Insular stroke is associated with acute sympathetic hyperactivation and immunodepression

Walter, Uwe; Kolbaske, Stephan; Patejdl, Robert; Steinhagen, Volker; Abu-Mugheisib, Mazen; Großmann, Annette; Zingler, Christiana; Benecke, Reiner

doi:10.1111/j.1468-1331.2012.03818.x

Cited by 91 publications

(68 citation statements)

References 28 publications

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“…19 Stroke localization and stroke lateralization have been suggested to contribute to the extent of immunologic changes seen in patients with stroke. [27][28][29] This could explain our finding that oxidative burst was not correlated to stroke severity in our cohort.…”

Section: Discussionsupporting

confidence: 51%

Stroke Alters Respiratory Burst in Neutrophils and Monocytes

Ruhnau

Schulze

Gaida

et al. 2014

Stroke

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Background and Purpose— Stroke-induced immune alterations predispose patients to infections. Although the relationship between stroke and the adaptive immune system has been investigated in detail, to date it is unknown whether the innate immune system, which forms the first line of antibacterial defense, is also impaired in patients with stroke. Therefore, we investigated whether chemotaxis, phagocytosis, oxidative burst, degranulation of defensins, and NETosis in monocytes and in neutrophil granulocytes are altered in patients with stroke compared with controls. Methods— Sixty-three patients having acute ischemic stroke were recruited within 12 hours of symptom onset; blood was sampled on admission and on days 1, 3, 5, and 7. Thirty-seven age-matched controls were also recruited. Cell migration, phagocytosis, and oxidative burst of phagocytes were determined in vitro. Human neutrophil peptides 1 to 3 and serum metanephrine levels were measured by enzyme-linked immunosorbent assay, and NETosis was quantified by immunohistochemistry. Results— The key mechanisms required for bacterial killing, oxidative burst, and NETosis were significantly reduced in samples taken from patients with stroke compared with controls, whereas migration, phagocytic function, and defensin production remained unimpaired in monocytes and granulocytes from patients with stroke. Conclusions— Stroke-induced immune alterations include impairment of the first-line defense performed by specialized phagocytes against bacteria. The hypothesis that these changes enhance susceptibility to acquired infections is supported by our observation that on admission oxidative burst in monocytes was more impaired in patients with stroke with subsequent stroke-associated infections.

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Section: Discussionsupporting

confidence: 51%

Stroke Alters Respiratory Burst in Neutrophils and Monocytes

Ruhnau

Schulze

Gaida

et al. 2014

Stroke

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“…Because a right insular stroke is associated with an acute and prolonged sympathetic stimulation,9, 30, 31 we next evaluated the impact of the autonomic nervous system on the development of chronic cardiac dysfunction after right hemispheric tMCAO. For this purpose, we analyzed the brain tissue mRNA levels of TH, which is the rate‐limiting enzyme in catecholamine synthesis.…”

Section: Resultsmentioning

confidence: 99%

“…Thereby, autonomic dysfunction is underlying the impaired physiologic regulation of heart rate and blood pressure as well as the increased secretion of catecholamines and cortisol 6, 37, 38, 39. The insular cortex has been identified as a crucial area within the central nervous system relevant for autonomic regulation 11, 30, 40, 41, 42. Furthermore, there is increased evidence that the lateralization of the insular area is associated with autonomic responses, where the right side focuses on sympathetic and the left side on parasympathetic function 9.…”

Section: Discussionmentioning

confidence: 99%

Stroke‐induced chronic systolic dysfunction driven by sympathetic overactivity

Bieber

Werner

Tanai

et al. 2017

Annals of Neurology

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ObjectiveCardiac diseases are established risk factors for ischemic stroke incidence and severity. Conversely, there is increasing evidence that brain ischemia can cause cardiac dysfunction. The mechanisms underlying this neurogenic heart disease are incompletely understood. Although it is established that ischemic stroke is associated with cardiac arrhythmias, myocardial damage, elevated cardiac enzymes, and plasma catecholamines in the acute phase, nothing is known about the delayed consequences of ischemic stroke on cardiovascular function.MethodsTo determine the long‐term cardiac consequences of a focal cerebral ischemia, we subjected young and aged mice to a 30‐minute transient middle cerebral artery occlusion and analyzed cardiac function by serial transthoracic echocardiography and hemodynamic measurements up to week 8 after surgery. Finally, animals were treated with metoprolol to evaluate a pharmacologic treatment option to prevent the development of heart failure.ResultsFocal cerebral ischemia induced a long‐term cardiac dysfunction with a reduction in left ventricular ejection fraction and an increase in left ventricular volumes; this development was associated with higher peripheral sympathetic activity. Metoprolol treatment prevented the development of chronic cardiac dysfunction by decelerating extracellular cardiac remodeling and inhibiting sympathetic signaling relevant to chronic autonomic dysfunction.InterpretationFocal cerebral ischemia in mice leads to the development of chronic systolic dysfunction driven by increased sympathetic activity. If these results can be confirmed in a clinical setting, treating physicians should be attentive to clinical signs of heart failure in every patient after ischemic stroke. Therapeutically, the successful β‐blockade with metoprolol in mice could also have future clinical implications. Ann Neurol 2017;82:729–743

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“…Sympathetic activation following AIS appears to play a crucial part in stroke-induced immunodepression [6]. These changes are mostly prominent among patients with large strokes [31,32] and they may have a predilection for the stroke location such as the involvement of the insular cortex [35]. …”

Section: The Pathophysiology Of Sap: the Traditional Aspiration Theormentioning

confidence: 99%

Stroke-Associated Pneumonia: Major Advances and Obstacles

et al. 2013

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Background: Stroke-associated pneumonia (SAP) has been implicated in the morbidity, mortality and increased medical cost after acute ischemic stroke. The annual cost of SAP during hospitalization in the United States approaches USD 459 million. The incidence and prognosis of SAP among intensive care unit (ICU) patients have not been thoroughly investigated. We reviewed the pathophysiology, microbiology, incidence, risk factors, outcomes and prophylaxis of SAP with special attention to ICU studies. Methods: To determine the incidence, risk factors and prognosis of acute SAP, PubMed was searched using the terms ‘pneumonia' AND ‘neurology intensive unit' and the MeSH terms ‘stroke' AND ‘pneumonia'. Non-English literature, case reports and chronic SAP studies were excluded. Studies were classified into 5 categories according to the setting they were performed in: neurological intensive care units (NICUs), medical intensive care units (MICUs), stroke units, mixed studies combining more than one setting or when the settings were not specified and rehabilitation studies. Results: The incidences of SAP in the following settings were: NICUs 4.1-56.6%, MICUs 17-50%, stroke units 3.9-44%, mixed studies 3.9-23.8% and rehabilitation 3.2-11%. The majority of NICU and MICU studies were heterogeneous including different neurovascular diseases, which partly explains the wide range of SAP incidence. The higher incidence in the majority of ICU studies compared to stroke units or acute floor studies is likely explained by the presence of mechanical ventilation, higher stroke severity causing higher rates of aspiration and stroke-induced immunodepression among ICU patients. The short-term mortality of SAP was increased among the mixed and stroke unit studies ranging between 10.1 and 37.3%. SAP was associated with worse functional outcome in the majority of stroke unit and floor studies. Mortality was less consistent among NICU and MICU studies. This difference could be due to the heterogeneity of ICU studies and the effect of small sample size or other independent risk factors for mortality such as the larger neurological deficit, mechanical ventilation, and age, which may simultaneously increase the risk of SAP and mortality confounding the outcomes of SAP itself. The pathophysiology of SAP is likely explained by aspiration combined with stroke-induced immunodepression through complex humeral and neural pathways that include the hypothalamic-pituitary-adrenal axis, parasympathetic and sympathetic systems. Conclusions: A unified definition of SAP, strict inclusion criteria, and the presence of a long-term follow-up need to be applied to the future prospective studies to better identify the incidence and prognosis of SAP, especially among ICU patients.

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Insular stroke is associated with acute sympathetic hyperactivation and immunodepression

Abstract: These findings suggest a specific role of insular lesion in the pathogenesis of stroke-induced sympathetic hyperactivation and immunodepression. Neuroimaging studies applying lesion volume calculation techniques are warranted to confirm these findings.

Cited by 91 publications

References 28 publications

Stroke Alters Respiratory Burst in Neutrophils and Monocytes

Stroke Alters Respiratory Burst in Neutrophils and Monocytes

Stroke‐induced chronic systolic dysfunction driven by sympathetic overactivity

Stroke-Associated Pneumonia: Major Advances and Obstacles

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