gms | German Medical Science

60th Annual Meeting of the German Society of Neurosurgery (DGNC)
Joint Meeting with the Benelux countries and Bulgaria

German Society of Neurosurgery (DGNC)

24 - 27 May 2009, Münster

The role of cannabinoids in cerebral ischemia

Meeting Abstract

  • M. Schomacher - Klinik für Neurochirurgie, Charite – Universitätsmedizin Berlin
  • H. Müller - Institut für Neuropathologie, Johannes-Gutenberg-Universität Mainz
  • C. Berger - Klinik für Neurologie, Universitätsklinikum Heidelberg
  • S. Schwab - Klinik für Neurologie, Universitätsklinikum Erlangen
  • C. Sommer - Institut für Neuropathologie, Johannes-Gutenberg-Universität Mainz
  • W.R. Schäbitz - Klinik für Neurologie, Universitätsklinikum Münster

Deutsche Gesellschaft für Neurochirurgie. 60. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie (DGNC), Joint Meeting mit den Benelux-Ländern und Bulgarien. Münster, 24.-27.05.2009. Düsseldorf: German Medical Science GMS Publishing House; 2009. DocMO.12-01

DOI: 10.3205/09dgnc080, URN: urn:nbn:de:0183-09dgnc0806

Published: May 20, 2009

© 2009 Schomacher 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

Text

Objective: The neuroprotective potential of cannabinoids and cannabinoid receptor antagonists is currently under controversial discussion. In an experimental animal setting of acute stroke (tMCAO), the neuroprotective efficacy of the endocannbinoids palmitoylethanolamide (PEA) and anandamide (AEA) was investigated.

Furthermore we analyzed whether the cannabinoid (CB1) receptor antagonist SR141716A may act via modulation of postischemic ligand binding to the CB1-, the excitatory NMDA- and/or AMPA-receptor.

Methods: The neuroprotective potential of PEA was investigated by infarct measurement after high (30 mg/kg body weight) and low dosage administration (10 mg/kg body weight) in 49 male Wistar rats. In addition, the infarct volumes of 22 male Wistar rats receiving AEA (10 mg/kg body weight) or placebo were evaluated. Neurological outcome was assessed after 24 h and infarct volume was calculated on the basis of 2.3.5-triphenyltetrazolium chloride (TTC) staining.

For investigation of possible modulation of ligand binding to CB1-, NMDA- and/or AMPA receptor, a group of rats (n=12) were treated 30 min. after permanent cerebral ischemia (pMCAO) with SR141716A (1 mg/kg) or either intravenous saline (control). Quantitative receptor autoradiography was performed using [3H]CP 55,940, [3H]MK-801 and [3H]AMPA for specific receptor labeling. Ligand binding was analyzed within the infarct core, cortical penumbra and corresponding areas of the contralateral hemisphere and compared to sham-operated rats (n=5).

Results: The PEA high-dose group showed significant infarct reduction of 35% and AEA treated rats presented a significant infarct-reducing effect of 26% compared to controls. Neurological scores showed no significant differences between the groups.

The [3H]CP 55,940 ligand binding was in ischemic controls and SR141716A-treated rats not specifically regulated. It is important that reduced infarct volumes in SR141716A-treated rats were associated with maintained [3H]MK-801 binding to excitotoxic NMDA receptors in the penumbra, compared to a decrease in the control group.

Conclusions: The endocannabinoids AEA and PEA achieved a significant neuroprotective effect by reducing the size of infarcted tissue after tMCAO. Both endocannabinoids may have the potential to treat acute stroke and exert neuroprotection.

The cannabinoid receptor antagonist SR141716A may possess additional intrinsic neuroprotective properties independent of receptor-coupled pathways or due to action as a partial agonist.