Inhibition of injury-induced cell proliferation in the dentate gyrus of the hippocampus impairs spontaneous cognitive recovery after traumatic brain injury
Open accessAbstract
Neurogenesis persists throughout life in the neurogenic regions of the mature mammalian brain, and this response is enhanced after traumatic brain injury (TBI). In the hippocampus, adult neurogenesis plays an important role in hippocampal-dependent learning and memory functions and is thought to contribute to the spontaneous cognitive recovery observed after TBI. Utilizing an antimitotic agent, arabinofuranosyl cytidine (Ara-C), the current study investigated the direct association of injury-induced hippocampal neurogenesis with cognitive recovery. In this study, adult rats received a moderate lateral fluid percussion injury followed by a 7-day intraventricular infusion of 2% Ara-C or vehicle. To examine the effect of Ara-C on cell proliferation, animals received intraperitoneal injections of 5-bromo-2-deoxyuridine (BrdU), to label dividing cells, and were sacrificed at 7 days after injury. Brain sections were immunostained for BrdU or doublecortin (DCX), and the total number of BrdU(+) or DCX(+) cells in the hippocampus was quantified. To examine the outcome of inhibiting the injury-induced cell proliferative response on cognitive recovery, animals were assessed on Morris water maze (MWM) tasks at 21-25 or 56-60 days postinjury. We found that a 7-day infusion of Ara-C significantly reduced the total number of BrdU(+) and DCX(+) cells in the dentate gyrus (DG) in both hemispheres. Moreover, inhibition of the injury-induced cell proliferative response in the DG completely abolished the innate cognitive recovery on MWM performance at 56-60 days postinjury. These results support the causal relationship of injury-induced hippocampal neurogenesis on cognitive functional recovery and suggest the importance of this endogenous repair mechanism on restoration of hippocampal function.
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Brain injury models such as stroke, seizure, and blunt trauma all increase the rate of adult neurogenesis, yet each of these conditions is associated with reduced cognitive function.
“Brain injury models, such as stroke, seizure, and blunt trauma, all increase the rate of adult neurogenesis (Table 1), yet each of these conditions is associated with reduced cognitive function (Cuartero et al., 2019; Parent and Lowenstein, 2002; Sun et al., 2015).”
From Adult neurogenesis, glia, and the extracellular matrix (2019) · cites this paper as Sun et al., 2015
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Adult neurogenesis, glia, and the extracellular matrix
Cope, E. C., & Gould, E. (2019) · Cell Stem Cell · doi:10.1016/j.stem.2019.03.023 · Cited by 236 · see citing works
- Authors
- Sun, D., Daniels, T. E., Rolfe, A., Waters, M., & Hamm, R.
- Affiliations
- Virginia Commonwealth University (US)
- Corresponding author
- Sun, Dong
- ORCID
- Daniels, Teresa E.
- Venue
- Journal of Neurotrauma
- Publisher
- SAGE Publications
- Published
- 2015-04
- Volume
- 32
- Issue
- 7
- Pages
- 495-505
- ISSN
- 0897-7151 (ISSN-L)
- 1557-9042
- PMC
- PMC4376486
- OpenAlex
- W2331252089
- Cited by
- 77
- References
- 55
- Citations by year
- 2026: 3 · 2025: 3 · 2024: 5 · 2023: 3 · 2022: 4 · 2021: 12 · 2020: 11 · 2019: 10 · 2018: 9 · 2017: 5 · 2016: 8 · 2015: 4
- FWCI
- 1.97
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Journal of Neurotrauma (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Virginia Commonwealth University
- National Institutes of Health
- National Institute of Neurological Disorders and Stroke (NS055086, NS078710, P30NS047463, R01NS055086, R21NS078710)
- Topics
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Health Sciences › Medicine › Neurology › Traumatic Brain Injury and Neurovascular Disturbances
- Health Sciences › Medicine › Epidemiology › Traumatic Brain Injury Research
- Keywords
- traumatic brain injury, adult neurogenesis, dentate gyrus, hippocampus, cognitive recovery, antimitotic agents, cell proliferation, lateral fluid percussion injury, doublecortin, BrdU labeling, spatial learning and memory, endogenous repair
- MeSH terms
- Doublecortin Protein, Animals, Brain Injuries, Cognition, Cytarabine, Male, Neurons, Rats, Sprague-Dawley, Maze Learning, Dentate Gyrus, Recovery of Function, Cell Proliferation, Rats, Neurogenesis
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