title: Dexamethasone significantly attenuates sub-arachnoid hemorrhage-induced elevation in cerebrospinal fluid citrulline and leukocytes.
abstract: OBJECTIVE
  Cerebral vasospasm is a leading cause of death and disability following aneurysmal subarachnoid hemorrhage (SAH). Nitric oxide (NO) is a potent mediator of vasodilation, and citrulline is a known contributor to NO production. The leukocytosis inflammatory response can increase vasoconstrictive compounds that may also contribute to vasospasm. Dexamethasone is a glucocorticosteroid commonly administered after SAH, which may alter the production of leukocytes and citrulline. The goal of this project was to study the effects of dexamethasone on leukocytosis, citrulline, and angiographic vasospasm.
  
  
  METHODS
  Experimental SAH was induced in 18 New Zealand white rabbits. Intravenous dexamethasone was administered to one group (N.=9) at 2 mg/kg/day. A placebo group (N.=9) was given a saline infusion with otherwise identical procedures. CSF citrulline, leukocytes, protein, and glucose, as well as plasma citrulline were measured at baseline and 3 days post-SAH in a blinded fashion. Basilar artery angiography was performed at baseline and repeated 3 days post-SAH.
  
  
  RESULTS
  The change in CSF citrulline from day 0 to day 3 was significantly lower in the dexamethasone group compared to controls (P=0.002). The change in CSF white blood cells was also significantly lower (P=0.005). There was no significant change in plasma citrulline levels or angiographic vasospasm.
  
  
  CONCLUSIONS
  Dexamethasone significantly decreases CSF citrulline and CSF leukocytosis after experimental SAH. It is possible this could lead to a relative vasoconstriction and vasodilation, respectively. These processes could cancel-out opposing effects of dexamethasone on cerebral vasospasm, partially contributing to the recognized, multifactorial, inconsistent effects of glucocorticoids on vasospasm.
authors.affiliation: Department of Radiation Oncology, Memorial-Sloan Kettering, New York, NY, USA.
authors.forename: D E
authors.initials: DE
authors.lastname: Spratt
authors.forename: V K
authors.initials: VK
authors.lastname: Reddy
authors.forename: A A
authors.initials: AA
authors.lastname: Choxi
authors.forename: S D
authors.initials: SD
authors.lastname: Simon
authors.forename: S D
authors.initials: SD
authors.lastname: Shay
authors.forename: M A
authors.initials: MA
authors.lastname: Davidson
authors.forename: F E
authors.initials: FE
authors.lastname: Barr
authors.forename: M L
authors.initials: ML
authors.lastname: Summar
authors.forename: R A
authors.initials: RA
authors.lastname: Mericle
mesh_terms: D000818:Animals; D002956:Citrulline / Q000134:cerebrospinal fluid*; D003907:Dexamethasone / Q000494:pharmacology / Q000627:therapeutic use*; D004195:Disease Models, Animal; D005938:Glucocorticoids / Q000494:pharmacology / Q000627:therapeutic use*; D007962:Leukocytes / Q000187:drug effects*; D009569:Nitric Oxide / Q000134:cerebrospinal fluid; D011817:Rabbits; D013345:Subarachnoid Hemorrhage / Q000134:cerebrospinal fluid / Q000150:complications / Q000188:drug therapy*; D020301:Vasospasm, Intracranial / Q000134:cerebrospinal fluid / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism
chemical_list: D005938:Glucocorticoids; D002956:Citrulline; D009569:Nitric Oxide; D003907:Dexamethasone