Novel treatments after experimental brain injury

Michael V. Johnston, William Trescher, Akira Ishida, Wako Nakajima

Research output: Contribution to journalArticlepeer-review

58 Scopus citations


Perinatal hypoxic-ischaemic encephalopathy(HIE) is being studied in laboratory models that allow the delayed cascade of events triggered by the energetic insult to be examined in detail. The concept of the 'excitotoxic cascade' provides a conceptual framework for thinking about the pathogenesis of HIE. Major events in the cascade triggered by hypoxia-ischaemia include overstimulation of N-methyl-D-aspartate type glutamate receptors, calcium entry into cells, activation of calcium-sensitive enzymes such as nitric oxide synthase, production of oxygen free radicals, injury to mitochondria, leading in turn to necrosis or apoptosis. New experimental approaches to salvaging brain tissue from the effects of HIE include inhibition of neuronal nitric oxide synthase, administration of neuronal growth factors, and inhibition of the caspase enzymes that execute apoptosis. Recent experimental work suggests that these approaches may be effective during a longer 'therapeutic window' after the insult, because they are acting on events that are relatively delayed. Application of modest hypothermia may allow these agents to be neuroprotective at even longer intervals after hypoxia- ischaemia. (C) 2000 Harcourt Publishers Ltd.

Original languageEnglish (US)
Pages (from-to)75-86
Number of pages12
JournalSeminars in Neonatology
Issue number1
StatePublished - Feb 2000

All Science Journal Classification (ASJC) codes

  • Pediatrics, Perinatology, and Child Health


Dive into the research topics of 'Novel treatments after experimental brain injury'. Together they form a unique fingerprint.

Cite this