PMID- 11307622
OWN - NLM
STAT- MEDLINE
DCOM- 20010830
LR  - 20220317
IS  - 0001-6322 (Print)
IS  - 0001-6322 (Linking)
VI  - 101
IP  - 3
DP  - 2001 Mar
TI  - Brain-derived neurotrophic factor reduces cortical cell death by ischemia after 
      middle cerebral artery occlusion in the rat.
PG  - 229-38
AB  - Stroke is the major cause of adult brain dysfunction. In an experimental approach 
      to evaluate the possible beneficial effects of administration of neurotrophic 
      factors in stroke, we have used a model of distal middle cerebral artery (MCA) 
      occlusion in adult rats. In this model, we found: (1) a permanent reduction of 
      brain-derived neurotrophic factor (BDNF) and its full-length receptor, TrkB, in 
      the infarcted core; (2) a transient increase in BDNF immunoreactivity in the 
      internal region of the border of the infarct (penumbra area) at 12 h after MCA 
      occlusion; (3) increased truncated TrkB immunoreactivity in astrocytes 
      surrounding the area of the infarction; and (4) increased full-length TrkB 
      immunoreactivity in scattered neurons, distant from the infarct, in ipsilateral 
      and contralateral cortices at 24 and 48 h after MCA occlusion. We next studied 
      the regulation of TrkB expression by BDNF, after ischemia, and its 
      neuroprotective effects in vivo. In control non-ischemic rats, grafting of mock- 
      or BDNF-transfected fibroblasts (F3A-MT or F3N-BDNF cell lines, respectively) in 
      the medial part of the somatosensory cortex increased truncated TrkB 
      immunoreactivity in neighboring astrocytes. Grafting alone also increased 
      full-length TrkB in the vicinity of the mock graft (at 24 and 48 h) and the 
      BDNF-grafted graft (at 4 days). Interestingly, ischemic animals grafted with the 
      mock-transfected cell line did not show any further regulation of TrkB receptors. 
      However, ischemic animals grafted with the BDNF cell line showed an up-regulation 
      of full-length TrkB expression in neurons located in the internal border of the 
      infarct. Analysis of nuclear DNA fragmentation in situ, combined with 
      microtubule-associated protein 2 immunohistochemistry, revealed that most cells 
      dying in the borders of the infarct (penumbra area) at 48 h following MCA 
      occlusion were neurons. No differences in the infarct size were found between MCA 
      occluded, mock-transfected MCA-occluded, and BDNF-transfected MCA-occluded rats. 
      Moreover, cell death was similar in nongrafted and mock-grafted rats subjected to 
      MCA occlusion. However, the number of cells with nuclear DNA breaks was 
      significantly reduced in the penumbra area close to the BDNF graft in ischemic 
      rats. Thus, our results show that BDNF specifically up-regulates its full-length 
      TrkB receptor in cortical neurons of the penumbra area and prevents their death 
      in an in vivo model of focal ischemia.
FAU - Ferrer, I
AU  - Ferrer I
AD  - Unitat de Neuropatologia, Servei d'Anatomia Patologica, Hospital Princeps 
      d'Espanya, Campus de Bellvitge, 08907 Hospitalet de Llobregat, Spain. 
      iferrer@sakma.es
FAU - Krupinski, J
AU  - Krupinski J
FAU - Goutan, E
AU  - Goutan E
FAU - Marti, E
AU  - Marti E
FAU - Ambrosio, S
AU  - Ambrosio S
FAU - Arenas, E
AU  - Arenas E
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - Germany
TA  - Acta Neuropathol
JT  - Acta neuropathologica
JID - 0412041
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - EC 2.7.10.1 (Receptor, trkB)
SB  - IM
MH  - Animals
MH  - Astrocytes/cytology/metabolism/transplantation
MH  - Brain Ischemia/*metabolism/physiopathology/surgery
MH  - Brain Tissue Transplantation
MH  - Brain-Derived Neurotrophic Factor/genetics/*metabolism
MH  - Cell Death/*physiology
MH  - Cerebral Cortex/*injuries/physiopathology/surgery
MH  - DNA Fragmentation/physiology
MH  - Disease Models, Animal
MH  - Immunohistochemistry
MH  - In Situ Nick-End Labeling
MH  - Infarction, Middle Cerebral Artery/*metabolism/physiopathology/surgery
MH  - Male
MH  - Nerve Degeneration/metabolism/physiopathology/prevention & control
MH  - Neurons/*metabolism/pathology
MH  - Oligodendroglia/cytology/metabolism
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Receptor, trkB/genetics/metabolism
MH  - Transfection
MH  - Up-Regulation/physiology
EDAT- 2001/04/20 10:00
MHDA- 2001/08/31 10:01
CRDT- 2001/04/20 10:00
PHST- 2001/04/20 10:00 [pubmed]
PHST- 2001/08/31 10:01 [medline]
PHST- 2001/04/20 10:00 [entrez]
AID - 10.1007/s004010000268 [doi]
PST - ppublish
SO  - Acta Neuropathol. 2001 Mar;101(3):229-38. doi: 10.1007/s004010000268.