PMID- 11716145
OWN - NLM
STAT- MEDLINE
DCOM- 20020429
LR  - 20151119
IS  - 0300-9564 (Print)
IS  - 0300-9564 (Linking)
VI  - 108
IP  - 8-9
DP  - 2001
TI  - Rasagiline and its (S) enantiomer increase survival and prevent stroke in 
      salt-loaded stroke-prone spontaneously hypertensive rats.
PG  - 909-23
AB  - The aim of this study was to determine whether chronic treatment with the 
      selective MAO-B inhibitor rasagiline, N-propargyl-1-(R)-aminoindan (R-PAI), can 
      prevent or delay stroke or improve its outcome in salt-loaded stroke-prone 
      spontaneously hypertensive rats (SHRSP). The S-enantiomer of rasagiline, S-PAI a 
      much weaker MAO inhibitor was included in the study in order to expose a possible 
      contribution from MAO inhibition to any beneficial effect by R-PAI. SHRSP were 
      isolated, fed rat stroke prone diet and given 1% NaCl instead of water. Drugs 
      were administered in the drinking fluid for 84 days. Rats were grouped as 
      follows: (1) Untreated control; (2) R-PAI 1 mg/kg/day; (3) R-PAI 3 mg/kg/day; (4) 
      S-PAI 3 mg/kg/day; (5) S-PAI 6 mg/kg/day. Survival, stroke frequency and 
      neurological severity score following stroke were determined. R-PAI at 3 
      mg/kg/day significantly increased cumulative survival from 56.09 +/- 1.77 days in 
      the untreated to 73.6 +/- 2.22 days in the R-PAI treated; S-PAI at 6 mg/kg/day to 
      78.61 +/- 2.05 (censored at 84 days). In these groups stroke was delayed, its 
      incidence was decreased and its outcome was less severe than in the control 
      group. Proteinurea observed in the untreated rats and in both lower dose groups 
      of R-PAI and S-PAI was absent in the higher dose groups of both drugs. 
      Histological examination of the brains and kidneys showed that the effects on 
      stroke and survival were associated with decreased infarcts and hemorrhages in 
      the brains and decreased tubular nephropathy and glomerulopathy. The 
      time-dependent rise in systolic blood pressure in the untreated rats was 
      significantly attenuated only in the R-PAI group at 3 mg/kg/day but not in the 
      S-PAI group. There were no significant effects on heart rate. MAO-B activity in 
      the brain was 95% blocked by both doses of R-PAI but only 62% by S-PAI at 6 
      mg/kg/day. In salt-loaded SHRSP chronic therapy with either R-PAI or S-PAI 
      prevented stroke and severe vascular lesions in the kidney. When stroke did occur 
      its neurological outcome was less severe. The drugs were equipotent when they 
      were given at a ratio of 1:2. The mechanism has yet to be elucidated. The 
      differential effects of the drugs on blood pressure and MAO inhibition rule out 
      either effect as the sole explanation.
FAU - Eliash, S
AU  - Eliash S
AD  - Department of Physiology and Pharmacology, Sackler School of Medicine, Tel Aviv 
      University, Israel. seliash@ccsg.tau.ac.il
FAU - Speiser, Z
AU  - Speiser Z
FAU - Cohen, S
AU  - Cohen S
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - Austria
TA  - J Neural Transm (Vienna)
JT  - Journal of neural transmission (Vienna, Austria : 1996)
JID - 9702341
RN  - 0 (Indans)
RN  - 0 (Monoamine Oxidase Inhibitors)
RN  - 0 (Neuroprotective Agents)
RN  - 003N66TS6T (rasagiline)
RN  - 451W47IQ8X (Sodium Chloride)
SB  - IM
MH  - Animals
MH  - Blood Pressure/drug effects/physiology
MH  - Dose-Response Relationship, Drug
MH  - Heart Rate/drug effects/physiology
MH  - Hypertension/blood/*chemically induced/physiopathology
MH  - Indans/*blood
MH  - Male
MH  - Monoamine Oxidase Inhibitors/*pharmacology
MH  - Neuroprotective Agents/*pharmacology
MH  - Rats
MH  - Rats, Inbred SHR/*metabolism
MH  - Sodium Chloride/pharmacology
MH  - Stereoisomerism
MH  - Stroke/blood/*prevention & control
MH  - Survival Rate
MH  - Treatment Outcome
EDAT- 2001/11/22 10:00
MHDA- 2002/05/01 10:01
CRDT- 2001/11/22 10:00
PHST- 2001/11/22 10:00 [pubmed]
PHST- 2002/05/01 10:01 [medline]
PHST- 2001/11/22 10:00 [entrez]
AID - 10.1007/s007020170012 [doi]
PST - ppublish
SO  - J Neural Transm (Vienna). 2001;108(8-9):909-23. doi: 10.1007/s007020170012.