[Abstract Title]. - Society for Neuroscience

alance and cognitive changes which have collectively demonstrated the feasibility of
reproducing significant features of human spasticity and other disabilities in this model. Thus
this animal model became amenable to applications of rigorous outcome measures and potential
treatment approaches that can have direct translational potential. We used two rehabilitative
approaches using a custom made bicycle locomotor training and Transcranial magnetic
stimulation (TMS) to expand the evidence base for new rehabilitative interventions to document
the extent to which these can safely reduce symptoms of MS-disabilities, and how these
interventions influence the underlying neurobiology. By week-5 post-inoculation (pi, MBP in
CFA), the EAE rats revealed significant velocity-dependent ankle extensor spasticity which
contained both dynamic (higher velocities) and tonic component (at low velocities) and increased
over time (to pi week 17). Moreover, TMS motor-evoked potentials (tcMMEPs) amplitudes
increased in soleus (SOL) and tibialis anterior (TA) and forelimb flexor (FF) at pi week 3 (in
acute stage of the disease) and drastically decreased or absent (~ 50%) especially in SOL & TA
and remained increased in FF from pi week 5 through 17. Interestingly, there was a recovery in
TA tcMMEPs amplitudes at pi week 17 which was not observed in SOL. In addition, these
animals showed significant motor weakness in the forelimbs, a cognitive deficit for serial
learning in MWM, and a significant reduction in balance tested on a rotorod. Our data to date
indicate that EAE animals treated using cycle training (two 20 min. sessions for 3 weeks) or
TMS (25 single magnetic pulses with graded stimulus intensities from 30% to 70% of Max)
revealed significantly decreased spasticity, increased forelimb grip strength, improved scores for
serial learning, and increased balance performance. We propose that a significant portion of
these disabilities are companion disorders correlated with decreased noradrenergic (NE) function
in neural regions that are critical to these functions. We hypothesize that the therapeutic
treatments using locomotor training or TMS significantly improved MS symptoms through a
upragulation of NE function in selected spinal, brainstem, and cortical regions. These data
support the exploration of these treatment modalities for delaying and reducing the severity of
MS symptoms.
Disclosures: P.K. Bose, None; J. Hou, None; C. Phadke , None; R. Smith, None; R. Parmer,
None; Y. Cheng, None; P.M. Hoffman, None; W. Streit, None; F.J. Thompson, None.
Poster
252. Demyelinating Disorders: Mechanisms and Therapeutics II
Time: Sunday, November 16, 2008, 1:00 pm - 5:00 pm
Program#/Poster#: 252.10/W34
Topic: C.08.d. Therapeutic strategies
Title: Reinforced cinematic feedback for the treatment of balance disorders in multiple sclerosis