Cerebral ischemia is a major cause of death and the later development of neurodegenerative diseases (de la Torre, 2004), which are characterized by neuronal damage and accumulation of phosphorylated tau protein (Alonso et al., 1997). However, cerebral ischemia induced cellular damage that initiates neurodegerative disease remain poorly understood and does not receive proper attention for developing new drug treatment strategies. This is primarily due to lack of clinically relevant models that are highly reproducible as the pathophysiology of cerebral ischemia in animal models is modulated by numerous factors including the species, type of blood vessels occluded, occlusion period and reperfusion time (Hossmann, 1998). The present study aims to optimise a murine model of cerebral ischemia and examine neuronal degeneration and tau pathology in this model. Experiments were performed on 10- 12-week-old (26-30 g) C57BL/6 mice (Harlan-Olac, Bicester, UK) under appropriate UK Home Office licence and adhered to regulations as specified in the Animals Scientific Procedures Act (1986). Cerebral ischemia was induced by transient bilateral occlusion of the common carotid arteries using arterial clips under anaesthesia (4% isoflurane saturated with oxygen). Following 5- 20 minutes occlusion the clips were removed and skin wound closed. Sham-operated mice underwent the same procedure except that the carotid arteries were not occluded. Following 1-7 days reperfusion time the mice were re-anesthetised and perfused with 4% paraformaldehyde in phosphate buffered saline (pH 7.0-7.2). Brain sections (50 um) cut on a vibratome were either stained with cresyl violet to assess neuronal damage or processed for immunohistochemistry using specific antibodies to neuronal specific nuclear protein, myelin associated protein, glial fibrillary acidic protein, glutamine synthetase and hyper- phosphory-lated Tau protein to examine the extent of neuronal, glial cell and myelin sheath damage and tau pathology. Antigen-antibody reaction sites were detected either by standard avidin-biotin complex and diaminobenzidine reaction or by using species specific anti-rabbit immu-noglobulin G conjugated to Cy3/ Alexa488. Sections were analysed using an AxioImager Z.1 epifluorescence microscope (Carl Zeiss, Welwyn Garden City, UK). The results showed consistent neuronal and white matter damage and tau pathology in the cortex, striatum and the hippocampus following 15 minutes occlusion and 3-7 days reperfusion. This murine model of cerebral ischemia may be an ideal model to study ischemia induced neurodegen-eration and to develop therapeutic strategies for prevention and treatment of these diseases. Supported by the Alzheimer’s Research-UK, Yorkshire Brach