Biomedical subjects

E Sirimanne

Publications and source records attributed to E Sirimanne.

23 records · Page 2Linked to original sources

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

Differential expression of insulin-like growth factor binding proteins (IGFBP) 4 and 5 mRNA in the rat brain after transient hypoxic-ischemic injury.

Recent studies suggest a role for the insulin-like growth factor (IGF) system in the repair of damaged tissue following hypoxic-ischemic injury in the infant rat brain. We have used a unilateral model of hypoxic-ischemic injury to assess the possible involvement of two IGF binding proteins (IGFBPs), IGFBP-4 and IGFBP-5, in the post-asphyxial response. Ligation of the right carotid artery of 21-day-old rats was followed by either 15 min or 60 min exposure to 8% oxygen to produce moderate and severe damage respectively. Using in situ hybridization, the distribution of IGFBP-4 and IGFBP-5 mRNA was determined in brains collected over 10 days following the insult. In the control brains (no damage), both IGFBPs were expressed in distinct regions. IGFBP-4 mRNA was detected in limited areas of the hippocampus and in several cortical layers, while IGFBP-5 mRNA was found primarily in the thalamus. In response to hypoxic-ischemic injury, IGFBP-4 mRNA expression was reduced in regions of neuronal loss, suggesting a neuronal origin for IGFBP-4. The expression of IGFBP-5 mRNA was not altered by the 15 min insult, but was heavily induced from 3 days following the 60 min insult, particularly in the subependymal layer and adjacent white matter on the ligated hemisphere. This suggests that IGFBP-5 may be involved in recovery from severe hypoxic-ischemic injury and may be important in the regeneration of oligodendrocytes.

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PubMed1992

A role for IGF-1 in the rescue of CNS neurons following hypoxic-ischemic injury.

Three days after unilateral hypoxic-ischemic injury in infant rats insulin-like growth factor 1 (IGF-1) production by astrocytes was enhanced in the injured region. This was associated with increased expression of mRNA for IGF binding protein-3 but not for binding protein-1. In adult rats a single lateral cerebroventricular injection of IGF-1 two hours following a similar injury markedly reduced neuronal loss. It is suggested that endogenous IGF-1 is neurotrophic and that centrally administered IGF-1 may have therapeutic potential for brain injury.

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PubMed1992

Hypoxia-ischemia induces transforming growth factor beta 1 mRNA in the infant rat brain.

Transforming growth factor beta 1 (TGF beta 1) mRNA expression was examined after hypoxia-ischemia in rat brains using in situ hybridization. Twenty-one-day-old Wistar rats had unilateral ligation of the right carotid artery followed by either 15 or 90 min inhalational hypoxia. Fifteen min of hypoxia resulted in moderate damage with selective neuronal loss in cortical layer 3 and in the hippocampus of the ligated hemisphere. Seventy-two hours after hypoxia TGF beta 1 expression was markedly increased above control levels in those sites. Levels were normal after 120 h. Ninety min of hypoxia led to an infarction of the lateral cerebral cortex and hippocampus of the ligated hemisphere. One hour after hypoxia TGF beta 1 mRNA was expressed in the hippocampus of the damaged side. Seventy-two and 120 h after hypoxia, expressing cells were found throughout the cerebral cortex, piriform cortex, striatum, thalamus and hippocampus of the infarcted side. These data show that TGF beta 1 mRNA expression is induced after a hypoxic-ischemic insult in the brain. TGF beta 1 may be involved in post-asphyxial repair mechanisms.

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PubMed1992

Accumulation of calcitonin-gene related peptide-like immunoreactivity after hypoxic-ischaemic brain injury in the infant rat.

Unilateral carotid ligation in immature rats, followed by either 15 min (moderate group) or 90 min (severe group) of hypoxia were used to assess the effects of hypoxia-ischaemia (HI) on the accumulation of the neuropeptide calcitonin-gene related peptide (CGRP). Severe, but not moderate, HI produced a massive time-dependent increase in CGRP-like immunoreactivity throughout the damaged regions of the brain (neocortex, caudate-putamen, hippocampus) beginning at 24 h and maximal at 3-5 days after HI. By 11 days after HI levels appeared to have returned to baseline. The increased immunoreactivity was largely localized to presumed axon terminals contacting neurons, blood vessels and non-nerve cells. Scattered neurons in the cingulate cortex, piriform cortex and striatum also showed increased immunoreactivity in their soma. These results raise the possibility that CGRP may be involved in neuronal repair after HI in the infant brain.

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