Neuroprotective Effects of Gacyclidine After Experimental Photochemical Spinal Cord Lesion in Adult Rats: Dose-Window and Time-Window Effects

Abstract

The aim of this study was to evaluate the efficacy, optimal dose, and optimal time-window of gacyclidine, a novel N-methyl-D-aspartate (NMDA) receptor antagonist, in terms of its functional, histopathological, and electrophysiological effects after experimental spinal cord injury. The spinal cord of rats was damaged by a photochemical method and the animals were treated by saline or gacyclidine at doses of 1, 2.5, or 5 mg/kg 10 min after injury or gacyclidine 1 mg/kg 10, 30, 60, and 120 min after injury. The time-course of the motor score (walking and inclined-plane stability) was evaluated until day 18, and somatosensory evoked potentials were determined on day 18. The animals were then sacrificed, and the cross-sectional area of the spinal cord (at the epicenter of the injury, above and below the injury) was measured. Walking recovery was better in most of the groups treated after injury than in the untreated injured animals. Motor performances were related to preservation of a larger undamaged area of spinal cord at the level of the injury and, interestingly, with prevention of extension of the anatomical lesion above the level of the injury. Somatosensory evoked potential amplitudes were often higher in treated groups. These results confirm that gacyclidine induces dose-dependent and time-dependent attenuation of spinal cord damage after an experimental vascular lesion. Although all three doses induced neuroprotective effects, recovery was greater and very homogeneous in the group treated with 1 mg/kg. Moreover, recovery was slightly better and more homogeneous within the groups treated 10 and 30 min after injury compared to the other groups. It appears that, according to the existing evidence, NMDA antagonists are an essential component in the elaboration of a neuroprotective strategy after spinal cord trauma.

A Mouse Model of Acute Ischemic Spinal Cord Injury

“…* /1/w p , 0.05; ** /11/w w p , 0.01; *** /111 /w w w p , 0.001. (Gaviria et al, 2000b;Pencalet et al, 1993) and 5 min in Watson's studies (Prado et al, 1987), was most inadequate in mice, which constrained us to apply significantly longer irradiation times.…”

“…Since ischemia represents one of the main aspects of traumatic SCI, the infarct model developed by Watson in rats (Cameron et al, 1990;Prado et al, 1987;Watson et al, 1986) has been extremely useful in investigating this component of traumatic SCI (Bunge et al, 1994;Gaviria et al, 2000b;Olby and Blakemore, 1996;Pencalet et al, 1993;Sampath et al, 1995;Van Reempts and Borgers, 1994). Our results demonstrate that a consistent progression of behavioral and histopathological abnormalities could be established, reproducing experimentally controlled, graded ischemic SCI in mice.…”

“…The initial experiments were carried out with the 5-mm fiberoptics used in rats, having as a reference the irradiation time of our previous works, that is, 4 min (Gaviria et al, 2000b;Pencalet et al, 1993). Thus, a first and second group were irradiated for 3 and 4 min, respectively, without functional changes, which required an increase in the irradiation time (5 and 6 min, respectively), obtaining then some functional alterations.…”

“…Over the past two decades, the photochemical model of SCI, developed by Watson, has been one of the most reliable and reproducible graded experimental models of SCI in rats (Prado et al, 1987;Watson et al, 1986) widely used in neurotrauma research (Bunge et al, 1994;Gaviria et al, 2000b;Pencalet et al, 1993;Privat et al, 1994;Sampath et al, 1995;Wrathall, 1992). The aim of the present work was to adapt this model of experimental ischemic SCI to the mouse.…”

Delayed Neurologic Deficit after Thoracolumbar Kyphosis Correction: One Case Report

“…For instance, Vitamin C and E are strong antioxidant, which can provide best protection against cord ischemia [18][19][20]. A novel N-methyl-D-aspartate (NMDA) antagonist, Gacyclidine, owns its capacity for reducing the extent of an ischemic lesion and may promise its future use [21,22]. If medical managements don't reveal significant improvement of delayed neurologic compromise, surgery that return spinal cord to its former kyphotic position by releasing part of the correction may be considered [4,23].…”