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Head down tilt 15° to preserve salvageable brain tissue in acute ischemic stroke: A pre-clinical pooled analysis, with focus on cerebral hemodynamics.

  • Diamanti, Susanna1, 2, 3, 4
  • Mariani, Jacopo1, 2, 4
  • Versace, Alessandro1
  • Riva, Matteo1
  • Cuccione, Elisa1
  • Cai, Ruiyao1
  • Monza, Laura1
  • Viganò, Martina1
  • Bolbos, Radu5
  • Chauveau, Fabien5
  • Cho, Tae-Hee5
  • Carone, Davide6
  • Ferrarese, Carlo1, 3, 4
  • Beretta, Simone1, 3, 4
  • 1 Laboratory of Experimental Stroke Research, School of Medicine and Surgery, University of Milano-Bicocca, Monza, Italy. , (Italy)
  • 2 PhD Program in Neuroscience, School of Medicine and Surgery, University of Milano-Bicocca, Monza, Italy. , (Italy)
  • 3 Department of Neurology, San Gerardo Hospital, ASST Monza, Monza, Italy. , (Italy)
  • 4 Milan Center for Neuroscience (NeuroMi), Milano, Italy. , (Italy)
  • 5 Lyon Neuroscience Research Centre; CNRS UMR5292; INSERM U1028; Univ. Lyon 1, Lyon, France. , (France)
  • 6 Acute Vascular Imaging Centre, Radcliffe Department of Medicine, University of Oxford, Oxford, UK.
Published Article
European Journal of Neuroscience
Wiley (Blackwell Publishing)
Publication Date
Jun 01, 2023
DOI: 10.1111/ejn.15852
PMID: 36300727


Neurological outcome after ischemic stroke depends on residual salvageable brain tissue at the time of recanalization. Head down tilt 15° (HDT15) was proven effective in reducing infarct size and improving functional outcome in rats with transient middle cerebral artery occlusion (t-MCAO) by increasing cerebral perfusion within the ischemic penumbra. In this pooled analysis, individual animal-level data from three experimental series were combined in a study population of 104 t-MCAO rats (45 in HDT15 group and 59 in flat position group). Co-primary outcomes were infarct size and functional outcome at 24 h in both groups. The secondary outcome was hemodynamic change induced by HDT15 in ischemic and non-ischemic hemispheres in a subgroup of animals. Infarct size at 24 h was smaller in HDT15 group than in flat position group (absolute mean difference 31.69 mm3 , 95% CI 9.1-54.2, Cohen's d 0.56, p = 0.006). Functional outcome at 24 h was better in HDT15 group than in flat position group (median [IQR]: 13[10-16] vs. 11), with a shift in the distribution of the neurobehavioural scores in favour of HDT15. Mean cerebral perfusion in the ischemic hemisphere was higher during HDT15 than before its application (Perfusion Unit [P.U.], mean ± SD: 52.5 ± 19.52 P.U. vs. 41.25 ± 14.54 P.U., mean of differences 13.36, 95% CI 7.5-19.18, p = 0.0002). Mean cerebral perfusion in the non-ischemic hemisphere before and during HDT15 was unchanged (P.U., mean ± SD: 94.1 ± 33.8 P.U. vs. 100.25 ± 25.34 P.U., mean of differences 3.95, 95%, CI -1.9 to 9.6, p = 0.1576). This study confirmed that HDT15 improves the outcome in t-MCAO rats by promoting cerebral perfusion in the ischemic territory, without disrupting hemodynamics in non-ischemic areas. © 2022 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

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