iMed Open Access

Roles of Astrocytes in Radiation-Induced Brain Injury: Pathophysiological Mechanisms and Therapeutic Strategies

Radiation-induced brain injury (RIBI), a common adverse effect of cranial radiotherapy for head malignancies, causes severe complications, including blood-brain barrier (BBB) disruption, neuroinflammation, cognitive decline, and radiation necrosis (RN) that impair patients’ quality of life. The pathophysiology of RIBI involves intricate crosstalk between various central nervous system (CNS) cell types, with astrocytes, the principal CNS glial cells, serving as key mediators. Under physiological conditions, they sustain brain homeostasis, but their transition to reactive phenotypes and subsequent dysfunction propel RIBI development. This review summarizes recent advances in astrocytes’ pathophysiological roles in RIBI, focusing on mechanisms like reactive astrocyte polarization, neuroinflammation, BBB impairment, radiation-induced senescence, astrocyte-mediated RN progression, and pathological crosstalk with other CNS cells. It also outlines astrocyte-targeted therapeutic strategies with preclinical efficacy, including anti-inflammatory therapies, anti-vascular endothelial growth factor A (VEGFA) interventions, TSPO ligands, RAS blockers, apolipoprotein E (ApoE) regulation, Δ133p53, and microRNAs (miRNAs), which alleviate RIBI by targeting these pathological processes. A comprehensive understanding of astrocyte-mediated mechanisms and preclinical evidence will lay the foundation for developing targeted, low-toxicity therapies to mitigate RIBI in cranial radiotherapy patients.

Therapeutic Plasma Exchange Rapidly Restores Red Blood Cell Deformability in Waldenström Macroglobulinemia

Waldenström macroglobulinemia (WM) is a lymphoplasmacytic lymphoma characterized by monoclonal immunoglobulin M (IgM) overproduction, leading to hyperviscosity syndrome and microvascular complications. While increased plasma viscosity is a well-recognized feature of WM, the impact of extreme IgM elevation on intrinsic red blood cell (RBC) mechanical properties remain incompletely characterized. Here, we report a case of WM with markedly elevated IgM associated with profound impairment of RBC deformability. Therapeutic plasma exchange rapidly reduced serum IgM levels, accompanied by parallel and sustained improvement in RBC deformability. Given the importance of RBC deformability in microvascular blood flow, these findings highlight a reversible, IgM-mediated alteration in RBC mechanics and provide novel insights into microcirculatory dysfunction in WM.

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Spontaneous Cell Fusion as the Mechanism of Cancer Progression and Metastasis

The mechanism of prostate cancer (PCa) progression and metastasis remains unclear. Spontaneous cancer cell fusion is one theory of etiology. This essay takes a reductionist approach to highlight spontaneous cancer cell fusion as the primary mechanism of PCa progression and metastasis. PCa cells can fuse with adjacent cancer cells or various bystander cells in the tumor microenvironment. The fate of the fusion hybrids is determined by the similarity of cell cycle timing between the fusing cancer cell and the cell being fused. A tumor cell with high proliferative activity, when fused with a non-proliferating neighbor, results in growth arrest. However, fusion with a proliferative cell may lead to abnormal hybrid cell division, causing the hybrid genome to undergo random recombination. This creates a hybrid derivative clone with a genotype and phenotype distinct from those of both the parental cancer cell and the cell being fused. The progression of tumor cell heterogeneity is dynamic, as the hybrid derivative clone can inherit the ability to fuse. Their fusion with various proliferative cells in the tumor microenvironment generates additional hybrid clones, each with a new genomic makeup and altered phenotype. The spontaneity of PCa cell fusogenicity enables an ever-changing tumor cell heterogeneity, which is the root cause of the pathological behavior of PCa progression and metastasis.

Spontaneous Cell Fusion as the Mechanism of Cancer Progression and Metastasis

The mechanism of prostate cancer (PCa) progression and metastasis remains unclear. Spontaneous cancer cell fusion is one theory of etiology. This essay takes a reductionist approach to highlight spontaneous cancer cell fusion as the primary mechanism of PCa progression and metastasis. PCa cells can fuse with adjacent cancer cells or various bystander cells in the tumor microenvironment. The fate of the fusion hybrids is determined by the similarity of cell cycle timing between the fusing cancer cell and the cell being fused. A tumor cell with high proliferative activity, when fused with a non-proliferating neighbor, results in growth arrest. However, fusion with a proliferative cell may lead to abnormal hybrid cell division, causing the hybrid genome to undergo random recombination. This creates a hybrid derivative clone with a genotype and phenotype distinct from those of both the parental cancer cell and the cell being fused. The progression of tumor cell heterogeneity is dynamic, as the hybrid derivative clone can inherit the ability to fuse. Their fusion with various proliferative cells in the tumor microenvironment generates additional hybrid clones, each with a new genomic makeup and altered phenotype. The spontaneity of PCa cell fusogenicity enables an ever-changing tumor cell heterogeneity, which is the root cause of the pathological behavior of PCa progression and metastasis.utf-8

Roles of Astrocytes in Radiation-Induced Brain Injury: Pathophysiological Mechanisms and Therapeutic Strategies

Radiation-induced brain injury (RIBI), a common adverse effect of cranial radiotherapy for head malignancies, causes severe complications, including blood-brain barrier (BBB) disruption, neuroinflammation, cognitive decline, and radiation necrosis (RN) that impair patients’ quality of life. The pathophysiology of RIBI involves intricate crosstalk between various central nervous system (CNS) cell types, with astrocytes, the principal CNS glial cells, serving as key mediators. Under physiological conditions, they sustain brain homeostasis, but their transition to reactive phenotypes and subsequent dysfunction propel RIBI development. This review summarizes recent advances in astrocytes’ pathophysiological roles in RIBI, focusing on mechanisms like reactive astrocyte polarization, neuroinflammation, BBB impairment, radiation-induced senescence, astrocyte-mediated RN progression, and pathological crosstalk with other CNS cells. It also outlines astrocyte-targeted therapeutic strategies with preclinical efficacy, including anti-inflammatory therapies, anti-vascular endothelial growth factor A (VEGFA) interventions, TSPO ligands, RAS blockers, apolipoprotein E (ApoE) regulation, Δ133p53, and microRNAs (miRNAs), which alleviate RIBI by targeting these pathological processes. A comprehensive understanding of astrocyte-mediated mechanisms and preclinical evidence will lay the foundation for developing targeted, low-toxicity therapies to mitigate RIBI in cranial radiotherapy patients.utf-8

Therapeutic Plasma Exchange Rapidly Restores Red Blood Cell Deformability in Waldenström Macroglobulinemia

Waldenström macroglobulinemia (WM) is a lymphoplasmacytic lymphoma characterized by monoclonal immunoglobulin M (IgM) overproduction, leading to hyperviscosity syndrome and microvascular complications. While increased plasma viscosity is a well-recognized feature of WM, the impact of extreme IgM elevation on intrinsic red blood cell (RBC) mechanical properties remain incompletely characterized. Here, we report a case of WM with markedly elevated IgM associated with profound impairment of RBC deformability. Therapeutic plasma exchange rapidly reduced serum IgM levels, accompanied by parallel and sustained improvement in RBC deformability. Given the importance of RBC deformability in microvascular blood flow, these findings highlight a reversible, IgM-mediated alteration in RBC mechanics and provide novel insights into microcirculatory dysfunction in WM.utf-8

iMed: A Global Academic Platform for Innovation, Medical Research and Translation