Intracerebral hemorrhage: mechanisms and therapies.

We welcome you to this special issue of TranslationalStroke Research on intracerebral hemorrhage (ICH). Thereare about two million cases of ICH in the world each year,accounting for about 10–15 % of all strokes in the USA,Europe, and Australia and 20–30 % of strokes in Asia. It hasa very high mortality rate (∼40 %), and most survivors facelong-term disability [1, 2]. Despite this, ICH has historicallyreceived much less focus than ischemic stroke. However, inthe last years, there has been a marked increase in interest.Thus, Medline reported 374, 442, 590, 945, and 1,614articles on intracerebral hemorrhage in the years from1986–1990, 1991–1995, 1996–2000, 2001–2005, and2006–2010, respectively. This upswing in interest isreflected by this special issue which includes 19 papers byleading experts in the field including clinical and preclinicalstudies, reviews and new research, and three editorials.Rincon and Mayer [3] provide an extensive clinical over-view of current management of ICH as well as ongoingclinical trials. Those trials include several aimed at clotevacuation with or without the use of tissue plasminogenactivator (tPA) to aid in clot lysis [4, 5]. Tissue plasminogenactivator is also being examined in the CLEAR IVH trial [6]for intraventricular hemorrhage (IVH). Ventricular exten-sion worsens ICH-induced injury [7]. In this issue, Strahleet al. review evidence on the mechanisms of IVH-inducedinjury [8]. This is particularly important in relation to hem-orrhage of the germinal matrix in premature neonates.Neonatal hemorrhage is also the subject of an editorial byBouz [9].In treating cerebral ischemia with tPA, patients develop-ing ICH is a major concern. Similarly, treating ICH patientswith hemostatic agents to prevent hematoma expansion maycause thromboembolic events [10]. In addition, as discussedby Fisher et al. in this issue, ischemic and hemorrhagiccerebrovascular disease frequently coexists in the same pa-tient (mixed cerebrovascular disease) raising a conundrumof how to treat such patients. Fisher et al. discuss potentialways to solve that problem [11].Questions have also been raised over whether tPA mayhave some adverse consequences in the brain includingcausing delayed edema formation. In this issue, Keric etal. present data in a porcine ICH model that plasminogenactivator inhibitor-1 can reduce that edema formation [12].Polymorphisms in the APOE gene are associated with therisk of developing ICH and prognosis after ICH [13, 14]. Inthis issue, Lei et al. [15] report finding an interaction be-tween APOE polymorphism and gender in determiningICH-induced injury. TOMM40 is a gene in close proximityto APOE. Valant et al. have examined the role of TOMM40in cerebral amyloid angiopathy [16]. They report that singlenucleotide polymorphisms in TOMM40 are associated withvascular amyloid deposition but not ICH.The mechanisms that appear to underlie ICH injury differsubstantially from those of cerebral ischemia [17]. Indeed,there is evidence that ischemia plays little role in most ICH[17], and it is dangerous to infer a potential therapeuticapproach from one type of stroke to another. A case in pointis hyperglycemia where there has been considerable interestin regulating glucose levels in ischemic patients (e.g., theGASP and current SHINE clinical trials; [18]) but, as indi-cated by the study of Feng et al., the evidence for a role of