Development of a safe and effective treatment for acute neurological disorders, especially those related to ischemia in the brain, remains one of the pre-eminent challenges in all of biomedical sciences. Acute Ischemic Stroke (AIS), Subarachnoid Hemorrhage (SAH) and Procedurally Induced Strokes (PIS) affect millions of people each year.
Every year, stroke and neurotrauma afflict approximately 800,000 and 275,000 North American individuals, respectively, and about 137,000 stroke and 53,000 trauma victims will die (US, 2013). Globally, over 16.9 million people a year suffer a stroke (2010). In addition, in the United States (U.S.) in 2007, an estimated 1,061,000 inpatient cardiac catheterizations were performed and, according to National Center for Health Statistics (NCHS) estimates, 405,000 coronary artery bypass surgeries were performed on 232,000 patients. In the same year, an estimated 618,000 percutaneous coronary interventions (balloon angioplasty of the coronary artery or coronary atherectomy) procedures were performed in the U.S. Moreover, about 93,000 carotid endarterectomies are performed each year in the U.S2 common denominator for all of these procedures is involvement of the great vessels of the heart with a risk of dislodging emboli that may induce ischemic brain damage.
Most strokes, around 85 per cent, are ischemic. The other 15 per cent of strokes are hemorrhagic3.
A stroke occurs when there is a blockage of a blood vessel supplying the brain (ischemic), or bleeding into or around the brain (hemorrhagic). Brain cells die when they no longer receive oxygen and nutrients from the blood or when they are damaged by sudden bleeding into or around the brain. Ischemia is the term used to describe the loss of oxygen and nutrients for brain cells when there is inadequate blood flow. Ischemia ultimately leads to infarction. When blood flow to the brain is interrupted, some brain cells die immediately, while others remain at risk for death. These damaged cells make up the ischemic penumbra and can linger in a compromised state for up to approximately three hours.
These risks are compounded further by interventions that directly involve blood vessels in transit to, or within, the brain, such as the carotid arteries during cerebral angiography and carotid angioplasty procedures, or during the endovascular repair of brain vascular malformations such as cerebral aneurysms.
Given that there is a critical time, a “therapeutic window”, which may vary from minutes to a few hours in which cerebral ischemia can be reversed or mitigated, stroke should be treated as a medical emergency. There are no stroke therapies which have been shown to be effective if administered after 3-4.5 hours from symptom onset. The phrase “time is brain” emphasizes that brain tissue is rapidly and irretrievably lost as stroke progresses and that early intervention is critical to improve a stroke victim’s outcome.
In ischemic stroke, intervention may include thrombolytic medications such as tissue plasminogen activator (tPA). As tPA is contra-indicated in patients with a hemorrhagic stroke4, it is usually given only in a hospital setting after diagnostic imaging procedures have been performed to exclude a brain hemorrhage. Additionally, certain patients – those with ischemic strokes caused by large vessel occlusions and in whom the stroke damage is not complete, may qualify for endovascular intervention to mechanically restore blood flow to the ischemic area by removing the occluding thrombus (thrombectomy). However, stroke damage progresses quickly, and all interventions must be administered as promptly as possible to ensure that they are given before stroke damage is too extensive.