What is the optimal anesthetic protocol for measurements of cerebral autoregulation in spontaneously breathing mice?

Abstract

Autoregulation, an important feature of the cerebral circulation, is affected in many diseases. Since genetically modified mice are a fundamental tool in biomedical research, including neuro(bio)logy also in this specie measurements of cerebral autoregulation (CA) are mandatory. However, this requires anesthesia that unfortunately significantly impacts cerebral perfusion and consequently might distort CA measurements directly or by altering arterial pCO(2). The latter can be avoided by artificial ventilation but requires several control measurements of blood gases, each consuming at least 100 μl of blood or 5% of a mouse's blood volume. To avoid such diagnostic hemorrhage, we systematically analyzed the effect of different common anesthetic protocols used for rodents in spontaneously breathing mice on CA measured with Laser speckle perfusion imaging. Halothane, Isoflurane and Pentobarbital abrogated CA and Ketamin/Xylazine as well as Chloralose had a moderate reproducibility. In contrast, the rather rarely used anesthetic Ethomidate applied in low doses combined with local anesthetics had the best reproducibility. Although with this anesthesia the lower CA limit was lower than with Ketamin/Xylazine and Chloralose as reported in the handful of papers so far dealing with CA in mice, we suggest Ethomidate as the anesthetic of choice for CA measurements in spontaneously breathing mice.

A Murine Model of Subarachnoid Hemorrhage

“…This combination has a relatively small effect on blood pressure and vessel reactivity 11 . In contrast, isoflurane, a widely used anesthetic in SAH research, leads to peripheral vasodilation, severely impaired cerebral autoregulation 13 , and low blood pressure immediately after SAH 12 , findings which are not regularly associated with the early pathophysiology of SAH in humans. Hence, the use of an anesthetic protocol that does not disturb posthemorrhagic pathophysiology is an important prerequisite for a valid experimental SAH model.…”

Anaesthesia for positron emission tomography scanning of animal brains

“…33 However, both compounds tend to increase CBF and to disrupt cerebral autoregulation in animals. 34 In summary, CBF and cerebral blood volume (CBV) are typically decreased by anaesthesia produced by propofol and increased by ketamine and isoflurane/halothane in animals used for PET neuroimaging. 30 12,20,45,46 These changes are particularly important in quantitative kinetic analysis of brain glucose metabolism, although reduced neural activity caused by anaesthesia may also affect the outcome of PET studies on new drugs such as CNS stimulants.…”

“…Because anaesthesia can inhibit an animal's homeostasis, which indirectly can influence PET results, 33 careful monitoring is important. 34 Hypothermia can develop, for …”

Beyond neurovascular coupling, role of astrocytes in the regulation of vascular tone

“…Moreover, vasoconstriction was favored in parenchymal arterioles with minimal or no tone (Blanco et al, 2008). Lastly, for in vivo studies, anesthesia has been shown to significantly alter astrocyte activity (Thrane et al, 2012) as well as cerebrovascular function (Ayata et al, 2004, Kuga et al, 2009, Wang et al, 2010). Thus, careful considerations of these two parameters must be made when interpreting in vivo observations.…”