International journal of molecular sciences · 2025
Influence of Exogenous Neuropeptides on the Astrocyte Response Under Conditions of Continuous and Cyclic Hypoxia and Red Blood Cell Lysate.
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Kojder Klaudyna, Gąssowska-Dobrowolska Magdalena, Żwierełło Wojciech, Kłos Patrycja, Piotrowska Katarzyna, Wszołek Agata, Maruszewska Agnieszka, Gutowska Izabela, Chlubek Dariusz, Baranowska-Bosiacka Irena
Аннотация
Acute brain injury includes different pathologies: stroke, traumatic injury, subarachnoidale haemorhhage. In the pathophysiology of acute brain injury, secondary injury with hyperactivation of glia plays a crucial role. Activated glial cells induce prolonged inflammation that impacts the recovery and further cognitive functions of patients. In our study, we have examined the neuroprotective impact of exogenous neuropeptides-Cerebrolysin on astrocytes under different conditions. In a model that simulates central nervous system damage associated with brain injury, stroke, and subarachnoid hemorrhage, the U87MG human brain cancer (glioblastoma astrocytoma like) cells were treated with Cerebrolysin and exposed to conditions of continuous and cyclic hypoxia and red blood cell lysate overload. The activity and expression of cyclooxygenases COX-1 and COX-2 and on cytokines (IL-8, IL-1β, IL-6, IL-10) and chemokines (CCL5/RANTES, CXCL9/MIG, CCL2/MCP-1, and CXCL10/IP-10) concentration were assessed. Cerebrolysin lowers IL-1β and IL-6 and increases IL-10 under all conditions. Cerebrolysin may exhibit a neuroimmunotrophic function, reducing inflammation under conditions that replicate traumatic brain injury and hemorrhagic insults to the central nervous system. By modulating both pro-inflammatory and anti-inflammatory cytokines, Cerebrolysin can help create a more balanced immune response conducive to tissue repair and reduced secondary damage. Its ability to lower harmful mediators like IL-1β and IL-6 while enhancing protective factors such as IL-10 suggests a promising therapeutic strategy in stroke, traumatic brain injury, and subarachnoid hemorrhage. Alongside other mechanisms such as neurotrophic factor enhancement and glial cell regulation, this cytokine modulation underscores the therapeutic potential of Cerebrolysin in a variety of central nervous system disorders.