Aquaporin-1-mediated cerebral edema following traumatic brain injury: Effects of acidosis and corticosteroid administration

Nam D. Tran, Stefan Kim, Heather K. Vincent, Anthony Rodriguez, David R. Hinton, Ross Bullock, Harold F. Young

Research output: Contribution to journalArticle

34 Citations (Scopus)

Abstract

Object. Dysregulation of water homeostasis induces cerebral edema. Edema is a major cause of morbidity and mortality following traumatic brain injury (TBI). Aquaporin-1 (AQP-1), a water channel found in the brain, can function as a transporter for CO2 across the cellular membrane. Additionally, AQP-1's promoter contains a glucocorticoid response element. Thus, AQP-1 may be involved with edema-related brain injury and might be modulated by external conditions such as the pH and the presence of steroids. In this study, the authors investigated the hypotheses that: 1) AQP-1 participates in brain water homeostasis following TBI; 2) secondary injury (for example, acidosis) alters the expression of AQP-1 and exacerbates cerebral edema; and 3) corticosteroids augment brain AQP-1 expression and differentially affect cerebral edema under nonacidotic and acidotic conditions. Methods. Anesthetized Sprague-Dawley rats were subjected to moderate to severe TBI (2.5-3.5 atm) or surgery without injury, and they were randomized to receive a 3-mg/kg bolus of intravenous dexamethasone within 10 minutes after injury or surgery, a 3-mg/kg bolus of dexamethasone followed by 1-mg/kg maintenance doses every 8 hours for 24 hours, or saline boluses at similar time intervals. A second group of animals was subjected to respiratory acidosis with target arterial blood pH 6.8-7.2 for 1 hour following the surgery or injury. To evaluate selective blockage of AQP-1, some animals received a single intraperitoneal dose of HgCl2 (0.3-30.0 mmol/L) within 30 minutes of injury or surgery. At 4 or 24 hours postinjury, animals were killed and their brains were harvested for mRNA, protein, or water content analyses. Results. The authors demonstrated elevated cerebral edema levels at 4 and 24 hours following TBI. Dexamethasone administration within 1 hour of TBI attenuated the cerebral edema under nonacidotic conditions but worsened it under acidotic conditions. Selective blockage of AQP-1 channels with HgCl2 attenuated the edematous effects of corticosteroids and acidosis. Reverse transcriptase polymerase chain reaction and immunohistochemical analyses demonstrated a paucity of AQP-1 in the cerebral cortices of the uninjured animals. In contrast, AQP-1 mRNA and protein levels were higher in the cerebral cortices of animals that sustained a TBI. Conclusions. These findings implicate an important, modifiable role for AQP-1 in water homeostasis within the CNS following TBI.

Original languageEnglish
Pages (from-to)1095-1104
Number of pages10
JournalJournal of Neurosurgery
Volume112
Issue number5
DOIs
StatePublished - May 1 2010

Fingerprint

Aquaporin 1
Brain Edema
Acidosis
Adrenal Cortex Hormones
Dexamethasone
Wounds and Injuries
Mercuric Chloride
Homeostasis
Water
Brain
Cerebral Cortex
Edema
Traumatic Brain Injury
Respiratory Acidosis
Messenger RNA
Aquaporins
Response Elements
Reverse Transcriptase Polymerase Chain Reaction
Brain Injuries
Glucocorticoids

Keywords

  • Aquaporin-1
  • Cerebral cortex
  • Edema
  • Traumatic brain injury

ASJC Scopus subject areas

  • Clinical Neurology
  • Surgery

Cite this

Tran, N. D., Kim, S., Vincent, H. K., Rodriguez, A., Hinton, D. R., Bullock, R., & Young, H. F. (2010). Aquaporin-1-mediated cerebral edema following traumatic brain injury: Effects of acidosis and corticosteroid administration. Journal of Neurosurgery, 112(5), 1095-1104. https://doi.org/10.3171/2009.8.JNS081704

Aquaporin-1-mediated cerebral edema following traumatic brain injury : Effects of acidosis and corticosteroid administration. / Tran, Nam D.; Kim, Stefan; Vincent, Heather K.; Rodriguez, Anthony; Hinton, David R.; Bullock, Ross; Young, Harold F.

In: Journal of Neurosurgery, Vol. 112, No. 5, 01.05.2010, p. 1095-1104.

Research output: Contribution to journalArticle

Tran, ND, Kim, S, Vincent, HK, Rodriguez, A, Hinton, DR, Bullock, R & Young, HF 2010, 'Aquaporin-1-mediated cerebral edema following traumatic brain injury: Effects of acidosis and corticosteroid administration', Journal of Neurosurgery, vol. 112, no. 5, pp. 1095-1104. https://doi.org/10.3171/2009.8.JNS081704
Tran, Nam D. ; Kim, Stefan ; Vincent, Heather K. ; Rodriguez, Anthony ; Hinton, David R. ; Bullock, Ross ; Young, Harold F. / Aquaporin-1-mediated cerebral edema following traumatic brain injury : Effects of acidosis and corticosteroid administration. In: Journal of Neurosurgery. 2010 ; Vol. 112, No. 5. pp. 1095-1104.
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