Editors' ChoiceNeuronal Disease

Vessel and Nerve Growth Go Hand in Hand

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Science Translational Medicine  24 Oct 2012:
Vol. 4, Issue 157, pp. 157ec192
DOI: 10.1126/scitranslmed.3005158

Diseases of the central nervous system (CNS)—most often caused by inflammation and ischemia—severely impair motor, sensory, and cognitive abilities in patients. It was previously thought that once a neural network is disrupted in CNS disease, nerve tracts will never reconnect and regain function. However, Muramatsu and colleagues now propose that neuronal remodeling does occur, in a process that is triggered by angiogenesis and the ensuing release of prostacyclins in the immediate environment of newly formed vessels.

Angiogenesis in CNS disease is driven by the initial inflammatory process. To link it to neural remodeling, the authors first demonstrated that in a mouse model of localized experimental autoimmune encephalomyelitis (EAE), an established mouse disease mimicking human multiple sclerosis, disrupted corticospinal tract fibres (CTFs) formed new pathways. Formation of new vessels within the diseased region preceded CTF rewiring. Muramatsu et al. used in vitro coculture assays to identify prostacyclin and its mediators as the soluble factors released by endothelial cells in newly formed vessels to promote neuronal growth. Specifically, endothelial-secreted prostacyclin acted on the type I prostaglandin (IP) receptor expressed by neuronal cells. In vivo in the EAE model, the authors demonstrated the importance of the neuronal-expressed IP receptor and endothelial-secreted prostacyclin for motor recovery and CTF reorganization. Interestingly, the authors were able to promote motor recovery in their animal model by treatment with locally infused iloprost—an IP receptor agonist that is already approved for treatment of patients with pulmonary hypertension.

Muramatsu et al. reveal a new endogenous pathway that drives neuronal regeneration and may be a new target for therapeutic intervention. By identifying the prostacyclin-IP receptor axis specifically, the authors were able to demonstrate that treatment of animals with CNS disease with iloprost facilitated rewiring of the injured CTF. Further studies need to clarify whether Muramatsu’s findings can be reproduced in humans and whether diseased patients would benefit from iloprost treatment. Of equal interest is timing of iloprost treatment with regard to the onset of disease and the mode of drug delivery.

R. Muramatsu et al., Angiogenesis induced by CNS inflammation promotes neuronal remodeling through vessel-derived prostacyclins. Nat. Med., 7 October 2012 (10.1038/nm.2943). [Abstract]

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