Age-Dependent Increase in Infarct Volume Following Photochemically Induced Cerebral Infarction: Putative Role of Astroglia

Kharlamov, Alexander; Kharlamov, Elena A.; Armstrong, David M.

doi:10.1093/gerona/55.3.b135

Cited by 55 publications

(35 citation statements)

References 38 publications

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“…The behavioral outcome in aged animals has been reported to be impaired compared with young animals (Zhang et al, 2005;Popa-Wagner et al, 2007;Petcu et al, 2008). The effect of age on the infarct size in preclinical studies has resulted in somewhat contradictory findings depending on the ischemia model used (Davis et al, 1995;Kharlamov et al, 2000;Shapira et al, 2002;Rosen et al, 2005). In this current study, the infarct size in aged mice was similar compared with young mice, a finding that is in agreement with a previously published study using a photothrombotic model of brain ischemia (Zhao et al, 2005).…”

Section: Discussionsupporting

confidence: 90%

“…It is thus still unclear whether aging exerts its effects via stimulation of excessive or dysregulated inflammatory responses. This hypothesis is supported by previous studies showing that aged animals have altered immune responses resulting from ischemic insult (Kharlamov et al, 2000;PopaWagner et al, 2007;Dinapoli et al, 2010;Sieber et al, 2011), intracerebral hemorrhage (Lee et al, 2009) or mechanical injury (Kyrkanides et al, 2001). However, mechanisms through which aging interacts with systemic inflammation to influence cerebrovascular pathologies remain unclear.…”

Section: Introductionsupporting

confidence: 62%

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Aging aggravates ischemic stroke-induced brain damage in mice with chronic peripheral infection

et al. 2013

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SummaryIschemic stroke is confounded by conditions such as atherosclerosis, diabetes, and infection, all of which alter peripheral inflammatory processes with concomitant impact on stroke outcome. The majority of the stroke patients are elderly, but the impact of interactions between aging and inflammation on stroke remains unknown. We thus investigated the influence of age on the outcome of stroke in animals predisposed to systemic chronic infection. Th1-polarized chronic systemic infection was induced in 18-22 month and 4-month-old C57BL/6j mice by administration of Trichuris muris (gut parasite). One month after infection, mice underwent permanent middle cerebral artery occlusion and infarct size, brain gliosis, and brain and plasma cytokine profiles were analyzed. Chronic infection increased the infarct size in aged but not in young mice at 24 h. Aged, ischemic mice showed altered plasma and brain cytokine responses, while the lesion size correlated with plasma prestroke levels of RANTES. Moreover, the old, infected mice exhibited significantly increased neutrophil recruitment and upregulation of both plasma interleukin-17a and tumor necrosis factor-a levels. Neither age nor infection status alone or in combination altered the ischemia-induced brain microgliosis. Our results show that chronic peripheral infection in aged animals renders the brain more vulnerable to ischemic insults, possibly by increasing the invasion of neutrophils and altering the inflammation status in the blood and brain. Understanding the interactions between age and infections is crucial for developing a better therapeutic regimen for ischemic stroke and when modeling it as a disease of the elderly.

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Section: Discussionsupporting

confidence: 90%

Section: Introductionsupporting

confidence: 62%

Aging aggravates ischemic stroke-induced brain damage in mice with chronic peripheral infection

et al. 2013

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“…Although Nissl staining suggested that the hippocampus was spared direct injury by cortical photothrombosis and FJB-positive somata were not detected in the hippocampus at any time following photothrombosis, reduced NeuN IR in the hippocampus suggested some degree of neuronal dysfunction and/or a changed phosphorylation state of the NeuN protein (Lind et al, 2005). The distribution of increased GFAP IR was similar to that previously reported for the photothrombosis model (Bidmon et al, 2001b;Kharlamov et al, 2000;Oermann et al, 2004;Schroeter et al, 1995).…”

Section: Discussionsupporting

confidence: 85%

Changes in neuropeptide Y protein expression following photothrombotic brain infarction and epileptogenesis

Kharlamov

Kelly

2007

Brain Research

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This study characterized morphological changes in the cortex and hippocampus of Sprague-Dawley rats following photothrombotic infarction and epileptogenesis with emphasis on the distribution of neuropeptide Y (NPY) expression. Animals were lesioned in the left sensorimotor cortex and compared with age-matched naïve and sham-operated controls by immunohistochemical techniques at 1, 3, 7, and 180 days post-lesioning (DPL). NPY immunostaining was assessed by light microscopy and quantified by the optical fractionator technique using unbiased stereological methods. At 1, 3, and 7 DPL, the number of NPY-positive somata in the lesioned cortex was increased significantly compared to controls and the contralateral cortex. At 180 DPL, lesioned epileptic animals with frequent seizure activity demonstrated significant increases of NPY expression in the cortex, CA1, CA3, hilar interneurons, and granule cells of the dentate gyrus. In addition to NPY immunostaining, neuronal degeneration, cell death/cell loss, and astroglial response were assessed with cell-specific markers. Nissl and NeuN staining showed reproducible infarctions at each investigated time point. FJB-positive somata were most abundant in the infarct core at 1 DPL, decreased markedly at 3 DPL, and virtually absent by 7 DPL. Activated astroglia were detected in the cortex and hippocampus following lesioning and the development of seizure activity. In summary, NPY protein expression and morphological changes following cortical photothrombosis were time-, region-and pathologic state-dependent. Alterations in NPY expression may reflect reactive or compensatory responses of the rat brain to acute infarction and to the development and expression of epileptic seizures.

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“…Studies using aged rodents demonstrated increased brain injury size and behavioral deficits, which were associated with modulation of the number or function of mononuclear phagocytes at the injury site [168,194,195]. Increased CD8 + T cells in the aged CNS were associated with compromised proinflammatory functions in microglia.…”

Section: Agingmentioning

confidence: 98%

Microglia and Monocyte-Derived Macrophages in Stroke

2016

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Historically, the brain has been considered an immune-privileged organ separated from the peripheral immune system by the blood-brain barrier. However, immune responses do occur in the brain in neurological conditions in which the integrity of the blood-brain barrier is compromised, exposing the brain to peripheral antigens and endogenous danger signals. While most of the associated pathological processes occur in the central nervous system, it is now clear that peripheral immune cells, especially mononuclear phagocytes, that infiltrate into the injury site play a key role in modulating the progression of primary brain injury development. As inflammation is a necessary and critical component for the subsequent injury resolution process, understanding the contribution of mononuclear phagocytes on the regulation of inflammatory responses may provide novel approaches for potential therapies. Furthermore, predisposed comorbid conditions at the time of stroke cause the alteration of stroke-induced immune and inflammatory responses and subsequently influence stroke outcome. In this review, we summarize a role for microglia and monocytes/macrophages in acute ischemic stroke in the context of normal and metabolically compromised conditions.

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Age-Dependent Increase in Infarct Volume Following Photochemically Induced Cerebral Infarction: Putative Role of Astroglia

Cited by 55 publications

References 38 publications

Aging aggravates ischemic stroke-induced brain damage in mice with chronic peripheral infection

Aging aggravates ischemic stroke-induced brain damage in mice with chronic peripheral infection

Changes in neuropeptide Y protein expression following photothrombotic brain infarction and epileptogenesis

Microglia and Monocyte-Derived Macrophages in Stroke

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