Interleukin-4 Ameliorates the Functional Recovery of Intracerebral Hemorrhage Through the Alternative Activation of Microglia/Macrophage

Abstract

Neuro-inflammation plays an important role in the recovery of brain injury after stroke. Microglia/macrophage is the major executor in the neuro-inflammation, which can be polarized into two distinct phenotypes: injurious/toxic classical activation (M1 phenotype) and protective alternative activation (M2 phenotype). Here, we investigated whether intracerebral administration of interleukin-4 (IL-4) at an early stage could affect the activation of microglia/macrophage and the corresponding outcome after intracerebral hemorrhage (ICH). The neuro-behavior was recorded between different groups in the rat ICH model. The M1 and M2 markers were then determined by qRT-PCR, western blotting, ELISA, and immunofluorescence, respectively. We observed aberrant activation of microglia/macrophage after ICH. After intracerebral injection of IL-4, M1 activation was greatly inhibited while M2 activation was enhanced, along with improving neurobehavioral recovery from deficits after ICH. Our study showed that early intracerebral injection of IL-4 potentially promotes neuro-functional recovery, probably through enhancing the alternative activation of microglia/macrophage.

Immune changes in peripheral blood and hematoma of patients with intracerebral hemorrhage

“…IL‐17, IL‐23, IL‐4, IL‐10, and TGF‐β can be released from neurons and glial cells or the infiltrating macrophages, lymphocytes, and neutrophils in the ischemic and hemorrhagic brain . These same cytokines can also modulate the chemotaxis of inflammatory cells and the activation and polarization of M/MΦ and/or neutrophils . To further understand the characteristics of molecular inflammatory response after ICH in humans, we explored changes in concentrations of various cytokines in the peripheral blood and hematoma.…”

Modulators of microglial activation and polarization after intracerebral haemorrhage

“…94) and transforming growth factor (TGF) β1 (REF. 60) exert anti-inflammatory effects, promote M2-like microglial responses, and improve functional recovery after ICH.…”

“…50), arginase-1, Ym1 and CD206 (REF. 94) — increased within 1 day after collagenase-induced ICH, whereas mRNA levels of TGFβ 53 and both mRNA and protein levels of IL-4 (REF. 56) were substantially increased on day 3 post-ICH.…”

“…Two studies revealed changes over time in M1-like and M2-like markers in models of ICH 94,107 . We 62 and others 60 also demonstrated a similar M1 to M2 transition in both the collagenase-induced 62 and blood-induced 60 models of ICH.…”

The Role of Macrophages in Damage Recovery of Central Nervous System: New Options for Treatment of Neurological Disorders

“…Внутривенное введение клеток микроглии человека (линии HMO6) зна-чимо уменьшает неврологический дефицит в мо-дели ишемического инсульта, что ассоциируется с подавлением воспалительной реакции (умень-шение глиоза, снижение количества апоптоти-ческих клеток) и усилением экспрессии генов нейротрофических факторов (GDNF, BDNF, VEGF, BMP-7) и противовоспалительных цито-кинов (IL-4, IL-5) [60]. Поляризация в сторону М2-макрофагов на фоне интрацеребрального введения IL-4 также существенно улучшает вос-становление неврологического статуса и пове-денческих реакций в модели геморрагического инсульта [88]. С М2-поляризующей активностью связывают неврологическое улучшение в модели рассеянного склероза на фоне применения гла-тирамер ацетата [65], а также в моделях травма-тического и ишемического поражения головного мозга и различных нейровоспалительных заболе- Note.…”