Methodological quality of animal studies on neuroprotection in focal cerebral ischaemia - PubMed (original) (raw)

Review

Methodological quality of animal studies on neuroprotection in focal cerebral ischaemia

H Bart van der Worp et al. J Neurol. 2005 Sep.

Abstract

Background: The recurrent failure of apparently promising neuroprotective drugs to improve outcome in trials of patients with acute ischaemic stroke may partially be explained by over-optimistic conclusions about efficacy as a result of methodological shortcomings in preclinical studies. We assessed the methodological quality of animal studies of five different neuroprotective agents that have been tested in 21 clinical trials including a total of more than 12,000 patients with acute ischaemic stroke.

Methods: We performed a literature search restricted to full publications on the effects of clomethiazole, gavestinel, lubeluzole, selfotel, or tirilazad mesylate on infarct volume or functional outcome in animal models of acute focal cerebral ischaemia. We used a rating scale to assess the methodological quality of the included studies. One point was attributed to each of 10 items. A score of 4 to 6 points was considered "medium" and a score above 7 "high."

Results: A total of 45 articles were included. The median score on the methodological quality index was 3; 18 studies had a medium score and one a high score. Randomised treatment allocation was mentioned in 19 studies (42 %), blinded administration of study medication in 10 (22 %), and blinded outcome assessment in 18 (40 %). The study drug was administered at a median of 10 min (range, -60 to 360 min) after the onset of ischaemia.

Conclusion: The evidence for neuroprotective efficacy that formed the basis for initiating the 21 trials was obtained in animal studies with a methodological quality that would, in retrospect, not justify such a decision. More rigorous preclinical study methodology may lead to more reliable and reproducible results.

PubMed Disclaimer

Similar articles

• Methodological quality of animal studies of neuroprotective agents currently in phase II/III acute ischemic stroke trials.
  Philip M, Benatar M, Fisher M, Savitz SI. Philip M, et al. Stroke. 2009 Feb;40(2):577-81. doi: 10.1161/STROKEAHA.108.524330. Epub 2008 Dec 12. Stroke. 2009. PMID: 19074479
• [In vivo exploration of cerebral ischemia: use of neuroprotective agents in animal studies].
  Lestage P, Lockhart B, Roger A. Lestage P, et al. Therapie. 2002 Nov-Dec;57(6):554-63. Therapie. 2002. PMID: 12666263 Review. French.
• Neuroprotection in cerebral ischaemia: facts and fancies--the need for new approaches.
  Wahlgren NG, Ahmed N. Wahlgren NG, et al. Cerebrovasc Dis. 2004;17 Suppl 1:153-66. doi: 10.1159/000074808. Cerebrovasc Dis. 2004. PMID: 14694293 Review.
• To what extent have functional studies of ischaemia in animals been useful in the assessment of potential neuroprotective agents?
  Hunter AJ, Mackay KB, Rogers DC. Hunter AJ, et al. Trends Pharmacol Sci. 1998 Feb;19(2):59-66. doi: 10.1016/s0165-6147(97)01157-7. Trends Pharmacol Sci. 1998. PMID: 9550943 Review.
• Is magnesium neuroprotective following global and focal cerebral ischaemia? A review of published studies.
  Meloni BP, Zhu H, Knuckey NW. Meloni BP, et al. Magnes Res. 2006 Jun;19(2):123-37. Magnes Res. 2006. PMID: 16955724 Review.

Cited by

• Post-stroke inhibition of induced NADPH oxidase type 4 prevents oxidative stress and neurodegeneration.
  Kleinschnitz C, Grund H, Wingler K, Armitage ME, Jones E, Mittal M, Barit D, Schwarz T, Geis C, Kraft P, Barthel K, Schuhmann MK, Herrmann AM, Meuth SG, Stoll G, Meurer S, Schrewe A, Becker L, Gailus-Durner V, Fuchs H, Klopstock T, de Angelis MH, Jandeleit-Dahm K, Shah AM, Weissmann N, Schmidt HH. Kleinschnitz C, et al. PLoS Biol. 2010 Sep 21;8(9):e1000479. doi: 10.1371/journal.pbio.1000479. PLoS Biol. 2010. PMID: 20877715 Free PMC article.
• Therapeutic hypothermia for acute ischemic stroke: ready to start large randomized trials?
  van der Worp HB, Macleod MR, Kollmar R; European Stroke Research Network for Hypothermia (EuroHYP). van der Worp HB, et al. J Cereb Blood Flow Metab. 2010 Jun;30(6):1079-93. doi: 10.1038/jcbfm.2010.44. Epub 2010 Mar 31. J Cereb Blood Flow Metab. 2010. PMID: 20354545 Free PMC article. Review.
• Sex differences in stroke therapies.
  Sohrabji F, Park MJ, Mahnke AH. Sohrabji F, et al. J Neurosci Res. 2017 Jan 2;95(1-2):681-691. doi: 10.1002/jnr.23855. J Neurosci Res. 2017. PMID: 27870437 Free PMC article. Review.
• Sex differences in the brain: Implications for behavioral and biomedical research.
  Choleris E, Galea LAM, Sohrabji F, Frick KM. Choleris E, et al. Neurosci Biobehav Rev. 2018 Feb;85:126-145. doi: 10.1016/j.neubiorev.2017.07.005. Neurosci Biobehav Rev. 2018. PMID: 29287628 Free PMC article. Review.
• Bias in animal studies of estrogen effects on cardiovascular disease: A systematic review and meta-analysis.
  Friis Berntsen C, Rootwelt P, Dahm AEA. Friis Berntsen C, et al. Res Pract Thromb Haemost. 2021 May 5;5(4):e12507. doi: 10.1002/rth2.12507. eCollection 2021 May. Res Pract Thromb Haemost. 2021. PMID: 34013151 Free PMC article.

References

1. 1. Stroke. 2002 Jan;33(1):308-9 - PubMed
2. 1. Stroke. 2000 Dec;31(12 ):2912-9 - PubMed
3. 1. Lancet. 2002 Feb 23;359(9307):696-700 - PubMed
4. 1. Stroke. 2002 Aug;33(8):2123-36 - PubMed
5. 1. Stroke. 2001 Jul;32(7):1598-606 - PubMed

Publication types

MeSH terms

Substances

LinkOut - more resources

• Full Text Sources

  • Ovid Technologies, Inc.
  • Springer