gms | German Medical Science

58. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie e. V. (DGNC)

Deutsche Gesellschaft für Neurochirurgie (DGNC) e. V.

26. bis 29.04.2007, Leipzig

The possible contribution of acetylcholine receptors to the cognitive impairments after experimental traumatic brain injury

Mögliche Beteiligung von Acetylcholinrezeptoren an den kognitiven Beeinträchtigungen nach Schädel-Hirn-Trauma

Meeting Abstract

  • corresponding author C. Donat - Institut für Interdisziplinäre Isotopenforschung Leipzig
  • C. Voigt - Klinik für Neurochirurgie am Universitätsklinikum Leipzig
  • J. Meixensberger - Klinik für Neurochirurgie am Universitätsklinikum Leipzig
  • M. U. Schuhmann - Klinik für Neurochirurgie am Universitätsklinikum Leipzig
  • P. Brust - Institut für Interdisziplinäre Isotopenforschung Leipzig

Deutsche Gesellschaft für Neurochirurgie. 58. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie e.V. (DGNC). Leipzig, 26.-29.04.2007. Düsseldorf: German Medical Science GMS Publishing House; 2007. DocP 002

Die elektronische Version dieses Artikels ist vollständig und ist verfügbar unter:

Veröffentlicht: 11. April 2007

© 2007 Donat et al.
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Objective: Traumatic brain injury (TBI) is one of the leading causes of death and disability mainly among young people. Patients with TBI often suffer from cognitive impairments as a result of the injury. Working memory deficits shown in animal models are believed to be connected with deficits of the cholinergic system, especially of the acetylcholine receptors (AChR). There are previous findings from different animal models. The present study was conducted to evaluate these findings in one animal model with special attention regarding the time-course of posttraumatic events and critical brain regions. The identification of sensitive targets within the cholinergic system is a precondition for diagnostic neuroimaging in TBI-patients with Positron-Emission-Tomography (PET).

Methods: Three groups of male Sprague-Dawley rats (post-TBI survival time: 2 h, 24 h and 72 h) were anaesthetized and subjected to sham injury (control, n=8) or controlled-cortical-impact injury (CCI) (n=8) with 2mm depth of impact at a velocity of 4m/sec. To quantify the receptor density, 12µm cryostat brain sections were incubated with 2 nM[3H]-Epibatidine, a ligand for nicotinic acetylcholine receptors (nAChR), for 90 min or 8 nM [3H]-QNB, specific for muscarinic acetylcholine receptors (mAChR), for 120 minutes. Non-specific binding was determined in the presence of 300µM nicotine or 1µM atropine, respectively. All slides were preincubated with assay buffer (50mM TRIS-HCl, pH 7.4, 120mM NaCl, 5 mM KCl, 2.5mM CaCl2, 1 mM MgCl2) for 15 minutes and experiments were carried out at room temperature. Additionally acetylcholinesterase (AchE) staining was performed using acetylcholiniodide.

Results: A significant decline in the receptor density of the nAChR in thalamus (72 h: 25%), motor cortex (72 h:20%) and hypothalamus (24 h:20%) was observed 24 h and 72 h after TBI. The mAChR show a similar, time-dependent reduction in these regions (e.g. thalamus 72 h: 20%) and additionally in the corpus callosum and basal forebrain. Histochemical staining indicates an increase in AChE activity in the basal forebrain 2 h after TBI (120% increase of optical density compared to control activity). A decreased enzyme activity was found in the hippocampus (85% of control activity).

Conclusions: The cholinergic transmission is significantly impaired after experimental TBI. Considering the role of the AChR for cognition in the brain, it seems likely that the decline in receptor density contributes to attention and memory deficits as found in behavioural experiments.