Article
Intrathecal neuroprotection in acute focal cerebral ischemia in rats
Intrathekale Neuroprotektion im akuten fokalen zerebralen Schlaganfall der Ratte
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Published: | May 8, 2006 |
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Objective: To evaluate the neuroprotective efficacy of the intrathecally administered steroid triamcinolonacetonide (TCA) on infarction volume in acute focal cerebral ischemia in rats.
Methods: Focal cerebral ischemia was induced in 102 Wistar rats using an endovascular occlusion technique of the middle cerebral artery (MCAO). In a first dose-finding study, different doses of TCA (0.3, 0.03, 0.012, 0.006, or 0.003 mg/kg b.w.) were administered into the cisterna magna of 12 rats every 30 minutes after MCAO. Twelve animals received equivolumetric saline intrathecally. In a second MR-controlled confirmation study, the neuroprotective efficacy of the most effective dose was compared to controls in 15 rats each. Within 1 hour after intrathecal administration diffusion-weighted MRI and T1-weighted MRI was performed to confirm successful MCAO and successful drug administration by enhancement of the intrathecal TCA/Gd-DTPA-mixture. Final infarction volume was calculated 24 hours after MCAO by TTC-staining in all animals.
Results: Experiment 1: Compared to controls (18.2±5.0%), infarction volume was significantly reduced using TCA at a dose of 0.012 mg/kg (13.4±5.3%, p=0.04). TCA 0.03 mg/kg (17.7±6.9%, p=0.84), 0.006 mg/kg (15.9±4.2%, p=0.24), and 0.003 mg/kg (14.5±5.2%, p=0.11) did not significantly reduce infarction size, whereas TCA 0.3 mg/kg resulted in bilateral infarction with increased infarction volume (19.8±5.0%, p=0.49).
Experiment 2: Successful MCAO and intrathecal drug administration was confirmed in all animals using diffusion-weighted MRI and T1-weighted images. Compared to controls (20.0± 8.0%) final infarction volume was significantly reduced in animals treated with TCA 0.012 mg/kg (13.4±6,5%, p=0.02).
Conclusions: Intrathecal steroids may significantly reduce infarction volume in permanent focal cerebral ischemia in rats. Further studies, focusing on long-term effects and clinical outcome, are necessary to assess the therapeutic value. MRI is suitable for non-invasive monitoring of intrathecal neuroprotection.