Ischemic stroke is a medical emergency mainly caused by sudden interruption of the blood supply to the brain, and hence obstructed the delivery of oxygen and nutrients which brain need. The blocking consequently causes the damage and the death of the brain cells around the ischemic region, and brain dysfunction. If patients suffer from such dysfunction do not receive prompt treatments, they may have moderate to severe disabilities. In other words, they have to rely on others’ cares to achieve basic tasks of daily life. At worst, the stroke damage can cause coma or death. Stroke patients may have different degrees of damage or necrosis in their brain tissues, so they may have different degrees of disabilities, including motor, language, and cognitive skills. These largely affect their abilities of long-term daily living and self-care. Ischemic stroke is the no.3 among the top 10 principal causes of death in Taiwan, certainly being one of the biggest killers in the nation.

The rate of stroke is especially higher in the elderly and it is the main cause of elder disabilities. Stroke has huge impacts and damaging effects on individuals, families, societies and even the nation. However, the treatment for strokes is still limited. Post-stroke rehabilitations through physical therapy, occupational therapy or speech therapy, are the main ways to improve the quality of life for stroke patients. Restoring patients’ daily lives, with assistance from family education, can reduce complications after a stroke.

Ischemic stroke is one kind of stroke caused by three types of obstruction of blood vessels supplying blood to the brain:

• Thrombotic stroke: It is also called atherothrombotic brain infarction that occurs when a blood vessel is blocked by a blood clot, which is complicated by problems such as atheroscleorotic plaques, vascular stenosis, or coagulation disorders.
• Embolic stroke (Cardioembolic brain infarction): It refers to a brain's blood vessel blocked by a blood clot that forms at another location in the circulatory system, usually the heart and large arteries. A majority of this type of stroke is found in patients with unsteady blood flows or recent problems of myocardial infarction. These create conditions where clots can form from dislodged debris of heart valve or necrotic heart wall, and block a brain vessel. Around 10% - 15% of ischemic strokes are embolic strokes.
• Hemodynamic stroke: This type of ischaemic stroke is caused by hemodynamic decrease in microcirculation that may be due to an elevation of blood viscosity, increased platelet agglutination, increased plasma fibrinogen, or stiffened RBC membranes. The necrosis of brain tissues caused by blockage of bloodstream in blood arteries or a lack of blood flows is also called cerebral infarction.

The brain and neurons are very sensitive to the concentration of oxygens. The volume of blood in the adult brain takes around one fifth of the total circulatory blood volume (i.e. 1 L per minute). The oxygen demand of brain tissues is around one fourth of the whole body (i.e. 500 - 600 ml of oxygen per minute). The degree of brain damage during the period of ischemia varies among individuals, depending on the degree of blockage and the duration of ischemia the patient experienced. Within the period of ischemia, the bloodstream supplying to a brain is blocked and hence cause an imbalance of ions and cellular energy metabolism. Subsequently, the conditions induce a series of pathophysiological responses, namely ischemic cascade. Moreover, the occurrence of brain damage is not only limited to the period of ischemia, but also the reperfusion stage at which the supply of oxygen and nutrients from bloodstreams has been restored.

Sources: Meridigen Biotech. Co., Ltd.

Annually, around 15 million people suffer from stroke worldwide, among which 75% are Ischemic strokes. Ischemic stroke is the no.3 among the top 10 principal causes of death in Taiwan, one of the biggest killers in the nation. The death rate in Taiwan is higher than it in Japan, Singapore, and many other western Europe countries. It is also the first cause of adult disabilities. Based on the death rate of stroke at 0.0005 in Taiwan, there are approximately 11,700 people died from strokes.  Apart from the high incidence rate, from the trend, we can know the chance of stroke increases as years passed.

Stroke causes not only high death rate during acute stage but also sequelae after the chronic stage and it has had a tremendous impacts on the society. Taking the US as an example, there are 730 thousand new cases and around 4 million survivors. Together with stroke is a huge economic burden estimated as around 40 billion annually, including direct and indirect costs of caring stroke patients.
The global market of stroke pharmaceuticals has been forecasted to have a sustainable growth. From 2013 to 2015, its market scale jumps from 19.2 billion to 21.9 billion and with a CAGR (compound annual growth rate) of 6.7%. It has been reported that from 2016 onwards, the market size can increase by at least 1.4 billion, reaching to 30.2 billion in 2020.

There are two main treatments used at the acute stage of ischemic stroke, including mechanical thrombectomy and administration of intravenous (IV) recombinant tissue plasminogen activator (rtPA). Currently, rt-PA is the only recognized effective drug for acute ischemic stroke. However, rt-PA would enhance the intracranial haemorrhage rate.

It is unfortunate that all current drugs have their limits and side effects, so to develop new treatments for acute ischemic stroke is necessary. MSCs, as we detailed previously, have multifunction of cell protection and modulation, such as promoting endogenous neural cell activation, promoting maturation of neural cells, neuroprotection, anti-apoptosis, promoting angiogenesis, and immunomodulation. The multifunction is certainly unachievable by a single use of other drugs.