Abstract:
Acute inflammation following spinal cord injury results in secondary injury and promotes glial scar formation (reactive astrogliosis and extracellular scar formation). Glial scar is a chemical and mechanical barrier for regenerating axons.
Cyclooxygenases (COX) are key enzymes in the conversion of arachidonic acid into prostanoids which mediate immunomodulation, mitogenesis, apoptosis, blood flow and inflammation. The non-steroidal antiinflammatory drug Indometacin is a potent non-selective cyclooxygenase inhibitor. In this study the impact of COX inhibition (Indomethacin, 1mg/kg, i.p.) on glial scar formation (reactive astrogliosis, extracellular matrix, ECM, formation) following experimental spinal cord injury in rat was investigated by immunohistochemistry. Unspecific COX inhibition over 3 and 14 days resulted in significantly reduced numbers of lesional COX-1+ and COX-2+ cells. Indometacin treatment significantly reduced numbers of activated astrocytes as compared to controls. Furthermore, at day 14, average length and width of fibronectin+ ECM structures were significantly diminished by 50%. Delay and reduction of scar formation after spinal cord injury by cyclooxygenase blockade suggests an adjuvant approach to prolong the therapeutic time frame for neuroregenerative, pharmakological and cellular interventions.