A murine photochemical stroke model with histologic correlates of apoptotic and nonapoptotic mechanisms.
BACKGROUND
The neuronal cell death that occurs after ischemia-induced cerebral infarction (stroke) contains elements of apoptosis and necrosis, an intermediary form of the two, and a distinct excitotoxic process. We previously developed a photochemical model of stroke in the rat. We have now adapted this model for use in the mouse. The present manuscript describes the mouse model.


METHODS
Minimal beam intensity (0.1 W/cm(2)) cold white light (8 min exposure) was used to evoke discrete infarcts in the parietal lobes of 11 mice sensitized by the administration of fresh Rose Bengal (10 mg/kg by rapid iv infusion).


RESULTS
At 2 h, five out of five mice and at 6 h, six out of six mice demonstrated light microscopic histologic features like those in the rat model. These included a superior ischemic zone with shrunken and pyknotic nuclei, a middle transition zone of edematous vacuolated neuropil but normal neurons with open chromatin and retained Nissl granules, and an inferior zone with normal neurons. There was widespread nuclear terminal deoxynucleotidyl-transferase-mediated dUTP nick end labeling (TUNEL) in the superior infarct zone in 11/11 mice. However, in the edematous vacuolated transition zone, 11/11 mice had TUNEL positive and negative nuclei randomly mixed. Light microscopic analysis of that same transition zone showed no pyknosis or chromatin bodies in the TUNEL positive or negative cells.


CONCLUSIONS
In mice, photoactivation of Rose Bengal evoked similar infarct and transition zone patterns found previously in rats, with TUNEL evidence of apoptotic and nonapoptotic events. Thus, it will be possible to use this model for further quantitative study of apoptotic and excitotoxic events in wild and transgenic mice.
Eichenbaum
Joseph W
JW
Department of Ophthalmology, Mount Sinai School of Medicine, 1050 Park Avenue, New York, NY 10028, USA. eichij01@earthlink.net
Pevsner
Paul H
PH
Pivawer
Gabriel
G
Kleinman
George M
GM
Chiriboga
Luis
L
Stern
Arnold
A
Rosenbach
Ari
A
Iannuzzi
Kathryn
K
Miller
Douglas C
DC
D000818:Animals; D017209:Apoptosis / Q000528:radiation effects; D016923:Cell Death / Q000528:radiation effects; D002544:Cerebral Infarction / Q000473:pathology*; D004195:Disease Models, Animal; D005260:Female; D020287:In Situ Nick-End Labeling; D008027:Light; D051379:Mice; D009474:Neurons / Q000473:pathology* / Q000528:radiation effects; D010296:Parietal Lobe / Q000473:pathology / Q000528:radiation effects; D017319:Photosensitizing Agents; D012395:Rose Bengal; D020521:Stroke / Q000473:pathology*
D017319:Photosensitizing Agents; D012395:Rose Bengal