Intracerebral Hemorrhage Leads to Infiltration of Several Leukocyte Populations with Concomitant Pathophysiological Changes

Abstract

Intracerebral hemorrhage (ICH) is a stroke subtype with high rates of mortality and morbidity. The immune system, particularly complement and cytokine signaling, has been implicated in brain injury after ICH. However, the cellular immunology associated with ICH has been understudied. In this report, we use flow cytometry to quantitatively profile immune cell populations that infiltrate the brain 1 and 4 days post-ICH. At 1 day CD45 hi GR-1 + cells were increased 2.0-fold compared with saline controls (Pp0.05); however, we did not observe changes in any other cell populations analyzed. At 4 days ICH mice presented with a 2.4-fold increase in CD45 hi cells, a 1.9-fold increase in CD45 hi GR-1 À cells, a 3.4-fold increase in CD45 hi GR-1 + cells, and most notably, a 1.7-fold increase in CD4 + cells (Pp0.05 for all groups), compared with control mice. We did not observe changes in the numbers of CD8 + cells or CD45 lo GR-1 À cells (P = 0.43 and 0.49, respectively). Thus, we have shown the first use of flow cytometry to analyze leukocyte infiltration in response to ICH. Our finding of a CD4 T-cell infiltrate is novel and suggests a role for the adaptive immune system in the response to ICH.

RETRACTED: Regulatory T cells ameliorate intracerebral hemorrhage-induced inflammatory injury by modulating microglia/macrophage polarization through the IL-10/GSK3β/PTEN axis

“…6,25 Briefly, 3-4 hemorrhagic hemispheres were pooled for FACS analysis each time. Each hemisphere was digested in 1640 RPMI supplemented with 1 mg/mL collagenase IV (Sigma-Aldrich, C5138), 100 U/mL DNAse I (Sigma-Aldrich, D4263), 5 mM CaCl 2 , and 10% fetal bovine serum (FBS) for 40 min at 37…”

“…Meanwhile, the infiltration of inflammatory cells from the periphery further increases the inflammatory injury. [6][7][8] Inhibiting peripheral inflammatory cell infiltration using fingolimod can reduce inflammatory damage after ICH. 9,10 However, another study showed that fingolimod therapy is associated with increased neuroinflammation.…”

Erythrocyte efferocytosis modulates macrophages towards recovery after intracerebral hemorrhage

“…ICH is initiated by blood vessel rupture within brain parenchyma, resulting in mechanical and metabolic insults from the hematoma mass and blood components, respectively. These primary insults induce secondary inflammatory responses in the perihematomal region characterized by inflammatory cytokine production and leukocyte recruitment, which exacerbate brain damage (7)(8)(9). We have shown that inhibition of early inflammatory responses from MDMs ameliorates acute disability in murine ICH models (10,11), but the contribution of these cells to immune resolution and functional recovery has not been studied.…”

Erythropoietin reduces brain injury after intracerebral hemorrhagic stroke in rats

“…ICH initiates prominent inf lammatory responses, including the activation of resident glial cells and infiltration of circulating inflammatory cells into the brain (3,29,30). These inflammatory cells produce a number of proinflammatory mediators, such as TNF-α, IL-1β and IL-6 (31).…”