title: The response of cerebral cortex to haemorrhagic damage: experimental evidence from a penetrating injury model.
abstract: Understanding the response of the brain to haemorrhagic damage is important in haemorrhagic stroke and increasingly in the understanding the cerebral degeneration and dementia that follow head trauma and head-impact sports. In addition, there is growing evidence that haemorrhage from small cerebral vessels is important in the pathogenesis of age-related dementia (Alzheimer's disease). In a penetration injury model of rat cerebral cortex, we have examined the neuropathology induced by a needlestick injury, with emphasis on features prominent in the ageing and dementing human brain, particularly plaque-like depositions and the expression of related proteins. Needlestick lesions were made in neo- and hippocampal cortex in Sprague Dawley rats aged 3-5 months. Brains were examined after 1-30 d survival, for haemorrhage, for the expression of hyperphosphorylated tau, Aβ, amyloid precursor protein (APP), for gliosis and for neuronal death. Temporal cortex from humans diagnosed with Alzheimer's disease was examined with the same techniques. Needlestick injury induced long-lasting changes-haem deposition, cell death, plaque-like deposits and glial invasion-along the needle track. Around the track, the lesion induced more transient changes, particularly upregulation of Aβ, APP and hyperphosporylated tau in neurons and astrocytes. Reactions were similar in hippocampus and neocortex, except that neuronal death was more widespread in the hippocampus. In summary, experimental haemorrhagic injury to rat cerebral cortex induced both permanent and transient changes. The more permanent changes reproduced features of human senile plaques, including the formation of extracellular deposits in which haem and Aβ-related proteins co-localised, neuronal loss and gliosis. The transient changes, observed in tissue around the direct lesion, included the upregulation of Aβ, APP and hyperphosphorylated tau, not associated with cell death. The findings support the possibility that haemorrhagic damage to the brain can lead to plaque-like pathology.
authors.affiliation: Bosch Institute and Discipline of Physiology, University of Sydney, Sydney, NSW, Australia.
authors.forename: Sivaraman
authors.initials: S
authors.lastname: Purushothuman
authors.forename: Lauren
authors.initials: L
authors.lastname: Marotte
authors.forename: Sally
authors.initials: S
authors.lastname: Stowe
authors.forename: Daniel M
authors.initials: DM
authors.lastname: Johnstone
authors.forename: Jonathan
authors.initials: J
authors.lastname: Stone
mesh_terms: D016229:Amyloid beta-Peptides / Q000378:metabolism; D016564:Amyloid beta-Protein Precursor / Q000378:metabolism; D000818:Animals; D001253:Astrocytes / Q000473:pathology; D052160:Benzothiazoles; D001921:Brain / Q000473:pathology*; D001930:Brain Injuries / Q000473:pathology*; D016923:Cell Death; D002540:Cerebral Cortex / Q000473:pathology*; D003224:Congo Red; D004195:Disease Models, Animal; D005260:Female; D005295:Ferrocyanides; D006418:Heme / Q000737:chemistry; D006470:Hemorrhage / Q000175:diagnosis / Q000473:pathology*; D006624:Hippocampus / Q000473:pathology*; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D019579:Neocortex / Q000473:pathology; D009474:Neurons / Q000473:pathology; D010766:Phosphorylation; D051381:Rats; D017207:Rats, Sprague-Dawley; D013702:Temporal Lobe / Q000473:pathology; D013844:Thiazoles; D014950:Wounds, Penetrating; D016875:tau Proteins / Q000378:metabolism
chemical_list: D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D052160:Benzothiazoles; D005295:Ferrocyanides; D013844:Thiazoles; D016875:tau Proteins; C009462:thioflavin T; D003224:Congo Red; D006418:Heme; C000170:ferric ferrocyanide
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