Letter by Takeuchi and Nawashiro regarding article, "Role of iron in brain injury after intraventricular hemorrhage".

Stroke welcomes Letters to the Editor and will publish them, if suitable, as space permits. Letters must reference a Stroke published-ahead-of-print article or an article printed within the past 3 weeks. The maximum length is 750 words including no more than 5 references and 3 authors. Please submit letters typed double-spaced. Letters may be shortened or edited. Include a completed copyright transfer agreement form (available online at To the Editor: We read with interest the recent study by Chen et al, 1 which showed that intraventricular hemorrhage caused iron accumulation in the periventricular area (especially in glia-like cells) and bilateral enlargement of the lateral ventricles. We present a speculative hypothesis regarding the mechanism responsible for ventricular enlargement after intraventricular hemorrhage, based on the authors' results. Aquaporin (AQP)-4 is one of the main aquaporins in the central nervous system and acts as a water channel. 2 It is located primarily in astrocytic end-feet, glial-limiting membranes, and the basolateral membrane of the ventricular ependymal cells. 2 Qing et al 3 reported a strong correlation between iron accumulation and AQP-4 expression after intracerebral hemorrhage in rats and also found that AQP-4 upregulation was inhibited by the iron chelator, deferoxamine. Furthermore, several studies have examined the roles of AQP-4 in ventricular enlargement. Li et al 4 reported that the majority of AQP-4-null mice demonstrated smaller ventricular sizes and reduced cerebrospinal fluid production, whereas Tour-dias et al 5 reported that the degree of hydrocephalus was correlated with upregulation of AQP-4. Based on the results of these studies, we hypothesize that iron accumulation in the periventricular area after intraventricular hemorrhage may cause upregulation of AQP-4, resulting in ventricular enlargement. Further investigations into the relationships between intraventricular hemorrhage and AQP-4 are required to elucidate the mechanisms responsible for the development of hydrocephalus after intraventricular hemorrhage. Aquaporin 4 correlates with apparent diffusion coefficient and hydrocephalus severity in the rat brain: a combined MRI-histological study.