gms | German Medical Science

63rd Annual Meeting of the German Society of Neurosurgery (DGNC)
Joint Meeting with the Japanese Neurosurgical Society (JNS)

German Society of Neurosurgery (DGNC)

13 - 16 June 2012, Leipzig

Pharmacological inhibition of neuronal voltage-gated Cav2.1 (P/Q-type) channels reduces posttraumatic brain damage after experimental traumatic brain injury

Meeting Abstract

  • N. Terpolilli - Klinik und Poliklinik für Neurochirurgie, Ludwig-Maximilians-Universität, München
  • R. Dolp - Klinik und Poliklinik für Neurochirurgie, Ludwig-Maximilians-Universität, München
  • A.M.J.M. van den Maagdenberg - Abteilung für Humangenetik, Universität Leiden, Niederlande; Neurologie, Universität Leiden, Niederlande
  • M.D. Ferrari - Neurologie, Universität Leiden, Niederlande
  • N. Plesnila - Institut für Demez- und Schlaganfallforschung, Ludwig-Maximilians-Universität, München

Deutsche Gesellschaft für Neurochirurgie. Japanische Gesellschaft für Neurochirurgie. 63. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie (DGNC), Joint Meeting mit der Japanischen Gesellschaft für Neurochirurgie (JNS). Leipzig, 13.-16.06.2012. Düsseldorf: German Medical Science GMS Publishing House; 2012. DocDO.17.01

doi: 10.3205/12dgnc153, urn:nbn:de:0183-12dgnc1532

Published: June 4, 2012

© 2012 Terpolilli et al.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( You are free: to Share – to copy, distribute and transmit the work, provided the original author and source are credited.



Objective: Traumatic brain damage (TBI) is a major cause of death and disabilty in industrialized countries. So far there is no effective causal treatment for reducing posttraumatic brain damage.

Previous investigations in our laboratory suggest a significant role of neuronal voltage-gated Cav2.1 (P/Q-type) channels in the development of posttraumatic brain edema formation. It was shown that mice carrying gain-of-function mutations in the CACA1A gene that encodes the pore forming subunit of neuronal voltage-gated Cav2.1 (P/Q-type) Ca2+ channels suffer from significantly increased secondary brain damage after mild experimental TBI.

We therefore hypothesized that pharmacological inhibition of neuronal voltage-gated Cav2.1 channels by the selective inhibitor alpha-eudesmol may be neuroprotective in experimental TBI.

Methods: Male C57/bl 6 mice were subjected to Controlled Cortical Impact (CCI) trauma. For toxicity screening, the mice were anesthetized, intubated and ventilated under continuous measurement of end tidal CO2. Mean arterial blood pressure (MAP) was measured in the femoral artery, cerebral blood flow (CBF) by Laser Doppler fluxmetry over both MCA territories.

Selective P/Q channel blocker α-Eudesmol or vehicle was applied intracerebroventricularly (i.c.v.) at increasing doses 10 minutes before and at 100nmol 10 minutes after trauma. Brain water content, lesion volume and intracranial pressure were measured 24h after trauma.

Results: α-Eudesmol did not influence MAP, CBF, blood gas or blood electrolyte parameters. Pharmacological inhibition of Cav2.1 channels led to a dose-dependent reduction in brain water content 24 hours after trauma. After i.c.v. injection of the drug in concentrations of 100 nmol, 500 nmol and 1 mmol, the brain water content was significantly lower in the traumatized as well as in the non-traumatized hemisphere compared to control animals. While α-eudesmol at 100 nmol significantly reduced ICP after 24h and tended to reduce lesion volume, no further impovement was detected at higher doses. When it was applied after trauma at a low dose (100nmol), no significant changes occurred.

Conclusions: Pharmacological inhibition of neuronal voltage-gated Cav2.1 (P/Q-type) Ca2+ channels dose-dependently reduced secondary brain damage, especially brain edema formation, after experimental traumatic brain injury and might therefore constitute a promising treatment strategy for the reduction of posttraumatic brain damage. Further studies are needed to further elucidate the protective mechanism.