title: Attenuation of reactive gliosis does not affect infarct volume in neonatal hypoxic-ischemic brain injury in mice.
abstract: BACKGROUND
  Astroglial cells are activated following injury and up-regulate the expression of the intermediate filament proteins glial fibrillary acidic protein (GFAP) and vimentin. Adult mice lacking the intermediate filament proteins GFAP and vimentin (GFAP(-/-)Vim(-/-)) show attenuated reactive gliosis, reduced glial scar formation and improved regeneration of neuronal synapses after neurotrauma. GFAP(-/-)Vim(-/-) mice exhibit larger brain infarcts after middle cerebral artery occlusion suggesting protective role of reactive gliosis after adult focal brain ischemia. However, the role of astrocyte activation and reactive gliosis in the injured developing brain is unknown.
  
  
  RESULTS
  We subjected GFAP(-/-)Vim(-/-) and wild-type mice to unilateral hypoxia-ischemia (HI) at postnatal day 9 (P9). Bromodeoxyuridine (BrdU; 25 mg/kg) was injected intraperitoneally twice daily from P9 to P12. On P12 and P31, the animals were perfused intracardially. Immunohistochemistry with MAP-2, BrdU, NeuN, and S100 antibodies was performed on coronal sections. We found no difference in the hemisphere or infarct volume between GFAP(-/-)Vim(-/-) and wild-type mice at P12 and P31, i.e. 3 and 22 days after HI. At P31, the number of NeuN(+) neurons in the ischemic and contralateral hemisphere was comparable between GFAP(-/-)Vim(-/-) and wild-type mice. In wild-type mice, the number of S100(+) astrocytes was lower in the ipsilateral compared to contralateral hemisphere (65.0+/-50.1 vs. 85.6+/-34.0, p<0.05). In the GFAP(-/-)Vim(-/-) mice, the number of S100(+) astrocytes did not differ between the ischemic and contralateral hemisphere at P31. At P31, GFAP(-/-)Vim(-/-) mice showed an increase in NeuN(+)BrdU(+) (surviving newly born) neurons in the ischemic cortex compared to wild-type mice (6.7+/-7.7; n = 29 versus 2.9+/-3.6; n = 28, respectively, p<0.05), but a comparable number of S100(+)BrdU(+) (surviving newly born) astrocytes.
  
  
  CONCLUSIONS
  Our results suggest that attenuation of reactive gliosis in the developing brain does not affect the hemisphere or infarct volume after HI, but increases the number of surviving newborn neurons.
authors.affiliation: Perinatal Center, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
authors.forename: Katarina
authors.initials: K
authors.lastname: Järlestedt
authors.forename: Catherine I
authors.initials: CI
authors.lastname: Rousset
authors.forename: Maryam
authors.initials: M
authors.lastname: Faiz
authors.forename: Ulrika
authors.initials: U
authors.lastname: Wilhelmsson
authors.forename: Anders
authors.initials: A
authors.lastname: Ståhlberg
authors.forename: Hana
authors.initials: H
authors.lastname: Sourkova
authors.forename: Marcela
authors.initials: M
authors.lastname: Pekna
authors.forename: Carina
authors.initials: C
authors.lastname: Mallard
authors.forename: Henrik
authors.initials: H
authors.lastname: Hagberg
authors.forename: Milos
authors.initials: M
authors.lastname: Pekny
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001253:Astrocytes; D020520:Brain Infarction / Q000473:pathology*; D002470:Cell Survival; D005904:Glial Fibrillary Acidic Protein / Q000172:deficiency; D005911:Gliosis / Q000473:pathology*; D020925:Hypoxia-Ischemia, Brain / Q000473:pathology*; D051379:Mice; D018345:Mice, Knockout; D009474:Neurons
chemical_list: D005904:Glial Fibrillary Acidic Protein