title: Cellular markers of neuroinflammation and neurogenesis after ischemic brain injury in the long-term survival rat model.
abstract: MRI was employed to follow the neurodegenerative foci and the localization of inflammatory cells by magnetically labeled CD4+ or CD8+ lymphocytes in the ischemia/reperfusion long-lived rats (9 and 13 months after 10 min of cardiac arrest). MRI of ischemic rats showed: (1) blood-brain barrier (BBB) leakage in the area of the dorsal hippocampus and brainstem-hindbrain level in basal cerebellum, (2) unlike anti-CD8 magnetic antibodies anti-CD4 ultra small paramagnetic iron oxide particles (USPIO) antibodies revealed hypointense areas in the brainstem-interbrain region and caudoputamen not found in animals that were not injected with USPIO antibodies, and (3) dilation in the retrosplenial area. Immunocytochemistry revealed microglial activation in the hippocampus and striatum, with indications of activation in thalamic lateral dorsal nuclei and the subventricular zone. In the CA1 and CA3 regions, it was noted that OX42- and ED1-positive granules appear in neuronal somata. Immunostaining of lymphocytes with TCR confirmed the T-cell presence in ischemic brain parenchyma of the hippocampus and striatum. The above observations thus point to a persistent dysfunction of BBB that in long-term may still lead to infiltration of T cells that are predominantly of helper (CD4+) type. Such inflammatory processes are backed by microglial activity even up to 1 year after ischemia/reperfusion. Moreover, in these animals an augmented expression of neurogenesis markers and neuroblast migration was also revealed in the subventricular zone. Thus, a balance of degenerative processes and inflammatory surveillance with neurogenesis could determine the long-term outcome of global ischemia survival or the previously proposed formation of amyloid plaques and Alzheimer's-type dementia.
authors.affiliation: Faculty of Biology, Department of Physiology and Biochemistry, Center for Laser Microscopy, University of Belgrade, P.O. Box 52, Studentski trg 16, 11000, Belgrade, Serbia.
authors.forename: Vera
authors.initials: V
authors.lastname: Sekeljic
authors.forename: Danijela
authors.initials: D
authors.lastname: Bataveljic
authors.forename: Stefan
authors.initials: S
authors.lastname: Stamenkovic
authors.forename: Marzena
authors.initials: M
authors.lastname: Ułamek
authors.forename: Mirosław
authors.initials: M
authors.lastname: Jabłoński
authors.forename: Lidija
authors.initials: L
authors.lastname: Radenovic
authors.forename: Ryszard
authors.initials: R
authors.lastname: Pluta
authors.forename: Pavle R
authors.initials: PR
authors.lastname: Andjus
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D001812:Blood-Brain Barrier / Q000503:physiopathology; D001930:Brain Injuries / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D001933:Brain Stem / Q000378:metabolism / Q000473:pathology; D039481:CD11b Antigen / Q000378:metabolism*; D015704:CD4 Antigens / Q000378:metabolism; D016827:CD8 Antigens / Q000378:metabolism; D053358:Ectodermal Dysplasia 1, Anhidrotic / Q000378:metabolism*; D004660:Encephalitis / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D005260:Female; D006624:Hippocampus / Q000378:metabolism / Q000473:pathology; D008279:Magnetic Resonance Imaging; D023421:Models, Animal; D055495:Neurogenesis / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D012249:Rhombencephalon / Q000378:metabolism / Q000473:pathology; D015996:Survival Rate; D013997:Time Factors
chemical_list: D015415:Biomarkers; D039481:CD11b Antigen; D015704:CD4 Antigens; D016827:CD8 Antigens