Introduction to Molecular Neurosurgery

The term molecular neurosurgery has been applied to several different experimental strategies, including a variety of genetic manipulations. For the purposes of this book, the term is used to refer to the use of targeted cytotoxins to produce highly selective neural lesions. Used in this sense, the term is relevant to both experimental and potential clinical applications. The body of work addressed in this volume grew out of initial experiments in the laboratory of Donald J. Reis in 1980–1981. The initial experimental challenge was how to selectively destroy baroreceptor afferents that make up a small portion of the vagus and glossopharyngeal nerves. The strategy chosen was to develop a technique using toxin retrogradely transported from an application site on the peripheral baroreceptor nerves in the neck. First attempts used low-molecular-weight cytotoxic drugs, such as doxorubicin, and were unsuccessful. Reasoning that the initial lack of success reflected inadequate delivery of toxin to the cell bodies, a plan was developed to attach these drugs to a well-transported agent, such as wheat germ agglutinin, which at the time was introduced as a highly effective anatomical tracer (1). However, a simpler option seemed attractive. If a lectin such as wheat germ agglutinin was well transported, then perhaps a toxic lectin such as ricin or abrin would work. In retrospect, Harper and colleagues (2) had previously shown evidence for retrograde axonal transport of ricin, but this publication was discovered only after the initial suicide transport experiments applied ricin to the vagus nerve (3).