Cerebrovascular Responses under Controlled and Monitored Physiological Conditions in the Anesthetized Mouse

Abstract

Control of physiological parameters such as respiration, blood pressure, and arterial blood gases has been difficult in the mouse due to the lack of technology required to monitor these parameters in small animals. Here we report that anesthetized and artificially ventilated mice can be maintained under physiological control for several hours with apparently normal cerebrovascular reactivity to hypercapnia and mechanical vibrissal stimulation. SV-129 mice were anesthetized with urethane (750 mg/kg i.p.) and α-chloralose (50 mg/kg i.p.), intubated, paralyzed, and artificially ventilated. Respiratory control was maintained within physiological range by reducing the inspiratory phase of the respiratory cycle to <0.1 s and by adjusting end-tidal CO2 to give a Pco2 of 35 ± 3 mm Hg. In these mice, mean arterial pressure (95 ± 9 mm Hg), heart rate (545 ± 78 beats/min), and arterial pH (7.27 ± 0.10) could be maintained for several hours. Body temperature was kept at 36.5–37.5°C. We observed stable regional CBF (rCBF) measurements (as determined by laser–Doppler flowmetry) when systemic arterial blood pressure was varied between 40 and 130 mm Hg. Hypercapnia led to a 38 ± 15% (5% CO2) and 77 ± 34% (10% CO2) increase in rCBF. Mechanical stimulation of contralateral vibrissae for 1 min increased rCBF by 14 ± 4%. Changes in rCBF compare favorably with those observed previously in another rodent species, the Sprague–Dawley rat. After placement of a closed cranial window, cerebrovascular reactivity to hypercapnia and whisker stimulation was intact and well maintained during 2-h superfusion with artificial CSF.