| Traumatic peripheral nerve injury affects several highly differentiated cell types including peripheral nerve fibers, Schwann cells, perineural fibroblasts, and recruited monocytes. To promote functional recovery, the cellular responses to traumatic nerve injury must be investigated further. In this dissertation, is it reported that primary Schwann cells express EP2, EP4, IP, and TP prostanoid receptors. Stimulation of Schwann cells with either prostaglandin E2 (PGE2), and prostaglandin I2 (PGI2), or U46619, a stable metabolite of thromboxane A2 (TXA2) elevates intracellular cyclic adenosine 3′ 5′-monophosphate (cAMP) and increases the phosphorylation of cAMP response element binding protein in these cells. Prior to these studies, the physiologic sources of prostanoids for Schwann cells were not known. Schwann cells isolated from Lewis rats have been shown to produce PGE2 and TXA2 in response to inflammatory cytokines (Constable et al., 1994). Furthermore, though the cellular sources are not known, acutely prepared peripheral nerve homogenates have been shown to metabolize AA predominantly in to PGE2; but also into PGD2, PGF2α, PGI2, and TXA2 (Goswami and Gould, 1985). Studies in this dissertation show that large amounts of PGE2 and PGI 2 are produced by injured sciatic nerve. In addition, primary Schwann cells and perineural fibroblasts were found to be responsible for prostanoid synthesis following traumatic nerve injury. Finally, it was found that macrophages also contribute to PGE2 production during recruitment to injured peripheral nerve but not during the process of phagocytosing peripheral nerve debris. The studies reported in this dissertation describe a system by which Schwann cells, perineural fibroblasts, and macrophages communicate with one another following peripheral nerve injury. The large elevation in prostanoid production may coordinate the response of peripheral nerve cells to injury and the ultimate formation of an environment that supports peripheral nerve regeneration. |
