icatibant and Infarction--Middle-Cerebral-Artery

A potential complication after intravenous administration of recombinant tissue plasminogen activators (rtPAs) for thrombolysis in acute ischaemic stroke is orolingual angioedema, with an incidence of 0.4%-7.9%. In the herewith reported case, we discuss potential links between a history of sarcoidosis and the occurrence of orolingual angioedema after rtPA administration. Sarcoidosis is often accompanied by an elevated ACE level. In contrast, low ACE levels appear to play a role in the pathomechanism currently assumed to trigger angioedema, that is, the activation of the bradykinin and complement pathways. Medication with ACE inhibitors is considered a risk factor for angioedema. Based on these considerations, the patient was also treated with icatibant, a bradykinin B2-receptor antagonist, which has been found useful in recent publications on treating orolingual angioedema after intravenous lysis in ischaemic stroke.

Topics: Angioedema; Bradykinin; Computed Tomography Angiography; Female; Humans; Infarction, Middle Cerebral Artery; Infusions, Intravenous; Intubation, Intratracheal; Lip; Middle Aged; Recombinant Proteins; Sarcoidosis; Thrombolytic Therapy; Tissue Plasminogen Activator; Tongue; Treatment Failure

Remote ischemic conditionings, such as pre- and per-conditioning, are known to provide cardioprotection in animal models of ischemia. However, little is known about the neuroprotection effect of postconditioning after cerebral ischemia. In this study, we aim to evaluate the motor function rescuing effect of remote limb ischemic postconditioning (RIPostC) in a rat model of acute cerebral stroke.. Left middle cerebral artery occlusion (MCAO) was performed to generate the rat model of ischemic stroke, followed by daily RIPostC treatment for maximum 21 days. The motor function after RIPostC was assessed with foot fault test and balance beam test. Local infarct volume was measured through MRI scanning. Neuronal status was evaluated with Nissl's, HE, and MAP2 immunostaining. Lectin immunostaining was performed to evaluate the microvessel density and area.. Daily RIPostC for more than 21 days promoted motor function recovery and provided long-lasting neuroprotection after MCAO. Reduced infarct volume, rescued neuronal loss, and enhanced microvessel density and size in the injured areas were observed. In addition, the RIPostC effect was associated with the up-regulation of endogenous tissue kallikrein (TK) level in circulating blood and local ischemic brain regions. A TK receptor antagonist HOE-140 partially reversed RIPostC-induced improvements, indicating the specificity of endogenous TK mediating the neuroprotection effect of RIPostC.. Our study demonstrates RIPostC treatment as an effective rehabilitation therapy to provide motor function recovery and alleviate brain impairment in a rat model of acute cerebral ischemia. We also for the first time provide evidence showing that the up-regulation of endogenous TK from remote conditioning regions underlies the observed effects of RIPostC.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Bradykinin; Disease Models, Animal; Infarction, Middle Cerebral Artery; Ischemic Postconditioning; Lectins; Magnetic Resonance Imaging; Male; Microtubule-Associated Proteins; Movement Disorders; Postural Balance; Rats; Rats, Sprague-Dawley; Recovery of Function; Tissue Kallikreins; Up-Regulation

Brain edema is detrimental in ischemic stroke and its treatment options are limited. Kinins are proinflammatory peptides that are released during tissue injury. The effects of kinins are mediated by 2 different receptors (B1 and B2 receptor [B1R and B2R]) and comprise induction of edema formation and release of proinflammatory mediators.. Focal cerebral ischemia was induced in B1R knockout, B2R knockout, and wild-type mice by transient middle cerebral artery occlusion. Infarct volumes were measured by planimetry. Evan's blue tracer was applied to determine the extent of brain edema. Postischemic inflammation was assessed by real-time reverse-transcriptase polymerase chain reaction and immunohistochemistry. To analyze the effect of a pharmacological kinin receptor blockade, B1R and B2R inhibitors were injected.. B1R knockout mice developed significantly smaller brain infarctions and less neurological deficits compared to wild-type controls (16.8+/-4.7 mm(3) vs 50.1+/-9.1 mm(3), respectively; P<0.0001). This was accompanied by a dramatic reduction of brain edema and endothelin-1 expression, as well as less postischemic inflammation. Pharmacological blockade of B1R likewise salvaged ischemic tissue (15.0+/-9.5 mm(3) vs 50.1+/-9.1 mm(3), respectively; P<0.01) in a dose-dependent manner, even when B1R inhibitor was applied 1 hour after transient middle cerebral artery occlusion. In contrast, B2R deficiency did not confer neuroprotection and had no effect on the development of tissue edema.. These data demonstrate that blocking of B1R can diminish brain infarction and edema formation in mice and may open new avenues for acute stroke treatment in humans.

Topics: Animals; Bradykinin; Bradykinin B1 Receptor Antagonists; Bradykinin B2 Receptor Antagonists; Brain Edema; Cerebral Arteries; Cerebral Infarction; Cerebrovascular Circulation; Disease Models, Animal; Dose-Response Relationship, Drug; Down-Regulation; Encephalitis; Endothelin-1; Gene Expression; Infarction, Middle Cerebral Artery; Mice; Mice, Inbred C57BL; Mice, Knockout; Receptor, Bradykinin B1; Receptor, Bradykinin B2; RNA, Messenger