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- von Euler, Mia, 1967-, et al.
(author)
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No protective effect of the NMDA antagonist memantine in experimental spinal cord injuries
- 1997
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In: Journal of Neurotrauma. - New York, USA : Mary Ann Liebert. - 0897-7151 .- 1557-9042. ; 14:1, s. 53-61
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Journal article (peer-reviewed)abstract
- We have investigated the effect of memantine, a clinically used NMDA receptor antagonist, in two experimental animals models of spinal cord injury. The lesions were laser-induced photothrombosis to induce focal spinal cord ischemia and clip compression to mimic traumatic spinal cord injury. Pre- or posttreatment of rats with a dose of memantine (20 mg/kg ip) previously shown to be neuroprotective in cerebral ischemia, failed to affect both the neurological and morphological outcome of ischemic spinal cord injury. Likewise, memantine had no effects on neurological and morphological outcome after experimental traumatic injury. In view of the regional heterogeneity of NMDA receptors, the affinity of memantine for spinal cord NMDA receptors was also determined by studying displacement of [3H] (+)-5-methyl-10,11-dihydro-5-H-dibenzo[a,d]cyclohepten-5-10-imine (MK-801) to rat and human spinal cord homogenates. We found that memantine had an affinity for NMDA receptors in the spinal cord (Ki = 0.58 microM) that was significantly lower compared to that of the cerebral cortex (Ki = 0.23 microM) and that the affinity for NMDA receptors in human spinal cord was even lower. We conclude that in view of available data, memantine should not be chosen for clinical studies on neuroprotection in spinal cord injuries and that the lack of protective effect is most likely due to insufficient affinity of memantine for spinal cord NMDA receptors.
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| 6. |
- von Euler, Mia, 1967-, et al.
(author)
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Clip compression injury in the spinal cord : a correlative study of neurological and morphological alterations
- 1997
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In: Experimental Neurology. - New York, USA : Academic Press. - 0014-4886 .- 1090-2430. ; 145:2 Pt 1, s. 502-510
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Journal article (peer-reviewed)abstract
- Rats subjected to experimental spinal cord compression of different degrees induced by aneurysm clips were neurologically tested 3 and 5 weeks postinjury. The development of spinal cord tissue destruction over time was similar to what has been described for other experimental spinal cord injuries with characteristics such as early edema, axonal swelling, and later necrosis. Three weeks after injury a reactive gliosis was found at the injury epicenter and regenerating axons could be identified in the otherwise necrotic cavity. The extent of degeneration was highly correlated with the closing force of the aneurysm clip. The results of a number of neurological tests were correlated to the degree of clip-induced compression, to lesion volume, and to the remaining area of white matter at the epicenter. The neurological tests with the highest correlation to morphological descriptors were beam walk (r(s) = 0.89-0.95) and motor performance score (r(s) = 0.88-0.92). We conclude that the motor performance score, previously validated for photochemically induced ischemic spinal cord injuries, is equally suitable for clip compression injuries as a fast and reliable neurological test paradigm.
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| 7. |
- von Euler, Mia, 1967-, et al.
(author)
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Morphological characterization of the evolving rat spinal cord injury after photochemically induced ischemia
- 1997
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In: Acta Neuropathologica. - : Springer. - 0001-6322 .- 1432-0533. ; 94:3, s. 232-239
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Journal article (peer-reviewed)abstract
- We have characterized the evolving morphological changes in the adult rat spinal cord following photochemically induced spinal cord ischemia. In cresyl violet-stained sections, disintegration of the tissue at the epicenter was evident at 6 h. This was preceded at 1 h post ischemia by an albumin immunoreactivity. The albumin immunoreactivity was increased at 6 and even more so at 24 h post ischemia. At 72 h post ischemia the albumin immunoreactivity was decreased. The size of the lesion was established by 3 days after the onset of ischemia. During the 1st week post ischemia, neurofilament (NF) immunohistochemistry showed swollen axons adjacent to the injured tissue. From 2 weeks post ischemia an increasing number of regrowing NF-immunoreactive axons could be seen in the center of the necrotic cavity. At 3 weeks after ischemia, a developing gliosis was observed around and rostral to the lesion cavity, as evidenced by increased glial fibrillary acidic protein (GFAP) immunoreactivity. The gliosis became more pronounced until 6 weeks post ischemia, at which time enlarged GFAP-immunoreactive cells could be seen in the remaining viable tissue bordering the necrotic areas. In this study we show that several traits in the development of a spinal cord lesion after photochemically induced ischemia are similar to those described previously after traumatic spinal cord lesions.
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| 8. |
- von Euler, Mia, 1967-, et al.
(author)
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Motor Performance Score : A New Algorithm for Accurate Behavioral Testing of Spinal Cord Injury in Rats
- 1996
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In: Experimental Neurology. - New York, USA : Academic Press. - 0014-4886 .- 1090-2430. ; 137:2, s. 242-254
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Journal article (peer-reviewed)abstract
- To evaluate the usefulness of standard neurological tests in predicting the neurological outcome after photochemically induced spinal cord lesions in rats, we inflicted injuries of different severity to adult female rats. The behavior of the rats was followed for 6 weeks and the results of the behavioral tests were correlated with morphological indicators of tissue destruction at the end of this period. We found many behavioral tests to be highly correlated with the loss of tissue, whereas some tests were inaccurate in correlating with degree of tissue destruction. Motor score, beam walk, and righting reflex were all highly correlated with the volume of the lesion as well as with the depth of the lesion cavity at its epicenter. We propose a protocol for neurological evaluation of this type of spinal cord injury consisting of six individual tests, hierarchally organized such that injured rats can be divided into 11 groups of neurological deficit, scored from 10 to 0. This so-called motor performance score is fast and easy to perform and shows high correlation with the lesion volume, and is thus suitable for neurological evaluation of photochemically induced spinal cord injury.
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