Reduced Dilator and Constrictor Response of the Middle Cerebral Artery after Cold Lesion of the Rat Parietal Cortex

Abstract

Cold injury to the exposed brain through the intact dura was used as the model for brain injury in the present study (Klatzo et al., 1958). The histological features of the cold lesion in the rat resemble those of human cortical contusion. Although the freezing injury is an artificial insult of the brain compared with the complexity of traumatic damage in humans, the model is highly standardized and yields reproducible focal disruption of the blood brain barrier (BBB) (Stoffel et al., 1997). The resulting brain edema leads to secondary brain damage, thus increasing the necrosis due to the primary insult (Eriskat et al., 1994). In this respect, this experimental approach mimics the pathophysiology of mild human traumatic head injury (Klatzo et al., 1958, Wahl et al., 1988). In this model of brain injury in the parietal cortex we tested in vitro the vasoreactivity of middle cerebral artery (MCA) and its distal branches, a main artery which supplies the lesioned area with blood. We investigated the vascular response to endothelin (ET)-l. This compound has been suggested as a possible mediator of secondary brain damage due to its high potency and extremely long-lasting action (Feger et al., 1994). Furthermore, the cerebral tissue concentration of ET-1 is increased after brain injury or ischemia (Barone et al., 1994; Yamada et al., 1995). Because of the ET-NO network (Ehrenreich and Schilling, 1995) we also examined whether the NO system was functionally altered in the MCA, with a focus on the ET-3-induced dilation. Since we found that neurotrauma reduces the vasomotor responses to ETs we also examined vasoreactivity in response to some other stimuli.