High Susceptibility to Cerebral Ischemia in GFAP-Null Mice

• Published in: Journal of cerebral blood flow and metabolism 2000-07, Vol.20 (7), p.1040-1044
• Main Authors: Nawashiro, Hiroshi, Brenner, Michael, Fukui, Shinji, Shima, Katsuji, Hallenbeck, John M.
• Format: Article
• Language: English
• Subjects: Animals; Biological and medical sciences; Brain - pathology; Brain Ischemia - etiology; Brain Ischemia - pathology; Brain Ischemia - physiopathology; Cerebrovascular Circulation; Disease Susceptibility; Gene Deletion; Glial Fibrillary Acidic Protein - deficiency; Glial Fibrillary Acidic Protein - genetics; Laser-Doppler Flowmetry; Medical sciences; Mice; Mice, Mutant Strains - genetics; Neurology; Reference Values; Vascular diseases and vascular malformations of the nervous system
• ISSN: 0271-678X; 1559-7016
• DOI: 10.1097/00004647-200007000-00003

Astrocytes perform a variety of functions in the adult central nervous system (CNS) that contribute to the survival of neurons. Thus, it is likely that the activities of astrocytes affect the extent of brain damage after ischemic stroke. The authors tested this hypothesis by using a mouse ischemia model to compare the infarct volume produced in wild-type mice with that produced 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 barrier, and volume regulation; therefore, they might be compromised in their ability to protect the CNS after injury. The authors reported here that 48 hours after combined permanent middle cerebral artery occlusion (MCAO) and 15 minutes transient carotid artery occlusion (CAO) GFAP-null mice had a significantly (P < 0.001) larger cortical infarct volume (16.7 ± 2.2 mm3) than their wild-type littermates (10.1 ± 3.9 mm3). Laser-Doppler flowmetry revealed that the GFAP-null mice had a more extensive and profound decrease in cortical cerebral blood flow within 2 minutes after MCAO with CAO. These results indicated a high susceptibility to cerebral ischemia in GFAP-null mice and suggested an important role for astrocytes and GFAP in the progress of ischemic brain damage after focal cerebral ischemia with partial reperfusion.