d Neurosurg 71:403-416, 1989 The effect of nimodipine and dextran on axonal function and blood flow following experimental spinal cord injury MICHAEL G. FEHLINGS, M.D., PH.D., CHARLES H. TATOR, M.D., PH.D., F.R.C.S.(C), AND R. DEAN LINDEN, PH.D. Canadian Paraplegic Association Spinal Cord Injury Research Laboratory, Division of Neurosurgery, and Playfair Neuroscience Unit, Toronto Western Hospital and University of Toronto, Toronto, Ontario, Canada u- There is evidence that posttraumatic ischemia is important in the pathogenesis of acute spinal cord injury (SCI). In the present study spinal cord blood flow (SCBF), measured by the hydrogen clearance technique, and motor and somatosensory evoked potentials (MEP and SSEP) were recorded to evaluate whether the admin- istration of nimodipine and dextran 40, alone or in combination, could increase posttraumatic SCBF and im- prove axonal function in the cord after acute SCI. Thirty rats received a 53-gm clip compression injury on the cord at T-1 and were then randomly and blindly allocated to one of six treatment groups (five rats in each). Each group was given an intravenous infusion of one of the following over 1 hour, commencing 1 hour after SCI: placebo and saline; placebo and dextran 40; nimodipine 0.02 mg/kg and saline; nimodipine 0.02 mg/kg and dextran 40; nimodipine 0.05 mg/kg and saline; and nimodipine 0.05 mg/kg and dextran 40. The preinjury physiological parameters, including the SCBF at T-1 (mean + standard error of the mean: 56.84 + 4.51 ml/100 gm/min), were not significantly different (p > 0.05) among the treatment groups. Following SCI, there was a significant decrease in the SCBF at T-1 (24.55 + 2.99 ml/100 gm/min; p < 0.0001) as well as significant changes in the MEP recorded from the spinal cord (MEP-C) (p < 0.0001), the MEP recorded from the sciatic nerve (MEP-N) (p < 0.0001), and the SSEP (p < 0.002). Only the combination of nimodipine 0.02 mg/kg and dextran 40 increased the SCBF at T-1 (43.69 _+6.09 ml/100 gm/min; p < 0.003) and improved the MEP-C (p < 0.0001), MEP-N (p < 0.04), and SSEP (p < 0.002) following SCI. With this combination, the changes in SCBF were significantly related to improvement in axonal function in the motor tracts (p < 0.0001) and somatosensory tracts (p < 0.0001) of the cord. This study provides quantitative evidence that an increase in posttraumatic SCBF can significantly improve the function of injured spinal cord axons, and strongly implicates posttraumatic ischemia in the pathogenesis of acute SCI. KEY WORDS " spinal cord injury 9 axon 9 nimodipine 9 dextran 9 rat T HERE is evidence that spinal cord injury (SCI) in the acute phase is caused by two separate mech- anisms: the initial mechanical damage and secondary changes due to vascular or biochemical ef- fects. 2"6"36"37 Indeed, measurements of spinal cord blood flow (SCBF) 2"9"12"18"19"35"47 as well as microangiographic studies 4"H'47 have shown ischemia at and extending away from the injury site. With recording of SCBF and motor and somatosensory evoked potentials (MEP's and SSEP's) from the cord with intraspinal microelec- trodes, Fehlings, et al., ~'~ recently characterized the relationships among the severity of SCI, the extent of posttraumatic cord ischemia, and the resultant changes in axonal function. Their data showed that the reduc- tion in posttraumatic SCBF varied as a linear function of injury severity and that axonal dysfunction after SCI was related both to the force of cord injury and to the degree of ischemia. These data suggested that it may be possible to improve axonal function after SCI by in- creasing the posttraumatic SCBF. To date, this hypoth- esis has not been validated. There is considerable evidence that Ca ++ ions play a key role in the pathogenesis of posttraumatic ischemia and ischemic cell death. ~'5 For example, ischemic de- polarization of cell membranes is associated with an in- tracellular shift of Ca ++ which promotes smooth-mus- cle contraction and vasospasm, impairs mitochondrial function, and enhances the production of vasoactive prostanoids. 2~ Nimodipine, a dihydropyridine cal- cium channel blocker, has recently been shown to in- crease posttraumatic SCBF, '~ although the effect on re- covery of posttraumatic axonal function is not known. J. Neurosurg. / Volume 71/September, 1989 403