Preclinical evaluation of a novel intracerebral microinjection instrument permitting electrophysiologically guided delivery of therapeutics.

OBJECTIVE

This series of studies was designed to evaluate the function of a new neurosurgical instrument for precision injection of therapeutics within the central nervous system.

METHODS

An intracerebral microinjection instrument was designed to 1) allow multiple injections to be placed in three-dimensional space within a target structure from a single proximal brain penetration, 2) incur minimal injury at the site of injection, 3) enable accurate microvolume injections, and 4) permit electrophysiological recording during the injection procedure. Rats received injections of fluorescent microspheres or suspensions of labeled cells to test instrument function and level of induced trauma. A rodent model of stroke was used to test the instrument's ability to record electrocorticograms or somatosensory evoked potentials from normal and damaged tissue.

RESULTS

Microliter volumes of fluorescent microspheres were accurately placed at predetermined sites within the rat striatum. Reactive gliosis was markedly reduced using the intracerebral microinjection instrument when compared with standard cannulas. In a stroke model, electrophysiological recording with the instrument allowed discrimination between viable and nonviable ischemic tissue, and function of pathways or circuits was assessed using evoked potentials. Embryonic stem cells grafted immediately after electrophysiological recordings demonstrated robust long-term survival.

CONCLUSION

The intracerebral microinjection instrument enables electrophysiologically guided microinjection of therapeutics to target areas with exquisite accuracy while incurring minimal local trauma and reactive gliosis at the injection site. The instrument also permits minimally invasive, multiple injections to be disseminated in three-dimensional space within the target region from a single proximal penetration of the brain.