Moderate traumatic brain injury promotes proliferation of quiescent neural progenitors in the adult hippocampus - PubMed (original) (raw)

Moderate traumatic brain injury promotes proliferation of quiescent neural progenitors in the adult hippocampus

Xiang Gao et al. Exp Neurol. 2009 Oct.

Abstract

Recent evidence shows that traumatic brain injury (TBI) regulates proliferation of neural stem/progenitor cells in the dentate gyrus (DG) of adult hippocampus. There are distinct classes of neural stem/progenitor cells in the adult DG, including quiescent neural progenitors (QNPs), which carry stem cell properties, and their progeny, amplifying neural progenitors (ANPs). The response of each class of progenitors to TBI is not clear. We here used a transgenic reporter Nestin-GFP mouse line, in which QNP and ANP cells are easily visualized and quantified, to determine the targets of the TBI in the DG. We examined changes in proliferation of QNPs and ANPs in the acute phase following TBI and found that QNPs were induced by TBI insult to enter the cell cycle whereas proliferation of ANPs was not significantly affected. These results indicate that different subtypes of neural stem/progenitor cells respond differently to TBI insult. Stem cell activation by the TBI may reflect the induction of innate repair and plasticity mechanisms by the injured brain.

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Figures

Fig. 1

Fig. 1

TBI insult promotes cell proliferation in the adult hippocampus. (a, b) Immunostaining with antibody against BrdU (red) to identify proliferating cells in the hippocampus of sham-operated mice (a, b) or of mice after TBI surgery (c, d). Nuclei are stained with DAPI (blue) to show the DG structure. Quantification shows the distribution of proliferating cells in the different subregions of hippocampus. ML: molecular layer; GCL: granule cell layer. SGZ: subgranular zone.

Fig. 2

Fig. 2

Determining the cell types the proliferating cells in the hippocampus following moderate TBI. (a–g) Double immunostaining with antibody against BrdU (red) and Nestin (green) was performed to visualize the proliferating neural stem/progenitor cells in the SGZ of the hippocampus after TBI. (a) BrdU. (b) Nestin. (c) DAPI. (d) Merge of (a) to (c). White arrows indicate proliferating neural stem/progenitor cells. (e–g) Confocal microscopy was performed to verify the colocalization of BrdU with Nestin in the cells within the white box in panel (d). (h–n) Double immunostaining with antibody against BrdU (red) and GFAP (green) was performed to show the reactive astrocytes in the ML of the hippocampus after TBI. (h) BrdU. (i) GFAP. (j) DAPI. (k) Merge of (h) to (j). White arrows indicate the reactive astrocytes. (e–g) Confocal microscopy was performed to verify the colocalization of BrdU with GFAP in the cells within the white box in panel (k).

Fig. 3

Fig. 3

Quiescent neural progenitors (QNPs) and amplifying neural progenitors (ANPs) are distinguishable in the hippocampus of Nestin-EGFP transgenic mice. (a, b) EGFP immunostaining was performed to reveal the QNPs and ANPs in the adult hippocampus of Nestin-EGFP transgenic mice. QNPs are marked by white arrows, while the ANPs are marked by white arrowheads. (c, d). Quantification of QNPs and ANPs in the adult hippocampus of Nestin-EGFP transgenic mice.

Fig. 4

Fig. 4

Assessing the proliferation of QNPs and ANPs in the hippocampus following moderate TBI. Double immunostainings were performed to reveal the proliferating QNPs and ANPs in the adult hippocampus with antibodies against EGFP and BrdU. (a–c). Proliferation of QNPs and ANPs in the adult hippocampus of moderate CCI-injured mice. (d–f). Proliferation of QNPs and ANPs in the adult hippocampus of moderate CCI-injured mice. Nuclei are stained with DAPI (blue) to show the DG structure. QNPs are marked by white arrows, while the ANPs are marked by white arrowheads. (g) The proliferation rates of QNP and ANP were obtained in CCI-injured mice and control mice. Their relative proliferation rates in fold were calculated by comparing the proliferation rates in CCI-injured mice to control mice.

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References

    1. Ariza M, Serra-Grabulosa JM, Junque C, Ramirez B, Mataro M, Poca A, Bargallo N, Sahuquillo J. Hippocampal head atrophy after traumatic brain injury. Neuropsychologia. 2006;44:1956–1961. - PubMed
    1. Bhattacharjee Y. Neuroscience. Shell shock revisited: solving the puzzle of blast trauma. Science. 2008;319:406–408. - PubMed
    1. Bonislawski DP, Schwarzbach EP, Cohen AS. Brain injury impairs dentate gyrus inhibitory efficacy. Neurobiol. Dis. 2007;25:163–169. - PMC - PubMed
    1. Bull ND, Bartlett PF. The adult mouse hippocampal progenitor is neurogenic but not a stem cell. J. Neurosci. 2005;25:10815–10821. - PMC - PubMed
    1. Cameron HA, McKay RD. Adult neurogenesis produces a large pool of new granule cells in the dentate gyrus. J. Comp. Neurol. 2001;435:406–417. - PubMed

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