ABSTRACT
A one-year-old female cat was unable to stand. Magnetic resonance imaging was performed, and an enlargement of the lateral, third, and fourth ventricles and syringomyelia were detected. The cat was diagnosed with an isolated fourth ventricle (IFV) with syringomyelia. The serum isoantibody test for the feline infectious peritonitis (FIP) virus was 1:3,200. After the cat died, a pathological examination revealed nonsuppurative encephalomyelitis. We suspected that the IFV, detected in the cat, was associated with FIP encephalomyelitis. To our knowledge, there has been no report on IFV in veterinary medicine.
Subject(s)
Feline Infectious Peritonitis/complications , Fourth Ventricle/pathology , Syringomyelia/veterinary , Animals , Cats , Fatal Outcome , Feline Infectious Peritonitis/pathology , Feline Infectious Peritonitis/therapy , Feline Infectious Peritonitis/virology , Female , Fourth Ventricle/virology , Syringomyelia/complications , Syringomyelia/therapy , Syringomyelia/virology , Tomography, X-Ray Computed/veterinaryABSTRACT
Future gene therapy for brainstem variant amyotrophic lateral sclerosis may be technically difficult if gene therapy vectors are injected near vital cardiorespiratory centers or if large portions of the tongue and pharyngeal muscles must be peripherally injected for retrograde transport of vectors to motor neurons. In this study we show that it is possible to deliver recombinant proteins to the hypoglossal nuclei without brainstem or muscle injections, by taking advantage of enhanced uptake of fusion proteins containing the protein transduction domain from the human immunodeficiency virus TAT protein. Adenoviral vectors expressing either TAT-modified or native beta-glucuronidase (beta-gluc) were injected into the lateral cerebral ventricles of mice, transducing ventricular epithelium down to the level of the obex in the brainstem. There was significant uptake into the hypoglossal nuclei of TAT-modified but not native beta-glucuronidase. The TAT-modified beta-gluc appeared to encompass half or more of the hypoglossal nuclei as visualized by retrograde labeling with cholera toxin subunit b in adjacent sections. TAT-modification of gene products may allow a relatively non-invasive approach to brainstem gene therapy via cerebroventricular injection.