Intracerebral Hemorrhage Affects the Extrapyramidal System and Promotes Endogenous Neurogenesis in the Subventricular Zone and Hippocampus

R. H. Andres; L. Andereggen; A. D. Ducray; P. Mordasini; R. Guzman; A. Barth; A. Raabe; H. R. Widmer

doi:10.1055/s-0032-1316234

Journal of Neurological Surgery Part A: Central European Neurosurgery, Table of Contents

Intracerebral Hemorrhage Affects the Extrapyramidal System and Promotes Endogenous Neurogenesis in the Subventricular Zone and Hippocampus

R. H. Andres ¹, L. Andereggen ¹, A. D. Ducray ¹, P. Mordasini ¹, R. Guzman ², A. Barth ¹, A. Raabe ¹, H. R. Widmer ¹

¹Department of Neurosurgery, University of Berne, Inselspital, Berne, Switzerland
²Department of Neurosurgery, Stanford University School of Medicine, Palo Alto, United States

Abstract

Aims: 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 might 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 üL 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 days 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.