gms | German Medical Science

59. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie (DGNC)
3. Joint Meeting mit der Italienischen Gesellschaft für Neurochirurgie (SINch)

Deutsche Gesellschaft für Neurochirurgie (DGNC) e. V.

01. - 04.06.2008, Würzburg

Mechanisms of effect of mild hypothermia-induced neuroprotection on Matrix-Metalloproteinase (MMP) activity after experimental subarachnoid hemorrhage (SAH): The differential roles of MMP-2 and MMP-9

Beeinflussung der Matrix-Metalloproteinase-Aktivität im Rahmen einer Hypothermie-induzierten Neuroprotektion nach experimenteller Subarachnoidalblutung: Unterschiedliche Bedeutungen von MMP-2 und MMP-9

Meeting Abstract

  • corresponding author K. Schöller - Neurochirurgische Klinik, Klinikum der Universität München-Großhadern
  • E. Török - Institut für Chirurgische Forschung, Klinikum der Universität München-Großhadern
  • A. Trinkl - Neurologische Klinik, Klinikum der Universität München-Großhadern
  • S. Zausinger - Neurochirurgische Klinik, Klinikum der Universität München-Großhadern
  • N. Plesnila - Neurochirurgische Klinik, Klinikum der Universität München-Großhadern

Deutsche Gesellschaft für Neurochirurgie. Società Italiana di Neurochirurgia. 59. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie e.V. (DGNC), 3. Joint Meeting mit der Italienischen Gesellschaft für Neurochirurgie (SINch). Würzburg, 01.-04.06.2008. Düsseldorf: German Medical Science GMS Publishing House; 2008. DocP 060

Die elektronische Version dieses Artikels ist vollständig und ist verfügbar unter: http://www.egms.de/de/meetings/dgnc2008/08dgnc329.shtml

Veröffentlicht: 30. Mai 2008

© 2008 Schöller et al.
Dieser Artikel ist ein Open Access-Artikel und steht unter den Creative Commons Lizenzbedingungen (http://creativecommons.org/licenses/by-nc-nd/3.0/deed.de). Er darf vervielf&aauml;ltigt, verbreitet und &oauml;ffentlich zug&aauml;nglich gemacht werden, vorausgesetzt dass Autor und Quelle genannt werden.


Gliederung

Text

Objective: Mild hypothermia (33°C) improves functional recovery following experimental SAH without affecting regional cerebral blood flow (rCBF), intracranial pressure (ICP), or brain edema formation. The current study investigated MMP-2 and MMP-9 activation, a process potentially involved in the development of vasospasm and blood-brain barrier opening, as a potential molecular target of hypothermia treatment after SAH.

Methods: Rats were subjected to SAH by endovascular puncture and assigned to a control group and two groups with induction of two hours hypothermia 60 and 180 minutes after SAH (n=10 per group). Bilateral rCBF, ICP, blood pressure (MABP), and cerebral perfusion pressure (CPP) were continuously monitored for 6 hours. MMP-2 & -9 activities were quantified 7 days thereafter in cortical and subcortical brain regions using gelatine zymography.

Results: Animals were allocated to 3 groups depending on the extent of SAH: °I = immediately lethal (death during monitoring period; 14%), °II = protracted lethal (death within 24 hours; 23%), °III = nonlethal (animals surviving 24 hours; 63%). In SAH °I and °II rCBF remained below 20% of baseline whereas in °III rCBF recovered to 60% baseline. In SAH °II and °III CPP remained in the range of 40-60 mmHg (°I: <30mmHg). rCBF and CPP did not correlate indicating early vasoconstriction depending on the grade of SAH. As reported previously, hypothermia did not influence post-hemorrhagic rCBF and ICP. MMP-2 but not MMP-9 expression was reduced in subcortical regions in both hypothermia groups.

Conclusions: Early rCBF reduction most likely caused by acute vasospasm seems to play a pivotal role for early survival of animals following SAH. In animals surviving SAH, MMP-9 is not reduced by hypothermia thereby explaining the missing effect on brain edema formation. Accordingly, hypothermia-induced neuroprotection may be mediated by a reduction of MMP-2 activity.