Neurotrophic ACTH(4-9) analogue therapy normalizes electroencephalographicalterations in chronic experimental allergic encephalomyelitis

Chronic experimental allergic encephalomyelitis (CEAE) is an established ex perimental model for multiple sclerosis (MS). The demyelinating lesions in the white matter of the central nervous system observed in CEAE and in MS a re accompanied by various neurophysiological alterations. Among the best de fined electrophysiological abnormalities are the changes in event-related p otentials, in particular evoked potentials involving the spinal cord, i.e. motor and sensory evoked potentials. Less familiar are the changes observed in the electroencephalogram of CEAE-affected animals, which are also encou ntered in the human equivalent, MS. In the present experiment we evaluated the therapeutic value of a neurotrophic peptide treatment [H-Met(O-2)Glu-Hi s-Phe-D-Lys-Phe-OH, an ACTH(4-9) analogue] and its effect on the delayed fl ash visual evoked potentials (VEP) and power spectra of the electroencephal ogram, during a 17-week follow-up of CEAE. CEAE animals treated with the ne urotrophic peptide were protected against the development of neurological s ymptoms during the course of the demyelinating syndrome. VEPs of animals su ffering from CEAE showed a delay of the latencies of the late components wh ich was significantly counteracted by peptide treatment. The peak-to-peak a mplitude of the VEP afterdischarge recorded from CEAE animals was significa ntly increased during the course of CEAE and correlated closely with the pr ogression of the myelinopathy. Furthermore, CEAE animals showed an increase of electroencephalogram (EEG) beta activity of up to 500% as compared with the age-matched control group. This increase in beta power mainly consiste d of a prevailing 20-21 Hz peak, a frequency that normally is not dominant in control EEG recordings of the rat during passive wakefulness. All these electrophysiological phenomena were absent in ACTH(4-9) analogue-treated an imals. The present findings underscore the potential importance of a neurot rophic peptide treatment in the pharmacotherapy of central demyelinating sy ndromes, and possibly of MS.