Effect of hypotension and carbon dioxide changes in an improved genuine closed cranial window rat model

Abstract

The genuine closed cranial window model, in which the thinned parietal bone constitutes the covering of the preparation, has contributed to a better understanding of the pathophysiological mechanisms in migraine. In its present form, only measurements of the middle meningeal artery (MMA) are performed. The aim of this study was, in addition, to measure pial artery/arteriole (PA) diameter and cortical cerebral blood flux in the same cranial window. The model was evaluated by studying the effects of hypotension and changes in arterial carbon dioxide pressure (PaCO2), because these parameters might influence the interpretation of pharmacological experiments. Out of 23 successful experiments it was possible to measure all three parameters in 19 animals. In four, PA diameter could not be measured, while MMA diameter and local cortical cerebral blood flux (LCBFFlux) always could. Haemorrhage-induced hypotension (-64 ± 0.8 mmHg) caused an increase of MMA diameter of 11.8 ± 8.4%, PA diameter of 61.2 ± 7.7% and a decrease in LCBFFlux of -36.4 ± 2.5%. The decrease in blood pressure did not significantly change the MMA (P = 0.38); however, the PA diameter and the LCBF-Flux were affected (P < 0.001). All three parameters were sensitive to hypo- and hypercapnia. In conclusion, we have shown that not only MMA but also PA diameter and LCBFFlux can be measured in the same cranial window. Tight control of PaCO2 is essential in pharmacological experiments. If test substances possess hypotensive actions, it may be difficult to interpret whether the PA dilation is caused by the induced hypotension per se or is a direct pharmacological action or a combination. In contrast, the MMA does not autoregulate and MMA diameter changes in pharmacological studies may exclusively be due to direct pharmacological effects.