Rasagiline and its (S) enantiomer increase survival and prevent stroke in salt-loaded stroke-prone spontaneously hypertensive rats

S. Eliash*, Z. Speiser, S. Cohen

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review


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 1mg/kg/day; (3) R-PAI 3mg/kg/day; (4) S-PAI 3mg/kg/day; (5) S-PAI 6mg/kg/day. Survival, stroke frequency and neurological severity score following stroke were determined. R-PAI at 3mg/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 6mg/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 3mg/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 6mg/kg/day. In salt-loaded SHRSP chronic therapy with either R-PAI or SPAI 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 radio of 1:2. The mechanism has het to be elucidated. The differential effects of the drugs on blood pressure and MAO inhibition rule out either effect as the sole explanation.

Original languageEnglish
Pages (from-to)909-923
Number of pages15
JournalJournal of Neurology
Issue number9
StatePublished - 2001


  • Rasagiline
  • Stroke
  • Survival


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