title: Alterations in hippocampal neurogenesis following traumatic brain injury in mice.
abstract: Clinical and experimental data show that traumatic brain injury (TBI)-induced cognitive changes are often manifest as deficits in hippocampal-dependent functions of spatial information processing. The underlying mechanisms for these effects have remained elusive, although recent studies have suggested that the changes in neuronal precursor cells in the dentate subgranular zone (SGZ) of the hippocampus might be involved. Here, we assessed the effects of unilateral controlled cortical impact on neurogenic cell populations in the SGZ in 2-month-old male C57BL6 mice by quantifying numbers of dying cells (TUNEL), proliferating cells (Ki-67) and immature neurons (Doublecortin, Dcx) up to 14 days after TBI. Dying cells were seen 6 h after injury, peaked at 24 h and returned to control levels at 14 days. Proliferating cells were decreased on the ipsilateral and contralateral sides at all the time points studied except 48 h after injury when a transient increase was seen. Simultaneously, immature neurons were reduced up to 84% relative to controls on the ipsilateral side. In the first week post-TBI, reduced numbers of Dcx-positive cells were also seen in the contralateral side; a return to control levels occurred at 14 days. To determine if these changes translated into longer-term effects, BrdU was administered 1 week post-injury and 3 weeks later the phenotypes of the newly born cells were assessed. TBI induced decreases in the numbers of BrdU-positive cells and new neurons (BrdU/NeuN) on the ipsilateral side without apparent changes on the contralateral side, whereas astrocytes (BrdU/GFAP) were increased on the ipsilateral side and activated microglia (BrdU/CD68) were increased on both ipsi- and contralateral sides. No differences were noted in oligodendrocytes (BrdU/NG2). Taken together, these data demonstrate that TBI alters both neurogenesis and gliogenesis. Such alterations may play a contributory role in TBI-induced cognitive impairment.
authors.affiliation: Department of Neurological Surgery, University of California, San Francisco, San Francisco, CA 94143, USA.
authors.forename: Radoslaw
authors.initials: R
authors.lastname: Rola
authors.forename: Shinichiro
authors.initials: S
authors.lastname: Mizumatsu
authors.forename: Shinji
authors.initials: S
authors.lastname: Otsuka
authors.forename: Duncan R
authors.initials: DR
authors.lastname: Morhardt
authors.forename: Linda J
authors.initials: LJ
authors.lastname: Noble-Haeusslein
authors.forename: Kelly
authors.initials: K
authors.lastname: Fishman
authors.forename: Matthew B
authors.initials: MB
authors.lastname: Potts
authors.forename: John R
authors.initials: JR
authors.lastname: Fike
mesh_terms: D000818:Animals; D001930:Brain Injuries / Q000473:pathology* / Q000503:physiopathology*; D001973:Bromodeoxyuridine / Q000378:metabolism; D016923:Cell Death / Q000502:physiology; D049109:Cell Proliferation; D004195:Disease Models, Animal; D000089662:Doublecortin Protein; D007839:Functional Laterality; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D006624:Hippocampus / Q000473:pathology*; D007150:Immunohistochemistry / Q000379:methods; D020287:In Situ Nick-End Labeling / Q000379:methods; D019394:Ki-67 Antigen / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009474:Neurons / Q000502:physiology*; D038081:Organogenesis / Q000502:physiology*; D054390:Receptors, CCR2; D019707:Receptors, Chemokine / Q000378:metabolism; D013234:Stem Cells / Q000473:pathology; D013997:Time Factors
chemical_list: C515335:Ccr2 protein, mouse; C000714847:Dcx protein, mouse; D000089662:Doublecortin Protein; D005904:Glial Fibrillary Acidic Protein; D019394:Ki-67 Antigen; D054390:Receptors, CCR2; D019707:Receptors, Chemokine; D001973:Bromodeoxyuridine