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Intracerebroventricularly administered neurotrophins attenuate blood cerebrospinal fluid barrier breakdown and brain pathology following whole-body hyperthermia: an experimental study in the rat using biochemical and morphological approaches
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
2007 (English)In: Neuroprotective agents: Eighth international neuroprotection society meeting / [ed] Slikker W; Andrew RJ; Trembly B, 2007, Vol. 1122, 112-129 p.Conference paper (Refereed)
Abstract [en]

Previous studies from our laboratory show that apart from blood–brain barrier (BBB) disruption, the blood–cerebrospinal fluid (CSF) barrier (BCSFB) for proteins is also broken down following whole-body hyperthermia (WBH) in a rat model. Breakdown of the BCSFB alters brain homeostasis and adversely affects the structure and function of the central nervous system (CNS). Since neurotrophins and growth factors (e.g., brain-derived growth factor [BDNF], glial cell line–derived neurotrophic factor [GDNF], and insulin-like growth factor 1 [IGF-1]) are known neuroprotective agents in traumatic and ischemic brain injuries, a possibility exists that these neurotrophins will also attenuate neuronal and choroidal injury in WBH. Subjection of adult rats to 4 h of WBH at 38°C in a biological oxygen demand (BOD) incubator exhibited a profound increase in BCSFB permeability to Evans blue and radioiodine. Degeneration of choroidal epithelial cells and underlying ependyma, dilatation of the lateral ventricular space, and degenerative changes in the adjacent neuropil were frequent. The hippocampus, caudate nucleus, thalamus, and hypothalamus showed profound BBB disruption and brain edema formation. Intracerebroventricular (i.c.v.) administration of BDNF, GDNF, and IGF-1 into the right lateral cerebral ventricle (1, 2, or 5 μg in 30 μL, 24 h before WBH) significantly reduced the BCSFB and BBB breakdown, brain edema formation, and cellular/tissue injuries. These beneficial effects were most pronounced in GDNF- or IGF-1–pretreated animals. These novel observations suggest that neurotrophins administered into ventricular CSF can attenuate BCSFB and BBB damage following WBH and thereby confer neuroprotection. Stabilization of BCSFB function is thus one of the crucial factors in achieving neuroprotection in WBH.

Place, publisher, year, edition, pages
2007. Vol. 1122, 112-129 p.
, Annals of the New York academy of sciences, ISSN 0077-8923 ; 1122
Keyword [en]
Analysis of Variance, Animals, Behavior; Animal/physiology, Blood-Brain Barrier/drug effects/pathology/physiopathology, Body Temperature/drug effects, Brain/drug effects/*pathology/ultrastructure, Brain Edema/etiology/prevention & control, Disease Models; Animal, Evans Blue/diagnostic use, Hyperthermia; Induced/*adverse effects, Injections; Intraventricular/methods, Male, Microscopy; Electron; Transmission/methods, Nerve Growth Factors/*administration & dosage, Neuroprotective Agents/*administration & dosage, Rats, Rats; Sprague-Dawley, Stress/complications/etiology/pathology
National Category
Medical and Health Sciences
URN: urn:nbn:se:uu:diva-17158DOI: 10.1196/annals.1403.008ISI: 000252267100008PubMedID: 18077568ISBN: 978-1-57331-685-9OAI: oai:DiVA.org:uu-17158DiVA: diva2:44929
8th International Conference on Neuroprotective Agents Mackinac Isl, MI, SEP 18-20, 2006
Available from: 2008-06-17 Created: 2008-06-17 Last updated: 2011-03-24Bibliographically approved

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Publisher's full textPubMedhttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Retrieve&list_uids=18077568&dopt=Citation

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