Infection After Acute Ischemic Stroke

Abstract

Background and Purpose-Infection after experimental focal ischemia may result from brain-induced immunodepression, but it is unsettled whether a similar syndrome occurs in human stroke. Summary of Review-Many patients develop infections shortly after acute stroke regardless of optimal management.Mortality is higher in these patients and the severity of stroke is the strongest determinant of the infectious risk. However, it is controversial whether infections promote neurological worsening or alternatively represent a marker of severe disease. The brain and the immune system are functionally linked through neural and humoral pathways, and decreased immune competence with higher incidence of infections has been demonstrated in several acute neurological conditions. In experimental brain ischemia, infections are associated with the activation of the autonomous nervous system and neuroendocrine pathways, which increase the strength of anti-inflammatory signals. A strong cytokinemediated anti-inflammatory response was recently observed in stroke patients at higher risk of infection, although infection could not demonstrate an independent association with the progression of the symptoms. Conclusions-The appearance of infection in patients with acute stroke obeys in part to immunological mechanisms triggered by acute brain injury. An excessive anti-inflammatory response is a key facilitating factor for the development of infection, and it is likely that this immunological response represents an adaptive mechanism to brain ischemia. Contrarily, it is unclear whether infection contributes independently to poor outcome in human stroke. Overall, a better understanding of the cross-talk between the brain and the immune system might lead to more effective therapies in patients with acute stroke.

Microglia and Monocyte-Derived Macrophages in Stroke

“…Some studies have suggested that lymphopenia and immunosuppression occur as a compensatory mechanism against brain damage by attenuating autoreactive T-cell targeting of CNS self-antigens [14,15]. Other studies have demonstrated that stroke-induced immune suppression increases the risk of secondary infections and increases mortality rates in patients [16,17]. Up to 65 % of patients with stroke suffer from pneumonia and urinary tract infections [18,19], and approximately 30 % of them die from stroke-related infections [20][21][22].…”

Clinical Trials of Immunomodulation in Ischemic Stroke

“…Moreover, several of these mechanisms are turned on with sufficient delay after ischemia onset to make them amenable to therapeutic intervention. However, there are concerns that immune modulation in patients with stroke may exacerbate poststroke immune depression and result in increased infectious complications [9][10][11][12].…”

Immunopathogenetic Aspects of Ischemic Stroke

“…Механизмы развития иммунной недоста-точности во многом связывают с активацией симпатоадреналовой системы и повышенным высвобождением глюкокортикоидов и катехо-ламинов [3,76]. Действительно, у пациентов с инсультом выявляется повышенный уровень в сыворотке крови кортизола и катехоламинов, высокая концентрация которых является пре-диктором летального исхода [3,16]. Взаимодей-ствуя с β2-адренорецепторами, катехоламины подавляют антигенпрезентирующую функцию дендритных клеток и моноцитов; индуцируют толерогенные дендритные клетки, способные вызывать анергию Т-лимфоцитов и генерацию Тreg [44].…”

“…Поэтому, учитывая на-личие адренергических рецепторов на иммунных клетках, гиперактивация симпатоадреналовой системы при инсульте во многом обусловливает развитие глубокой иммуносупрессии [132]. При-частность указанных медиаторов к развитию ин-фекционных осложнений подтверждается тем, что пациенты с повышенным уровнем кортизола и катехоламинов более чувствительны к разви-тию инфекционных осложнений [16]. Антагони-сты стероидов или β-адренергических рецепто-ров (пропанолол) в моделях экспериментального инсульта предотвращают развитие апоптоза лим-фоцитов и уменьшают чувствительность к ин-фекциям [94].…”