Neuroprotective effect of cocaine- and amphetamine-regulated transcript peptide in spinal cord injury in mice

• Published in: Neuropharmacology Vol. 67; pp. 126 - 135
• Main Authors: Bharne, Ashish P., Upadhya, Manoj A., Shelkar, Gajanan P., Singru, Praful S., Subhedar, Nishikant K., Kokare, Dadasaheb M.
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.04.2013
• Subjects: Animals; Cocaine- and amphetamine-regulated transcript peptide; Glial fibrillary acidic protein; Gliosis - pathology; Gliosis - physiopathology; Gliosis - prevention & control; Injections, Intraventricular; Locomotor recovery; Male; Methylprednisolone; Methylprednisolone - administration & dosage; Mice; Motor Activity - drug effects; Motor Activity - physiology; Motor Skills - drug effects; Motor Skills - physiology; Nerve Tissue Proteins - administration & dosage; Neuroprotective Agents - administration & dosage; Neurotransmitter Agents - administration & dosage; Spinal Cord Injuries - pathology; Spinal Cord Injuries - physiopathology; Spinal Cord Injuries - prevention & control; Spinal cord injury; PBS; MP; Locomotor recovery; BDNF; Glial fibrillary acidic protein; Cocaine- and amphetamine-regulated transcript peptide; i.p; Methylprednisolone; Spinal cord injury; GFAP; i.v; ANOVA; ROS; SCI; SEM; MFS; CART
• ISSN: 0028-3908; 1873-7064
• DOI: 10.1016/j.neuropharm.2012.10.028

We explored the effect of cocaine- and amphetamine-regulated transcript peptide (CART), alone and in combination with methylprednisolone (MP), on the cellular pathology and locomotor recovery of mice following spinal cord injury (SCI). While cellular pathology was evaluated in terms of spinal cord histology and profile of astrocytes following immunolabeling with antibodies against glial fibrillary acidic protein (GFAP), locomotor recovery was monitored using hindlimb motor function scoring system. At 24 h post-SCI, there was a massive loss of motor function and cysts formation in the spinal cord. The SCI mice, following 3 days and onwards, showed a significant (P < 0.001) increase in the population and hypertrophy of GFAP + astrocytes, suggesting the occurrence of reactive astrogliosis. Intra-fourth ventricular administration of CART (54–102) or intravenous treatment with MP, dose dependently improved motor function score, while CART-antibody (intra-fourth ventricular) was ineffective. This neuroprotective effect of MP was potentiated by the subeffective dose of CART and antagonized by CART-antibody. CART or MP treatment not only prevented the cysts formation, but also significantly attenuated the population of GFAP + astrocytes at days 3, 7, 14, 21 and 28 post-SCI and the hypertrophy of astrocytes at day 14 and 28. The histological consequence of SCI, like cysts formation in the spinal cord, was rapidly improved by CART and/or MP. Taken together, the data suggest that CART may exert its neuroprotective effect via inhibition of post-SCI astrogliosis and participate in the MP mediated neuroprotection. ► CART produced neuroprotective effect in SCI. ► SCI induced expression of GFAP + astrocytes was reduced by CART. ► CART prevented cysts formation and improved locomotor recovery following SCI. ► Pretreatment with CART potentiated the neuroprotective effect of MP. ► Pretreatment with CART-antibody blocked the MP mediated neuroprotection.