Progesterone treatment normalizes the levels of cell proliferation and cell death in the dentate gyrus of the hippocampus after traumatic brain injury

Cindy K. Barha, Tauheed Ishrat, Jonathan R. Epp, Liisa A.M. Galea, Donald G. Stein

Research output: Contribution to journalArticle

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Abstract

Traumatic brain injury (TBI) increases cell death in the hippocampus and impairs hippocampus-dependent cognition. The hippocampus is also the site of ongoing neurogenesis throughout the lifespan. Progesterone treatment improves behavioral recovery and reduces inflammation, apoptosis, lesion volume, and edema, when given after TBI. The aim of the present study was to determine whether progesterone altered cell proliferation and short-term survival in the dentate gyrus after TBI. Male Sprague-Dawley rats with bilateral contusions of the frontal cortex or sham operations received progesterone or vehicle at 1 and 6. h post-surgery and daily through post-surgery Day 7, and a single injection of bromodeoxyuridine (BrdU) 48. h after injury. Brains were then processed for Ki67 (endogenous marker of cell proliferation), BrdU (short-term cell survival), doublecortin (endogenous marker of immature neurons), and Fluoro-Jade B (marker of degenerating neurons). TBI increased cell proliferation compared to shams and progesterone normalized cell proliferation in injured rats. Progesterone alone increased cell proliferation in intact rats. Interestingly, injury and/or progesterone treatment did not influence short-term cell survival of BrdU-ir cells. All treatments increased the percentage of BrdU-ir cells that were co-labeled with doublecortin (an immature neuronal marker in this case labeling new neurons that survived 5. days), indicating that cell fate is influenced independently by TBI and progesterone treatment. The number of immature neurons that survived 5. days was increased following TBI, but progesterone treatment reduced this effect. Furthermore, TBI increased cell death and progesterone treatment reduced cell death to levels seen in intact rats. Together these findings suggest that progesterone treatment after TBI normalizes the levels of cell proliferation and cell death in the dentate gyrus of the hippocampus.

Original languageEnglish (US)
Pages (from-to)72-81
Number of pages10
JournalExperimental Neurology
Volume231
Issue number1
DOIs
StatePublished - Sep 1 2011
Externally publishedYes

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Parahippocampal Gyrus
Dentate Gyrus
Progesterone
Cell Death
Cell Proliferation
Bromodeoxyuridine
Therapeutics
Neurons
Hippocampus
Cell Survival
Traumatic Brain Injury
Contusions
Neurogenesis
Wounds and Injuries
Frontal Lobe
Ambulatory Surgical Procedures
Cognition
Sprague Dawley Rats
Edema
Apoptosis

All Science Journal Classification (ASJC) codes

  • Neurology
  • Developmental Neuroscience

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Progesterone treatment normalizes the levels of cell proliferation and cell death in the dentate gyrus of the hippocampus after traumatic brain injury. / Barha, Cindy K.; Ishrat, Tauheed; Epp, Jonathan R.; Galea, Liisa A.M.; Stein, Donald G.

In: Experimental Neurology, Vol. 231, No. 1, 01.09.2011, p. 72-81.

Research output: Contribution to journalArticle

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