High susceptibility to cerebral ischemia in GFAP-null mice

Astrocytes perform a variety of functions in the adult central nervous syst em (CNS) that contribute to the survival of neurons. Thus, it is likely tha t the activities of astrocytes affect the extent of brain damage after isch emic stroke. The authors tested this hypothesis by using a mouse ischemia m odel to compare the infarct volume produced in wild-type mice with that pro duced in mice lacking glial fibrillary acidic protein (GFAP), an astrocyte specific intermediate filament component. Astrocytes lacking GFAP have been shown to have defects in process formation, induction of the blood-brain b arrier, and volume regulation; therefore, they might be compromised in thei r ability to protect the CNS after injury. The authors reported here that 4 8 hours after combined permanent middle cerebral artery occlusion (MCAO) an d 15 minutes transient carotid artery occlusion (CAO) GFAP-null mice had a significantly (P < 0.001) larger cortical infarct volume (16.7 +/- 2.2 mm(3 )) than their wild-type littermates (10.1 +/- 3.9 mm(3)). Laser-Doppler flo wmetry revealed that the GFAP-null mice had a more extensive and profound d ecrease in cortical cerebral blood flow within 2 minutes after MCAO with CA O. These results indicated a high susceptibility to cerebral ischemia in GF AP-null mice and suggested an important role for astrocytes and GFAP in the progress of ischemic with partial reperfusion.