Article
Cerebral perfusion and cortical signaling following SAH in Cav2.3-deficient mice
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Authors
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Marcel A. Kamp
- Neurochirurgische Klinik, Heinrich-Heine-Universität, Düsseldorf, Germany; Institut für Neurophysiologie, Universität zu Köln, Germany
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Maxine Dibué
- Neurochirurgische Klinik, Heinrich-Heine-Universität, Düsseldorf, Germany; Institut für Neurophysiologie, Universität zu Köln, Germany; Zentrum für Molekulare Medizin Köln, Germany
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Hans-Jakob Steiger
- Neurochirurgische Klinik, Heinrich-Heine-Universität, Düsseldorf, Germany
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Toni Schneider
- Institut für Neurophysiologie, Universität zu Köln, Germany; Zentrum für Molekulare Medizin Köln, Germany
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Daniel Hänggi
- Neurochirurgische Klinik, Heinrich-Heine-Universität, Düsseldorf, Germany; Neurochirurgische Klinik, Universitätsmedizin Mannheim, Medizinische Fakultät Mannheim der Universität Heidelberg, Germany
| Published: | June 8, 2016 |
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Outline
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Objective: The molecular pathways of early brain injury (EBI) and delayed cerebral ischemia (DCI) after subarachnoid hemorrhage (SAH) remain poorly understood. Besides L-type voltage-gated calcium channels (VCGG), the Cav2.3 containing E-/R-type VGCC is believed to play an essential role in the genesis of DCI. The aim of the present study was to analyze the role of Cav2.3 VGCC in the pathophysiology of EBI and DCI.
Method: SAH was induced by injection of 50 µl freshly-drawn blood into the cisterna magna (or saline for the saline injection group or no injection but perforation of the atlanto-occipital membrane for the sham group). Relative cerebellar and cerebral regional cerebral blood flow (rCBF) was evaluated by Laser-Doppler-Flowmetry before and after induction of SAH and at the time point of maximal angiographical vasospasm 6 hours after SAH. Telemetric electrocorticograms (ECoG) from the S1 cortex recorded by implanted transmitters were continuously collected and were used to calculate absolute and relative power of frequency bands.
Results: Totally, 40 mice (18 Cav2.3 -/- mice and 22 Cav2.3 +/+ animals) were analyzed. In native animals, induction of SAH lead to an acute significant impairment of rCBF and total ECoG power as compared to the control groups. Cerebral perfusion immediately after SAH was not significantly reduced in Cav2.3 -/- mice as compared to the saline control group (p = 0.1) but significantly better than in comparison to wild-type animals (p = 0.04 for the rCBF). Difference of SAH-related total ECoG power impairment between both genetic groups also reached significance (p = .024). During DCI, cerebral and cerebellar rCBF were significantly reduced compared to both control groups in Cav2.3 +|+ mice, whereas rCBF in the S1 and cerebellum of Cav2.3 -|- mice was not significantly impaired compared to the saline control. Cav2.3 -/- mice displayed a significant improved rCBF of the S1 region (p = 0.04) but not of the cerebellum compared to Cav2.3 +/+ mice during DCI after 6 hours. For the saline-injected animals, rCBF did not significantly differ. During DCI, total ECoG power did not significantly differ between both genetic groups.
Conclusions: Cav2.3 containing E-/R-type VGCCs are involved in the genesis of EBI and DCI after SAH in a SAH mouse model. Therefore, weakly sensitive E-/R-type VGCCs, in addition to L-type VGCC should be considered in the development of new therapeutic strategies addressing EBI and DCI.
