A systematic review of nitric oxide donors and L-arginine in experimental stroke; effects on infarct size and cerebral blood flow

Nitric Oxide. 2005 May;12(3):141-9. doi: 10.1016/j.niox.2005.01.003.


Background: Nitric oxide (NO) is a candidate treatment for acute ischaemic stroke, however published studies in experimental stroke have given conflicting results.

Methods: We performed a systematic review of published controlled studies of L-arginine (the precursor for NO) and NO donors in experimental stroke. Data were analysed using the Cochrane Collaboration Review Manager software. Standardised mean difference (SMD) and 95% confidence intervals (95% CI) were calculated.

Results: Altogether, 25 studies(s) were identified. L-Arginine and NO donors reduced total cerebral infarct volume in permanent (SMD -1.21, 95% CI -1.69 to -0.73, p < 0.01, s = 10) and transient models of ischaemia (SMD -0.78, 95% CI -1.21 to -0.35, p < 0.01, s = 7). Drug administration increased cortical CBF in permanent (SMD +0.86, 95% CI 0.52-1.21, p < 0.01, s = 8) but not transient models (SMD +0.34, 95% CI -0.02 to 0.70, p = 0.07, s = 4).

Conclusions: Administration of NO in experimental stroke reduces stroke lesion volume in permanent and transient models. This may be mediated, in part, by increased cerebral perfusion in permanent models. These data support clinical trials in stroke patients, although the presence of a narrow therapeutic time window may be a limiting factor.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.
  • Review
  • Systematic Review

MeSH terms

  • Animals
  • Arginine / therapeutic use*
  • Cerebral Infarction / drug therapy*
  • Cerebrovascular Circulation / drug effects*
  • Disease Models, Animal
  • Female
  • Male
  • Nitric Oxide Donors / therapeutic use*
  • Rabbits
  • Rats
  • Time Factors


  • Nitric Oxide Donors
  • Arginine