title: BrdU-positive cells in the neonatal mouse hippocampus following hypoxic-ischemic brain injury.
abstract: BACKGROUND
  Mechanisms that affect recovery from fetal and neonatal hypoxic-ischemic (H-I) brain injury have not been fully elucidated. The incidence of intrapartum asphyxia is approximately 2.5%, but the occurrence of adverse clinical outcome is much lower. One of the factors which may account for this relatively good outcome is the process of neurogenesis, which has been described in adult animals. We used a neonatal mouse model to assess new cells in the hippocampus after H-I injury.
  
  
  RESULTS
  Neonatal mice underwent permanent unilateral carotid ligation on the seventh postnatal day followed by exposure to 8% hypoxia for 75 minutes. The presence of new cells was determined by bromodeoxyuridine (BrdU) incorporation into cells with sacrifice of the animals at intervals. Brain sections were stained for BrdU in combination with neuronal, glial, endothelial and microglial stains. We found a significant increase in BrdU-positive cells in the neonatal mouse hippocampus in the injured area compared to the non-injured area, most prominent in the dentate gyrus (DG) (154.5 +/- 59.6 v. 92.9 +/- 32.7 at 3 days after injury; 68.9 +/- 23.4 v. 52.4 +/- 17.1 at 35 days after injury, p < 0.0011). Among the cells which showed differentiation, those which were stained as either microglial or endothelial cells showed a peak increase at three days after the injury in the DG, injured versus non-injured side (30.5 +/- 17.8 v. 2.7 +/- 2.6, p < 0.0002). As in the adult animal, neurogenesis was significantly increased in the DG with injury (15.0 +/- 4.6 v. 5.2 +/- 1.6 at 35 days after injury, p < 0.0002), and this increase was subsequent to the appearance of the other dividing cells. Numbers of new oligodendrocytes were significantly higher in the DG on the non-injured side (7.0 +/- 24.2 v. 0.1 +/- 0.3, p < 0.0002), suggesting that oligodendrocyte synthesis was reduced in the injured hippocampus.
  
  
  CONCLUSIONS
  These findings demonstrate that the neonatal animal responds to brain injury with neurogenesis, much like the adult animal. In addition, H-I insult leads to more neurogenesis than hypoxia alone. This process may play a role in the recovery of the neonatal animal from H-I insult, and if so, enhancement of the process may improve recovery.
authors.affiliation: The Department of Neurology, The Medical College of Georgia, Augusta, GA 30912, USA. jbartley@mail.mcg.edu <jbartley@mail.mcg.edu>
authors.forename: John
authors.initials: J
authors.lastname: Bartley
authors.forename: Thomas
authors.initials: T
authors.lastname: Soltau
authors.forename: Hereward
authors.initials: H
authors.lastname: Wimborne
authors.forename: Sunjun
authors.initials: S
authors.lastname: Kim
authors.forename: Angeline
authors.initials: A
authors.lastname: Martin-Studdard
authors.forename: David
authors.initials: D
authors.lastname: Hess
authors.forename: William
authors.initials: W
authors.lastname: Hill
authors.forename: Jennifer
authors.initials: J
authors.lastname: Waller
authors.forename: James
authors.initials: J
authors.lastname: Carroll
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001973:Bromodeoxyuridine / Q000032:analysis*; D002452:Cell Count / Q000379:methods; D006624:Hippocampus / Q000737:chemistry / Q000254:growth & development* / Q000473:pathology*; D020925:Hypoxia-Ischemia, Brain / Q000473:pathology*; D051379:Mice; D008810:Mice, Inbred C57BL
chemical_list: D001973:Bromodeoxyuridine
references.citation: Int J Dev Neurosci. 2001 Apr;19(2):197-208
references.pmid: 11255033
references.citation: Pediatr Res. 2004 Apr;55(4):561-7
references.pmid: 14739363
references.citation: Exp Brain Res. 2001 Feb;136(3):313-20
references.pmid: 11243473
references.citation: J Neurosci. 1998 Oct 1;18(19):7768-78
references.pmid: 9742147
references.citation: Brain Res Dev Brain Res. 2003 Apr 14;142(1):67-76
references.pmid: 12694945
references.citation: Neuroscience. 2002;112(4):977-91
references.pmid: 12088755
references.citation: Neuropathol Appl Neurobiol. 2003 Aug;29(4):350-60
references.pmid: 12887595
references.citation: J Neurotrauma. 2003 Oct;20(10):929-41
references.pmid: 14588110
references.citation: Brain Res. 1998 Nov 9;810(1-2):114-22
references.pmid: 9813271
references.citation: J Neurosci. 2004 Nov 24;24(47):10763-72
references.pmid: 15564594
references.citation: J Neuropathol Exp Neurol. 1999 Apr;58(4):313-20
references.pmid: 10218626
references.citation: Dev Neurosci. 2001;23(3):234-47
references.pmid: 11598326
references.citation: Glia. 2004 May;46(4):380-90
references.pmid: 15095368
references.citation: Proc Natl Acad Sci U S A. 2001 Apr 10;98(8):4710-5
references.pmid: 11296300
references.citation: Brain Res Dev Brain Res. 2002 Mar 31;134(1-2):23-30
references.pmid: 11947934
references.citation: Pediatr Res. 2002 Jan;51(1):25-33
references.pmid: 11756636
references.citation: Curr Opin Neurobiol. 2003 Feb;13(1):127-32
references.pmid: 12593991
references.citation: Stroke. 2001 Aug;32(8):1890-6
references.pmid: 11486122
references.citation: Glia. 2003 Nov;44(2):140-52
references.pmid: 14515330
references.citation: Am J Pathol. 1960 Jan;36:1-17
references.pmid: 14416289
references.citation: Neurosci Lett. 2002 Dec 16;334(3):153-6
references.pmid: 12453618
references.citation: Brain Res Dev Brain Res. 1989 Oct 1;49(2):311-7
references.pmid: 2805336
references.citation: Ann Neurol. 1981 Feb;9(2):131-41
references.pmid: 7235629
references.citation: J Neuropathol Exp Neurol. 1999 Jun;58(6):654-66
references.pmid: 10374756
references.citation: Ann Neurol. 1997 Sep;42(3):335-48
references.pmid: 9307255
references.citation: J Neurosci. 1998 Aug 15;18(16):6241-53
references.pmid: 9698317
references.citation: Brain Res. 1999 Jun 12;831(1-2):283-7
references.pmid: 10412007
references.citation: J Neurosci. 2002 Jan 15;22(2):455-63
references.pmid: 11784790
references.citation: Nat Med. 1998 Nov;4(11):1313-7
references.pmid: 9809557
references.citation: J Clin Epidemiol. 2001 Apr;54(4):407-10
references.pmid: 11297890
references.citation: Neuropathology. 2002 Sep;22(3):106-32
references.pmid: 12416551
references.citation: Brain Res Dev Brain Res. 1997 Jun 18;100(2):149-60
references.pmid: 9205806
references.citation: Brain Res. 2001 Apr 13;898(1):126-35
references.pmid: 11292456