Stroke, Vol 24, 1702-1708, Copyright © 1993 by American Heart Association
T Sereghy, K Overgaard and G Boysen
BACKGROUND AND PURPOSE: The effects of delayed thrombolysis with alteplase
and neuroprotection with an excitatory amino acid receptor antagonist and
their combination were tested in an embolic stroke model. METHODS: In 61
rats the carotid artery territory was embolized with arterial-like
fibrin-rich clots. Hemispheric cerebral blood flow before and after
embolization was measured by intra-arterial 133Xe injection method. The
animals were assigned to one of the following treatments: (1)
vehicle-treated controls (n = 15); (2) dizocilpine 1 mg/kg i.v. 5 minutes
after embolization (n = 16); (3) alteplase 20 mg/kg as an intravenous
continuous infusion starting 2 hours after embolization (n = 16); and (4)
both agents (n = 14). Carotid angiography displayed the site of occlusion
of the cerebral arterial tree immediately after and 3 hours after
embolization, and the clinical neurological score was assessed after the
rats recovered from anesthesia and before the rats were killed. Brains were
fixed after 2 days and evaluated neuropathologically; infarct volume
affecting cortical and deep brain structures was measured separately.
RESULTS: Both alteplase and dizocilpine reduced the total infarct volume (P
= .05 and P = .04, respectively, Mann-Whitney tests). Dizocilpine reduced
the incidence of cortical infarctions by 48% (P < .001, Fisher's test).
Only the combined treatment significantly reduced deep brain infarctions (P
= .03, Mann-Whitney test). The combined treatment also improved the
clinical score by 83% compared with controls, by 75% compared with the
group treated by dizocilpine alone, and by 50% compared with the group
treated by alteplase alone. Sixty-seven percent of thrombolytic-treated
animals recanalized completely compared with 39% of those given no
thrombolytics (P = .05, Fisher's test). The clinical outcome correlated
with infarct size (P < .01, Spearman test). CONCLUSIONS: Our results
document comparable efficacy of delayed thrombolysis and excitatory amino
acid receptor antagonism in this model and suggest that combination of
these two therapeutic approaches may yield additional benefit in treatment
of thromboembolic stroke, particularly in cases where deep brain
(end-artery-supplied) structures are affected.
ARTICLES
Neuroprotection by excitatory amino acid antagonist augments the benefit of thrombolysis in embolic stroke in rats [published erratum appears in Stroke 1997 Feb;28(2):466]
Department of Neurology, University Hospital of Copenhagen, Rigshospitalet, Denmark.
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