Spinal cord injury drives chronic brain changes

LABOMBARDA F

Simposio; The role of glial cells in health and disease of hte Nervous System; 2017

Afterspinal cord injury (SCI), patients exhibit cognitive deficits that could berelated to hippocampal alterations. In this regard, we have previouslydescribed microglial and astrocyte activation and neurogenesis reduction afterchronic SCI in rats. In the present work we have used the Nestin-GFP micecombined with multiple immunolabeling (BrdU, Ki67, GFAP, doublecortin, NeuN)and confocal microscopy in order to determine which step in the neurogenicprocess was altered both in the acute and chronic phases after spinal cordcompression. Survival and mitotic capacity of radia glial cells(Nestin-GFP+/GFAP+ cells) and amplifying progenitors (Nestin-GFP +/ GFAP-cells) were assessed by labeling those cells with BrdU and/or ki67. Reactive astrocyteswere defined as star-shaped cells GFAP+/Nestin-GFP +. In the acute period (7days post injury, 7dpi) we have observed a reduction in the number ofproliferating cells (ki67 + cells), amplifying progenitors (Nestin-GFP + / GFAP-) and neuroblast (doublecortin + cells) in the dentate gyrus. The number ofcFos positive cells in the granular cell layer was decreased indicatingneuronal reduced activity that could be related to diminished neurogenesis. Wehave also found an increase in astrocyte activation in different regions of thehippocampus especially in the stratum radiatum. Fifty days after injury animalsmaintained neurogenesis reduction, astrocyte activation and a decrease in cFospositive neurons indicating that SCI drove irreversible changes in neurogenesisand neuronal activity of the dentate gyrus. These hippocampal changes couldexplain cognitive deficits reported in humans.