Cellular and Molecular Events Underlying the Dysregulated Response of the Aged Brain to Stroke: A Mini-Review

Petcu, Eugen Bogdan; Sfredel, Veronica; Platt, D.; Herndon, James G.; Kessler, Christof; Popa‐Wagner, Aurel

doi:10.1159/000112845

Cited by 74 publications

(67 citation statements)

References 147 publications

(142 reference statements)

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“…This finding has implications for rehabilitation approaches following stroke in older adults. Studies have shown decreased neuroplasticity in the aging brain, which may limit the extent of recovery, 38 though it is also possible that older adults are not receiving the full extent of rehabilitative services to reach their potential. Our findings are consistent with prior studies that have found worse functional outcomes in older adults.…”

Section: Resultsmentioning

confidence: 99%

Interventional Stroke Therapies in the Elderly: Are We Helping?

Zeevi¹,

Kuchel²,

Lee³

et al. 2011

AJNR Am J Neuroradiol

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Section: Resultsmentioning

confidence: 99%

Interventional Stroke Therapies in the Elderly: Are We Helping?

Zeevi¹,

Kuchel²,

Lee³

et al. 2011

AJNR Am J Neuroradiol

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“…Age has been shown to influence the outcome of stroke in the clinical setting (Nakayama et al, 1994). 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).…”

Section: Discussionmentioning

confidence: 99%

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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“…However, based on data from experimental stroke models, it has been proposed that the timing of the cellular and genetic response to cerebral insult is dysregulated in aged animals. Thus, following stroke the critical, age-related differences apparent in the cytological response is accompanied by acceleration of the establishment of the glial scar (Petcu et al, 2008;Popa-Wagner et al, 2007). It is plausible that a similar mechanism could be at work following TBI.…”

Section: Mellergå Rd Et Almentioning

confidence: 99%

The Cerebral Extracellular Release of Glycerol, Glutamate, and FGF2 Is Increased in Older Patients following Severe Traumatic Brain Injury

Mellergård

Sjögren

Hillman

2012

Journal of Neurotrauma

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Old age is associated with a poor recovery from traumatic brain injury (TBI). In a retrospective study we investigated if the biochemical response following TBI is age dependent. Extracellular fluids were continuously sampled by microdialysis in 69 patients admitted to our NSICU following severe TBI. The concentrations of glycerol, glutamate, lactate, pyruvate, and eight different cytokines (IL-1b, IL-6, IL-10, IL-8, MIP-1b, RANTES, FGF2, and VEGF) were determined by fluorescence multiplex bead technology. Patients in the oldest age group ( ‡ 65 years) had significantly higher microdialysate concentrations of glycerol and glutamate compared to younger patients: the mean microdialysate concentration of glycerol increased from 55.9 lmol/L (25-44 year) to 252 lmol/L ( ‡ 65 years; p < 0.0001); similarly glutamate increased from 15.8 mmol/L to 92.2 mmol/L ( p < 0.0001). The lactate-pyruvate ratio was also significantly higher in the patients ‡ 65 years of age (63.9) compared with all the other age groups. The patterns of cytokine responses varied. For some cytokines (IL-1b, IL-10, and IL-8) there were no differences between age groups, while for others (MIP-1b, RANTES, VEGF, and IL-6) some differences were observed, but with no clear correlation with increasing age. For FGF2 the mean microdialysate concentration was 43 pg/mL in patients ‡ 65 years old, significantly higher compared to all other age groups ( p < 0.0001). Increased concentrations of glycerol and glutamate would indicate more extensive damaging processes in the elderly. An increase in concentration of FGF2 could serve a protective function, but could also be related to a dysregulation of the timing in the cellular response in elderly patients.

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Cellular and Molecular Events Underlying the Dysregulated Response of the Aged Brain to Stroke: A Mini-Review

Cited by 74 publications

References 147 publications

Interventional Stroke Therapies in the Elderly: Are We Helping?

Interventional Stroke Therapies in the Elderly: Are We Helping?

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

The Cerebral Extracellular Release of Glycerol, Glutamate, and FGF2 Is Increased in Older Patients following Severe Traumatic Brain Injury

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