ReviewInflammation following stroke
Introduction
Stroke is one of the leading causes of mortality and morbidity in the world. According to The World Health Report, which was released by the World Health Organization in 2002, stroke was responsible for 9.6% of deaths around the world in 2001.1 It was secondary only to the death rate of ischaemic heart disease, which caused 12.7% of deaths in the world in same year.1 The loss of disability adjusted life years (DALY) because of stroke was about 5% in men and women over the age of 15 years in 2002 world-wide.2 Owing to increasing life expectancy, the incidence and the prevalence of stroke will increase gradually with time.
There are numerous causes of stroke and these can be broadly classified as either ischaemic or haemorrhagic stroke. The introduction of the thrombolytic drug, rtPA, in patients with acute ischaemic stroke is one of the major advances in modern medicine. The reperfusion of the cerebral tissue is aimed at rescuing potentially salvageable brain tissue before inevitable infarction. This region of rescued brain tissue is called the ischaemic penumbra. A substantial number of patients who come to the hospital with ischaemic stroke are not eligible for rtPA therapy. The reasons for this include late presentation of the patient beyond the therapeutic time window of 3 hours from the onset of symptoms and the high risk of systemic bleeding. Clinical audits have shown that only 10–20% of acute stroke patients received rtPA, even in specialised units.3 Although rtPA has been of significant benefit to many, there is still room for improvement in that mortality is not improved and perhaps even greater therapeutic benefit is possible.
Therefore, it is essential to explore other therapeutic strategies that might improve clinical outcomes. To gain the maximum clinical benefit an ideal intervention should demonstrate therapeutic effect in all three phases of illness; that is, acute, subacute and chronic. Furthermore, it is vital to discover ways to reduce side-effects and increase the therapeutic efficacy of rtPA. One of these may be through a better understanding of the inflammatory process occurring after stroke. In this article, we will review the available animal and human data of inflammation associated with ischaemic and haemorrhagic stroke.
Section snippets
Inflammation following ischaemic stroke
Inflammation can be defined as the reaction of vascularised living tissue to local injury. It has cellular as well as molecular components. The circulating leukocytes, including neutrophils, lymphocytes and macrophages, as well as capillary endothelial cells, are actively involved in the inflammatory process. Moreover, specific cells like microglia, astrocytes and neurons are active contributors to inflammation in the brain parenchyma.
Inflammatory molecules are those that are up-regulated with
Inflammation following stroke in humans
Numerous investigators have demonstrated local and systemic inflammatory responses after stroke in humans. Peripheral white blood cell (WBC) count, C-reactive protein (CRP) level and erythrocyte sedimentation rate (ESR) are increased within 24 h after the onset of stroke.[81], [82], [83] Sequential blood studies demonstrate significantly elevated CRP, ESR and WBC counts even 3 months after the onset of stroke.84 Hence, there is good evidence for prolonged activity of the post-ischaemic
Conclusion
Just after the onset of stroke in animals and in humans a range of inflammatory cells are activated. Some of them are brain parenchymal cells whereas others are recruited into the region from the blood. Meanwhile, inflammatory molecules are up-regulated and play an important role in the inflammatory process. This process lasts several months or even years.
Suppression of the activities of some inflammatory components is associated with reduction of infarct volume and better behavioural outcomes
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Dr. Henry HK Ma is supported by a National Health and Medical Research Council (NHMRC) Research Scholarship for Medical Graduates (2005) and a Cardiovascular Lipid Grant (Pfizer, 2005).