Extracellular Mitochondria for Therapy and Diagnosis in Acute Central Nervous System Injury

Abstract

Objective: Acute central nervous system (CNS) injury after stroke and trauma remains a clinical challenge with limited diagnostic and therapeutic approaches. In this article, we review studies suggesting that after CNS injury, mitochondria can be released into extracellular space as a "help-me" signal to augment recovery. Results are taken from experimental studies in cell and animal models and an initial proof-of-concept analysis in humans suggesting the functional relevance of extracellular mitochondria after acute CNS injury.

Observations: After acute CNS injury, (1) mitochondria may be released into extracellular space, (2) mitochondria may be transferred between cells, and (3) levels of extracellular mitochondria may serve as potential biomarkers for recovery.

Conclusions and relevance: Further translational and clinical studies are warranted to assess the overall hypothesis of using extracellular mitochondria as a therapy and biomarker in the CNS after stroke and trauma.

Figure.. Extracellular Mitochondria for Therapy and Diagnosis

Mitochondrial release or transfer has been reported in mesenchymal stem cells (MSC), neurons,^, astrocytes,^, microglia, and endothelial cells.^, Whether other central nervous system (CNS) cells can also participate in this phenomenon should be investigated in future studies. Transplant of exogenous mitochondria may offer novel ways to augment neurorepair after CNS injury.^, To complement transplant approaches, extracellular mitochondria may also be preconditioned to further amplify therapeutic benefit. Finally, insofar as extracellular mitochondria may reflect intracellular metabolism, they may also represent a novel class of biomarkers in the CNS. EPC indicates endothelial progenitor cells; NSC, neuronal stem cells; OPC, oligodendrocyte precursor cells.