oxytocin and Cerebral-Hemorrhage

Tocolytics are potent drugs that are used to interdict preterm labour. Although all of these agents have some side effects, if not frankly adverse effects under certain clinical situations, two of these drugs, the beta-mimetics and magnesium sulphate (MgSO(4)), have been found to have considerable potential for adverse maternal cardiovascular and respiratory effects. Furthermore, magnesium sulphate has been shown to have harmful, indeed, sometimes lethal, effects in some babies. Although less well established, NSAIDs, the most common example of which is indomethacin, also have some important adverse effects in fetuses. Within the limits of contemporary scientific knowledge, calcium channel blockers, such as nifedipine, appear to be among the more efficacious and safer drugs that are currently being used for tocolysis.

Topics: Adrenergic beta-Agonists; Adult; Calcium Channel Blockers; Cerebral Hemorrhage; Cerebral Palsy; Cyclooxygenase Inhibitors; Female; Fetal Diseases; Hormone Antagonists; Humans; Infant, Newborn; Magnesium Sulfate; Neuroprotective Agents; Obstetric Labor, Premature; Oxytocin; Pre-Eclampsia; Pregnancy; Risk Assessment; Tocolysis; Tocolytic Agents

We report of a woman with post-partum cerebral angiopathy (PCA), in whom we repetitively performed transcranial Doppler sonography (TCD), MR imaging (MRI), and MR angiography (MRA) to evaluate the underlying pathophysiology. A 31-year-old woman, Gemini pregnant, complained of severe throbbing frontal headache four days after an uneventful delivery by Cesarean section. Blurred vision occurred eight days after delivery, followed by three generalized tonic-clonic seizures. Neurological examination revealed a somnolent woman without focal neurological deficits. At the day of the seizures increased flow velocities and disturbed flow were observed in the right posterior and anterior cerebral artery on transcranial Doppler (TCD). MRI showed infra- and supratentorial patchy hyperintensities in T2-weighted images and in the FLAIR sequence. Diffusion-weighted imaging revealed corresponding multi-focal hyperintense areas indicating increased diffusion and MRA showed a diffuse multisegmental narrowing of all pial arteries. MRI at day 10 was completely normal, but MRA still revealed vascular narrowing in the right posterior cerebral artery. General slight flow accelerations in all basal arteries occurred after 10 days and lasted for three weeks. PCA is apparently associated with a vascular narrowing causing cerebral ischemia with increased diffusion. Later reactive cerebral hyperperfusion is observed. Vascular narrowing and cerebral hyperperfusion still persist after MRI has normalized.

Topics: Acetates; Adult; Amines; Anti-Inflammatory Agents, Non-Steroidal; Anticonvulsants; Aspirin; Brain Edema; Cerebral Angiography; Cerebral Arteries; Cerebral Hemorrhage; Cerebrovascular Circulation; Cyclohexanecarboxylic Acids; Echoencephalography; Eclampsia; Female; Gabapentin; gamma-Aminobutyric Acid; Humans; Magnetic Resonance Angiography; Magnetic Resonance Imaging; Observer Variation; Oxytocin; Postpartum Period; Pregnancy; Sensitivity and Specificity; Time Factors; Ultrasonography, Doppler, Transcranial

Intracerebral hemorrhage (ICH) causes severe sensorimotor dysfunction and cognitive decline which are aggravated by secondary brain injury, yet there are no effective management to alleviate these outcomes. Pyroptosis is strongly related to neuroinflammation, which plays a crucial role in the pathophysiological processes of secondary brain injury after ICH. OXT (oxytocin), as a pleiotropic neuropeptide, has multiple functions including anti-inflammation and antioxidation. This study aims to investigate the role of OXT in improving ICH outcomes and the underlying mechanisms.. C57BL/6 mice were used to establish the ICH model by autologous blood injection. OXT was administered intranasally (0.2 μg/g) after ICH. Combing behavioral tests, Western blot, immunofluorescence staining, electron microscopy, and pharmacological approaches, we evaluated the effect of intranasal OXT application on neurological outcomes after ICH and explored the underlying mechanism.. Endogenous OXT level was decreased, whereas OXTR (oxytocin receptor) expression was increased after ICH. OXT treatment improved the short-term and long-term neurological functions and alleviated neuronal pyroptosis and neuroinflammation. In addition, OXT reduced excessive mitochondrial fission and mitochondrial-derived oxidative stress 3 days after ICH. OXT decreased the expression of pyroptotic and proinflammatory factors including NLRP3 (NOD-like receptor protein 3), ASC (apoptosis-associated speck-like protein containing a CARD), GSDMD (gasdermin D), caspase-1, IL (interleukin)-1β, and IL-18 and increased the expression of p-PKA (phospho-protein kinase A) and p-DRP1 (S637; DRP1 [dynamin-related protein 1] phosphorylation at Ser637). OXT-induced neuroprotective effects were blocked by either OXTR inhibitor or PKA inhibitor.. Intranasal application of OXT can ameliorate neurological deficits and alleviate neural pyroptosis, inflammation, and excessive mitochondrial fission via OXTR/p-PKA/DRP1 signaling pathway after ICH. Thus, OXT administration may be a potential therapeutic strategy to improve the prognosis of ICH.

Topics: Animals; Brain Injuries; Cerebral Hemorrhage; Mice; Mice, Inbred C57BL; Mitochondrial Dynamics; Neuroinflammatory Diseases; Oxytocin; Pyroptosis

To evaluate whether uterotrophic agents increase the risk of fatal hemorrhagic brain stroke.. Between 1991 and 1992, there were 230 maternal deaths among 2,420,000 pregnant women in Japan and the causes of these deaths was investigated in 1994. Using information provided in this report, we identified 35 women who died from or were assumed to die from hemorrhagic brain stroke. We assumed that 93% of women would have tried vaginal delivery. The risk of fatal hemorrhagic brain stroke after uterotrophic agent use was calculated according to the assumption that 5.0-40% of women received uterotrophic agents.. Use of uterotrophic agents for induction/augmentation of labor was confirmed in five (14.3%) of the 35 women who died from hemorrhagic brain stroke. The incidence of fatal brain stroke after the use of uterotrophic agents was only significantly higher than that for spontaneous hemorrhagic brain stroke if these agents were administered in ≤ 6.0% of women.. Because more than 6.0% of women received uterotrophic agents, these agents are unlikely to increase the risk of fatal hemorrhagic brain stroke.

Topics: Cerebral Hemorrhage; Dinoprost; Dinoprostone; Female; Humans; Japan; Oxytocics; Oxytocin; Pregnancy; Risk Assessment; Stroke

Normonatremic and chronically hyponatremic rats were pretreated with naloxone (5 mg/kg) or isotonic (150 mM) NaCl, then were given i.v. injections of 2 M NaCl (2 ml) or were hemorrhaged (20 ml/kg). Baseline and post-stimulus blood samples were withdrawn through indwelling jugular venous catheters. Baseline levels of plasma vasopressin (AVP) and oxytocin (OT) were similar in both normonatremic and hyponatremic rats and did not change after naloxone pretreatment. Increases in plasma AVP and OT levels in response to both hypertonic saline and hemorrhage were markedly blunted in the hyponatremic rats compared to the normonatremic rats. Naloxone pretreatment caused augmented AVP and OT secretion in response to hypertonic saline stimulation and hemorrhage in both the normonatremic and hyponatremic rats; the magnitude of the naloxone augmentations in the hyponatremic rats were sufficient to normalize the OT response to hypertonic saline and both the OT and AVP responses to hemorrhage. Our results therefore suggest that endogenous opioids are likely involved in the inhibition of stimulus-induced AVP and OT release that accompanies chronic hypoosmolality.

Topics: Animals; Arginine Vasopressin; Cerebral Hemorrhage; Hypothalamus; Isotonic Solutions; Male; Naloxone; Osmolar Concentration; Oxytocin; Rats; Rats, Sprague-Dawley; Sodium; Sodium Chloride; Water-Electrolyte Imbalance

Topics: Adult; Cerebral Hemorrhage; Cesarean Section; Ergonovine; Female; Humans; Injections, Intramuscular; Maternal Mortality; Obstetric Labor Complications; Oxytocin; Pre-Eclampsia; Pregnancy; Prenatal Care; Pulmonary Embolism