piperidines and Intracranial-Hemorrhages

Topics: Adenine; Aged; Brain; Humans; Intracranial Hemorrhages; Leukemia, Lymphocytic, Chronic, B-Cell; Male; Piperidines; Protein Kinase Inhibitors

We describe the successful administration of remifentanil as part of the anesthetic technique used for cesarean section performed under general anesthesia in a 24-year-old woman with intracranial re-hemorrhage caused by re-ruptured arteriovenous malformation. A low dose of remifentanil was useful to obtund the hypertensive response during induction and maintenance of anesthesia without neonatal respiratory depression.

Topics: Anesthesia, General; Anesthesia, Obstetrical; Cesarean Section; Female; Humans; Intracranial Arteriovenous Malformations; Intracranial Hemorrhages; Piperidines; Pregnancy; Pregnancy Complications; Remifentanil; Young Adult

Neural networks that regulate an organism's internal environment must sense perturbations, respond appropriately, and then reset. These adaptations should be reflected as changes in the efficacy of the synapses that drive the final output of these homeostatic networks. Here we show that hemorrhage, an in vivo challenge to fluid homeostasis, induces LTD at glutamate synapses onto hypothalamic magnocellular neurosecretory cells (MNCs). LTD requires the activation of postsynaptic alpha2-adrenoceptors and the production of endocannabinoids that act in a retrograde fashion to inhibit glutamate release. In addition, both hemorrhage and noradrenaline downregulate presynaptic group III mGluRs. This loss of mGluR function allows high-frequency activity to potentiate these synapses from their depressed state. These findings demonstrate that noradrenaline controls a form of metaplasticity that may underlie the resetting of homeostatic networks following a successful response to an acute physiological challenge.

Topics: Adrenergic alpha-Agonists; Adrenergic alpha-Antagonists; Animals; Animals, Newborn; Biophysics; Carbolines; Clonidine; Down-Regulation; Drug Interactions; Egtazic Acid; Electric Stimulation; Excitatory Amino Acid Agents; Excitatory Postsynaptic Potentials; Glutamic Acid; Guanosine Diphosphate; Hypothalamus; In Vitro Techniques; Intracranial Hemorrhages; Long-Term Synaptic Depression; Male; Microinjections; Neurons; Patch-Clamp Techniques; Piperidines; Pyrazoles; Rats; Rats, Sprague-Dawley; Receptor, Cannabinoid, CB1; Receptors, Metabotropic Glutamate; Synapses; Thionucleotides; Yohimbine

The germinal matrix of premature infants is selectively vulnerable to hemorrhage within the first 48 h of life. To assess the role of vascular immaturity in germinal matrix hemorrhage (GMH), we evaluated germinal matrix angiogenesis in human fetuses and premature infants, as well as in premature rabbit pups, and noted active vessel remodeling in all three. Vascular endothelial growth factor (VEGF), angiopoietin-2 and endothelial cell proliferation were present at consistently higher levels in the germinal matrix relative to the white matter anlagen and cortical mantle. On that basis, we asked whether prenatal treatment with either of two angiogenic inhibitors, the COX-2 inhibitor celecoxib, or the VEGFR2 inhibitor ZD6474, could suppress the incidence of GMH in premature rabbit pups. Celecoxib treatment decreased angiopoietin-2 and VEGF levels as well as germinal matrix endothelial proliferation. Furthermore, treatment with celecoxib or ZD6474 substantially decreased the incidence of GMH. Thus, by suppressing germinal matrix angiogenesis, prenatal celecoxib or ZD6474 treatment may be able to reduce both the incidence and severity of GMH in susceptible premature infants.

Topics: Aborted Fetus; Angiopoietin-2; Animals; Blotting, Western; Brain; Celecoxib; Cell Proliferation; Cyclooxygenase 2 Inhibitors; Endothelial Cells; Humans; Immunohistochemistry; Infant, Newborn; Infant, Premature; Intracranial Hemorrhages; Neovascularization, Physiologic; Piperidines; Pyrazoles; Quinazolines; Rabbits; Sulfonamides; Vascular Endothelial Growth Factor Receptor-2

Intracerebral hemorrhage (ICH) is the most serious side effect of antithrombotic agents, especially in cases of cerebrovascular disease. In the present study, we compared the exacerbation of ICH and prolongation of bleeding time (BT) in guinea pigs with recombinant tissue plasminogen activator (rt-PA), heparin, aspirin, and FK419, a novel nonpeptide platelet glycoprotein (GP) IIb/IIIa receptor antagonist. ICH was induced by injection of bacterial collagenase into the caudate nucleus; BT was measured with a Simplate R device. Neither heparin nor aspirin prolonged BT. In contrast, rt-PA at the highest dose used in the study did prolong BT, and FK419 caused a dose-dependent prolongation of BT. Moreover, rt-PA and heparin increased the degree of ICH in a dose-dependent manner, leading to death in more than half of the animals treated with higher doses of these drugs. These findings show that the prohemorrhagic mechanisms underlying the prolongation of BT differ from those in collagenase-induced ICH, and that the risk of an agent with antithrombotic effects potentiating hemorrhage in the collagenase-induced model of ICH more closely parallels that in stroke patients than does the effect of the agent on BT. The findings also suggest that antiplatelet agents, including FK419, may be safer than thrombolytic or anticoagulant agents for use in patients at risk for ICH, such as those with stroke or cerebral aneurysm.

Topics: Animals; Aspirin; Bleeding Time; Collagenases; Dose-Response Relationship, Drug; Fibrinolytic Agents; Guinea Pigs; Heparin; Intracranial Hemorrhages; Male; Piperidines; Platelet Aggregation; Platelet Glycoprotein GPIIb-IIIa Complex; Propionates; Recombinant Proteins; Tissue Plasminogen Activator; Whole Blood Coagulation Time