Exosomes promote restoration after intracerebral hemorrhage

Exosomes are gaining importance because they show great promise in therapeutic applications for several diseases. Particularly in stroke, exosomes derived from mesenchymal stem cell (MSC) therapy work as paracrine effectors responsible for promoting neurovascular remodeling and functional recovery. Researchers from the Autonomous University of Madrid subjected adult male rats to intracerebral hemorrhage (ICH) by intrastriatal injection of collagenase type IV; 24 h after surgery, MSC-derived exosomes were administered through the tail vein. The rats were euthanized at 7 or 28 days after treatment. Functional evaluation, lesion size, fiber tract integrity, axonal sprouting and white matter repair markers, biodistribution of exosomes and secretome proteomics were analyzed. DiI-labeled exosomes were found in the brains of the ICH-treated group and in the liver, lung and spleen. Animals receiving treatment with exosomes showed significantly better results in terms of functional recovery, lesion size, fiber tract integrity, axonal sprouting and white matter repair markers compared with the control group 28 days after stroke. Proteomics analysis of the exosomes identified more than 2000 proteins that could be implicated in brain repair function. In conclusion, white matter integrity was partly restored by exosome administration mediated by molecular repair factors. Exosomes as a treatment could be a heterogeneous process by nature and presents many factors that can influence brain plasticity in an adaptable and versatile manner.

Experimental protocol schematic

(a) Rats were subjected to an ICH by collagenase IV injection. Twenty-four hours later, rats received treatment (saline or exosomes). At 48 h, histological studies for biodistribution of exosomes were performed. (b) Rats were injected with collagenase IV to induce hemorrhagic stroke. During the same surgery, animals were inoculated with CTB as retrograde tracer. At 24 h poststroke, treatment (saline or exosomes) was administered through the tail vein. Later, 48 h after ICH and on day 7, behavior and imaging studies were evaluated. Seven days after ICH, histological studies were analyzed. (c) Rats were subjected to an ICH by collagenase IV and received treatment 24 h later (saline or exosomes). Forty-eight hours after ICH, on days 7 and 28, behavior and imaging studies were evaluated. BDA was injected as anterograde tracers 21 days after ICH. Histological studies were analyzed 28 days after ICH.