Stadelmann Christine, Franz Jonas, Nessler Stefan
Department of Neuropathology, University Medical Center Göttingen, Göttingen, Germany.
Curr Opin Neurol. 2025 Jun 1;38(3):173-179. doi: 10.1097/WCO.0000000000001370. Epub 2025 Apr 3.
Neuropathological studies in human brain tissue are indispensable for our understanding of disease mechanisms in multiple sclerosis (MS). They inform concepts of lesion evolution, tissue regeneration and disease progression, and ideally reveal new disease mechanisms and therapeutic targets. Here we review recent neuropathological studies that have advanced our knowledge of MS pathogenesis.
Recent cohort studies support the notion that different clinical MS disease phenotypes share underlying pathological features, and that clinical and pathological heterogeneity is derived from a variable combination of innate and adaptive inflammation, demyelinating activity, and neuroaxonal loss. Importantly, emerging technologies for spatial transcriptome analysis enable an unprecedented glimpse into the cellular composition and molecular mechanisms involved in lesion evolution. These promising technologies will help identify the identification of molecular hubs governing tissue damage and regeneration.
Recent neuropathological studies helped to identify tissue correlates of disability and disease progression. Substantial progress in molecular brain tissue analysis revealed the complexity of MS-related tissue features. Close collaboration between tissue-based, molecular, bioinformatic, pharmacologic, imaging and clinical experts is needed to continue to advance the field, particularly for the benefit of people with progressive MS.
对人类脑组织进行神经病理学研究对于我们理解多发性硬化症(MS)的疾病机制至关重要。这些研究为病变演变、组织再生和疾病进展的概念提供了依据,并且理想情况下能揭示新的疾病机制和治疗靶点。在此,我们综述了近期推进我们对MS发病机制认识的神经病理学研究。
近期队列研究支持这样一种观点,即不同的临床MS疾病表型具有共同的潜在病理特征,并且临床和病理异质性源自先天性和适应性炎症、脱髓鞘活性以及神经轴突损失的可变组合。重要的是,新兴的空间转录组分析技术使我们能够以前所未有的视角了解病变演变中涉及的细胞组成和分子机制。这些有前景的技术将有助于识别控制组织损伤和再生的分子枢纽。
近期的神经病理学研究有助于确定残疾和疾病进展的组织相关因素。分子脑组织分析的重大进展揭示了MS相关组织特征的复杂性。需要基于组织、分子、生物信息学、药理学、影像学和临床专家之间的密切合作,以继续推动该领域的发展,特别是为了进展型MS患者的利益。