Use of thrombolysis in acute
ischaemic stroke may be limited by a narrow benefit/risk ratio. Pharmacological inhibition of the ischaemic cascade may constitute an effective and safer approach to
stroke treatment. This study compared the effects of high doses of
cytidine diphosphate-choline (
CDP-choline; 1000 mg/kg) with recombinant
tissue plasminogen activator (rt-PA; 5 mg/kg) in an experimental animal model of
embolic stroke. Fifteen rats were embolized in the right internal carotid artery with an autologous clot and were divided into three groups: (1)
infarct; (2) intravenous rt-PA 5 mg/kg 30 minutes post-embolization; and (3)
CDP-choline 1000 mg/kg, intraperitoneal, three doses, 30 minutes, 24 hours, and 48 hours post-embolization. Functional evaluation scores were evaluated using Rogers test, lesion volume by haematoxylin and
eosin staining, cell death with
transferase-mediated dUTP nick-end labelling, and plasma levels of
interleukin-6 (IL-6) and
tumor necrosis factor-alpha with
enzyme-linked
immunosorbent assay. In this study,
CDP-choline and rt-PA produced a significant reduction in brain damage considering
infarct volume, cell death, and inflammatory
cytokines (tumour
necrosis factor-alpha and IL-6) compared with the
infarct group. Additionally,
CDP-choline significantly decreased
infarct volume, cell death, and
IL-6 levels with respect to the rt-PA group. From these results, we conclude that high-dose
CDP-choline may be an effective treatment for acute
ischaemic stroke even in absence of thrombolysis.