title: The reaction of cerebral cortex to a nearby lesion: damage, survival, self-protection.
abstract: A needlestick injury to cerebral cortex causes immediate damage along the track of the needle (haemorrhage, cell death) and sequelae (the formation of amyloid-positive plaques, extracellular deposits of hyperphosphorylated tau protein, microglial proliferation, astrogliosis) that are long lasting, and mimic the neuropathology associated with Alzheimer's disease. We report here that the same injury also elicits a distinctive response in the cortex flanking (up to 1mm from) the direct injury. Needlestick injury was made in the neo- and hippocampal cortex of young (3 months) healthy Sprague-Dawley rats. After survival times of up to 7d, the response of the cortex was assessed with histology, immunohistochemistry and stereology. Uptake of FluoroJade B at 1d survival and labelling for 4-hydroxynonenal (4-HNE) gave measures of membrane damage; labelling for 8-hydroxy-2'-deoxyguanosine (8-OHDG) gave a measure of DNA damage, and labelling with the AT8 antibody gave a measure of the hyperphosphorylation of tau. Two probes, for neuroglobin and basic fibroblast growth factor (FGF-2), gave measures of a self-protective response in the tissue. Results indicate that neurones in the flanking region are damaged by the nearby lesion, and within 1d upregulate self-protective mechanisms. Over the next 6d survival, evidence of neuronal damage reduces markedly. In summary, cells in the region flanking a lesion are stressed by the lesion, and react to the stress with a self-protective response, which prevents their death. This response may be an important, previously unrecognised feature of brain tissue close to a focus of stress, such as a microhaemorrhage.
authors.affiliation: Discipline of Physiology and Bosch Institute, School of Medical Sciences, Faculty of Medicine, The University of Sydney, Camperdown, NSW 2006, Australia; Discipline of Clinical Ophthalmology & Save Sight Institute, The University of Sydney & Sydney Eye Hospital, Sydney NSW 2000, Australia. Electronic address: sivap@physiol.usyd.edu.au.
authors.forename: Sivaraman
authors.initials: S
authors.lastname: Purushothuman
authors.affiliation: Discipline of Physiology and Bosch Institute, School of Medical Sciences, Faculty of Medicine, The University of Sydney, Camperdown, NSW 2006, Australia. Electronic address: jonstone@eye.usyd.edu.au.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Stone
mesh_terms: D000818:Animals; D001930:Brain Injuries / Q000378:metabolism* / Q000473:pathology*; D002470:Cell Survival; D002540:Cerebral Cortex / Q000378:metabolism* / Q000473:pathology*; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism; D005914:Globins / Q000378:metabolism; D006624:Hippocampus / Q000378:metabolism / Q000473:pathology; D019579:Neocortex / Q000378:metabolism / Q000473:pathology; D009419:Nerve Tissue Proteins / Q000378:metabolism; D000078787:Neuroglobin; D009474:Neurons / Q000378:metabolism* / Q000473:pathology*; D018384:Oxidative Stress; D010766:Phosphorylation; D051381:Rats; D017207:Rats, Sprague-Dawley; D016875:tau Proteins / Q000378:metabolism
chemical_list: D009419:Nerve Tissue Proteins; D000078787:Neuroglobin; D016875:tau Proteins; D016222:Fibroblast Growth Factor 2; D005914:Globins
keywords: Microhemorrhage; Neurotrophic factors; Oxidative stress; Self-protection