title: Intracranial pressure elevation after ischemic stroke in rats: cerebral edema is not the only cause, and short-duration mild hypothermia is a highly effective preventive therapy.
abstract: In both the human and animal literature, it has largely been assumed that edema is the primary cause of intracranial pressure (ICP) elevation after stroke and that more edema equates to higher ICP. We recently demonstrated a dramatic ICP elevation 24 hours after small ischemic strokes in rats, with minimal edema. This ICP elevation was completely prevented by short-duration moderate hypothermia soon after stroke. Here, our aims were to determine the importance of edema in ICP elevation after stroke and whether mild hypothermia could prevent the ICP rise. Experimental stroke was performed in rats. ICP was monitored and short-duration mild (35 °C) or moderate (32.5 °C) hypothermia, or normothermia (37 °C) was induced after stroke onset. Edema was measured in three studies, using wet-dry weight calculations, T2-weighted magnetic resonance imaging, or histology. ICP increased 24 hours after stroke onset in all normothermic animals. Short-duration mild or moderate hypothermia prevented this rise. No correlation was seen between ΔICP and edema or infarct volumes. Calculated rates of edema growth were orders of magnitude less than normal cerebrospinal fluid production rates. These data challenge current concepts and suggest that factors other than cerebral edema are the primary cause of the ICP elevation 24 hours after stroke onset.
authors.affiliation: 1] University of Newcastle and Hunter Medical Research Institute, New Lambton, New South Wales, Australia [2] Glasgow Experimental MRI Centre, Institute of Neuroscience and Psychology, College of Medicine, Veterinary and Life Sciences, University of Glasgow, Glasgow, UK.
authors.forename: Lucy A
authors.initials: LA
authors.lastname: Murtha
authors.affiliation: University of Newcastle and Hunter Medical Research Institute, New Lambton, New South Wales, Australia.
authors.forename: Damian D
authors.initials: DD
authors.lastname: McLeod
authors.affiliation: University of Newcastle and Hunter Medical Research Institute, New Lambton, New South Wales, Australia.
authors.forename: Debbie
authors.initials: D
authors.lastname: Pepperall
authors.affiliation: University of Newcastle and Hunter Medical Research Institute, New Lambton, New South Wales, Australia.
authors.forename: Sarah K
authors.initials: SK
authors.lastname: McCann
authors.affiliation: University of Newcastle and Hunter Medical Research Institute, New Lambton, New South Wales, Australia.
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Beard
authors.affiliation: University of Newcastle and Hunter Medical Research Institute, New Lambton, New South Wales, Australia.
authors.forename: Amelia J
authors.initials: AJ
authors.lastname: Tomkins
authors.affiliation: Glasgow Experimental MRI Centre, Institute of Neuroscience and Psychology, College of Medicine, Veterinary and Life Sciences, University of Glasgow, Glasgow, UK.
authors.forename: William M
authors.initials: WM
authors.lastname: Holmes
authors.affiliation: Glasgow Experimental MRI Centre, Institute of Neuroscience and Psychology, College of Medicine, Veterinary and Life Sciences, University of Glasgow, Glasgow, UK.
authors.forename: Christopher
authors.initials: C
authors.lastname: McCabe
authors.affiliation: Glasgow Experimental MRI Centre, Institute of Neuroscience and Psychology, College of Medicine, Veterinary and Life Sciences, University of Glasgow, Glasgow, UK.
authors.forename: I Mhairi
authors.initials: IM
authors.lastname: Macrae
authors.affiliation: University of Newcastle and Hunter Medical Research Institute, New Lambton, New South Wales, Australia.
authors.forename: Neil J
authors.initials: NJ
authors.lastname: Spratt
mesh_terms: D000818:Animals; D001921:Brain / Q000503:physiopathology*; D001929:Brain Edema / Q000150:complications / Q000503:physiopathology*; D002545:Brain Ischemia / Q000150:complications / Q000503:physiopathology*; D007036:Hypothermia, Induced / Q000379:methods; D019586:Intracranial Hypertension / Q000209:etiology / Q000503:physiopathology* / Q000628:therapy*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D020521:Stroke / Q000150:complications / Q000503:physiopathology