Contributions
Abstract: P408
Type: Poster
Abstract Category: Pathology and pathogenesis of MS - Experimental models
Cortical demyelination is a common finding in patients with chronic multiple sclerosis (MS) and is thought to contribute to disease progression and overall disability. The exact pathomechanism of the cortical lesions is so far not clear. Recent studies of local traumatic injection of proinflammatory cytokines directly into the cortex (Merkler et al., 2006) and into the subarachnoidal space (Gardner et al., 2013) of rats subclinically preimmunized with Myelin Oligodendrocyte Glycoprotein ( MOG) produced a short lived cortical demyelination in the injected hemisphere, which was completely resolved within a few days.
In our experiment we implanted a catheter into the cortex of 11 weeks old male Dark Agouti rats. After a healing period of 14 days the rats were subclinically immunized with MOG dissolved in incomplete Freund"s Adjuvant. After building a stable anti-MOG antibody titer the animals received an injection of the proinflammatory cytokines TNF- alpha and IFN- gamma through the catheter. This avoided any additional mechanical trauma. Clinically, the animals showed a slightly slow behavior without any motor symptoms between day 9-15, which totally resolved after day 15. Rotarod performances dropped slightly between d3 and d15 and went back to preinjected values on d30. Animals were sacrificed at days 1, 3, 15 and 30 after cytokine injection. Tissues were embedded in paraffin and immunohistochemically stained for macrophages, T cells and proteolipid protein (PLP) to detect myelin. On day 1 we found some invading macrophages directly around the catheter site containing early myelin degradation products in luxol fast blue staining and some demyelinating activity. On day 3 already a marked demyelination around the catheter implantation site spreading towards the upper cortex area is visible, while only minor cellular infiltrates are detectable. On day 15 we see a marked demyelination with near absence of PLP immunoreactivity (PLP- IR) affecting not only the immediate catheter area, but extending over large parts of the cortex of both hemispheres. On day 30 animals still show patches of demyelinated cortex areas with loss of PLP-IR along with areas of partially restored PLP-IR. No spinal cord pathology was detected in any animal.
In our study we show that widespread demyelination of the cortex of both hemispheres can be induced in rats. This model might help to investigate the pathogenesis of cortical lesions in MS.
Disclosure: Hochmeister S: nothing to disclose
Ücal M : nothing to disclose
Haindl M : nothing to disclose
Theisl L: nothing to disclose
Zeitelhofer-Adzemovic M : nothing to disclose
Strasser J: nothing to disclose
Ropele S: nothing to disclose
Schäfer U: nothing to disclose
Fazekas F: nothing to disclose
We did not receive any specific funding for this work.
Abstract: P408
Type: Poster
Abstract Category: Pathology and pathogenesis of MS - Experimental models
Cortical demyelination is a common finding in patients with chronic multiple sclerosis (MS) and is thought to contribute to disease progression and overall disability. The exact pathomechanism of the cortical lesions is so far not clear. Recent studies of local traumatic injection of proinflammatory cytokines directly into the cortex (Merkler et al., 2006) and into the subarachnoidal space (Gardner et al., 2013) of rats subclinically preimmunized with Myelin Oligodendrocyte Glycoprotein ( MOG) produced a short lived cortical demyelination in the injected hemisphere, which was completely resolved within a few days.
In our experiment we implanted a catheter into the cortex of 11 weeks old male Dark Agouti rats. After a healing period of 14 days the rats were subclinically immunized with MOG dissolved in incomplete Freund"s Adjuvant. After building a stable anti-MOG antibody titer the animals received an injection of the proinflammatory cytokines TNF- alpha and IFN- gamma through the catheter. This avoided any additional mechanical trauma. Clinically, the animals showed a slightly slow behavior without any motor symptoms between day 9-15, which totally resolved after day 15. Rotarod performances dropped slightly between d3 and d15 and went back to preinjected values on d30. Animals were sacrificed at days 1, 3, 15 and 30 after cytokine injection. Tissues were embedded in paraffin and immunohistochemically stained for macrophages, T cells and proteolipid protein (PLP) to detect myelin. On day 1 we found some invading macrophages directly around the catheter site containing early myelin degradation products in luxol fast blue staining and some demyelinating activity. On day 3 already a marked demyelination around the catheter implantation site spreading towards the upper cortex area is visible, while only minor cellular infiltrates are detectable. On day 15 we see a marked demyelination with near absence of PLP immunoreactivity (PLP- IR) affecting not only the immediate catheter area, but extending over large parts of the cortex of both hemispheres. On day 30 animals still show patches of demyelinated cortex areas with loss of PLP-IR along with areas of partially restored PLP-IR. No spinal cord pathology was detected in any animal.
In our study we show that widespread demyelination of the cortex of both hemispheres can be induced in rats. This model might help to investigate the pathogenesis of cortical lesions in MS.
Disclosure: Hochmeister S: nothing to disclose
Ücal M : nothing to disclose
Haindl M : nothing to disclose
Theisl L: nothing to disclose
Zeitelhofer-Adzemovic M : nothing to disclose
Strasser J: nothing to disclose
Ropele S: nothing to disclose
Schäfer U: nothing to disclose
Fazekas F: nothing to disclose
We did not receive any specific funding for this work.