PMID- 18077568
OWN - NLM
STAT- MEDLINE
DCOM- 20080421
LR  - 20151119
IS  - 0077-8923 (Print)
IS  - 0077-8923 (Linking)
VI  - 1122
DP  - 2007 Dec
TI  - 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.
PG  - 112-29
AB  - 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 degrees 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 microg in 30 microL, 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.
FAU - Sharma, Hari Shanker
AU  - Sharma HS
AD  - Department of Surgical Sciences, University Hospital, Uppsala University, 
      SE-75421 Uppsala, Sweden. sharma@surgsci.uu.se
FAU - Johanson, Conrad E
AU  - Johanson CE
LA  - eng
GR  - R01 AG27910/AG/NIA NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Ann N Y Acad Sci
JT  - Annals of the New York Academy of Sciences
JID - 7506858
RN  - 0 (Nerve Growth Factors)
RN  - 0 (Neuroprotective Agents)
RN  - 45PG892GO1 (Evans Blue)
SB  - IM
MH  - Analysis of Variance
MH  - Animals
MH  - Behavior, Animal/physiology
MH  - *Blood-Brain Barrier/drug effects/pathology/physiopathology
MH  - Body Temperature/drug effects
MH  - Brain/drug effects/*pathology/ultrastructure
MH  - Brain Edema/etiology/prevention & control
MH  - Disease Models, Animal
MH  - Evans Blue
MH  - Hyperthermia, Induced/*adverse effects
MH  - Injections, Intraventricular/methods
MH  - Male
MH  - Microscopy, Electron, Transmission/methods
MH  - Nerve Growth Factors/*administration & dosage
MH  - Neuroprotective Agents/*administration & dosage
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - *Stress, Physiological/complications/etiology/pathology
EDAT- 2007/12/14 09:00
MHDA- 2008/04/22 09:00
CRDT- 2007/12/14 09:00
PHST- 2007/12/14 09:00 [pubmed]
PHST- 2008/04/22 09:00 [medline]
PHST- 2007/12/14 09:00 [entrez]
AID - 1122/1/112 [pii]
AID - 10.1196/annals.1403.008 [doi]
PST - ppublish
SO  - Ann N Y Acad Sci. 2007 Dec;1122:112-29. doi: 10.1196/annals.1403.008.