Monocytes in neonatal stroke and hypoxic‐ischemic encephalopathy: Pathophysiological mechanisms and therapeutic possibilities

Abstract

Neonatal arterial ischemic stroke (NAIS) and neonatal hypoxic‐ischemic encephalopathy (HIE) are common causes of neurological impairments in infants, for which treatment options are very limited. NAIS and HIE induce an innate immune response that involves the recruitment of peripheral immune cells, including monocytes, into the brain. Monocytes and monocyte‐derived cells have the potential to contribute to both harmful and beneficial pathophysiological processes, such as neuroinflammation and brain repair, but their roles in NAIS and HIE remain poorly understood. Furthermore, recent evidence indicates that monocyte‐derived macrophages can persist in the brain for several months following NAIS and HIE in mice, with possible long‐lasting consequences that are still unknown. This review provides a comprehensive overview of the mechanisms of monocyte infiltration and their potential functions in the ischemic brain, focusing on HIE and NAIS. Therapeutic strategies targeting monocytes and the possibility of using monocytes for cell‐based therapies are also discussed.

Inflammatory and Hematologic Liver and Platelet (HALP) Scores in Hypothermia-Treated Hypoxic–Ischemic Encephalopathy (HIE)

“…The variability in the cut-off values of markers such as NLR, PLR, and MLR across different clinics underscores the importance of contextual interpretation of these markers [20,21,24]. In our study, MLR demonstrated the most substantial predictive capability, suggesting its potential role as an efficacious tool in predicting critical clinical outcomes, facilitating early and precise interventions, and improving clinical outcomes in HIE patients.…”

“…Elevated WBC counts further accentuate this inference, emphasizing a heightened systemic inflammatory response posthypoxia. The neutrophil/lymphocyte ratio, a prominent systemic inflammatory marker, showed significant shifts [17,[21][22][23], echoing the findings of several studies that validated its prognostic utility in various conditions.…”

“…Markers like MLR, SII, and SIRI showed mixed responses, with some portraying evident variations and others, such as MLR and SII, reflecting subtler shifts [3,21,23,24]. Alterations in these markers merit further exploration given their touted significance as inflammatory and immune responses.…”

Long‐term recruitment of peripheral immune cells to brain scars after a neonatal insult

“…Monocyte-derived macrophages are involved in vascular repair, phagocytosis, immune regulation, and tissue repair (Milich et al, 2019). Their chronic recruitment to scars may have implications for the development of monocyte-based cell treatments (Garcia-Bonilla et al, 2018;Pimentel-Coelho, 2023) and immunotherapies (Rosenzweig et al, 2019).…”