The Effects of Anesthesia on Adult Hippocampal Neurogenesis

Abstract

In animal studies, prolonged sedation with general anesthetics has resulted in cognitive impairments that can last for days to weeks after exposure. One mechanism by which anesthesia may impair cognition is by decreasing adult hippocampal neurogenesis. Several studies have seen a reduction in cell survival after anesthesia in rodents with most studies focusing on two particularly vulnerable age windows: the neonatal period and old age. However, the extent to which sedation affects neurogenesis in young adults remains unclear. Adult neurogenesis in the dentate gyrus (DG) was analyzed in male and female rats 24 h after a 4-h period of sedation with isoflurane, propofol, midazolam, or dexmedetomidine. Three different cell populations were quantified: cells that were 1 week or 1 month old, labeled with the permanent birthdate markers EdU or BrdU, respectively, and precursor cells, identified by their expression of the endogenous dividing cell marker proliferating cell nuclear antigen (PCNA) at the time of sacrifice. Midazolam and dexmedetomidine reduced cell proliferation in the adult DG in both sexes but had no effect on postmitotic cells. Propofol reduced the number of relatively mature, 28-day old, neurons specifically in female rats and had no effects on younger cells. Isoflurane had no detectable effects on any of the cell populations examined. These findings show no general effect of sedation on adult-born neurons but demonstrate that certain sedatives do have drug-specific and sex-specific effects. The impacts observed on different cell populations predict that any cognitive effects of these sedatives would likely occur at different times, with propofol producing a rapid but short-lived impairment and midazolam and dexmedetomidine altering cognition after a several week delay. Taken together, these studies lend support to the hypothesis that decreased neurogenesis in the young adult DG may mediate the effects of sedation on cognitive function.

AAV ablates neurogenesis in the adult murine hippocampus

“…In any surgical manipulation of the DG, including our studies, abDGCs are exposed to a variety of experimental manipulations that might affect adult neurogenesis, including anesthesia, nonsteroidal anti-inflammatory drugs, and corticosteroids ( Cameron and Gould, 1994 ; Erasso et al, 2013 ; Kim et al, 2020 ; Lehmann et al, 2013 ; McGuiness et al, 2017 ; Monje et al, 2003 ; Saaltink and Vreugdenhil, 2014 ; Schoenfeld and Gould, 2013 ; Stratmann et al, 2009 ; Stratmann et al, 2010 ) utilized for animal comfort and humane experimentation. The effects of these pharmacological agents are largely accounted for by performing intra-subject comparisons, where the uninjected or saline-injected contralateral hippocampus is also exposed to these agents.…”

Isoflurane impairs olfaction by increasing neuronal activity in the olfactory bulb

“…Although the expression of OMP, which is a marker of mature OSNs, was not affected by isoflurane exposure, whether the function of OSNs was impaired is unknown. On the other hand, as both increased and decreased neurogenesis have been reported in the hippocampus after general anesthesia, 28,29 isoflurane exposure may directly influence the proliferation of basal cells in the MOE.…”

Disturbance of Key Cellular Subproteomes upon Propofol Treatment Is Associated with Increased Permeability of the Blood-Brain Barrier

“…It is obvious that metabolic stress, ROS metabolism and DDR are interconnected, and it may give an explanation for certain observed long-term actions of propofol such as impairment of cognitive function, associated with neuroapoptosis [ 56 , 57 ]. It may well be that an increase of metabolic stress and ROS contribute to apoptosis not only in endothelial cells of the BBB, but also in neurons.…”