Failure to improve the effect of thrombolysis by memantine in a rat embolic stroke model.
OBJECTIVE
Partial and delayed recanalization is a regular finding after thrombolysis in stroke patients who may benefit from additional therapy with neuroprotectants. To translate this scenario into an experiment, memantine was combined with thrombolysis in an embolic stroke model and tissue outcome was assessed in terms of complete and incomplete damage.


METHODS
Tissue plasminogen activator (tPA, 5 mg/kg, b.w.) was administered 1.5 or 3.5 hours after embolic middle cerebral artery (MCA) occlusion in rats. In both groups, rats were assigned to additional therapy with memantine (10 mg/kg, i.p.) or saline injection. Ischemia and eventual reperfusion were continuously monitored by laser-Doppler flowmetry. Reperfusion was defined as a lasting increase in post-thrombolytic cerebral blood flow to >60% of baseline (complete) or to a lesser degree (partial). Experiments were terminated 6 hours post-occlusion to obtain quantitative histopathology.


RESULTS
tPA induced complete or partial recanalization in 54% of treated animals. Successful reperfusion reduced total ischemic lesion volume by 42% compared with non-reperfused animals (p<0.05), but increased significantly the percentage of scattered neuronal injury from 25.6 (non-reperfusion) to 36.3% (reperfusion, p<0.05). Memantine did not improve the effect of tPA-induced recanalization on infarct morphology whether applied at 1.5 or 3.5 hours post-occlusion.


CONCLUSIONS
We conclude from our experiments that add-on therapy with memantine did not alter the effect of thrombolysis in an embolic stroke model. Recanalization appears to be a prerequisite to confer neuroprotective effects.
Back
Tobias
T
Department of Neurology, Klinikum Mannheim, University of Heidelberg, Mannheim, Germany. back@neuro.ma.uni-heidelberg.de
Otto
Dörte
D
Kittner
Daniela
D
Schüler
Olaf G
OG
Hennerici
Michael G
MG
Mennel
Hans-Dieter
HD
D000818:Animals; D004195:Disease Models, Animal; D005343:Fibrinolytic Agents / Q000627:therapeutic use*; D008297:Male; D008559:Memantine / Q000627:therapeutic use*; D051381:Rats; D017208:Rats, Wistar; D018709:Statistics, Nonparametric; D020521:Stroke / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D010959:Tissue Plasminogen Activator / Q000627:therapeutic use; D017211:Treatment Failure
D005343:Fibrinolytic Agents; D010959:Tissue Plasminogen Activator; D008559:Memantine