Morphometrical quantification of brain edema related to experimental multiple micro-infarcts in mice: assessment of neurotropin effect.

Cerebral micro-infarcts were induced in mice by injecting a standardized suspension of latex microbeads into one internal carotid artery. The animals were sacrificed after either 2 or 4 days. The importance of the lesions induced in each brain was morphometrically quantified on stratified samples of microscopic serial sections, whereas edema was evaluated in the same sections by comparing the section area of the injected hemisphere with that of the non-injected side. Lesion density and brain edema were found to significantly correlate. Neurotropin, an inhibitor of kinin release, was curatively administered twice a day to 20 experimental animals which were compared to 20 saline-treated counterparts. In the neurotropin-injected mice, after 4 days the global amount of cerebral edema was significantly smaller than that of the controls and the slope of the lesion/edema regression line was reduced, indicating a lower amount of edema for a given lesion. These findings support the theory that the kallikrein-kinin system plays a major role in the development of the vasogenic late phase of ischemic brain edema.