45, and 0.8/45; n = 6), epinephrine alone (45, 45, and 200 micro g/kg; n = 6), or saline placebo alone (n = 5). After 22 min of cardiac arrest, including 18 min of CPR, defibrillation was attempted to achieve the return of spontaneous circulation. Aortic diastolic pressure was significantly (P < 0.01) increased 90 s after each of 3 vasopressin/epinephrine injections versus epinephrine alone versus saline placebo alone (mean +/- SEM: 69 +/- 3 mm Hg versus 45 +/- 3 mm Hg versus 29 +/- 2 mm Hg, 63 +/- 4 mm Hg versus 27 +/- 3 mm Hg versus 23 +/- 1 mm Hg, and 52 +/- 4 mm Hg versus 21 +/- 3 mm Hg versus 16 +/- 3 mm Hg, respectively). Spontaneous circulation was restored in six of six vasopressin/epinephrine pigs, whereas six of six epinephrine and five of five saline placebo pigs died (P < 0.01). Neurologic evaluation 24 h after successful resuscitation revealed only an unsteady gait and was normal 5 days after the experiment in all vasopressin/epinephrine-treated animals. In conclusion, in this porcine model of prolonged CPR, repeated vasopressin/epinephrine administration, but not epinephrine or saline placebo alone, ensured long-term survival with full neurologic recovery.. We present a study to evaluate the effects of a combination of vasopressin and epinephrine during prolonged cardiopulmonary resuscitation on neurological outcome in pigs. We found that all pigs treated with a combination of vasopressin and epinephrine could be resuscitated and had full neurologic recovery observed over an entire period of 5 days.

Topics: Animals; Blood Gas Analysis; Blood Pressure; Body Weight; Cardiopulmonary Resuscitation; Drug Combinations; Electric Countershock; Electrocardiography; Epinephrine; Heart Arrest; Hemodynamics; Lactic Acid; Nervous System Diseases; Survival; Swine; Vasoconstrictor Agents; Vasopressins; Ventricular Fibrillation

In experimental cardiopulmonary resuscitation (CPR) aortic balloon occlusion, vasopressin, and hypertonic saline dextran administration improve cerebral blood flow. Free radical scavenger alpha-phenyl-N-tert-butyl-nitrone (PBN) and cyclosporine-A (CsA) alleviate neuronal damage after global ischemia. Combining these treatments, we investigated neurological outcome after experimental cardiac arrest.. : Thirty anesthetized piglets, randomly allocated into three groups, were subjected to 8 min of ventricular fibrillation followed by 5 min of closed-chest CPR. The combined treatment (CT) group received all the above-mentioned modalities; group B was treated with balloon occlusion and epinephrine; and group C had sham balloon occlusion with epinephrine. Indicators of oxidative stress (8-iso-PGF(2 alpha)), inflammation (15-keto-dihydro-PGF(2 alpha)), energy crisis (hypoxanthine and xanthine), and anoxia/hypoxia (lactate) were monitored in jugular bulb venous blood. Neurological outcome was evaluated 24 h after CPR.. : Restoration of spontaneous circulation (ROSC) was more rapidly achieved and neurological outcome was significantly better in the CT group, although there was no difference in coronary perfusion pressure between groups. The jugular venous PCO2 and cerebral oxygen extraction ratio were lower in the CT group at 5-15 min after ROSC. Jugular venous 8-iso-PGF(2 alpha) and hypoxanthine after ROSC were correlated to 24 h neurological outcome. : A combination of cerebral blood flow promoting measures and administration of alpha-phenyl-N-tert-butyl-nitrone and cyclosporine-A improved 24 h neurological outcome after 8 min of experimental normothermic cardiac arrest, indicating an ongoing neuronal injury in the reperfusion phase.

Topics: Angioplasty, Balloon, Coronary; Animals; Cardiopulmonary Resuscitation; Cerebrovascular Circulation; Cyclosporine; Dinoprost; Epinephrine; Free Radical Scavengers; Heart Arrest; Hypoxanthine; Lactic Acid; Nervous System Diseases; Saline Solution, Hypertonic; Swine; Treatment Outcome; Vasoconstrictor Agents; Vasopressins; Xanthine

We evaluated plasma osmolality (pOsm), thirst, and vasopressin response to hypertonic saline infusion in 14 patients with multiple system atrophy (MSA). This disease is characterized by the degeneration of noradrenergic neurons in the central nervous system and severe orthostatic hypotension. Seven patients were also characterized by the lack of vasopressin response to hypotension (group B) and seven by a preserved response (group A). In group A pOsm rose from 290 +/- 2 to 312 +/- 6 mosmol/kgH2O, vasopressin from 0.9 +/- 0.3 to 5.7 +/- 0.5 pmol/l, and thirst from 1.1 +/- 0.1 to 8.7 +/- 1.1 cm on the visual analog scale. After saline, patients drank 1,215 +/- 150 ml of water (no different from healthy controls). In group B patients' pOsm rose from 296 +/- 3 to 325 +/- 6 mosmol/kgH2O and vasopressin from 1.2 +/- 0.1 to 19.6 +/- 0.4 pmol/l (P < 0.01 vs. group A and controls). Group B patients had no thirst during saline and drank little after the challenge (175 +/- 50 ml; P < 0.01 vs. group A and control). Forced drinking decreased vasopressin in patients before changes in pOsm, showing that inhibitory afferents from oropharyngeal mucosa were intact. In MSA patients with altered afferent control of vasopressin there is a dissociation between the osmotic control of thirst and the osmotic control of vasopressin.

Topics: Afferent Pathways; Atrophy; Denervation; Drinking; Female; Hemodynamics; Humans; Hypotension, Orthostatic; Male; Middle Aged; Nervous System Diseases; Norepinephrine; Osmosis; Pressoreceptors; Saline Solution, Hypertonic; Sinus of Valsalva; Thirst; Vasopressins

Thyrotrophin-releasing hormone and gonadotrophin-releasing hormone were measured in lumbar CSF from patients with idiopathic senile dementia, cerebral tumours and spinal disc lesions. Somatostatin was also measured in lumbar CSF from patients with dementia and patients with other neurological disorders, but the numbers involved were much smaller. The levels of these neuropeptides were significantly reduced in the patients with senile dementia. These results suggest a possible involvement of hpothalamic neuropeptides in idiopathic senile dementia.

Topics: Aged; Brain Neoplasms; Dementia; Gonadotropin-Releasing Hormone; Humans; Intervertebral Disc Displacement; Nervous System Diseases; Somatostatin; Thyrotropin-Releasing Hormone; Vasopressins

We used dDAVP, the 1-desamino-8-D arginine analogue of arginine vasopressin with high antidiuretic and low vasopressor potency, to treat 29 patients with neurogenic diabetes insipidus for up to 22 months. Intranasal dDAVP, 2.5 to 15 microgram twice daily, provided excellent control in most patients. Individual responses were independent of age, weight, and severity of diabetes insipidus. Resistance to dDAVP may be a rare complication of prolonged therapy. Two patients with acute postoperative diabetes insipidus were effectively treated with 5 microgram of dDAVP every 14 to 18 h. Compared to previous therapy, side effects of dDAVP were minimal (headaches in two patients), and control of symptoms and urine volume was as good as with vasopressin tannate in oil or better than chlorpropamide and lysine vasopressin nasal spray. We conclude that intranasal dDAVP, because of efficacy, long duration of action, and infrequent side effects, is the preferred treatment of neurogenic diabetes insipidus in children and adults.

Topics: Adolescent; Adult; Aged; Arginine Vasopressin; Child; Diabetes Insipidus; Female; Humans; Male; Middle Aged; Nervous System Diseases; Osmolar Concentration; Postoperative Complications; Vasopressins

Five dysautonomic patients with the Shy-Drager syndrome were studied to determine the basis of their nocturnal polyuria. The results indicated excessive postural modification of renal function in dysautonomic patients. This may, in fact, relate to excessive release of ADH while these patients are up and about, and excessive inhibition while they are recumbent. Treatment with vasopressin produced an inconsistent response.

Topics: Aged; Circadian Rhythm; Dysautonomia, Familial; Evaluation Studies as Topic; Fecal Incontinence; Female; Humans; Hydrocortisone; Hypotension, Orthostatic; Kidney; Male; Middle Aged; Nervous System Diseases; Osmolar Concentration; Parkinson Disease; Posture; Potassium; Sodium; Syndrome; Urinary Incontinence; Vasopressins; Water Deprivation

Topics: Animals; Female; Humans; Male; Nervous System Diseases; Vasopressins

Topics: Adrenocorticotropic Hormone; Blood Glucose; Endocrine Glands; Female; Humans; Hydrocortisone; Hypoglycemia; Insulin; Lysine; Male; Multiple Sclerosis; Nervous System Diseases; Pituitary-Adrenal Function Tests; Vasopressins