Role of Inflammation in Stroke: Benefits or Harm?
At the onset of the 21st century, stroke is the third leading cause of death in most developed countries and the primary cardiovascular cause of death in Japan and China. The health burden of the disease is staggering as loss of productive life inflicts heavy toll on the patients, families and society. Yet, this disease has no effective therapeutic beyond a limited (<5%) treatment with thrombolytics that carry significant adverse effect. This situation is prominent in spite of intense research efforts and numerous clinical trials attempting to develop drugs that reduce morbidity and mortality from stroke. So far, the focus of drug development efforts targeted modulators of ion channels (Ca+2, Na+), scavengers of oxygen radicals and antagonists of excitotoxic neurotransmitters (primarily glutamate and glycine receptors). However, all clinical trials have failed so far due to lack of efficacy, adverse effects or other development difficulties. Debates on the reasons for the possible causes of failure include wrong animal models, wrong mechanism of action, poor clinical design, inadequate timing of treatment etc. While this debate is ongoing, the stroke research community seems to have been disenchanted from the ‘classical’ targets for drug development (vide supra) as evidence by emerging hope that other avenues such as ‘reconstruction’, ‘apoptosis’ and ‘inflammation’ are better pastures for future successes.
KeywordsMiddle Cerebral Artery Occlusion Focal Cerebral Ischemia Focal Ischemia Reduce Infarct Size Ischemic Brain Injury
Unable to display preview. Download preview PDF.
- Barone, F.C., White, R.F., Spera, P.A., Currie, R.W., Wang, X.K. and Feuerstein, G.Z., 1998, Ischemic preconditioning and brain tolerance: Temporal histologie and functional outcomes, protein synthesis requirement, and IL-1ra and early gene expression. Stroke 29: 1937–1951.PubMedCrossRefGoogle Scholar
- Feuerstein, G.Z., Wang, X.K. and Barone, F.C., 1998, Inflammatory mediators of ischemic injury: Cytokine gene regulation in stroke. In: Cerebrovascular Disease: Pathophysiology, Diagnosis and Management, M.D. Ginsberg, J. Bogousslavsky (Eds.), Blackwell Science Inc, pp.507–531.Google Scholar
- Goldblum, S.E. and Sun, W.L., 1990, Tumour necrosis factor-alpha augments pulmonary arterial transendothelial albumen flux in vitro. Am J Physiol 285: L57–L67.Google Scholar
- Millikan, C.H., McDowell, F., Easton, J.D., 1987, Stroke, Chapter 8, Lea Febiger, Philadelphia.Google Scholar
- Rapalino, O., Lazarov-Spiegeler, O., Agranov, E., Velan, G.J., Yoles, E., Fraidkis, M., Solomon, A., Gepstein, R., Katz, A., Belkin, M., Hadani, M., Schwartz, M., 1998, Implantation of stimulated homologous macrophages results in partial recovery of paraplegic rats. Nature Medicine 4: 814–821.PubMedCrossRefGoogle Scholar
- Rothwell, N.J. and Relton, J.K., 1993, Involvement of interleukin-1 and lipocortin-1 in ischemic brain damage. Cerebrovas Brain Metab Rev 5: 178–198.Google Scholar
- Stahel PF, Shohami E, Younis FM, Kariya K, Otto VI, Lenzlinger PM, Grosjean MB, Eugster HP, Trentz O, Kossman T, Morganti-Kossman MC., 2000, Experimental closed head injury: analysis of neurological outcome, blood brain Barrier, dysfnction, intracranial neutrophil infiltration, and neuronal cell death in mice deficient in genes for pro-inflammatory cytokines. J Cerebral Blood flow Metab 20: 369–380.CrossRefGoogle Scholar
- Vourte, J., Linsberg, P.J., Kaste, M., et al., 1999, Anti-ICAM-1 monoclonal antibody R65 (Enlimomab) promotes activation of neutrophils in whole blood. J Immunol 162: 2353–2357.Google Scholar