The chemokine CX3CL1/fractalkine is expressed by neurons as a transmembrane-anchored protein, which can be cleaved to yield a soluble isoform. However, the roles for these two types of endogenous CX3CL1 in neurodegenerative pathophysiology remain elusive. As such, it has been difficult to delineate the function of the two isoforms of CX3CL1, as both are natively present in the brain. In this study we examined each isoform’s ability to regulate neuroinflammation in a mouse model of Parkinson’s disease initiated by the neurotoxin 1-Methyl-4-Phenyl-1,2,3,6-Tetrahydropyridine (MPTP). We were able to delineate the function of both CX3CL1 isoforms by using AAV mediated gene therapy to selectively express synthetic variants of CX3CL1 that remain either permanently soluble or membrane-bound. In the present study we injected each CX3CL1 variant or a GFP expressing vector directly into the substantia nigra of CX3CL1−/− mice. Our results show that only the soluble isoform of CX3CL1 is sufficient for neuroprotection after exposure to MPTP. Specifically, we show that the soluble CX3CL1 isoform reduces impairment of motor coordination, decreases dopaminergic neuron loss, and ameliorates microglia activation and pro-inflammatory cytokine release, resulting from MPTP exposure. Furthermore, we show that the membrane-bound isoform provides no neuroprotective capability to MPTP-induced pathologies, exhibiting similar motor coordination impairment, dopaminergic neuron loss, and inflammatory phenotypes as MPTP-treated CX3CL1−/− mice, which received the GFP expressing control vector. Our results reveal that the neuroprotective capacity of CX3CL1 resides solely upon the soluble isoform in an MPTP-induced model of Parkinson’s disease.

Testicular prostheses are utilized to improve cosmetic outcomes and reduce the psychological impact of native tissue loss particularly related to trauma, neoplasm, or malignancy. Implant rupture is usually related to trauma and spontaneous prosthesis rupture is a rare event. We report a case of an incidental spontaneous rupture in an asymptomatic patient status post orchiectomy and silicone gel filled prosthesis insertion for left cryptorchidism. The role of imaging has become increasingly important for evaluating implant integrity. By recognizing the imaging characteristics associated with implant rupture, radiologists can aid in early complication detection prior to the onset of clinical symptoms.