title: Selective depletion of Mac-1-expressing microglia in rat subventricular zone does not alter neurogenic response early after stroke.
abstract: Ischemic stroke induces migration of newly formed neuroblasts, generated by neural stem cells in the adult rat subventricular zone (SVZ), towards the injured striatum where they differentiate into mature neurons. Stroke also leads to accumulation of microglia in the SVZ but their role for neurogenesis is unclear. Here we developed a method for selective depletion of the macrophage antigen complex-1 (Mac-1)-expressing microglia population in the SVZ by intraventricular injection of the immunotoxin Mac-1-saporin in rats. We found that the vast majority of Mac-1+ cells were Iba-1+ microglia. The Mac-1+ population was heterogeneous and included both a small proliferative pool of cells, which was not affected by middle cerebral artery occlusion (MCAO), and a larger subpopulation that changed morphologically into a semi-activated state in response to the insult. This subpopulation did not increase its expression of the phagocytic marker ED1 but exhibited high levels of triggering receptor expressed on myeloid cells-2 (TREM-2), associated with alternative microglia activation. A minor portion of the SVZ Mac-1+ cells originated from the blood early after stroke, but this macrophage population became much more substantial at later stages. Almost 80% reduction of Mac-1-expressing microglia, caused by Mac-1 saporin delivered just before and at 1 week after MCAO, did not alter the numbers of newly formed neuroblasts in the striatum or their migratory distance. These findings indicate that the Mac-1-expressing microglia in the SVZ do not play a major role either for the number of neuroblasts which exit the SVZ or their migration in the striatum early following stroke.
authors.affiliation: Laboratory of Neurogenesis and Cell Therapy, Wallenberg Neuroscience Center A11, University Hospital, SE-221 84 Lund, Sweden.
authors.forename: Ursula
authors.initials: U
authors.lastname: Heldmann
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Mine
authors.forename: Zaal
authors.initials: Z
authors.lastname: Kokaia
authors.forename: Christine T
authors.initials: CT
authors.lastname: Ekdahl
authors.forename: Olle
authors.initials: O
authors.lastname: Lindvall
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D002545:Brain Ischemia / Q000378:metabolism* / Q000503:physiopathology; D005455:Fluorescent Antibody Technique; D007150:Immunohistochemistry; D020547:Lateral Ventricles / Q000166:cytology / Q000378:metabolism* / Q000503:physiopathology; D016177:Macrophage-1 Antigen / Q000378:metabolism*; D008297:Male; D017628:Microglia / Q000378:metabolism*; D018613:Microscopy, Confocal; D055495:Neurogenesis / Q000502:physiology*; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D020521:Stroke / Q000378:metabolism* / Q000503:physiopathology
chemical_list: D016177:Macrophage-1 Antigen