, 2013b). Respiratory deficits are measured in these rodent models by plethysmography (Morrey et al., 2012), oxygen saturation (SaO2) (Morrey et al., FG-4592 supplier 2012), diaphragmatic electromyography (EMG) (Morrey et al., 2010), and optogenetic photoactivation

of phrenic motor neurons in the cervical cord (Wang et al., 2013b). Respiratory deficits are further identified by challenging the infected animals with hypercapnia (7% CO2) (Wang et al., 2013b). Representative tracings of whole body plethysmography are shown for mice (Fig. 3). The principle is that as the rodent breathes in the sealed chamber, changes in voltage are recorded from pressure-sensitive transducers. Qualitatively, one can tell the difference in the tracings between sham-infected and WNV-infected mice, particularly if the animals are noticeably moribund (Fig. 3). To quantitatively interpret the patterns, the shapes of the curves are mathematically described by 16 different algorithms with the apparatus used in a WNV study (minute volume, tidal volume, enhanced pause, end expiratory pause, end inspiratory pause, peak expiratory flow, peak inspiratory flow, frequency, inspiratory time, expiratory time, relaxation time, pause, time delay, specific airway resistance, specific airway conductance, mid-expiratory flow) (Morrey et al., 2012). Of the 8 parameters markedly affected by WNV infection, minute volume (MV) as

a measure of lung capacity over time was the most unambiguous indicator of WNV-induced respiratory Selleckchem Paclitaxel selleck compound stress. The suppression of MV during development of neurological disease is also supported by reduced SaO2 as measured by pulse oximetry (Morrey et al., 2012); however, pulse oximetry is less accurate in mice and is not performed on hamsters due to the lack of sufficient tail for the application of a cuff. The use of plethysmography facilitated the discovery that respiratory insufficiency is

the likely physiological mechanism of death for a subset of arboviral encephalitides, including WNV (Wang et al., 2013b). Respiratory insufficiency is the only physiological readout that correlates strongly with WNV-induced mortality (Morrey et al., 2012) (Fig. 4). No other disease parameters in WNV-infected rodents, i.e., cerebral edema, overt seizures, starvation or dehydration, cardiac abnormalities, paralysis, nose bleeding, front limb tremors, memory loss, or autonomic dysfunctions correlate with mortality (Morrey et al., 2004b, Morrey et al., 2008a, Morrey et al., 2008b, Siddharthan et al., 2009, Smeraski et al., 2011 and Wang et al., 2011). Remarkably, respiratory insufficiency as measured by% normal MV caused by Japanese encephalitis virus (JEV), neuro-adapted Sindbis virus (NSV), North American tick-borne encephalitis Powassan virus (not shown) also correlates strongly with mortality (Wang et al., 2013b) (Fig. 4).