Abstract
To study the causes of spatial and temporal evolution of progressive neuroinjury in focal brain ischemia, models with consistent lesion topography are required. In such models, continuous monitoring of the microcirculation in a penumbral area undergoing progressive damage could be possible. We used a fixed-pulse (1.0 s, 40 W) Nd-YAG laser (NYL) to produced discrete brain lesions in rats and monitored the cerebral blood flow (CBF) with laser-Doppler flowmetry (LDF) in nonirradiated areas directly adjacent to the maturing lesion. We also examined the time evolution of the lesion topography over a 4 day period. The lesion volume determined by histopathological methods increased from 3.1 ± 0.5 to 4.5 ± 0.5 mm3 (p < 0.05) during the first 2 h. Simultaneously, LDF indicated severe hypoperfusion (–60 ± 21%, p < 0.01) at a zone (1 mm distance from the laser lesion) where progressive neuronal degeneration and increased tissue water content (80.0 ± 3.3% versus 76.8 ± 2.1% in normal tissue, n = 7, p < 0.05) were also observed. At a 4 mm distance from the lesion, hyperemic CBF responses were observed, but no histopathological signs or edema. Secondary brain damage progressed up to 4 days (lesion volume of 6.0 ± 0.7 mm3). The NYL-induced brain lesion produced a highly reproducible focal injury and progressive neuronal death in a spatial relationship with micro-circulatory failure and edema formation. The model allows prospective study of tissue state at a discrete zone, which is separate from the initial injury, but susceptible to secondary brain damage.