ABSTRACT
Bradykinin is a potent mediator of inflammation both in the periphery and the central nervous system (CNS). In the cerebrovascular system and CNS, bradykinin causes vasodilation, increased capillary permeability, and breakdown of the blood brain barrier resulting in vasogenic edema (Unterberg et al., 1984; Unterberg and Baethmann, 1984; Whalley et al., 1987; Wahl et al., 1996; Elliott et al., 1996; Kamiya et al., 1993). Bradykinin can also produce neuronal damage and injury and death (Francel, 1992; Ellis, 1990), while simultaneously stimulating the release of a wide variety of mediators which augment the inflammatory response, such as eicosanoids and free radical products (Holland et al., 1990; Whalley et al., 1987; Wolfe and Pappius, 1983), interleukins, and TNF−α (Cunha et al., 1992). In addition, bradykinin has been shown to release excitatory amino acid transmitters from spinal neurons (Bhoola et al., 1987) and stimulate glutamate release via a calcium dependent mechanism, from neocortical astrocytes (Parpura et al., 1994). The release of calcium by bradykinin was seen only from neurones co-cultured with astrocytes, an effect blocked by an NMDA antagonist. This suggests an intimate link between the kinin-mediated activation of CNS astrocytes, glutamate release, and neuronal calcium elevation, which in extreme situations can result in cell death due to excitotoxicity (Parpura et al., 1994).
