Characterisation of gene expression changes following permanent MCAO in the rat using subtractive hybridisation

Failure of several putative neuroprotectants in large multicentred clinical trials has re-focussed attention on the predictability of pre-clinical ani mal models of stroke. Model characterisation and relationship to heterogene ous patient sub-groups remains of paramount importance. Information gained from magnetic resonance imaging (MRI) signatures indicates that the Zea Lon ga model of rat middle cerebral artery occlusion may be more representative of slowly evolving infarcts. Understanding the molecular changes over seve ral hours following cerebral ischaemia will allow detailed characterisation of the adaptive response to brain injury. Using a fully characterised mode l of Zea Longa middle cerebral artery occlusion we have used the representa tional difference analysis (RDA) subtractive hybridisation method to identi fy transcripts that accumulate in the ischaemic cortex. Along with a number of established ischaemia-induced gene products (including MCP-1, TIMP-1. h sp 70) we were also able to identify nine genes which have not previously b een shown to accumulate following focal ischaemia (including SOCS-3, GADD45 gamma, Xin). (C) 2001 Elsevier Science B.V. All rights reserved.