Year: 1995
Type: article
Abstract: The immature brain produces neurotrophic factors following injury.These may serve to restrict the extent of neuronal loss and/or to facilitate functional recovery.Therefore, we have examined the time course of cell death and expression of growth factors following moderate (15-minute) and severe (60-minute) unilateral hypoxic-ischemic injuries in the infant (21-day) rat.Following the moderate injury the neurons developed an apoptotic morphology, acidophilia and DNA laddering by 3 days after the initial injury.These changes were preceded by prolonged expression of the immediate early gene c-jun in the dying neurons.The apoptotic changes closely correlated temporally and spatially both with the microglial reaction and sites of transforming growth factor (TGFP,) mRNA expression.After the severe injury the apoptotic changes were accelerated particularly within the striatum where some DNA and mitochondria (triphenyltetrazolium chloride monohydrate (TTC) staining) remained intact and cells basophilic until after 10 h.Widespread necrosis with random DNA degradation developed by 24 h.The results indicate that there are two pathways to delayed cell death; selective neuronal loss which was apoptotic, and closely coupled with a microglial reaction and c-jun expression.In contrast delayed necrosis occurred independently from these processes.Insulin-like growth factor 1 (IGF-1).which is well known for its anabolic effects, is a potent trophic factor for most types of neurons.We have extensively studied the time course of changes in the IGF axis following these injuries.IGF-1 was induced in astrocytes from 3 days after the severe injury.Its binding proteins BP2 and 3 were also induced at this time; subsequently BP5 was induced at 5 days and IGF-2 in severely damaged regions from 7 days.These BPs are thought to modulate the targeting and activity of the IGFs.We studied the effects of rhIGF-1 (20 pg), rhIGF-2 (20 pg), insulin (20 pg), given 2 h into the lateral ventricle after 10-minute unilateral hypoxic-ischemic injury in adult rats.Only the IGF-1 improved outcome.This dose did not modify cortical temperature after injury.Peripheral administration treatment studies and tracer studies suggested that peripheral administration is unlikely to be effective due to low penetration of IGF-1 across the blood-brain barrier.Together these observations were compatible with the hypothesis that IGF-1 was acting centrally via type 1 receptors.
Institution: University of Auckland
Language: English
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
OpenAlex ID: W1998640837