Effects of selective blockade of CB1 and CB2 cannabinoid receptors on neuroprotection after crushing of spinal cord ventral roots

Abstract

Peripheral nerve injuries are frequent and affect the nervous system, and may result from a wide variety of events, such as trauma, tumors, and musculoskeletal disorders. The Endocannabinoid System, involved in neuroprotection and plasticity events after injuries, has two receptors discovered so far. The first one, CB1, is more abundantly expressed in the Central Nervous System, while the second, CB2, is in immune cells, microglia, and in pathological conditions such as chronic pain. Several scientific studies over the years have been looking for drugs that act through these receptors, expanding their neuroprotective actions, however, there are indications of the non-total effectiveness of their joint action, in addition to adverse effects caused by the particular activation of each cannabinoid receptor on neuroprotection and regeneration. In order to better understand such individual effects, mice will receive the antagonist's AM-251 and AM-630 for selective blockade of CB1 and CB2, respectively. The animals will be injured by crushing their spinal motor roots L4, L5 and L6 and will be divided into four groups: (1) injury + vehicle; (2) lesion + AM-251 1.0 mg/kg; (3) lesion + AM-630 1.0 mg/kg; and (4) lesion + AM-251 1.0 mg/kg + AM-630 1.0 mg/kg. Treatment will be daily and performed for two weeks and euthanasia will occur four weeks after the surgical procedure. The spinal cord will be processed for neuronal survival, immunohistochemical and morphological Sholl analysis, with emphasis on synaptic preservation and glial reaction (astrocytes and microglia). With this, results are sought to help and improve future strategies related to the treatment of injuries and degeneration of the nervous system.(AU)