Regulatory Forum Opinion Piece*: Effective Sectioning of Spinal Cord during Regulatory-type Nonclinical Toxicity Studies

Abstract

Regulatory guidelines for nonclinical neurotoxicity testing require spinal cord evaluation but do not specify a trimming scheme. The Society of Toxicologic Pathology (STP) “best practices” for nervous system sampling during nonclinical general toxicity studies recommend that spinal cord be assessed in both longitudinal/oblique and transverse sections. This article defines possible longitudinal/oblique orientations, describes their benefits and challenges, and provides an expert recommendation regarding suitable trimming planes. Longitudinal parasagittal (LP) sections follow a vertical plane just lateral to the midline, revealing sensory and motor tracts but little gray matter. Longitudinal horizontal sections transect only sensory or motor tracts and variable quantities of gray matter. Oblique vertical (OV) sections angle across the spinal cord from side to side. Oblique transverse (OT) sections slant through from top (dorsal [posterior]) to bottom (ventral [anterior]). Compared to longitudinal planes, oblique orientations demonstrate considerably more gray matter and white matter. Current STP “best practices” explicitly recommend the LP and OV options; the OT orientation also will yield suitable sections while permitting assessment of anatomic symmetry. Selection among the LP, OT, and OV planes should be at the discretion of the study pathologist. The bilaterally symmetrical OT sections likely will be analyzed most easily by nonneuropathologists.