Neuroprotection in cerebrovascular disease.
The role of neuroprotection in the management of acute cerebrovascular disease is reviewed. Neuroprotection is a valuable adjunct to thrombolytic therapy in acute cerebral ischaemia. Various pharmacological approaches for neuroprotection are based on the current knowledge of molecular events in the pathophysiology of cerebral ischaemia. Reperfusion injury following restitution of circulation is also considered to be mediated by free radicals. Various strategies include free radical scavengers, anti-excitotoxic agents, apoptosis (programmed cell death) inhibitors, anti-inflammatory agents, metal ion chelators, ion channel modulatory, antisense oligonucleotides and gene therapy. The various agents aim to prevent the progression of ischaemic cascade therefore reducing brain damage and some of these intervene at more than one point in the ischaemic cascade. Neuroprotection is considered as an adjunct to therapies designed to improve cerebral circulation such as thrombolytic agents for arterial thrombosis. Clinical effectiveness of some of the strategies has not be proven in clinical trials, some of which had to be abandoned due to adverse effects outweighing the beneficial effects. Efforts to develop new neuroprotective agents continue and prospects for the introduction of an effective neuroprotective agent(s) in the next few years are good. Apart from acute cerebrovascular disease, neuroprotective therapy has a role in preventing cerebral ischaemia in high risk cardiovascular procedures as well as in neurodegenerative disorders which has some common pathomechanisms with cerebrovascular disease. Currently, the most promising agents are free radical scavengers. In the near future, gene therapy approaches are likely to prove more effective in neuroprotection.
Jain
K K
KK
Jain PharmaBiotech, Bläsiring 7, CH-4057 Basel, Switzerland. jain@pharmabiotech.ch
D000818:Animals; D002545:Brain Ischemia / Q000188:drug therapy* / Q000503:physiopathology; D002561:Cerebrovascular Disorders / Q000188:drug therapy* / Q000503:physiopathology; D005343:Fibrinolytic Agents / Q000627:therapeutic use*; D006801:Humans; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D015912:Thrombolytic Therapy
D005343:Fibrinolytic Agents; D018696:Neuroprotective Agents