QUANTITATIVE-ANALYSIS OF ACUTE AXONAL PATHOLOGY IN EXPERIMENTAL SPINAL-CORD CONTUSION

The major sensorimotor deficits that result from traumatic spinal cord injury (SCI) are due to loss of axons in ascending and descending pat hways of the white matter (WM), Experimental treatments administered a fter a standardized SCI can reduce WM loss and long-term functional de ficits, Thus, a significant proportion of WM loss occurs secondary to the mechanical injury and may be a target for therapeutic intervention . Presently, we know little of how and when secondary injury mechanism s operate in the WM after SCI, We therefore used a standardized rat mo del of clinically relevant contusion injury to examine axonal patholog y over the first 24 h by light and electron microscopy. Based on quali tative evaluation of tissue at 15 min, 4 h, and 24 h after a ''mild'' SCI produced with a weight-drop device (10 g x 2.5 cm), we selected ar eas from the ventromedial WM at the lesion epicenter for quantitative analyses, We compared axon number and the proportion of axons with var ious axoplasmic and myelin abnormalities over time after SCI, as well as the effect of axon size on degree of pathology and loss, We found b y 4 h postinjury (pi) axonal pathology was more severe than at 15 min and that a significant loss of large diameter axons had occurred; no s ignificant additional loss of axons was seen by 24 h pi, When we compa red axonal pathology after a more severe contusion (10 g x 17.5 cm), w e found a greater loss of axons at 4 h, In addition, a higher proporti on of the remaining axons demonstrated pathological alterations, We de veloped a semiquantitative Axonal Injury Index (AII) as an overall mea sure of axonal pathology that was sensitive to the effects of injury s everity at 4 h pi, The AII has greater statistical power than our indi vidual measures of axonal pathology, Our results suggest that it may b e possible to use the AII at 4 h pi to assess effects of potential the rapeutic agents on acute axonal pathology after SCI.