No abstract

Brain cells produce cytokines and chemokines during the inflammatory process after stroke both in animal models and in patients. Monocyte chemoattractant protein 1 (MCP-1), one of the proinflammatory chemokines, can attract monocytes to the tissue where MCP-1 is overexpressed. However, the role of MCP-1 elevation in stroke has not been explored in detail. The authors hypothesized that elevated MCP-1 levels would lead to increased influx of monocytes and increased brain infarction size in stroke induced by middle cerebral artery occlusion with partial reperfusion. There were no differences in blood pressure, blood flow, or vascular architecture between wild-type mice and transgenic MBP-JE mice. Twenty-four to 48 hours after middle cerebral artery occlusion, brain infarction volumes after ischemia were significantly larger in MBP-JE mice than in wild-type controls and were accompanied by increased local transmigration and perivascular accumulation of macrophages and neutrophils. These results indicate that MCP-1 can contribute to inflammatory injury in stroke.

Old age is associated with enhanced susceptibility to and poor recovery from brain injury. An exacerbated microglial and astrocyte response to brain injury might be involved in poor outcomes observed in the elderly. The present study was therefore designed to quantitate the expression of markers of microglia and astrocyte activation using real-time RT-PCR, immunoblot and immunohistochemical analysis in aging brain in response to brain injury. We examined the hippocampus, a region that undergoes secondary neuron death, in aged (21-24 month) and adult (5-6 month) mice following controlled cortical impact (CCI) injury to the sensorimotor cortex. Basal mRNA expression of CD11b and Iba1, markers of activated microglia, was higher in aged hippocampus as compared to the adult. The mRNA expression of microglial markers increased and reached maximum 3 days post injury in both adult and aged mice, but was higher in the aged mice at all time points studied, and in the aged mice the return to baseline levels was delayed. Basal mRNA expression of GFAP and S100B, markers of activated astrocytes, was higher in aged mice. Both markers increased and reached maximum 7 days post injury. The mRNA expression of astrocyte markers returned to near basal levels rapidly after injury in the adult mice, whereas again in the aged mice return to baseline was delayed. Immunochemical analysis using Iba1 and GFAP antibodies indicate accentuated glial responses in the aged hippocampus after injury. The pronounced and prolonged activation of microglia and astrocytes in hippocampus may contribute to worse cognitive outcomes in the elderly following TBI.

No abstract

Iron, an essential element used for a multitude of biochemical reactions, abnormally accumulates in the central nervous system of patients with multiple sclerosis (MS). The mechanisms of abnormal iron deposition in MS are not fully understood, nor do we know whether these deposits have adverse consequences, i.e., contribute to pathogenesis. With some exceptions, excess levels of iron are represented concomitantly in multiple deep gray matter structures often with bilateral representation, while in white matter pathological iron deposits are usually located at sites of inflammation that are associated with veins. These distinct spatial patterns suggest disparate mechanisms of iron accumulation between these regions. Iron has been postulated to promote disease activity in MS by various means: 1) iron can amplify the activated state of microglia resulting in the increased production of proinflammatory mediators; 2) excess intracellular iron deposits could promote mitochondria dysfunction; and 3) improperly managed iron could catalyze the production of damaging reactive oxygen species. The pathological consequences of abnormal iron deposits may be dependent on the affected brain region and/or accumulation process. Here we review putative mechanisms of enhanced iron uptake in MS and address the likely roles of iron in the pathogenesis of this disease.