Stroke pathophysiology: management challenges and new treatment advances.
Stroke is the second leading cause of death and the first cause of lost disability-adjusted years in developed countries. During the past decade, new developments in thrombolytic therapy have led to the implementation of emergency intervention protocols for the treatment of ischemic stroke, replacing the widespread sense of therapeutic nihilism in the past. Treatment with rtPA has shown to be effective within the first 3 hours following stroke onset and the FDA and the European Medical Agency (EMEA) have approved its use. Acknowledging the urgency and intricacies of stroke, Stroke Units allow the monitoring of physiological parameters in the acute phase of stroke and are considered an important management tool that can significantly improve the quality of care provided to the patient. The concept of neuroprotective therapy for acute ischemic stroke to salvage tissue at risk and improve functional outcome is based on sound scientific principles and extensive preclinical animal studies demonstrating efficacy. However, most neuroprotective drugs in clinical trials have failed, possibly due to inadequate preclinical testing or flawed clinical development programs. Several new treatment strategies are under development and are being tested. This review is directed at understanding the management of acute ischemic stroke pathophysiology. We address the management challenges and new treatment advances by integrating the knowledge of possible pharmacological targets for acute ischemic stroke. We hope to shed new light upon the controversy surrounding the management of acute ischemic stroke in an attempt to elucidate why failed clinical trials continue to occur despite promising neuroprotective preclinical studies.
Jordán
J
J
Departamento de Ciencias Médicas, Facultad de Medicina, Universidad Castilla-La Mancha, Spain. joaquin.jordan@uclm.es
Ikuta
I
I
García-García
J
J
Calleja
S
S
Segura
T
T
D017209:Apoptosis / Q000187:drug effects; D002118:Calcium / Q000378:metabolism; D006801:Humans; D018696:Neuroprotective Agents / Q000627:therapeutic use; D011994:Recombinant Proteins / Q000627:therapeutic use; D020521:Stroke / Q000503:physiopathology* / Q000628:therapy*; D015912:Thrombolytic Therapy; D010959:Tissue Plasminogen Activator / Q000627:therapeutic use
D018696:Neuroprotective Agents; D011994:Recombinant Proteins; D010959:Tissue Plasminogen Activator; D002118:Calcium