The role of bradykinin in mediating ischemic brain edema in rats.

Abstract

Background and Purpose:We investigated the hypothesis that bradykinin generation may induce ischemic brain edema in spontaneously hypertensive rats.Methods: Cerebral ischemia lasting 3 hours was produced by bilateral common carotid artery occlusion in 67 rats. After the ischemic period, the rats were reperfused. Cerebral water content and energy metabolites (adenosine triphosphate, lactate, and pyruvate), as well as plasma and tissue bradykinin, were measured. Additionally, using the same experimental paradigm, bradykinin synthesis inhibitors (aprotinin [«=7] and soybean trypsin inhibitor [n=7]) were administered immediately after ischemia induction to determine the relation of bradykinin generation to the progression of ischemic brain edema.Results: Cerebral water content increased during the 3-hour ischemic period, peaked at 30 minutes of reperfusion, and declined thereafter. Bradykinin levels in plasma and tissue rose markedly 30 minutes after reperfusion and fell thereafter. The progressive loss of adenosine triphosphate was mirrored by the rise in lactate. In the treated groups, aprotinin and soybean trypsin inhibitor administration significantly attenuated cerebral edema (/?<0.01 and//<0.05, respectively). The treated groups also showed less lactate accumulation and more adenosine triphosphate preservation than did the controls.Conclusions: These results demonstrate that bradykinin levels in plasma and tissue corresponded to cerebral edema progression and that bradykinin suppression decreased edema formation. These novel findings indicate that bradykinin activation augments the progression of ischemic brain edema.

Increased brain lactate is central to the development of brain edema in rats with chronic liver disease

“…In the context of HE, increased glutamine levels are commonly observed even when brain edema is not present, as observed in portacaval-shunted rats [45]. However, in other neurological diseases such as cerebral ischemia, increased brain lactate levels have been associated with the development of brain edema, while brain glutamine levels were decreased [50], [51] and [52]. Although our study was performed in frontal cortex, it is possible other cerebral regions may be affected dissimilarly.…”

Rivaroxaban and Apixaban Reduce Hemorrhagic Transformation After Thrombolysis by Protection of Neurovascular Unit in Rat

“…This finding indicated a similar antithrombotic effect in the W+tPA, R+tPA, and A+tPA groups with each dose for obtaining 70% inhibition of clot formation in the rat venous thromboembolism model. [9][10][11][12] Various proinflammatory mediators, such as MMPs, thrombin, vascular endothelial growth factor, and bradykinin, are increased in the ischemic brain, [25][26][27][28] accompanied by brain edema, endothelial cell death, 29 disruption of tight junctions, and loss of the basal lamina/extracellular matrix (collagen IV, laminin-1, and fibronectin). These changes could be involved in intracerebral hemorrhage associated with tPA therapy.…”

Cerebral Microvessel Responses to Focal Ischemia

“…2) (Gotoh et al, 1985;Olesen, 1986;Dietrich et al, 1993;Okada et al, 1994a;Risau et al, 1998). There is evidence that loss of the blood-brain barrier and the microvascular ECM results from the actions of bradykinin (Kamiya et al, 1993;Aschner et al, 1997), VEGF Zhang et al, 2000), thrombin (Okada et al, 1994a;Aschner et al, 1997), active matrix metalloproteinases (MMPs) , proteases released by activated leukocytes (Hasty et al, 1990;Garcia et al, 1994;Armao et al, 1997;Opdenakker et al, 2001), and other protease activities (Hosomi et al, 2001). Blockade of bradykinin receptors has been associated with reduced injury and edema formation (Relton et al, 1997).…”