PMID- 11935065
OWN - NLM
STAT- MEDLINE
DCOM- 20020416
LR  - 20190727
IS  - 1524-4628 (Electronic)
IS  - 0039-2499 (Linking)
VI  - 33
IP  - 4
DP  - 2002 Apr
TI  - NAP, a femtomolar-acting peptide, protects the brain against ischemic injury by 
      reducing apoptotic death.
PG  - 1085-92
AB  - BACKGROUND AND PURPOSE: We sought to determine the cerebroprotective potential of 
      NAP, a synthetic octapeptide related to vasoactive intestinal peptide. 
      Activity-dependent neuroprotective protein mediates some of the protective 
      effects of vasoactive intestinal peptide. The neuroprotective NAP sequence is 
      derived from activity-dependent neuroprotective protein. METHODS: Spontaneously 
      hypertensive rats underwent permanent middle cerebral artery occlusion by 
      craniotomy and electrocoagulation. After dose-response and time-course 
      experiments, the animals were injected with NAP (3 microg/kg) or vehicle 
      intravenously 1 hour after stroke onset. Another group of rats was injected with 
      the D-amino acid isomer of NAP (D-NAP) and served as a negative control. Rats 
      were examined for motor and behavioral deficits 24 hours to 30 days later, and 
      infarct volumes were determined. The effect of NAP administration on apoptotic 
      death was determined by terminal deoxynucleotidyl transferase-mediated dUTP nick 
      end labeling (TUNEL) and caspase-3 stainings. RESULTS: NAP significantly reduced 
      motor disability and infarct volumes compared with vehicle or D-NAP when tested 
      at 24 hours after stroke onset (9.67+/-1.4% versus 17.04+/-1.18% and 19.19+/-1.9% 
      of hemispheric volume, respectively; P<0.05). NAP given 4 but not 6 hours after 
      permanent middle cerebral artery occlusion still conferred significant 
      neuroprotection (infarct volume 10.9+/-3.9% of hemispheric volume; P<0.05 versus 
      vehicle). Long-term studies demonstrated that infarct volumes and disability 
      scores remained significantly lower after 30 days in NAP-treated animals. NAP 
      significantly reduced the number of apoptotic cells. CONCLUSIONS: Our results 
      indicate that the durable cerebroprotection by NAP involves antiapoptotic 
      mechanisms.
FAU - Leker, Ronen R
AU  - Leker RR
AD  - Department of Neurology, Agnes Ginges Center for Human Neurogenetics, Hebrew 
      University-Hadassah Medical School, University Hospital, Jerusalem, Israel. 
      leker@cc.huji.ac.il
FAU - Teichner, Angella
AU  - Teichner A
FAU - Grigoriadis, Nikolas
AU  - Grigoriadis N
FAU - Ovadia, Haim
AU  - Ovadia H
FAU - Brenneman, Douglas E
AU  - Brenneman DE
FAU - Fridkin, Mati
AU  - Fridkin M
FAU - Giladi, Eli
AU  - Giladi E
FAU - Romano, Jacob
AU  - Romano J
FAU - Gozes, Illana
AU  - Gozes I
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, Non-P.H.S.
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Stroke
JT  - Stroke
JID - 0235266
RN  - 0 (Neuroprotective Agents)
RN  - 0 (Oligopeptides)
RN  - GF00K3IIWE (davunetide)
SB  - IM
MH  - Animals
MH  - Apoptosis/*drug effects
MH  - Behavior, Animal/drug effects
MH  - Brain/blood supply/*drug effects/pathology
MH  - Brain Chemistry
MH  - Cerebral Infarction/etiology/pathology/*prevention & control
MH  - Disease Models, Animal
MH  - Dose-Response Relationship, Drug
MH  - Drug Evaluation, Preclinical
MH  - Infarction, Middle Cerebral Artery/complications/*drug therapy/pathology
MH  - Injections, Intravenous
MH  - Liver/chemistry/metabolism
MH  - Male
MH  - Motor Activity/drug effects
MH  - Neuroprotective Agents/*pharmacology
MH  - Oligopeptides/analysis/pharmacokinetics/*pharmacology
MH  - Rats
MH  - Rats, Inbred SHR
MH  - Recovery of Function/drug effects
MH  - Time
MH  - Tissue Distribution
EDAT- 2002/04/06 10:00
MHDA- 2002/04/17 10:01
CRDT- 2002/04/06 10:00
PHST- 2002/04/06 10:00 [pubmed]
PHST- 2002/04/17 10:01 [medline]
PHST- 2002/04/06 10:00 [entrez]
AID - 10.1161/01.str.0000014207.05597.d7 [doi]
PST - ppublish
SO  - Stroke. 2002 Apr;33(4):1085-92. doi: 10.1161/01.str.0000014207.05597.d7.