Decreased myeloperoxidase expressing cells in the aged rat brain after excitotoxic damage

Abstract

Brain aging is associated to several morphological and functional alterations that influence the evolution and outcome of CNS damage. Acute brain injury such as an excitotoxic insult induces initial tissue damage followed by associated inflammation and oxidative stress, partly attributed to neutrophil recruitment and the expression of oxidative enzymes such as myeloperoxidase (MPO), among others. However, to date, very few studies have focused on how age can influence neutrophil infiltration after acute brain damage. Therefore, to evaluate the age-dependent pattern of neutrophil cell infiltration following an excitotoxic injury, intrastriatal injection of Nmethyl-D-aspartate was performed in young and aged male Wistar rats. Animals were sacrificed at different times between 12 hours post-lesion (hpl) to 14 days post-lesion (dpl). Cryostat sections were processed for myeloperoxidase (MPO) immunohistochemistry, and double labeling for either neuronal cells (NeuN), astrocytes (GFAP), perivascular macrophages (ED-2), or microglia/macrophages (tomato lectin histochemistry). Our observations showed that MPO+ cells were observed in the injured striatum from 12 hpl (when maximum values were found) until 7 dpl, when cell density was strongly diminished. However, at all survival times analyzed, the overall density of MPO+ cells was lower in the aged versus the adult injured striatum. MPO+ cells were mainly identified as neutrophils (especially at 12 hpl and 1 dpl), but it should be noted that MPO+ neurons and microglia/macrophages were also found. MPO+ neurons were most commonly observed at 12 hpl and reduced in the aged. MPO+ microglia/macrophages were the main population expressing MPO from 3 dpl, when density was also reduced in aged subjects.These results point to neutrophil infiltration as another important factor contributing to the different response of the adult and aged brain to damage, highlighting the need of using aged animals for the study of acute agerelated brain insults.

Selective estrogen receptor modulators regulate reactive microglia after penetrating brain injury

“…These observations are supported by other reports, where microglia is found reduced in aged rat brain following excitotoxic damage (Campuzano et al, 2011), intracerebral hemorrhage (Wasserman and Schlichter, 2008) and with normal aging (Cerbai et al, 2012). Although our results indicate that reactive microglia is decreased in aged animals, and that SERMs lowered this number, the reactive-like state of microglia, assessed by fractal analysis, in aged subjects is higher than that from young animals.…”

Cerebral inflammation and mobilization of the peripheral immune system following global hypoxia-ischemia in preterm sheep

“…Although microglia can also produce MPO, neutrophils and microglia can be easily distinguished by intensity of staining, localization and morphology [29-31]. Following global HI the total number of MPO-positive cells inside or adjacent to the cerebral vasculature significantly increased in the hippocampus (Figure  8A-C); sham geometric mean: 2.0 cells/field of view (FOV) (95% CI 1.7; 2.4) versus HI geometric mean: 8.5 cells/FOV (95% CI 2.7; 9.9), P <0.001.…”

Interleukin‐10 overexpression does not synergize with the neuroprotective action of RGD‐containing vectors after postnatal brain excitotoxicity but modulates the main inflammatory cell responses

“…Correlating with the IL‐10‐mediated increase in lesion volume and neurodegeneration, we observed, at 12 hpl, an increase in MPO + cells in the lesioned tissue with the morphological characteristics of neutrophils, the main cell type expressing the enzyme MPO at this early postlesion survival time after stroke or excitotoxicity (Breckwoldt et al,2008; Campuzano et al,2011). Previous reports have described neutrophil accumulation after acute damage to the postnatal CNS (Lawson and Perry,1995; Hudome et al,1997; Palmer et al,2004), which are thought to induce injury exacerbation by reducing the microvascular flow and releasing inflammatory and cytotoxic molecules (Kochanek and Hallenbeck,1992; Hartl et al,1996; Acarin et al,2002).…”