Role of lipocalin 2 in stroke

Neurobiol Dis. 2023 Apr:179:106044. doi: 10.1016/j.nbd.2023.106044. Epub 2023 Feb 17.

Abstract

Stroke is the second leading cause of death worldwide; however, the treatment choices available to neurologists are limited in clinical practice. Lipocalin 2 (LCN2) is a secreted protein, belonging to the lipocalin superfamily, with multiple biological functions in mediating innate immune response, inflammatory response, iron-homeostasis, cell migration and differentiation, energy metabolism, and other processes in the body. LCN2 is expressed at low levels in the brain under normal physiological conditions, but its expression is significantly up-regulated in multiple acute stimulations and chronic pathologies. An up-regulation of LCN2 has been found in the blood/cerebrospinal fluid of patients with ischemic/hemorrhagic stroke, and could serve as a potential biomarker for the prediction of the severity of acute stroke. LCN2 activates reactive astrocytes and microglia, promotes neutrophil infiltration, amplifies post-stroke inflammation, promotes blood-brain barrier disruption, white matter injury, and neuronal death. Moreover, LCN2 is involved in brain injury induced by thrombin and erythrocyte lysates, as well as microvascular thrombosis after hemorrhage. In this paper, we review the role of LCN2 in the pathological processes of ischemic stroke; intracerebral hemorrhage; subarachnoid hemorrhage; and stroke-related brain diseases, such as vascular dementia and post-stroke depression, and their underlying mechanisms. We hope that this review will help elucidate the value of LCN2 as a therapeutic target in stroke.

Keywords: Glial activation; Intracerebral hemorrhage; Ischemic stroke; Lipocalin 2; Neuroinflammation; Subarachnoid hemorrhage; White matter injury.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Astrocytes / metabolism
  • Brain / metabolism
  • Brain Injuries* / metabolism
  • Humans
  • Lipocalin-2 / metabolism
  • Lipocalins / metabolism
  • Stroke* / pathology

Substances

  • Lipocalin-2
  • Lipocalins
  • LCN2 protein, human