Effects of urethane and isoflurane on the sensory evoked response and local blood flow in the early postnatal rat somatosensory cortex

Abstract

Functional studies in the central nervous system are often conducted using anesthesia. While the dose-dependent effects of anesthesia on neuronal activity have been extensively characterized in adults, little is known about the effects of anesthesia on cortical activity and cerebral blood flow in the immature central nervous system. Substitution of electrophysiological recordings with the less-invasive technique of optical intrinsic signal imaging (OIS) in vivo allowed simultaneous recordings of sensory-evoked functional response and local blood flow changes in the neonatal rat barrel cortex. Using OIS we characterize the effects of two widely used anesthetics—urethane and isoflurane. We found that both anesthetics suppressed the sensory-evoked optical intrinsic signal in a dose-dependent manner. Dependence of the cortical response suppression matched the exponential decay model. At experimental levels of anesthesia, urethane affected the evoked cortical response less than isoflurane, which is in agreement with the results of electrophysiological recordings demonstrated by other authors. Changes in oxygenation and local blood flow also showed negative correlation with both anesthetics. The high similarity in immature patterns of activity recorded in different regions of the developing cortex suggested similar principles of development regardless of the cortical region. Therefore the indicated results should be taken into account during functional explorations in the entire developing cortex. Our results also point to urethane as the anesthetic of choice in non-survival experimental recordings in the developing brain as it produces less prominent impairment of cortical neuronal activity in neonatal animals.

Sensory computations in the cuneate nucleus of macaques

“…Isoflurane (1 to 2%) was then delivered continuously via inhalation and decreased during the neurophysiological recordings. While anesthesia can have a profound impact on neural responses ( 54 – 58 ), several observations suggest that the CN recordings were only minimally impacted. First, the impact of anesthesia tends to be more pronounced in the cortex ( 59 ).…”

Optic chiasmatic potential by endoscopically implanted skull base microinvasive biosensor: a brain-machine interface approach for anterior visual pathway assessment

“…Since the retino-geniculo-cortical pathway across the brain modulated f-VEP, its instability might originate from variable intra-cranial neuronal activities, which could be suppressed by isoflurane, a commonly used anesthetic, in a dose-dependent manner 17 , 18 . In contrast, f-OCP was less influenced by intra-cranial neuronal activities since it was recorded from ON extra-cranially.…”

The general anesthetic isoflurane inhibits calcium activity in cerebrovascular endothelial cells and disrupts vascular tone

“…Although we are not aware of previous reports on excitatory effects of ISO on cells of the neuro-glia-vascular unit, there have been numerous studies that demonstrated inhibitory effects of ISO and other general anesthetics on different neural cell types including neurons, astrocytes, mural cells, and microglia (Glück et al, 2021; Schummers et al, 2008; Thrane et al, 2012; Umpierre et al, 2020). Indeed, volatile anesthetics such as ISO, have multiple protein targets, are potent cerebral vasodilators and there exists a narrow range of isoflurane concentrations (1.0 to 1.5%) under which neurovascular coupling is preserved (Masamoto and Kano, 2012; O’Herron et al, 2016; Schlegel et al, 2015; Schummers et al, 2008; Shumkova et al, 2021). Interesting to us, previous reports in auditory brainstem slices showed that ISO reduced action potentials and neurotransmitter release at a half-maximum inhibitory concentration (IC50) of 1.5% (Wu et al, 2004; Wang et al, 2020).…”

“…Furthermore, general anesthetics such as isoflurane (ISO) have been shown to cause large disruptions in cerebral blood flow (Li et al, 2014;Shumkova et al, 2021), brain metabolism (Slupe and Kirsch, 2018), neurovascular coupling (Gao et al, 2016;Schlegel et al, 2015), and functional connectivity (Ciobanu et al, 2012;Constantinides and Murphy, 2016;Bukhari et al, 2018;Stenroos et al, 2021). One of the most recent studies used multi-exposure speckle imaging to examine the effects of ISO on the dynamics of the cerebral vasculature and blood flow in awake mice.…”

“…This issue is important since the functional properties of VECs may vary notably amongst different organs, including the brain, where an increase in neuronal activity leads to a local elevation in cerebral blood flow mediated by vasoactive compounds that act on cerebral blood vessels (Filippini et al, 2019; Guerra et al, 2018; Thakore and Earley, 2019). Furthermore, general anesthetics such as isoflurane (ISO) have been shown to cause large disruptions in cerebral blood flow (Li et al, 2014; Shumkova et al, 2021), brain metabolism (Slupe and Kirsch, 2018), neurovascular coupling (Gao et al, 2016; Schlegel et al, 2015), and functional connectivity (Ciobanu et al, 2012; Constantinides and Murphy, 2016; Bukhari et al, 2018; Stenroos et al, 2021). One of the most recent studies used multi-exposure speckle imaging to examine the effects of ISO on the dynamics of the cerebral vasculature and blood flow in awake mice.…”