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Neuroprotective effects of N-acetylcysteine amide on experimental focal penetrating brain injury in rats

Mattias Günther ; Johan Davidsson (Institutionen för tillämpad mekanik, Fordonssäkerhet) ; Stefan Plantman ; Maria Angeria ; Svante Norgren ; Tiit Mathiesen ; Mårten Risling
Neuroscience Meeting, Washington DC, 2014 Nov 15-21 p. 486.06. (2014)
[Konferensbidrag, övrigt]

Background The beneficial effects of N-acetylcysteine (NAC) on CNS ischemia and after TBI in animal models are well documented. However, the bioavailability of NAC is very low. N-acetylcysteine Amide (NACA) is a newly modified form of N-acetylcysteine that contains an amide group in place of the carboxyl group of NAC. NACA has more efficient membrane permeation and crosses the blood brain barrier. We examined the effects of NACA in the secondary inflammatory response following focal penetrating TBI in rats. Material and methods Focal penetrating TBI were produced in a total of 24 male Sprague-Dawley rats randomly selected for treatment (n=5), non-treatment (n=5) and sham (n=4). The treated animals were given NACA 300 mg/kg ip after 5 min and in the 24h survival group a bolus of 300 mg/kg ip after 4h. After 2h and 24h the brains were removed, cut in 14 µm coronal sections and subjected to immunohistochemistry, immunofluorescence, Fluoro-Jade and TUNEL analyses. Results NACA treatment decreased neuronal degeneration by Fluoro-Jade at 24h (p<.05). The levels of resident/invading macrophages/microglia in the perilesional area (ox-42) were elevated at 2h and 24h, not differing between groups. The NO-producing inflammatory enzyme iNOS was up-regulated 24h, not differing between groups. Oxidative stress measured by peroxynitrite surrogate marker 3-Nitrotyrosine was detectible at 2h and 24h, not differing between groups. Antioxidative enzyme MnSOD was up regulated at 2h and 24h, expressing higher levels at 24h in the NACA group (p<.05). NFkB located in the nuclei was up-regulated at 2h and 24h, not differing between groups. Apoptotic cells by TUNEL was up regulated at 2h and 24h, with decreased levels at 2h in the NACA group (p<.05). Total levels of Cytochrome c and Bcl-2 did not differ between groups. Conclusions NACA treatment decreased apoptosis and neuronal degeneration and increased antioxdative enzyme MnSOD. The antiapoptotic effect was not linked to alterations in total levels of Cytochrome c or Bcl-2. Our results suggest that NACA treatment after focal TBI may be beneficial in preventing brain tissue damage, thus showing potential for clinical implications.



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Denna post skapades 2015-01-15. Senast ändrad 2015-01-27.
CPL Pubid: 210783

 

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