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61st Annual Meeting of the German Society of Neurosurgery (DGNC) as part of the Neurowoche 2010
Joint Meeting with the Brazilian Society of Neurosurgery on the 20 September 2010

German Society of Neurosurgery (DGNC)

21 - 25 September 2010, Mannheim

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Intracerebral hemorrhage compromises the nigrostriatal dopaminergic projection system and promotes endogenous neural stem cell proliferation

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  • Robert H. Andres - Universitätsklinik für Neurochirurgie, Universität Bern, Inselspital, Switzerland; Department of Neurosurgery, Stanford University School of Medicine, Stanford, CA, USA
  • Angélique D. Ducray - Universitätsklinik für Neurochirurgie, Universität Bern, Inselspital, Switzerland
  • Pasquale Mordasini - Universitätsklinik für Neurochirurgie, Universität Bern, Inselspital, Switzerland
  • Alain Barth - Universitätsklinik für Neurochirurgie, Universität Bern, Inselspital, Switzerland; Universitätsklinik für Neurochirurgie, Medizinische Universität Graz, Austria
  • Andreas Raabe - Universitätsklinik für Neurochirurgie, Universität Bern, Inselspital, Switzerland
  • Hans R. Widmer - Universitätsklinik für Neurochirurgie, Universität Bern, Inselspital, Switzerland

Deutsche Gesellschaft für Neurochirurgie. 61. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie (DGNC) im Rahmen der Neurowoche 2010. Mannheim, 21.-25.09.2010. Düsseldorf: German Medical Science GMS Publishing House; 2010. DocP1870

doi: 10.3205/10dgnc341, urn:nbn:de:0183-10dgnc3413

Published: September 16, 2010

© 2010 Andres et al.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by-nc-nd/3.0/deed.en). You are free: to Share – to copy, distribute and transmit the work, provided the original author and source are credited.

Outline

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Objective: Intracerebral hemorrhage (ICH) constitutes one of the most devastating forms of cerebrovascular disease. Dysfunction of the nigrostriatal dopaminergic system might be involved in neurological deficits seen after striatal ICH. Stimulation of endogenous neural stem cell proliferation is supposed to be involved in structural brain plasticity after ICH. In the present study, we investigated the effects of deep basal ganglia hemorrhage on the dopaminergic projection system and on endogenous neurogenesis in a rat model of ICH.

Methods: ICH was induced in rats by combining a striatal microtrauma with slow infusion of 30 ul autologous blood. Amphetamine-induced rotational behavior was assessed after 7, 20 and 30 days, and the numbers of tyrosine hydroxylase (TH) expressing dopaminergic neurons and total neuronal cells in the SN were analyzed at days 2 and 30 post ICH. Effects on endogenous stem cell proliferation in the subventricular zone (SVZ) and hippocampus were assessed using the 5-bromo-2-deoxyuridine (BrdU) incorporation method.

Results: Rats suffering ICH showed an increase in ipsiversive rotational behavior at day 7 post ICH, followed by a partial recovery at days 20 and 30 (p<0.05). ICH resulted in a decrease of 45% and 15% in the number of TH-immunoreactive cells in the ipsilateral SN at day 2 and 30, respectively (p<0.05). In contrast, the loss of total neuronal cells was less pronounced with a decrease of only 25% at day 2 (p<0.05) and no significant difference at day 30. Rats with ICH also exhibited significantly higher numbers of BrdU-positive cells in the ipsilateral SVZ (p<0.05) and hippocampus (p<0.05). These observations indicate that ICH induces a transient downregulation of TH expression in a subpopulation of SN neurons and promotes endogenous stem cell proliferation.

Conclusions: Our results provide evidence that the ipsilateral nigrostriatal dopaminergic system is significantly affected by striatal ICH. Stimulation of neurogenesis might constitute a rudimentary endogenous repair mechanism after the insult. Neuroprotective strategies for dopaminergic neurons and/or dopamine substitution, as well as modulation of adult neural stem cell proliferation, might therefore be effective for improving the functional outcome after striatal ICH.