Effect of secondary insults upon aquaporin-4 water channels following experimental cortical contusion in rats.
Although secondary insults of hypoxia and hypotension (HH) are generally considered to cause fulminant brain edema in traumatic brain injury (TBI), the combined effect of TBI with HH on brain edema and specifically the expression of aquaporin-4 (AQP4) have not been fully elucidated. The goal of this study was to document the effect of secondary insults on brain water, AQP4 expression, electrolytes, and blood-brain barrier (BBB) permeability during the acute stage of edema development. We measured brain water content and electrolytes (series 1); BBB permeability based on Evans blue (EB) dye extravasation (series 2); and AQP4 expression using immunoblotting (series 3) at 1 h and 5 h following cortical contusion injury (CCI). Secondary insults significantly worsened BBB function at 5 h post injury. Moreover, a significant reduction of upregulation on AQP4 expression was observed in trauma, coupled with a mild secondary insult of hypoxia hypotension. These findings indicate that a secondary insult following CCI at 5 h post injury worsens brain edema, disrupts ionic homeostasis, and blunts the normal upregulation of AQP4 that occurs after trauma, suggesting that the blunting of AQP4 may contribute to the detrimental effects of secondary insults.
Taya
Keisuke
K
Department of Neurosurgery, Virginia Commonwealth University, Medical College of Virginia Campus, Richmond, Virginia 23298-0508, USA.
Marmarou
Christina R
CR
Okuno
Kenji
K
Prieto
Ruth
R
Marmarou
Anthony
A
D000818:Animals; D051401:Aquaporin 4 / Q000235:genetics / Q000378:metabolism*; D001812:Blood-Brain Barrier / Q000378:metabolism / Q000503:physiopathology; D001929:Brain Edema / Q000378:metabolism* / Q000503:physiopathology; D001930:Brain Injuries / Q000150:complications / Q000378:metabolism* / Q000503:physiopathology; D002540:Cerebral Cortex / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D004195:Disease Models, Animal; D018450:Disease Progression; D004573:Electrolytes / Q000378:metabolism; D005070:Evans Blue / Q000493:pharmacokinetics; D007022:Hypotension / Q000209:etiology / Q000378:metabolism* / Q000503:physiopathology; D000860:Hypoxia / Q000209:etiology / Q000378:metabolism* / Q000503:physiopathology; D007202:Indicators and Reagents; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D015854:Up-Regulation / Q000502:physiology; D014882:Water-Electrolyte Balance / Q000502:physiology
C496032:Aqp4 protein, rat; D051401:Aquaporin 4; D004573:Electrolytes; D007202:Indicators and Reagents; D005070:Evans Blue
J Neurosurg. 1997 Dec;87(6):900-7
9384402
Neurosurgery. 1987 Jun;20(6):848-53
3614563
J Neurotrauma. 1999 Nov;16(11):1035-47
10595820
Brain Res. 1996 Jul 1;725(2):184-91
8836524
J Neurotrauma. 2007 Oct;24(10):1609-17
17970624
J Neurosurg. 1988 Jan;68(1):129-36
3335898
J Neurotrauma. 2007 Feb;24(2):287-93
17375993
Acta Neurochir Suppl. 2006;96:393-7
16671492
FEBS Lett. 2003 Nov 27;555(1):72-8
14630322
Neurol Res. 2007 Apr;29(3):317-23
17509233
Neurosci Lett. 2002 May 17;324(2):105-8
11988338
Brain Res Mol Brain Res. 2000 May 31;78(1-2):131-7
10891592
J Neurosurg. 1996 Dec;85(6):1113-21
8929504
Behav Brain Res. 2005 May 7;160(1):25-33
15836897
Neurosci Res. 2003 Dec;47(4):437-44
14630348
J Neurotrauma. 1999 Jun;16(6):487-500
10391365
J Cereb Blood Flow Metab. 1987 Dec;7(6):759-67
3693431
J Cereb Blood Flow Metab. 2003 Oct;23(10):1212-8
14526231
J Neurosurg. 1996 Jan;84(1):97-103
8613843
Stroke. 1985 Jan-Feb;16(1):101-9
3966252
Lancet. 2000 Sep 9;356(9233):923-9
11036909
J Neurosci Methods. 1991 Oct;39(3):253-62
1787745
Neurosurgery. 2005 Mar;56(3):582-9; discussion 582-9
15730584
Brain Res Mol Brain Res. 1989 Jul;6(1):93-100
2770455
J Neurotrauma. 1997 Apr;14(4):179-89
9151767
Ann Med. 2002;34(3):192-200
12173689
New Horiz. 1995 Aug;3(3):366-75
7496744
J Neurosurg. 2003 Mar;98(3):565-9
12650429
Nat Med. 2000 Feb;6(2):159-63
10655103
Neurosci Lett. 2001 Mar 23;301(1):21-4
11239707
Physiol Rev. 1997 Jul;77(3):731-58
9234964
J Neurosurg. 2006 May;104(5):720-30
16703876
J Trauma. 1993 Feb;34(2):216-22
8459458
Acta Neurochir Suppl. 2006;96:303-6
16671476
J Neurotrauma. 1992 Winter;9(4):335-47
1291693
J Neurotrauma. 2005 Aug;22(8):857-72
16083353
FASEB J. 2004 Aug;18(11):1291-3
15208268
Biol Cell. 1997 Aug;89(5-6):307-12
9468601
JAMA. 1978 Aug 4;240(5):439-42
660888