Post-stroke gaseous hypothermia increases vascular density but not neurogenesis in the ischemic penumbra of aged rats

Article type: Research Article

Authors: Sandu, Raluca Elena^b | Uzoni, Adriana^{a; 1} | Ciobanu, Ovidiu^{b; d} | Moldovan, Mihai^c | Anghel, Andrei^e | Radu, Eugen^f | Coogan, Andrew N.^g | Popa-Wagner, Aurel^{a; b; *}

Affiliations: [a] Molecular Psychiatry, Department of Psychiatry, University of Medicine Rostock, Rostock, Germany | [b] University of Medicine and Pharmacy, Craiova, Romania | [c] Neuroscience and Pharmacology, Panum, University of Copenhagen, Copenhagen, Denmark | [d] Department of Psychiatry, University Medicine of Saarland, Homburg/Saar, Germany | [e] Department of Biochemistry, University of Medicine and Pharmacy “Victor Babes”, Timisoara, Romania | [f] University of Medicine and Pharmacy Carol Davila, Bucharest, Romania | [g] Department of Psychology, Maynooth University, National University of Ireland, Maynooth, Ireland

Correspondence: [*] Corresponding author: Aurel Popa-Wagner, MD, PhD, Department of Psychiatry, Medical University Rostock, Gehlsheimer Straße, 20, D-18147, Rostock, Germany. E-mail: aurel.popa-wagner@med.uni-rostock.de.

Note: [1] Equal contribution.

Abstract: Purpose: In aged humans, stroke is a major cause of disability for which no neuroprotective measures are available. In animal studies of focal ischemia, short-term hypothermia often reduces infarct size. Nevertheless, efficient neuroprotection requires long-term, regulated lowering of whole body temperature. Previously, we reported that post-stroke exposure to hydrogen sulfide (H2S) effectively lowers whole body temperature and confers neuroprotection in aged animals. Methods: In the present study using behavioral tests, MRI, telemetrical EEG, BP and temperature recordings, RT-PCR and immunofluorescence, we assessed infarct size, vascular density, neurogenesis and as well as the expression of genes coding for proteasomal proteins as well as in post-stroke aged Sprague-Dawley rats exposed to H2S- induced hypothermia. Results: Two days exposure to mild hypothermia diminishes the expression of several genes involved in protein degradation, thereby leading to better preservation of infarcted tissue. Further, hypothermia increased the density of newly formed blood vessels in the peri-lesional cortex did not enhance neurogenesis in the infarcted area of aged rats. Likewise, there was improved recovery of fine vestibulomotor function and asymmetric sensorimotor deficit. Conclusion: Long-term hypothermia may be a viable clinical approach by simultaneously targeting multiple processes including better tissue preservation, enhanced vascular density and improved behavioral performance.

Keywords: Aging, stroke, hypothermia, H₂S, proteasome, vascular density, neurogenesis

DOI: 10.3233/RNN-150600

Journal: Restorative Neurology and Neuroscience, vol. 34, no. 3, pp. 401-414, 2016