Stroke reperfusion

Table 11.2 Stroke reperfusion therapy IV/IA pretreatment phase ...

Table 11.3 Stroke reperfusion therapy IV t-PA treatment phase...

Ischemia-reperfusion damage Stroke (A,l), cardiac failure (A), transplantation (A)... 

PI (adenosine) receptors were explored as therapeutic targets before P2 receptors. Adenosine was identified early and is in current use to treat supraventricular tachycardia. A2a receptor antagonists are being investigated for the treatment of Parkinson s disease and patents have been lodged for the application of PI receptor subtype agonists and antagonists for myocardial ischaemia and reperfusion injury, cerebral ischaemia, stroke, intermittent claudication and renal insufficiency. 

Warach S, Latour LL. Evidence of reperfusion injury, exacerbated by thrombolytic therapy, in human focal brain ischemia using a novel imaging marker of early blood-brain barrier disruption. Stroke 2004 35 2659-2661. 

The Penumbra stroke system (Penumbra Inc., San Leandro, CA) includes two different revascularization options (1) thrombus debulking and aspiration may be achieved by a reperfusion catheter that aspirates the clot while a separator device fragments it, and (2) direct thrombus extraction may be performed by a ring retriever while a balloon guide catheter is used to temporarily arrest flow. This system has been tested in a pilot trial in Europe. Twenty patients (mean NIHSS 21) with a total of 21 vessel occlusions (7 ICA, 5 MCA, and 9 Basilar) were treated up to 8 hours after symptom onset. Recanalization prior to lA lysis was achieved in all cases (48% TIMI 2 52% TIMI 3). Seven patients were also treated with lA UK or rt-PA. Good outcome at 30 days (defined as mRS < 2 or NIHSS 4-point improvement) was demonstrated in 42%. The mortality rate was 45%, but there were no device-related deaths. There was one asymptomatic SAH and three symptomatic ICHs. A prospective, single-arm, multicenter trial is being conducted in the United States and Europe currently. 

Mohna CA, Saver JL. Extending reperfusion therapy for acute ischemic stroke emerging pharmacological, mechanical, and imaging strategies. Stroke 2005 36 2311-2320. 

Combination GP Ilb/IIIa and rt-PA Therapy for Acute Stroke The combination of antiplatelet and thrombolytic drugs has proven efficacy in the setting of myocardial ischemia where an additive effect is seen. In acute stroke thrombolysis with a very narrow time window and less than 50% optimal reperfusion rates,adjunctive therapy with antiplatelets may be a promising approach. However, MAST-I concluded that the group of patients receiving streptokinase plus aspirin had a marked increase in 10-day mortality. 

Juttler E, Kohrmann M, Schellinger PD. Therapy for early reperfusion after stroke. Nat Clin Prac Cardiovasc Med 2006 3 656-663. 

Dunn B, Davis LA, Todd JW, Chalela JA, Warach S, NINDS/NIH, Bethesda, MD for the ROSIE Investigators. Reperfusion of Stroke Safety Study Imaging Evaluation (ROSIE). Ongoing Clinical Trials Session, 29th International Stroke Conference 2004. 

Reperfusion of Stroke Safety Study Imaging Evaluation-2 Adjunctive Treatment to Standard Alteplase Therapy of Ischemic Stroke. Presented at the 29th International Stroke Conference Fehmary 2004. 

Moreover,bioactive lipids maybe considered dual messengers they modulate cell functions as messengers and they become part of the response of the nervous tissue to injury, broadly referred to as the inflammatory response. This response occurs in ischemia-reperfusion damage associated with stroke, various forms of neurotrauma, infectious diseases and neurodegenerative diseases such as Alzheimer s disease. Inflammation in the nervous system differs from that in other tissues. If the blood-brain barrier is broken, blood-borne inflammatory cells (e.g. polymorphonuclear leukocytes, monocytes, macrophages) invade the intercellular space and glial cells are activated, particularly microglia, which play a prominent role in the inflammatory response. These responses may... 

Ischemic stroke patients presenting within hours of symptom onset should be evaluated for reperfusion therapy. 

Since the early 1980s, much effort has focused on animal models of acute and chronic neurodegeneration in search of therapeutics for stroke. Neuronal cell death follows strokes, acute ischemic insults, and chronic neurodegeneration, such as Parkinson s disease, Alzheimer s disease (AD), epilepsy, and Huntington s disease. Up to 80% of all strokes result from focal infarcts and ischemia in the middle cerebral artery (MCA), so the commonly used animal models for neuroprotection are produced by temporary or permanent occlusion of the MCA.5 Lesions of the MCA include occlusion by electrocoagulation, intraluminal monofilaments, photochemical effects, thrombosis, and endothelin-1, but all of these models necessitate studying reperfusion events and validating MCA occlusion by behavioral assessments. 

Sunderland T, Tariot PN, Newhouse PA. (1988). Differential responsivity of mood, behavior, and cognition to cholinergic agents in elderly neuropsychiatric populations. Brain Res. 472 4y. 371-89. Tachikawa E, Kudo K, Flarada K, Kashimoto T, Miyate Y, Kakizaki A, Takahashi E. (1999). Effects of ginseng saponins on responses induced by various receptor stimuli. EurJ Pharmacol 369(1) 23-32. Tagami M, Ikeda K, Yamagata K, Nara Y, Fujino FI, Kubota A, Numano F, Yamori Y. (1999). Vitamin E prevents apoptosis in hippocampal neurons caused by cerebral ischemia and reperfusion in stroke-prone spontaneously hypertensive rats. Lab Invest. 79(5) 609-15. 

E. Therapeutic response Activase, and other thrombolytic agents, used in a timely manner during an evolving myocardial infarction, decrease mortality and improve left ventricular function. Resolution of chest pain, resolution of baseline EKG changes, reduced total creatine phospho-kinase (CPK) release, and preserved left ventricular function are evidence of cardiac reperfusion. Activase, administered within the first 3 hours of ischemic stroke onset, has been shown to improve recovery. 

Clemens, J. A., Stephenson, D. T., Smalstig, E. B., Dixon, E. R, and Little, S. P. (1997). Global ischemia activates nuclear factor-kappa B in forebrain neurons of rats. Stroke 28, 1073-1080. Crack, P. J., Taylor, J. M., Ali, U., Mansell, A., and Hertzog, P. J. (2006). Potential contribution of NF-kappaB in neuronal cell death in the glutathione peroxidase-1 knockout mouse in response to ischemia-reperfusion injury. Stroke 37, 1533-1538. 

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