Cortical microcirculation in a new model of focal laser-induced secondary brain damage.
To study the causes of spatial and temporal evolution of progressive neuro-injury 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 less than 0.05) during the first 2 h. Simultaneously, LDF indicated severe hypoperfusion (-60 +/- 21%, p less than 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 less than 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 microcirculatory 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.
Lindsberg
P J
PJ
Department of Neurology, F. Edward Hébert School of Medicine, Uniformed Services University of the Health Sciences, Bethesda, Maryland 20814.
Frerichs
K U
KU
Burris
J A
JA
Hallenbeck
J M
JM
Feuerstein
G
G
D000818:Animals; D001921:Brain / Q000473:pathology; D001927:Brain Diseases / Q000209:etiology* / Q000473:pathology / Q000503:physiopathology; D001929:Brain Edema; D002545:Brain Ischemia / Q000150:complications* / Q000209:etiology; D002540:Cerebral Cortex / Q000098:blood supply* / Q000473:pathology; D004195:Disease Models, Animal; D007834:Lasers; D008297:Male; D008833:Microcirculation / Q000503:physiopathology*; D009474:Neurons / Q000473:pathology; D051381:Rats; D011919:Rats, Inbred Strains