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Biomedical subjects

Simon J Read

Publications and source records attributed to Simon J Read.

2 recordsLinked to original sources

Introduction to stroke genomics.

Translation of the explosion in knowledge of acute ischemic stroke into satisfactory treatment regimens has yet to happen. At present tPA, intra-arterial prourokinase and low-molecular-weight heparin form the vanguard for therapeutic intervention, yet these treatments have a limited therapeutic window. Part of this expansion in understanding has been driven by the contribution of stroke genetics and genomics. However, despite the enormous preclinical and clinical information of receptors, enzymes, second messenger systems, and so forth, that are implicated in stroke pathophysiology, delivery of novel drug treatment has been slow. This introductory chapter discusses the multiple sources of clinical and preclinical genetic information. It will describe the importance of integrating expression information into multiple preclinical models with temporal and spatial roles in lesion pathology and, furthermore developing an understanding of function in the clinic before claiming a role in ischemic stroke. The goal of such a holistic integration of information is to increase the yield from current datasets of gene expression and ultimately to help expand the choice of treatment available to the physician and patient.

Animals↗

Programmable microchip monitoring of post-stroke pyrexia: effects of aspirin and paracetamol on temperature and infarct size in the rat.

BACKGROUND: Recent studies have demonstrated spontaneous and prolonged hyperthermia following stroke in both humans and rodents. However, a full characterization of these pyretic changes and the effects of anti-pyretic drugs on outcome is not available. METHODS: The aims of this study were to monitor conscious body temperature (n=10 per group) using programmable microchips for up to 24 h in rats following either permanent (p) or 90 min transient (t) middle cerebral artery occlusion (MCAO) or sham surgery, and to evaluate the relationship to hypothalamic damage. Also, the effects of anti-pyretic drug therapy on body temperature and infarct volume were evaluated in animals treated with vehicle, optimal doses of either aspirin or paracetamol (250 mg/kg i.p.) following pMCAO (n=10 per group). RESULTS: At 1 h, body temperature significantly (P<0.01) increased to 38.6+/-0.2 degrees C following tMCAO and 38.9+/-0.1 degrees C following pMCAO compared with sham-operated animals (37.1+/-0.1 degrees C). Sustained hyperthermia (> or =38.1 degrees C) was observed for up to 24 h following pMCAO but approached baseline within 30 min (37.6+/-0.2 degrees C) following tMCAO with reperfusion. The post-stroke pyrexia was related to the degree of ischemia where hypothalamic damage was observed in (80%) of the animals undergoing pMCAO and (0%) in the tMCAO group (P<0.05). Treatment with paracetamol (250 mg/kg i.p.) significantly attenuated (P<0.05) but did not normalize core body temperature up to 2 h (38.2+/-0.4 degrees C) compared with vehicle treated animals (39.3+/-0.1 degrees C). Aspirin had no effect on temperature under these conditions. Hypothalamic damage and lesion volume were not different between animals treated with paracetamol (253.3+/-8.5 mm(3)), aspirin (264.0+/-11.6 mm(3)) or vehicle (274.4+/-8.2 mm(3)). CONCLUSIONS: This study is the first to demonstrate the utility of programmable microchips to monitor serial changes in post-stroke hyperthermia. The sustained post-stroke pyrexia and negative effects of antipyretic treatment may be attributed to the extensive hypothalamic injury suggesting that better pharmacologic approaches to reduce body temperature should be identified and evaluated for brain protection in severe experimental stroke.

Acetaminophen↗