Head Down Tilt 15° in Acute Ischemic Stroke with Poor Collaterals: A Randomized Preclinical Trial

• Published in: Neuroscience Vol. 523; pp. 1 - 6
• Main Authors: Mariani, Jacopo, Beretta, Simone, Diamanti, Susanna, Versace, Alessandro, Martini, Beatrice, Viganò, Martina, Castiglioni, Laura, Sironi, Luigi, Carone, Davide, Cuccione, Elisa, Monza, Laura, Giussani, Carlo, Ferrarese, Carlo
• Format: Journal Article
• Language: English
• Published: United States Elsevier Ltd 15.07.2023
• Subjects: acute ischemic stroke; Animals; Brain Ischemia; cerebral collaterals; Cerebrovascular Circulation - physiology; collateral therapeutics; Head-Down Tilt; ischemic penumbra; Ischemic Stroke; Rats; Rats, Inbred SHR; Stroke; ischemic penumbra; SD; acute ischemic stroke; CBF; cerebral collaterals; collateral therapeutics; HDT15; MCA; head down tilt; SHR
• ISSN: 0306-4522; 1873-7544
• DOI: 10.1016/j.neuroscience.2023.05.011

[Display omitted] •Head down tilt 15° (HDT15) aims to increase collaterals in acute ischemic stroke.•HDT15 is a promising emergency treatment with low cost and high accessibility.•Efficacy of HDT15 was assessed in a stroke model with poor collaterals (SHR rats)•HDT15 acutely increased cerebral perfusion (+16.6%)•HDT15 reduced infarct size (- 21.89%) at 24 hours, but did not improve neuroscore.•A poor baseline collateral status is associated to a smaller HDT15 effect. Cerebral collaterals are recruited after arterial occlusion with a protective effect on tissue outcome in acute ischemic stroke. Head down tilt 15° (HDT15) is a simple, low cost and accessible procedure that could be applied as an emergency treatment, before recanalization therapies, with the aim to increase cerebral collateral flow. Spontaneously hypertensive rats have been shown to display anatomical differences in morphology and function of cerebral collaterals, compared to other rat strains, resulting in an overall poor collateral circulation. We investigate the efficacy and safety of HDT15 in spontaneously hypertensive (SHR) rats, which were considered as an animal stroke model with poor collaterals. Cerebral ischemia was induced by 90 minute endovascular occlusion of the middle cerebral artery (MCA). SHR rats were randomized to HDT15 or flat position (n = 19). HDT15 was applied 30 minutes after occlusion and lasted 60 minutes, until reperfusion. HDT15 application increased cerebral perfusion (+16.6% versus +6.1%; p = 0.0040) and resulted in a small reduction of infarct size (83.6 versus 107.1 mm3; − 21.89%; p = 0.0272), but it was not associated with early neurological improvement, compared to flat position. Our study suggests that the response to HDT15 during MCA occlusion is dependent on baseline collaterals. Nonetheless, HDT15 promoted a mild improvement of cerebral hemodynamics even in subjects with poor collaterals, without safety concerns.