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Sergiy V. Kushchayev, Morgan B. Giers, Doris Hom Eng, Nikolay L. Martirosyan, Jennifer M. Eschbacher, Martin M. Mortazavi, Nicholas Theodore, Alyssa Panitch and Mark C. Preul

OBJECTIVE

Spinal cord injury occurs in 2 phases. The initial trauma is followed by inflammation that leads to fibrous scar tissue, glial scarring, and cavity formation. Scarring causes further axon death around and above the injury. A reduction in secondary injury could lead to functional improvement. In this study, hyaluronic acid (HA) hydrogels were implanted into the gap formed in the hemisected spinal cord of Sprague-Dawley rats in an attempt to attenuate damage and regenerate tissue.

METHODS

A T-10 hemisection spinal cord injury was created in adult male Sprague-Dawley rats; the rats were assigned to a sham, control (phosphate-buffered saline), or HA hydrogel–treated group. One cohort of 23 animals was followed for 12 weeks and underwent weekly behavioral assessments. At 12 weeks, retrograde tracing was performed by injecting Fluoro-Gold in the left L-2 gray matter. At 14 weeks, the animals were killed. The volume of the lesion and the number of cells labeled from retrograde tracing were calculated. Animals in a separate cohort were killed at 8 or 16 weeks and perfused for immunohistochemical analysis and transmission electron microscopy. Samples were stained using H & E, neurofilament stain (neurons and axons), silver stain (disrupted axons), glial fibrillary acidic protein stain (astrocytes), and Iba1 stain (mononuclear cells).

RESULTS

The lesions were significantly smaller in size and there were more retrograde-labeled cells in the red nuclei of the HA hydrogel–treated rats than in those of the controls; however, the behavioral assessments revealed no differences between the groups. The immunohistochemical analyses revealed decreased fibrous scarring and increased retention of organized intact axonal tissue in the HA hydrogel–treated group. There was a decreased presence of inflammatory cells in the HA hydrogel–treated group. No axonal or neuronal regeneration was observed.

CONCLUSIONS

The results of these experiments show that HA hydrogel had a neuroprotective effect on the spinal cord by decreasing the magnitude of secondary injury after a lacerating spinal cord injury. Although regeneration and behavioral improvement were not observed, the reduction in disorganized scar tissue and the retention of neurons near and above the lesion are important for future regenerative efforts. In addition, this gel would be useful as the base substrate in the development of a more complex scaffold.

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Sergiy V. Kushchayev, Evgenii Belykh, Yakiv Fishchenko, Aliaksei Salei, Oleg M. Teytelboym, Leonid Shabaturov, Mark Cruse and Mark C. Preul

General Mikhail Kutuzov (circa 1745–1813) brilliantly repelled Napoleon’s invasion of Russia. Honored as a national hero and a savior of Russia, Kutuzov has a unique medical story. He was shot in the head twice while fighting the Turks (1774 and 1788) and survived the serious injuries seemingly against all odds. The first bullet “ran through the head from one temple to the other behind both eyes.” The second bullet entered the cheek, destroyed upper teeth, traveled through the head, and exited the occiput. Massot, a French surgeon with the Russian army, wrote after treating Kutuzov’s seemingly two mortal wounds: “It must be believed that fate appoints Kutuzov to something great, because he was still alive after two injuries, a death sentence by all the rules of medical science.” Aided by Massot’s expert surgical technique, Kutuzov lived to become intimately engaged in events that altered world history. His health did, however, suffer significant effects due to the bullet wounds. In 1812, as Napoleon’s Grande Armée approached, Kutuzov realized he could not confront Napoleon and he strategically retreated from Moscow, submitting the French to the harsh winter and Russian cavalry. Napoleon’s devastated army retreated to Paris, and Kutuzov became the personification of Russian spirit and character. Kutuzov’s survival of two nearly mortal head wounds created the legends, additional mystery, and drama surrounding him, not the least astonishing of which was the skilled neurosurgical care that probably saved his life.

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Oral Presentations

2010 AANS Annual Meeting Philadelphia, Pennsylvania May 1–5, 2010