Persistent accumulation of cyclooxygenase-1 (COX-1) expressing microglia/macrophages and upregulation by endothelium following spinal cord injury

Acute inflammation following spinal cord injury results in secondary injury and pathological reorganisation of the central nervous system (CNS) archit ecture. Cyclooxygenases (Prostaglandin Endoperoxide H Synthases, PGH) are k ey enzymes in the conversion of arachidonic acid into prostanoids which med iate immunomodulation, mitogenesis, apoptosis, blood flow, secondary injury (lipid peroxygenation) and inflammation. Here, we report cyclooxygenase-l (COX-I) expression following spinal cord injury. In control spinal cords, C OX-I expression was localized by immunohistochemistry to ependymal cells, s ome neurons, inclusive dorsal and ventral root ganglion cells, few endothel ial cells but rarely to brain microglia/macrophages. In injured spinal cord s, COX-1(+) microglia/macrophages accumulated highly significantly (P<0.000 1) at peri-lesional areas and in the developing necrotic core early after i njury. Here numbers of COX-1(+) cells remained persistently elevated up to 4 weeks following injury. Further, COX-1(+) cells were located in perivascu lar Virchow-Robin spaces, between spared axons and in areas of Wallerian de generation. Double labeling experiments confirmed co-expression of COX-1 by ED-1(+) and OX-42(+) microglia/macrophages. Transiently after infarction m ost COX-1(+) microglia/macrophages coexpress the activation antigen OX-6 (M HC class II). However, the prolonged accumulation of COX-1(+) microglia/mac rophages at the lesion site enduring the acute post injury inflammatory res ponse points to a role of COX-I in tissue remodeling or secondary injury. W e have identified and localized persistent accumulation of COX-I expressing cells which might be a potential pharmacological target following spinal c ord injury. Therefore, we suggest that approaches based on: (i) short-term; and (ii) selective COX-2 blocking alone might not be a sufficient tool to suppress the local synthesis of prostanoids. (C) 2000 Elsevier Science B.V. All rights reserved.