USE OF A FLUORINATED CANNABIDIOL DERIVATIVE (HUF-101) AFTER ROOT AXOTOMY: NEUROPROTECTION, IMMUNOMODULATION AND FUNCTIONAL RECOVERY

Abstract

Central nervous system injuries are highly complex, in terms of consequences and treatment management, due to the sensitivity and degree of interaction of its components. In view of the urgency of effective treatments after spinal cord injuries, different molecules have been investigated. In this context, cannabidiol (CBD) proved to be efficient in several models, in which it contributed significantly to neuroprotection and immunomodulation. Since then, efforts have been made to increase the effectiveness of CBD through changes in its molecular structure, generating synthetic derivatives. The effectiveness of synthetic fluorinated cannabidiol (HUF-101) in the same applications as CBD allows dose reduction, with better control of putative side effects, with even more significant results expected. Therefore, the present study aims at investigating the effectiveness of HUF-101 in mitigating retrograde responses in the spinal cord after ventral root crush (VRC) in adult mice. For this, C57BL/6J female mice, 6-8 weeks of age, will be divided into three experimental groups: VRC + vehicle (n=15), VRC + CBD (15mg/kg, i.p./daily for 14 days; n=15); VRC + HUF-101 (5mg/kg, i.p./daily for 14 days; n=15). The effectiveness of the treatments will be evaluated 2 and 8 weeks after the injury, using immunohistochemistry (glial reactivity and synaptic preservation), Nissl staining (motoneuron survival), electroneuromyography, gait analysis (CatWalk system) and RT-qPCR.