title: Acute, transient hemorrhagic hypotension does not aggravate structural damage or neurologic motor deficits but delays the long-term cognitive recovery following mild to moderate traumatic brain injury.
abstract: OBJECTIVE
  Posttraumatic hypotension is believed to increase morbidity and mortality in traumatically brain-injured patients. Using a clinically relevant model of combined traumatic brain injury with superimposed hemorrhagic hypotension in rats, the present study evaluated whether a reduction in mean arterial blood pressure aggravates regional brain edema formation, regional cell death, and neurologic motor/cognitive deficits associated with traumatic brain injury.
  
  
  METHODS
  Experimental prospective, randomized study in rodents.
  
  
  METHODS
  Experimental laboratory at a university hospital.
  
  
  METHODS
  One hundred nineteen male Sprague-Dawley rats weighing 350-385 g.
  
  
  METHODS
  Experimental traumatic brain injury of mild to moderate severity was induced using the lateral fluid percussion brain injury model in anesthetized rats (n = 89). Following traumatic brain injury, in surviving animals one group of animals was subjected to pressure-controlled hemorrhagic hypotension, maintaining the mean arterial blood pressure at 50-60 mm Hg for 30 mins (n = 47). The animals were subsequently either resuscitated with lactated Ringer's solution (three times shed blood volume, n = 18) or left uncompensated (n = 29). Other groups of animals included those with isolated traumatic brain injury (n = 34), those with isolated hemorrhagic hypotension (n = 8), and sham-injured control animals receiving anesthesia and surgery alone (n = 22).
  
  
  RESULTS
  The withdrawal of 6-7 mL of arterial blood significantly reduced mean arterial blood pressure by 50% without decreasing arterial oxygen saturation or Pao2. Brain injury induced significant cerebral edema (p < .001) in vulnerable brain regions and cortical tissue loss (p < .01) compared with sham-injured animals. Neither regional brain edema formation at 24 hrs postinjury nor the extent of cortical tissue loss assessed at 7 days postinjury was significantly aggravated by superimposed hemorrhagic hypotension. Brain injury-induced neurologic deficits persisted up to 20 wks after injury and were also not aggravated by the hemorrhagic hypotension. Cognitive dysfunction persisted for up to 16 wks postinjury. The superimposition of hemorrhagic hypotension significantly delayed the time course of cognitive recovery.
  
  
  CONCLUSIONS
  A single, acute hypotensive event lasting 30 mins did not aggravate the short- and long-term structural and motor deficits but delayed the speed of recovery of cognitive function associated with experimental traumatic brain injury.
authors.affiliation: From the Traumatic Brain Injury Laboratory, Department of Neurosurgery, University of Pennsylvania, Philadelphia, USA.
authors.forename: Christian
authors.initials: C
authors.lastname: Schütz
authors.forename: John F
authors.initials: JF
authors.lastname: Stover
authors.forename: Hilaire J
authors.initials: HJ
authors.lastname: Thompson
authors.forename: Rachel C
authors.initials: RC
authors.lastname: Hoover
authors.forename: Diego M
authors.initials: DM
authors.lastname: Morales
authors.forename: Joost W
authors.initials: JW
authors.lastname: Schouten
authors.forename: Asenia
authors.initials: A
authors.lastname: McMillan
authors.forename: Kristie
authors.initials: K
authors.lastname: Soltesz
authors.forename: Melissa
authors.initials: M
authors.lastname: Motta
authors.forename: Zachery
authors.initials: Z
authors.lastname: Spangler
authors.forename: Edmund
authors.initials: E
authors.lastname: Neugebauer
authors.forename: Tracy K
authors.initials: TK
authors.lastname: McIntosh
mesh_terms: D000818:Animals; D001784:Blood Gas Analysis; D001794:Blood Pressure; D001930:Brain Injuries / Q000150:complications*; D003072:Cognition Disorders / Q000209:etiology*; D005440:Fluid Therapy; D007022:Hypotension / Q000150:complications* / Q000628:therapy; D008297:Male; D011597:Psychomotor Performance; D051381:Rats; D017207:Rats, Sprague-Dawley; D012769:Shock / Q000150:complications* / Q000628:therapy; D013997:Time Factors