The MUNE is calculated as the average voltage of the increments divided into the CMAP (Shefner et al., 2006 and Shefner et al., 2002). The use of MUNE procedure successfully identifies slight motor function deficits where there is visually no overt paresis or paralysis, where there is paresis, or where the level of MUNE suppression is greatest with overt paralysis (Siddharthan et al., 2009) (Fig. 1). In this figure one can see the uninfected
hamster #617 has normal detectable M-waves with incremental jumps in the amplitude of the M-wave, whereas the WNV-infected #663 hamster does not show these features. In a study Dabrafenib mouse investigating the progression of WNV-induced MUNE suppression, MUNE is suppressed beginning at day 9 after subcutaneous WNV challenge, and continues beyond day 92 (Siddharthan
et al., 2009). To our knowledge this is the first animal model of WNV long-term neurological sequelae. Additionally, these studies reveal that reduced staining of cholineacetyltransferase in the motor neuron cell bodies strongly correlates with MUNE suppression at day 10, whereas the total number of neurons does not correlate, which suggests that loss the of motor neuron functions contributes more to motor deficits than simply death of neurons at http://www.selleckchem.com/products/sch-900776.html this point of disease progression. To confirm that defective motor neurons, not axonal degeneration, are the likely cause of the MUNE suppression, nerve conduction velocity (NCV) is performed, which is a measurement of the velocity that action potentials travel through motor and sensory fibers. NCV is obtained in WNV-infected hamsters by measuring the time-delay between stimulation of the sciatic nerve to measurement of the EMG of the gastrocnemius muscle. The time-delay of demyelinated axons are slower than normal axons. An experiment with
WNV-infected rodents demonstrated that axons or myelin sheaths are not degenerated, because the NCV is not slower in WNV-infected rodents (Wang et al., Thalidomide 2011). Therefore, therapeutic intervention should focus on treating motor neuron dysfunction and not demyelination. The advantage of the MUNE procedure is that it successfully detects WNV-induced motor function deficits specifically in hamsters where other electrophysiological procedures, such as H-reflex (unpublished data), fail due to technical or biological limitations. The disadvantage of the MUNE procedure in WNV-infected hamsters is that it requires 1–2 h to assay each hamster, and the detection of the incremental MUNE steps is subjective for each operator. An optogenetics approach has also been employed to measure motor function deficits. Transgenic mice are used that express the light-gated ion channel, channelrhodopsin-2 (ChR2).