Published clinical records and surveys indicate that some WNV-infected patients complain of memory problems (Carson et al., 2006, Cook et al., 2010 and Gottfried et al., 2005). Rodent models with Theiler’s murine encephalomyelitis Anticancer Compound Library virus (Buenz et al., 2006) and Borna disease virus (Rubin et al., 1998) develop spatial memory loss, which is associated with infection in the hippocampus. To experimentally evaluate spatial memory in WNND, infected hamsters are evaluated in a Morris water maze (MWM) test. Motor function tests are first used to identify surviving animals that have normal motor functions before entering them into the MWM test, so as to not confound the memory

results with their inability to swim normally (Smeraski et al., 2011). The MWM test consists of a circular water basin filled with cloudy water ERK phosphorylation placed under a video surveillance camera. Swimming animals are trained to remember the position of a submersible platform on which they can anticipate resting. Fifty-six percent of infected hamsters spend more time in the quadrant of the submersible platform than the other three quadrants, as compared to 92% of hamsters treated with a WNV-specific antibody (hE16) to prevent infection (Smeraski et al., 2011), which substantiates the notion that WNV-infected

persons can have memory deficits, and that these deficits can be investigated with the use of rodent models which may provide opportunities for therapeutic intervention. Due to the specialization of the procedures described in this review, and that neuro-physiological procedures are typically not found in ABSL-3 virology

laboratories, the utility of these procedures are limited by most investigators. Nevertheless, new avenues of discovery in basic neurovirology, preclinical therapeutic development, and clinical applications for viral encephalitis are likely available to those willing to make the financial and personnel investments in these neurological approaches. Plethysmography is very useful in detecting acute arbovirus-induced respiratory failure TCL in rodents, which is likely the physiological mechanism of death. Commercially available instrumentation for rodents facilitates operation after sufficient training by the supplier. Other benefits of whole body plethysmography are the use of non-sedated mice and time of the procedure that takes <2 min per mouse. If multiple chambers are available, multiple mice can be measured simultaneously. The utility for basic neurovirology is that plethysmography has been (Morrey et al., 2012 and Wang et al., 2013b), and should be useful in identifying the neuro-anatomical location of lesions responsible for respiratory failure, and the physiological, molecular, and cellular mechanisms of death. In preclinical development, this basic knowledge of pathogenesis should provide targets for therapeutic intervention.