Intracerebral haemorrhage (ICH) is a devastating stroke subtype lacking effective therapies. Understanding key pathological processes related to acute brain damage will help deliver better outcomes for ICH. Herein we provide evidence that myeloid cell trafficking to the parenchyma is a conserved feature of ICH in clinical and experimental settings. Consistent with others, we show monocytes contribute to acute brain damage following collagenase-induced murine ICH. Using RNA-seq, we identify the pro-inflammatory cytokine interleukin-1 (IL-1) as a potential upstream regulator of the acute inflammatory response, with histological data pinpointing mononuclear phagocytes as the principle cellular source of IL-1 in patient and animal tissue. In agreement, inhibition of IL-1 receptor 1 (IL-1R1) with IL-1 receptor antagonist (IL-1Ra) reduced recruitment of myeloid cells. However, IL-1R1 inhibition also worsened neuromotor outcomes and reduced cerebral blood flow (CBF) to the affected hemisphere. Thus, we reveal dichotomous actions of IL-1-dependent inflammation following brain haemorrhage. Although IL-1 regulates myeloid cell trafficking, it also appears to regulate CBF. Therefore, further investigation into the consequences of IL-1 signalling following brain haemorrhage is required to clarify future therapeutic options.
Barrington et al. (Thu,) studied this question.