GM1 reduces injury-induced metabolic deficits and degeneration in the rat optic nerve. Invest Ophthalmol Vis Sci

This study demonstrates the earliest reported effects of GM1 treatment on crush-injured axons of the mammalian optic nerve. GM1, administered intraperitoneally immediately after injury, was found to reduce the injury-induced metabolic deficit in nerve activity within 2 hr of injury, as measured by changes in the nicotine-amine adenine dinucleotide redox state. After 4 wk, transmission electron microscopy 1 mm distal to the site of injury revealed a sevenfold increase in axonal survival in GM1-treated compared to untreated injured nerves. These results emphasize the beneficial effect of GM1 on injured optic nerves as well as the correlation between immediate and long-term consequences of the injury. Thus, these results have implications for treating damaged optic nerves. Invest Ophthalmol Vis Sci 33: 3586-3591,1992. Injury of mammalian optic nerves leads to axonal degeneration followed by a loss of retinal ganglion cells, with failure of axonal regrowth. 1 " 3 Initial degeneration of the injured nerve probably results from direct neuronal damage. The associated physiologic and biochemical events that occur in the nerve immediately after injury probably are responsible for the subsequent degeneration, not only of directly injured axons but also of those that escaped the primary damage. These events may contribute significantly to the long-term functional outcome. Moreover, the events that take place at the site of the injury eventually determine the environment encountered by the regrowing axons. 4 " 9 This presumably will influence the ability of the injured nerve to regenerate. 410 The purpose of the present study was to examine the ability of GM1 to attenuate early injury-induced deficits in nerve function and hence the long-term morphologic outcome of injury. Accordingly, we examined the effect of GM1 on early post-traumatic metabolic changes occurring at the injury site as well as on the subsequent axonal morphology. GM1 was chosen based on reports of its effectiveness in vivo at reducing injury-induced behavioral Materials and Methods Metabolic Studies Animal preparation: Animals were used according to the ARVO Resolution on the Use of Animals in Research. Male Sprague-Dawley rats weighing 300-400 g were anesthetized with sodium pentobarbitone (35 mg/kg intraperitoneally). A cannula was introduced into the trachea for artificial ventilation, when required. With the animal's head held in place by a head holder, a lateral canthotomy was performed under a binocular operating microscope and the conjunctiva was incised lateral to the cornea. After the retractor bulbi muscles were separated, the optic nerve was identified and 3-3.5 mm was exposed near the eyeball by blunt dissection. The dura was left intact and care was taken not to injure the nerve. The first part of a light guide holder was inserted under the optic nerve and the nerve was gently eased into the light guide canal. The second part then was fixed in place so that the light guide was located on the surface Downloaded from iovs.arvojournals.org on 07/02/201