title: Immediate-early gene protein expression in neurons undergoing delayed death, but not necrosis, following hypoxic-ischaemic injury to the young rat brain.
abstract: A unilateral hypoxia-ischaemia (HI) 21-day-old rat preparation was used to assess the effects of HI on the expression of the immediate-early gene proteins (IEGPs) c-Fos/FRAs, Fos B, c-Jun, Jun B, Jun D, Krox 20, Krox 24, and on the mRNA for the neurotrophic factor, brain-derived neurotrophic factor (BDNF). Moderate HI (15 min hypoxia) produced delayed, selective neuronal death and was associated with a rapid induction of c-Fos, Fos B, Jun B, Jun D, and c-Jun proteins, but not Krox 20 protein or BDNF mRNA, in neurons on the side of HI and also a delayed expression of c-Jun (and to a lesser extent c-Fos/FRA's and Fos B) 24-48 h after HI in neurons that underwent delayed neuronal death. Krox 24 showed an initial induction followed by a long-lasting suppression of its expression in regions undergoing cell loss. Severe HI (60 min hypoxia) resulted in seizures and rapid neuronal loss and infarction (necrotic cell death) on the side of HI, and was associated with early induction of c-Fos, Fos B, c-Jun, Jun B, Jun D, Krox 20 and Krox 24 protein and BDNF mRNA in neurons on the non-ligated side of the brain. Fos, c-Jun, Jun B, Jun D and Krox 24, but not Krox 20, Fos B, or BDNF mRNA, were also induced in non-nerve cells on the damaged side of the brain after both moderate and severe HI, and many of these cells appeared to be dividing. Thus, moderate HI induces IEGP's in neurons and non-nerve cells in damaged regions, whereas severe HI induces IEGP's and BDNF in non-damaged regions. c-Jun (and to a lesser extent c-Fos/FRA's) showed a prolonged expression in neurons undergoing delayed, but not necrotic, cell death suggesting that they may be involved in the biochemical cascade that causes selective delayed neuronal death. BDNF was not induced by HI, and therefore, does not appear to play an endogenous neuroprotective role in the CNS.
authors.affiliation: Department of Pharmacology, School of Medicine, University of Auckland, New Zealand.
authors.forename: M
authors.initials: M
authors.lastname: Dragunow
authors.forename: E
authors.initials: E
authors.lastname: Beilharz
authors.forename: E
authors.initials: E
authors.lastname: Sirimanne
authors.forename: P
authors.initials: P
authors.lastname: Lawlor
authors.forename: C
authors.initials: C
authors.lastname: Williams
authors.forename: R
authors.initials: R
authors.lastname: Bravo
authors.forename: P
authors.initials: P
authors.lastname: Gluckman
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D001921:Brain / Q000378:metabolism* / Q000473:pathology; D002545:Brain Ischemia / Q000378:metabolism* / Q000473:pathology; D019208:Brain-Derived Neurotrophic Factor; D002534:Hypoxia, Brain / Q000378:metabolism* / Q000473:pathology; D017874:Immediate-Early Proteins / Q000096:biosynthesis*; D007150:Immunohistochemistry; D009336:Necrosis; D009414:Nerve Growth Factors / Q000032:analysis / Q000096:biosynthesis; D009419:Nerve Tissue Proteins / Q000032:analysis / Q000096:biosynthesis; D009474:Neurons / Q000378:metabolism* / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D017874:Immediate-Early Proteins; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins