CHANGES IN LOCAL MICROVASCULAR PERMEABILITY AND IN THE EFFECT OF INTERVENTION WITH 21-AMINOSTEROID (TIRILAZAD) IN A NEW EXPERIMENTAL-MODEL OF FOCAL CORTICAL INJURY IN THE RAT

In a new, reproducible model of rodent focal cortical injury, we have shown that in the absence of early traumatic disruption of the microva sculature and subsequent hemorrhage, delayed perivascular protein leak age and polymorphonuclear leukocyte infiltration of the injured cortex occur. In this study we employed a sensitive quantitative autoradiogr aphic technique (using alpha-aminoisobutyric acid as a tracer) to inve stigate the focal changes in microvascular permeability with time and to determine the effects of administration of a 21-aminosteroid (Tiril azad) initiated 5 min after induction of the cortical injury. At all t ime points studied, there was a significant increase in perilesional b lood-brain barrier permeability in lesioned animals treated with vehic le, compared to sham-operated animals, with the most marked increase i n blood-brain barrier permeability at 4 h postinjury (mean K-i +/- SE = 19.2 +/- 2.4/1000 min with cortical injury, 1.5 +/- 0.3/1000 min in shams) (mean volume +/- SE = 15.48 +/- 0.7 mm(3)). In animals with cor tical injury treated with Tirilazad (10 mg/kg), there was a significan t reduction in microvascular permeability at the site of injury (K-i = 3.1 +/- 0.5, p < 0.001) and a significant reduction in volume of incr eased permeability (4.86 +/- 0.7 mm(3), p < 0.01) at 4 h postinjury. I n this model of cortical injury, a delayed increase in microvascular p ermeability occurs, which is significantly attenuated by postinjury tr eatment with Tirilazad.