Recent Infection as a Risk Factor for Cerebrovascular Ischemia

Grau, Armin J.; Buggle, Florian; Heindl, S; Steichen-Wiehn, Christianne; Banerjee, Tomas; Maiwald, Matthias; Rohlfs, Marion; Suhr, Helge; Fiehn, W.; Becher, Heiko; Hacke, Werner

doi:10.1161/01.str.26.3.373

Cited by 219 publications

(196 citation statements)

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“…5,8,35,36 Our data clearly show that although pneumonia was associated with reduced pO 2 levels (with O 2 saturation unchanged) prior to stroke that could contribute to poor outcome, intervention against both IL-1 and platelet GPIba reversed infection-induced cerebrovascular inflammation, neuronal injury, and impaired functional outcome, arguing for a major role of inflammation in brain pathologies caused by systemic effects of pulmonary S. pneumoniae infection. It is also possible that local and/or systemic inflammation could compromise perfusion and oxygen uptake/release in various organs including the lung or the brain.…”

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confidence: 65%

Streptococcus pneumoniae worsens cerebral ischemia via interleukin 1 and platelet glycoprotein Ibα

Dénes

Pradillo

Drake

et al. 2014

Annals of Neurology

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Objective: Bacterial infection contributes to diverse noninfectious diseases and worsens outcome after stroke. Streptococcus pneumoniae, the most common infection in patients at risk of stroke, is a major cause of prolonged hospitalization and death of stroke patients, but how infection impacts clinical outcome is not known. Methods: We induced sustained pulmonary infection by a human S. pneumoniae isolate in naive and comorbid rodents to investigate the effect of infection on vascular and inflammatory responses prior to and after cerebral ischemia. Results: S. pneumoniae infection triggered atherogenesis, led to systemic induction of interleukin (IL) 1, and profoundly exacerbated (50-90%) ischemic brain injury in rats and mice, a response that was more severe in combination with old age and atherosclerosis. Systemic blockade of IL-1 with IL-1 receptor antagonist (IL-1Ra) fully reversed infection-induced exacerbation of brain injury and functional impairment caused by cerebral ischemia. We show that infection-induced systemic inflammation mediates its effects via increasing platelet activation and microvascular coagulation in the brain after cerebral ischemia, as confirmed by reduced brain injury in response to blockade of platelet glycoprotein (GP) Iba. IL-1 and platelet-mediated signals converge on microglia, as both IL-1Ra and GPIba blockade reversed the production of IL-1a by microglia in response to cerebral ischemia in infected animals. Interpretation: S. pneumoniae infection augments atherosclerosis and exacerbates ischemic brain injury via IL-1 and platelet-mediated systemic inflammation. These mechanisms may contribute to diverse cardio-and cerebrovascular pathologies in humans.

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confidence: 65%

Streptococcus pneumoniae worsens cerebral ischemia via interleukin 1 and platelet glycoprotein Ibα

Dénes

Pradillo

Drake

et al. 2014

Annals of Neurology

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“…Preceding infection is (although not uniformly) also associated with worse clinical outcome (Emsley and Hopkins 2008a; Grau et al 1995;Macko et al 1996). In mice, administration of LPS prior to MCAo results in worse neurological outcome, cerebral edema and increased BBB injury (McColl et al 2008(McColl et al , 2007Denes et al 2011a).…”

Section: Infectionmentioning

confidence: 99%

The Immune System in Stroke: Clinical Challenges and Their Translation to Experimental Research

Smith

Lawrence

Rodriguez‐Grande

et al. 2013

J Neuroimmune Pharmacol

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Stroke represents an unresolved challenge for both developed and developing countries and has a huge socio-economic impact. Although considerable effort has been made to limit stroke incidence and improve outcome, strategies aimed at protecting injured neurons in the brain have all failed. This failure is likely to be due to both the incompleteness of modelling the disease and its causes in experimental research, and also the lack of understanding of how systemic mechanisms lead to an acute cerebrovascular event or contribute to outcome.Inflammation has been implicated in all forms of brain injury and it is now clear that immune mechanisms profoundly influence (and are responsible for the development of) risk and causation of stroke, and the outcome following the onset of cerebral ischemia. Until very recently, systemic inflammatory mechanisms, with respect to common comorbidities in stroke, have largely been ignored in experimental studies. The main aim is therefore to understand interactions between the immune system and brain injury in order to develop novel therapeutic approaches. Recent data from clinical and experimental research clearly show that systemic inflammatory diseases -such as atherosclerosis, obesity, diabetes or infectionsimilar to stress and advanced age, are associated with dysregulated immune responses which can profoundly contribute to cerebrovascular inflammation and injury in the central nervous system. In this review, we summarize recent advances in the field of inflammation and stroke, focusing on the challenges of translation between pre-clinical and clinical studies, and potential anti-inflammatory/immunomodulatory therapeutic approaches.

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“…As lesões de etiologia infecciosa ocorrem através de distúrbios vasculares por ação direta do agente ou pela ação de produtos envolvidos na gênese e evolução do processo inflamatório 17 . Ficam evidentes estes achados, quando concentramos nossa atenção sobre fungos e Pseudomonas sp., agentes com especial tropismo vascular, e o reconhecido poder necrotizante do último.…”

Section: Discussionunclassified

Doenças cerebrovasculares em pacientes entre 15 e 40 anos: achados neuropatológicos em 47 casos

Maggio

Montemór-Netto

Gasparetto

et al. 2001

Arq. Neuro-Psiquiatr.

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RESUMO -As doenças cerebrovasculares em pacientes entre 15 e 40 anos são pouco estudadas na literatura latino americana, principalmente no que tange aos achados neuropatológicos. Analisamos 47 encéfalos provenientes de necrópsias completas realizadas no período de 1987 a 1997 selecionados com base na faixa etária e alteração neuropatológica básica envolvendo fenômenos vasculares. Destes 47 casos analisados, 26 eram (55,3%) do sexo feminino. Quanto à distribuição etária, 12,8% (n=06) acometeram pacientes entre 15 e 20 anos, 51,1% (n=24) entre 21 e 30 anos, 36,2% (n=17) entre 31 e 40 anos. As doenças básicas que culminaram no óbito foram agrupadas, sendo mais frequentes as doenças cardíacas e hematológicas (19,2%), alterações decorrentes de complicações de gestação (12,8%), doenças infecciosas, doenças dos vasos sanguíneos e doenças neurológicas (10,7%) entre outras. As alterações neuropatológicas incluíram hérnia cerebral e/ou cerebelar (16%), edema cerebral (13,8%), hemorragia subaracnóidea (10%), infarto cerebral recente (9%), hemorragia intraparequimatosa (8%), encefalopatia hipóxico-isquêmica (3%) e eventos menos comuns como a síndrome de Sneddon e vasculite lúpica. Tais achados expressam que os fenômenos cerebrovasculares têm, nesta faixa etária, perfil próprio com estreita relação com a doença de base. PALAVRAS-CHAVE: doenças cerebrovasculares, neuropatologia, jovens. Cerebrovascular diseases in patients aged 15 to 40 years: neuropathological findings in 47 casesABSTRACT -Cerebrovascular diseases in patients between 15 and 40 years old are not a frequent subject in Latin-American literature, especially when focusing on neuropathology. We analyzed 47 brains from necropsies performed from 1987 to 1997 and selected on a basis of age and the presence of vascular pathology. From the 47 analyzed brains, 26 belonged to females (55.3%). When distributed among age groups, 12.8% (n=6) affected patients from 15 to 20 yo, 51,1% (n=24) from 21 to 30 yo, 36,2% (n=17) from 31 to 40 yo. The underlying diseases were: cardiac and haemathologic (19.2%), pregnancy complications (12.76%), infections, diseases of blood vessels and neurological (10.1% each) amongst others. The neuropathological abnormalities included cerebral and/or cerebellar herniation (16%), cerebral edema (13.8%), subarachnoid hemorrhage (10%), recent cerebral infarction (9%), intraparenchymatous hemorrhage (8.14%), hypoxic-ischemic encephalopathy (3%) and other events such as Sneddon syndrome and Lupus vasculitis. These findings express that the cerebrovascular phenomena in this age group are unique and closely related with the underlying disease.KEY WORDS: cerebrovascular diseases, neuropathology, youth. Fenômenos cerebrovasculares em pacientes jovens vêm, gradativamente, recebendo atenção dos pesquisadores, em virtude de seus mecanismos etiopatogênicos serem distintos em relação à contraparte nos idosos [1][2][3][4] . Quando presentes, estes fenômenos mostram íntima correlação com a doença básica principal do paciente, a qual culminou no óbito 5-7 .Apresen...

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Recent Infection as a Risk Factor for Cerebrovascular Ischemia

Abstract: Recent infection, primarily of bacterial origin, may be a risk factor for cerebrovascular ischemia in older as well as younger patients.

Cited by 219 publications

References 33 publications

Streptococcus pneumoniae worsens cerebral ischemia via interleukin 1 and platelet glycoprotein Ibα

Streptococcus pneumoniae worsens cerebral ischemia via interleukin 1 and platelet glycoprotein Ibα

The Immune System in Stroke: Clinical Challenges and Their Translation to Experimental Research

Doenças cerebrovasculares em pacientes entre 15 e 40 anos: achados neuropatológicos em 47 casos

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