Glia
-
The studies on fractalkine and its unique receptor CX3CR1 in neurological disorders yielded contrasting results. We have explored the consequences of CX3CR1 deletion in ischemic (30' MCAo) mice on: (1) brain infarct size; (2) microglia dynamism and morphology; (3) expression of markers of microglia/macrophages (M/M) activation and polarization. We observed smaller infarcts in cx3cr1(-/-) (26.42 ± 7.41 mm(3) , mean ± sd) compared to wild type (36.29 ± 11.57) and cx3cr1(-/+) (34.49 ± 8.91) mice. ⋯ In cx3cr1(-/-) immunoreactivity for CD11b (M/M activation) and for CD68 (associated with phagocytosis) were decreased, while that for CD45(high) (macrophage and leukocyte recruitment) was increased. In addition, immunoreactivity for Ym1 (M2 polarization) was enhanced, while that for iNOS (M1) was decreased. Our data show that in cx3cr1(-/-) mice protection from ischemia at early time points after injury is associated with a protective inflammatory milieu, characterized by the promotion of M2 polarization markers.
-
Cyclooxygenase (COX) enzyme synthesizes prostaglandins (PGs) from arachidonic acid and exists as two major isozymes, COX-1 and COX-2. The crucial role of prostaglandins in the pathogenesis of inflammatory pain in peripheral tissue and the spinal cord has been established; however its expression dynamics after peripheral nerve injury and its role in neuropathic pain are not clear. In this study, we examined the detailed expression patterns of genes for COX, PGD2 and thromboxane A2 synthases and their receptors in the spinal cord. ⋯ Finally, we found that intrathecal injection of a COX-1 inhibitor and DP2 receptor antagonist significantly attenuated the mechanical allodynia. Our findings indicate that PGD2 produced by microglia is COX-1 dependent, and that neurons in the spinal cord can receive PGD2 from microglia following peripheral nerve injury. We believe that PGD2 signaling via DP2 signaling pathway from microglia to neurons is one of the triggering factors for mechanical allodynia in this neuropathic pain model.