Stins Monique F, Gramaglia Irene, Velez Joyce, Pardo Carlos A, van der Heyde Henri
Malaria Research Institute, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205, USA.
La Jolla Infectious Diseases Institute, LJIDI, San Diego, CA 92130, USA.
Cells. 2025 May 30;14(11):807. doi: 10.3390/cells14110807.
Cerebral malaria (CM) is a deadly complication of infection. Although adults with CM have a higher mortality rate, CM affects mostly children under the age of 5 years. Neurological symptoms and signs include impaired consciousness, coma, seizures, and increased intracranial hypertension. Upon survival of a CM episode, persistent neurologic deficits occur in a subset of surviving children. These sequelae include recurrent seizures, behavioral deficits, loss of developmental milestones, learning disabilities and attention deficit hyperactivity disorder, which can remain with the survivors. The underlying neuropathology of these post CM neurologic sequelae are unclear. Therefore, we probed the extensive neuronal damage that occurs in an experimental murine model of cerebral malaria (eCM), focusing on the hippocampus. In addition, we explored responses of neuro-progenitor cells (NPC's) and potential repair mechanisms. We report here that infection causes extensive neuronal damage in the hippocampus, characterized by a loss of neuronal NeuN and double cortin (DCX) immunostaining in eCM mice. On day 6 of eCM we also observed increased neurofilament light chain staining, indicative of neuronal fragmentation, which was accompanied by an increase in neurofilament light chain in CSF but not seen in plasma. A concomitant increase in the influx of neuroprogenitor cells in eCM was observed, suggesting ongoing neuronal repair.
脑型疟疾（CM）是感染的一种致命并发症。尽管成人患CM的死亡率较高，但CM主要影响5岁以下儿童。神经症状和体征包括意识障碍、昏迷、癫痫发作和颅内压升高。在CM发作存活后，一部分幸存儿童会出现持续性神经功能缺损。这些后遗症包括癫痫复发、行为缺陷、发育里程碑丧失、学习障碍和注意力缺陷多动障碍，这些问题会一直伴随幸存者。这些CM后神经后遗症的潜在神经病理学尚不清楚。因此，我们研究了在脑型疟疾实验小鼠模型（eCM）中发生的广泛神经元损伤，重点关注海马体。此外，我们还探索了神经祖细胞（NPC）的反应和潜在的修复机制。我们在此报告，感染会导致海马体中广泛的神经元损伤，其特征是eCM小鼠中神经元NeuN和双皮质素（DCX）免疫染色缺失。在eCM的第6天，我们还观察到神经丝轻链染色增加，表明神经元碎片化，同时脑脊液中神经丝轻链增加，但血浆中未观察到这种情况。同时观察到eCM中神经祖细胞流入增加，表明正在进行神经元修复。
