Thrombolysis and neuroprotection in cerebral ischemia.
Stroke is a major cause of death and disability worldwide. The resulting burden on society grows with the increase in the incidence of stroke. The term brain attack was introduced to describe the acute presentation of stroke and emphasize the need for urgent action to remedy the situation. Though a large number of therapeutic agents, like thrombolytics, NMDA receptor antagonists, calcium channel blockers and antioxidants, have been used or are being evaluated, there is still a large gap between the benefits of these agents and the properties of an ideal drug for stroke. So far, only thrombolysis with rtPA within a 3-hour time window has been shown to improve the outcome of patients with ischemic stroke. Understanding the mechanisms of injury and neuroprotection in these diseases is important to target news sites for treating ischemia. Better evaluation of the drugs and increased similarity between the results of animal experimentation and in the clinical setting requires critical assessment of the selection of animal models and the parameters to be evaluated. Our laboratory has employed a rat embolic stroke model to investigate the combination of rtPA with citicoline as compared to monotherapy alone and investigated whether neuroprotection should be provided before or after thrombolysis in order to achieve a greater reduction of ischemic brain damage.
Gutiérrez
M
M
Cerebrovascular Research Group, Hospital Universitario La Paz, Universidad Autónoma Madrid, Spain.
Díez Tejedor
E
E
Alonso de Leciñana
M
M
Fuentes
B
B
Carceller
F
F
Roda
J M
JM
D000818:Animals; D001921:Brain / Q000187:drug effects / Q000473:pathology; D002545:Brain Ischemia / Q000188:drug therapy* / Q000473:pathology; D002986:Clinical Trials as Topic; D003566:Cytidine Diphosphate Choline / Q000494:pharmacology / Q000627:therapeutic use; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical; D004359:Drug Therapy, Combination; D005343:Fibrinolytic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D018696:Neuroprotective Agents / Q000494:pharmacology / Q000627:therapeutic use*; D051381:Rats; D011994:Recombinant Proteins / Q000494:pharmacology / Q000627:therapeutic use; D020521:Stroke / Q000188:drug therapy* / Q000473:pathology; D015912:Thrombolytic Therapy; D013997:Time Factors; D010959:Tissue Plasminogen Activator / Q000235:genetics / Q000494:pharmacology / Q000627:therapeutic use*
D005343:Fibrinolytic Agents; D018696:Neuroprotective Agents; D011994:Recombinant Proteins; D003566:Cytidine Diphosphate Choline; D010959:Tissue Plasminogen Activator