title: The Cox-2 Inhibitor Meloxicam Ameliorates Neuroinflammation and Depressive Behavior in Adult Mice after Splenectomy.
abstract: BACKGROUND
  Peripheral surgical trauma may incite neuroinflammation that leads to neuronal dysfunction associated with both depression and cognitive deficits. In a previous study, we found that adult mice developed neuroinflammation and short-term working memory dysfunction in a delayed, transient manner after splenectomy that was ameliorated by the cyclooxygenase-2 inhibitor meloxicam. We tested the hypothesis that splenectomy in mice would also cause anhedonia, the diminished response to pleasure or rewarding stimuli that is a hallmark of depression, and that treatment with meloxicam would be ameliorative.
  
  
  METHODS
  After Institutional Animal Care and Use Committee approval, Swiss-Webster mice underwent sucrose preference training before being randomized into groups on day 0, when they had either splenectomy and anesthesia or anesthesia alone. Within each group, half were randomized to receive intraperitoneal saline at 24 hours, while the other half received intraperitoneal meloxicam at 24 hours. Sucrose preference ratios were determined on days 1, 5, 9, and 14. Additional mice were randomized into groups for brain histochemistry. Specimens were stained for glial fibrillary acidic protein (GFAP), a marker of astrocytes, and CD45, a protein tyrosine phosphatase that identifies microglial activation.
  
  
  RESULTS
  On day 5, mice receiving splenectomy and saline demonstrated diminished sucrose preference, which was not seen in mice receiving splenectomy and meloxicam. Semiquantitative analysis of histological slides taken from splenectomized mice treated with meloxicam revealed reduced microglial-based neuroinflammation and reactive astrocytosis compared to mice receiving saline.
  
  
  CONCLUSIONS
  Splenectomy in mice is associated with neuroinflammation and anhedonia, as evidenced by reactive microgliosis, astrocytosis, and behavioral changes. Postsurgical treatment with meloxicam attenuates both neuroinflammation and anhedonia. These findings suggest that cyclooxygenase-2-dependent mechanisms may play a role in the development of postoperative mood disorders, possibly via modulation of peripheral effects on neuroinflammation.
authors.affiliation: Department of Anesthesiology, New York University School of Medicine.
authors.forename: Michael
authors.initials: M
authors.lastname: Haile
authors.affiliation: Department of Neurology, New York University School of Medicine; Department of Psychiatry, New York University School of Medicine; Department of Physiology, Neuroscience, New York, New York; King Abdulaziz University, Jeddah, Saudi Arabia.
authors.forename: Allal
authors.initials: A
authors.lastname: Boutajangout
authors.affiliation: Department of Anesthesiology, New York University School of Medicine.
authors.forename: Kevin
authors.initials: K
authors.lastname: Chung
authors.affiliation: Department of Anesthesiology, New York University School of Medicine.
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Chan
authors.affiliation: Department of Anesthesiology, New York University School of Medicine.
authors.forename: Tanya
authors.initials: T
authors.lastname: Stolper
authors.affiliation: Department of Anesthesiology, New York University School of Medicine.
authors.forename: Nemahun
authors.initials: N
authors.lastname: Vincent
authors.affiliation: Department of Anesthesiology, New York University School of Medicine.
authors.forename: Marc
authors.initials: M
authors.lastname: Batchan
authors.affiliation: Department of Anesthesiology, New York University School of Medicine.
authors.forename: John
authors.initials: J
authors.lastname: D'Urso
authors.affiliation: Department of Psychiatry, New York University School of Medicine.
authors.forename: Yan
authors.initials: Y
authors.lastname: Lin
authors.affiliation: Department of Anesthesiology, New York University School of Medicine.
authors.forename: Richard
authors.initials: R
authors.lastname: Kline
authors.affiliation: Department of Neurology, New York University School of Medicine.
authors.forename: Faris
authors.initials: F
authors.lastname: Yaghmoor
authors.affiliation: Department of Neurology, New York University School of Medicine.
authors.forename: Saad
authors.initials: S
authors.lastname: Jahfal
authors.affiliation: Department of Neurology, New York University School of Medicine.
authors.forename: Robel
authors.initials: R
authors.lastname: Kamal
authors.affiliation: Department of Neurology, New York University School of Medicine.
authors.forename: Waleed
authors.initials: W
authors.lastname: Aljohani
authors.affiliation: Department of Anesthesiology, New York University School of Medicine.
authors.forename: Thomas
authors.initials: T
authors.lastname: Blanck
authors.affiliation: Rutgers New Jersey Medical School, New York University School of Medicine, New Jersey.
authors.forename: Alex
authors.initials: A
authors.lastname: Bekker
authors.affiliation: Department of Neurology, New York University School of Medicine; Department of Psychiatry, New York University School of Medicine; Department of Pathology, New York University School of Medicine.
authors.forename: Thomas
authors.initials: T
authors.lastname: Wisniewski
keywords: Anhedonia; Astrocytosis; Cyclooxygenase-2; Depression; Meloxicam; Microgliosis; Neuroinflammation; Splenectomy