PMID- 10978054
OWN - NLM
STAT- MEDLINE
DCOM- 20001017
LR  - 20220317
IS  - 1524-4628 (Electronic)
IS  - 0039-2499 (Linking)
VI  - 31
IP  - 9
DP  - 2000 Sep
TI  - Intravenous brain-derived neurotrophic factor reduces infarct size and 
      counterregulates Bax and Bcl-2 expression after temporary focal cerebral 
      ischemia.
PG  - 2212-7
AB  - BACKGROUND AND PURPOSE: Pretreatment with intraventricular brain-derived 
      neurotrophic factor (BDNF) reduces ischemic damage after focal cerebral ischemia. 
      In this experiment we studied the effect of intravenous BDNF delivered after 
      focal cerebral ischemia on neurological outcome, infarct size, and expression of 
      proapoptotic and antiapoptotic proteins Bax and Bcl-2, respectively. METHODS: 
      With the use of the suture occlusion technique, the right middle cerebral artery 
      in rats was temporarily occluded for 2 hours. Thirty minutes after vessel 
      occlusion, BDNF (300 microg/kg per hour in vehicle; n=12) or vehicle alone (n=13) 
      was continuously infused intravenously for 3 hours. After 24 hours the animals 
      were weighed and neurologically assessed on a 5-point scale. The animals were 
      then killed, and brains underwent either 2,3,5-triphenyltetrazolium chloride 
      staining for assessment of infarct volume or paraffin embedding for morphology 
      and immunohistochemistry (Bax, Bcl-2). RESULTS: Physiological parameters (mean 
      arterial blood pressure, PO(2), PCO(2), pH, body temperature, glucose) and weight 
      revealed no difference between groups. Neurological deficit was improved in 
      BDNF-treated animals versus controls (P:<0.05, unpaired, 2-tailed t test). 
      Mean+/-SD infarct volume was 229.7+/-97.7 mm(3) in controls and 121.3+/-80.2 
      mm(3) in BDNF-treated animals (P:<0.05, unpaired, 2-tailed t test). Cortical 
      infarct volume was 155.5+/-78.5 mm(3) in the placebo group and 69.9+/-50.2 mm(3) 
      in the BDNF-treated group (P:<0.05, unpaired, 2-tailed t test). Subcortical 
      infarct volume was 74.1+/-30.6 mm(3) in the placebo group and 51.1+/-26.8 mm(3) 
      in the BDNF-treated group (P:=NS). Bax-positive neurons were significantly 
      reduced in the ischemic penumbra in BDNF-treated animals (P:<0.05, unpaired, 
      2-tailed t test), whereas Bcl-2-positive neurons were significantly increased in 
      this area (P:<0.001, unpaired, 2-tailed t test). CONCLUSIONS: This study 
      demonstrates a neuroprotective effect of BDNF when delivered intravenously after 
      onset of focal cerebral ischemia. As shown here, one possible mechanism of action 
      of neuroprotection of BDNF after focal ischemia appears to be counterregulation 
      of Bax/Bcl-2 proteins within the ischemic penumbra.
FAU - Schabitz, W R
AU  - Schabitz WR
AD  - Department of Neurology, University of Heidelberg, Germany. 
      wolf_schaebitz@med.uni-heidelberg.de
FAU - Sommer, C
AU  - Sommer C
FAU - Zoder, W
AU  - Zoder W
FAU - Kiessling, M
AU  - Kiessling M
FAU - Schwaninger, M
AU  - Schwaninger M
FAU - Schwab, S
AU  - Schwab S
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Stroke
JT  - Stroke
JID - 0235266
RN  - 0 (Bak1 protein, rat)
RN  - 0 (Bax protein, rat)
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Coloring Agents)
RN  - 0 (Membrane Proteins)
RN  - 0 (Neuroprotective Agents)
RN  - 0 (Proto-Oncogene Proteins)
RN  - 0 (Proto-Oncogene Proteins c-bcl-2)
RN  - 0 (Tetrazolium Salts)
RN  - 0 (bcl-2 Homologous Antagonist-Killer Protein)
RN  - 0 (bcl-2-Associated X Protein)
RN  - 7OL20RET2I (triphenyltetrazolium)
SB  - IM
MH  - Animals
MH  - Apoptosis/drug effects
MH  - Brain/drug effects/*metabolism/pathology
MH  - Brain Ischemia/drug therapy/*metabolism/pathology
MH  - Brain-Derived Neurotrophic Factor/*pharmacology/therapeutic use
MH  - Coloring Agents
MH  - Immunohistochemistry
MH  - Infusions, Intravenous
MH  - Membrane Proteins/biosynthesis
MH  - Middle Cerebral Artery
MH  - Neurologic Examination
MH  - Neuroprotective Agents/*pharmacology
MH  - Proto-Oncogene Proteins/biosynthesis
MH  - *Proto-Oncogene Proteins c-bcl-2
MH  - Rats
MH  - Staining and Labeling
MH  - Tetrazolium Salts
MH  - bcl-2 Homologous Antagonist-Killer Protein
MH  - bcl-2-Associated X Protein
EDAT- 2000/09/08 00:00
MHDA- 2000/10/21 00:00
CRDT- 2000/09/08 00:00
PHST- 2000/09/08 00:00 [pubmed]
PHST- 2000/10/21 00:00 [medline]
PHST- 2000/09/08 00:00 [entrez]
AID - 10.1161/01.str.31.9.2212 [doi]
PST - ppublish
SO  - Stroke. 2000 Sep;31(9):2212-7. doi: 10.1161/01.str.31.9.2212.