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E Beilharz

Publications and source records attributed to E Beilharz.

7 recordsLinked to original sources
PubMed1999

Alterations in the neural growth hormone axis following hypoxic-ischemic brain injury.

Recently, there has been considerable interest in determining the role of the growth hormone receptor (GHR) in the central nervous system (CNS). The aim of this study was to investigate the role of circulating growth hormone (GH) and the neural GHR after hypoxic-ischemic (HI) brain injury in the 21-day old rat. We observed growth hormone receptor/binding protein (GHR/BP) immunoreactivity to be rapidly upregulated following a severe unilateral HI injury. There was a biphasic increase with an initial rise occurring in blood vessels within a few hours after injury followed by a secondary rise evident by 3 days post-hypoxia in microglia/macrophages, some of which are destined to express insulin-like growth factor-I (IGF-I). There was also an increased immunoreactivity in reactive astrocytes, some of which were in the process of dividing. Subsequently, we attempted to activate the endothelial GHR/BP which was found to be increased after injury by treating with 15 microgram g-1 day-1 s.c. bGH for 7 days. Circulating concentrations of IGF-I fell after injury and were restored with GH treatment (P=0.001), whereas treatment of normal animals had no effect on serum IGF-I. Peripheral GH treatment increased the cerebrospinal fluid (CSF) concentration of immunoreactive IGF-I in the injured rats (P=0.017). GH treatment also reversed the systemic catabolism caused by the injury but had no significant neuroprotective effects. These results indicate that GH therapy can be used to reverse the systemic catabolism that occurs after CNS injury. In addition, these data suggest a role for the neural GHR during the recovery from brain injury, both in terms of the induction of IGF-I and in terms of glial proliferation.

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PubMed1994

Immediate-early gene protein expression in neurons undergoing delayed death, but not necrosis, following hypoxic-ischaemic injury to the young rat brain.

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.

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PubMed1993

Brain-derived neurotrophic factor expression after long-term potentiation.

Long-term potentiation (LTP) of perforant-path dentate granule cell synapses, in awake rats, was followed by a time-dependent expression of brain-derived neurotrophic factor (BDNF) mRNA in dentate granule cells. This BDNF expression was blocked by the N-methyl-D-aspartate (NMDA) antagonist dizocilpine maleate (MK-801), which also blocked LTP induction, and by sodium pentobarbital, which shortens LTP persistence. These results suggest that BDNF may participate in the NMDA-receptor mediated cascade of events that result in LTP stabilization.

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PubMed1993

Is c-Jun involved in nerve cell death following status epilepticus and hypoxic-ischaemic brain injury?

Neurons undergoing delayed neuronal death produced by hypoxia-ischaemia (HI) or status epilepticus (SE) showed a massive expression of c-Jun in their nuclei 24 h after the insult. With SE there was also a weaker induction of c-Fos and Jun B in dying neurons. SE induced in the presence of the NMDA antagonist MK-801 produced no delayed c-Jun expression in the hippocampus and nerve cell death did not occur in this region, although there was a delayed c-jun expression in the amygdala/piriform region, and cell death occurred in this area. Activation of central muscarinic receptors with pilocarpine, or block of D2 dopamine receptors with haloperidol, treatments which do not cause neuronal damage, strongly induced Fos and Jun B in hippocampal and striatal neurons, but only induced c-Jun very weakly. Thus, c-Jun may participate in the genetic cascade of events that produce programmed cell death in neurons.

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PubMed1993

Brain-derived neurotrophic factor is induced as an immediate early gene following N-methyl-D-aspartate receptor activation.

Recent studies show that focal brain injury, cerebral ischaemia, hypoglycaemia and seizures increase the expression of c-fos and brain-derived neurotrophic factor in brain. Here we report that hippocampal focal brain injury transiently induces the immediate early genes c-fos, jun-B, c-jun and krox-24 (zif-268) messenger RNA and protein and brain-derived neurotrophic factor messenger RNA in rat dentate gyrus neurons, an effect that was blocked by the N-methyl-D-aspartate receptor antagonist MK-801. Prior administration of the protein synthesis inhibitor cycloheximide super-induced immediate early gene messenger RNA, abolished immediate early gene protein induction, but had no effect on injury-mediated induction of brain-derived neurotrophic factor messenger RNA. Thus, while N-methyl-D-aspartate receptor activation results in the induction of both immediate early genes and brain-derived neurotrophic factor messenger RNA, de novo synthesis of immediate early gene proteins is not critical for the increased expression of brain-derived neurotrophic factor messenger RNA seen in brain after focal injury. These results suggest that brain-derived neurotrophic factor is induced after injury as an immediate early gene.

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PubMed1993

MK801 induces immediate-early gene proteins and BDNF mRNA in rat cerebrocortical neurones.

Recent studies have shown that MK801, a potent phencyclidine receptor ligand, causes pathomorphological changes in rat cerebrocortical neurones. Here we report that doses of MK801 (1 and 5 mg kg-1) which have been shown to produce pathomorphological changes, induce the expression of immediate-early gene proteins (IEGPs) and brain-derived neurotrophic factor (BDNF) mRNA in rat cerebrocortical neurones. Blockade of central muscarinic receptors which has been shown to prevent MK801-induced pathomorphological changes in cerebrocortical neurones, also prevented MK801-induced expression of IEGPs and BDNF mRNA. The transiently increased expression of BDNF mRNA may be an acute compensatory response of these neurones to MK801-induced injury.

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