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Gregory Ford

Publications and source records attributed to Gregory Ford.

2 recordsLinked to original sources

Expression Analysis Systematic Explorer (EASE) analysis reveals differential gene expression in permanent and transient focal stroke rat models.

To gain greater insight on the molecular mechanisms that underlie ischemic stroke, we compared gene expression profiles in transient (tMCAO) and permanent middle cerebral artery occlusion (pMCAO) stroke models using Expression Analysis Systematic Explorer (EASE) pathway analysis software. Many transcripts were induced in both stroke models, including genes associated with transcriptional pathways, cell death, stress responses and metabolism. However, EASE analysis of the regulated genes indicated molecular functions and biological processes unique to each model. Pathways associated with tMCAO included inflammation, apoptosis and cell cycle, while pMCAO was associated with the induction of genes encoding neurotransmitter receptors, ion channels, growth factors and signaling molecules. An intriguing finding was the involvement of tyrosine kinases and phosphatases following pMCAO. These results provide evidence that neuronal death following tMCAO and pMCAO involves distinct mechanisms. These findings may give new insight to the molecular mechanisms involved in stroke and may lead to novel neuroprotective strategies.

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Neuregulin-1 is neuroprotective and attenuates inflammatory responses induced by ischemic stroke.

Recent work from our laboratory demonstrated that the expression neuregulin-1 in neurons was induced in the ischemic penumbra by focal stroke in the rat. Here, we show that a single intravascular injection of neuregulin-1beta (approximately 2.5 ng/kg) reduced cortical infarct volume by >98% when given immediately before middle cereral artery occlusion. Subcortical infarct volume was reduced by approximately 40%. Analysis of DNA fragmentation in brain tissues indicated that neuregulin-1 blocked apoptosis in cortical neurons in the penumbra. Neuregulin-1 prevented macrophage/microglial infiltration and astrocytic activation following focal ischemia. The neuroprotective effect of neuregulin-1 was also associated with a suppression of interleukin-1beta mRNA levels. These data suggest that neuregulin-1 protects neurons from delayed, ischemia-induced apoptotic cell death in the cortex by inhibiting pro-inflammatory responses. Neuregulins represent a novel, potent neuroprotective strategy that has potential therapeutic value in treating individuals after acute ischemic stroke.

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