Oligodendrocyte prosaposin restores subarachnoid haemorrhage-induced consciousness impairment.

Overview

1. Department of Neurosurgery & Brain and Nerve Research Laboratory, The First Affiliated Hospital of Soochow University, Soochow University, Suzhou, Jiangsu China
2. Jiangsu Key Laboratory of Drug Discovery and Translational Research for Brain Diseases, Institute of Stroke Research, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu China
3. Department of Physiology and Neurobiology, Suzhou Medical College of Soochow University, Suzhou, Jiangsu People’s Republic of China
4. Physiology and Pharmacology Department of Basic Sciences, Loma Linda University School of Medicine, Loma Linda, CA USA

Abstract

Subarachnoid haemorrhage (SAH) is a life-threatening cerebrovascular event frequently accompanied by consciousness disturbances, yet the underlying mechanisms remain poorly defined. Here, we identify oligodendrocytic prosaposin (PSAP) as a critical regulator of thalamocortical connectivity and consciousness following SAH. Using multimodal approaches, including electroencephalogram and electromyogram recordings, optogenetics, single-nucleus RNA sequencing, patch-clamp recording, and magnetic resonance imaging, we demonstrate that SAH disrupts the central lateral thalamus to medial prefrontal cortex pathway via Psap downregulation in oligodendrocytes, leading to impaired PSAP–GPR37 interactions, myelin damage and functional connectivity loss. Psap overexpression or recombinant human PSAP administration restored PSAP–GPR37 interactions, preserved myelin structure and rescued central lateral thalamus to medial prefrontal cortex connectivity after SAH, resulting in improved consciousness and spatial memory. Our findings highlight oligodendrocyte dysfunction as a key mechanism underlying SAH-induced disorders of consciousness and identify PSAP as a potential therapeutic target.

Reproduced under the paper's license (CC BY), from the paper cited above.

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Code availability

All original code has been deposited at Zenodo at 10.5281/zenodo.15275572 and is publicly available as of the date of publication. Any additional information required to reanalyse the data reported in this paper is available from the lead contact upon request.

Reproduced under the paper's license (CC BY), from the paper cited above.

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Data

Datasets cited

• geo:GSE295805, at NCBI GEO; found in “Data availability”

Data availability

Single-nucleus RNA sequencing data have been deposited at GEO and are publicly available as of the date of publication. Accession number is: GSE295805 (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE295805). All data reported in this paper will be shared by the lead contact upon request.

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Version 1, 27 September 2026: the first record

Recorded: type, language, journal, volume, issue, pages, dates, 11 authors, 1 keyword, 8 MeSH terms, 3 funders, 61 references.

Cite

This paper

Li, H., Li, X., Xu, Z., Cao, C., Lu, J., Ding, H., Bai, L., Tao, J., Peng, L., Tang, J., & Chen, G. (2026). Oligodendrocyte prosaposin restores subarachnoid haemorrhage-induced consciousness impairment. Experimental & molecular medicine, 58(7), 2184-2201. https://doi.org/10.1038/s12276-026-01764-6

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