The neuroprotective effects of intrathecal administration of the selective N-type calcium channel blocker ziconotide in a rat model of spinal ischemia

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The neuroprotective effects of intrathecal administration of the selective N-type calcium channel blocker ziconotide in a rat model of spinal ischemia Lindsay H. Burns, PhD, Zhen Jin, BS, S.Scott Bowersox, PhD Journal of Vascular Surgery Volume 30, Issue 2, Pages 334-343 (August 1999) DOI: 10.1016/S0741-5214(99)70145-X Copyright © 1999 Society for Vascular Surgery and International Society for Cardiovascular Surgery, North American Chapter Terms and Conditions

Fig. 1 Microtubule-associated protein type II (MAP2) staining of lumbar spinal sections in a control animal (A ) and animals receiving aortic occlusions of 8 minutes (B and C ), 9 minutes (D and E ), and 10 minutes (F and G ). Sections from saline-treated animals are shown in B, D, and F . A section from an animal receiving 300 ng/kg/h ziconotide is shown in C , and E and G show spinal cord sections from animals receiving 600 ng/kg/h ziconotide. Note the lighter staining in panels B, D, and F and the preservation of MAP2 staining by ziconotide after 8- and 9-minute aortic occlusions (C and E , respectively; original magnification, 100×). Journal of Vascular Surgery 1999 30, 334-343DOI: (10.1016/S0741-5214(99)70145-X) Copyright © 1999 Society for Vascular Surgery and International Society for Cardiovascular Surgery, North American Chapter Terms and Conditions

Fig. 2 Silver-stained lumbar spinal cord sections illustrating the range of damage and the corresponding rating scale for spinal neuronal damage in animals in these experiments. A and B, A typical section with a rating of 1 (less than 5% damage). Note that silver-stained neurons are restricted to the dorsal horn. C and D, A typical section with a rating of 3 (less than 50% damage). This level of damage includes cells in the intermediate zone. E and F, An example of neuronal damage rated as 5 (75% or more damage). Note the area of cell loss in the intermediate zone and the silver-staining of a ventral horn alpha motor neuron (Original magnification of A, C, and E, 100×; original magnification of B, D, and F, 160×). Journal of Vascular Surgery 1999 30, 334-343DOI: (10.1016/S0741-5214(99)70145-X) Copyright © 1999 Society for Vascular Surgery and International Society for Cardiovascular Surgery, North American Chapter Terms and Conditions

Fig. 3 Protective effect of continuous intrathecal infusion of 600 ng/kg/h ziconotide vs. saline or 300 ng/kg/h ziconotide started 24 hours before a 9-minute aortic occlusion. A, Motor behavior (P < .0001 for 600 ng/kg/h). B, Neuronal damage indicated by silver-staining ratings of lumbar spinal cord (P < .001 for 600 ng/kg/h). C, Microtubule-associated protein type II (MAP2) staining of lumbar spinal cord (P < .0001 for 600 ng/kg/h). Journal of Vascular Surgery 1999 30, 334-343DOI: (10.1016/S0741-5214(99)70145-X) Copyright © 1999 Society for Vascular Surgery and International Society for Cardiovascular Surgery, North American Chapter Terms and Conditions

Fig. 4 Effect on motor behavior of continuous intrathecal infusion of 600 ng/kg/h ziconotide vs. saline started 24 hours before a 10-minute aortic occlusion (P < .05 for time points of 2 and 4 hours). Journal of Vascular Surgery 1999 30, 334-343DOI: (10.1016/S0741-5214(99)70145-X) Copyright © 1999 Society for Vascular Surgery and International Society for Cardiovascular Surgery, North American Chapter Terms and Conditions

Fig. 5 Effect on motor behavior of a single intrathecal bolus of 0.3 μg ziconotide vs. saline delivered 30 to 45 minutes before a 9-minute aortic occlusion (P < .05 for treatment effect in two-way analysis of variance; individual time points not significant). Journal of Vascular Surgery 1999 30, 334-343DOI: (10.1016/S0741-5214(99)70145-X) Copyright © 1999 Society for Vascular Surgery and International Society for Cardiovascular Surgery, North American Chapter Terms and Conditions