Intracerebral Hematoma Contributes to Hydrocephalus After Intraventricular Hemorrhage via Aggravating Iron Accumulation.
OBJECTIVE
The intraventricular hemorrhage (IVH) secondary to intracerebral hemorrhage (ICH) was reported to be relevant to a higher incidence of hydrocephalus, which would result in poorer outcomes for patients with ICH. However, the mechanisms responsible for this relationship remain poorly characterized. Thus, this study was designed to further explore the development and progression of hydrocephalus after secondary IVH.


METHODS
Autologous blood injection model was induced to mimic ICH with ventricular extension (ICH/IVH) or primary IVH in Sprague-Dawley rats. Magnetic resonance imaging, Morris water maze, brain water content, Evans blue extravasation, immunohistochemistry staining, Western blot, iron determination, and electron microscopy were used in these rats. Then, deferoxamine treatment was used to clarify the involvement of iron in the development of hydrocephalus.


RESULTS
Despite the injection of equivalent blood volumes, ICH/IVH resulted in more significant ventricular dilation, ependymal cilia damage, and iron overload, as well as more severe early brain injury and neurological deficits compared with IVH alone. Systemic deferoxamine treatment more effectively reduced ventricular enlargement in ICH/IVH compared with primary IVH.


CONCLUSIONS
Our results show that ICH/IVH caused more significant chronic hydrocephalus and iron accumulation than primary IVH alone. Intracerebral hematoma plays a vital role in persistent iron overload and aggravated hydrocephalus after ICH/IVH.
From the Department of Neurosurgery, Southwest Hospital, Third Military Medical University, Chongqing, China (Q.C., J.T., L.T., J.G., Y.T., L.L., Y.C., X.L., Z.C., H.F.); and Department of Anesthesia, Neurosurgery and Physiology, Loma Linda University, CA (J.H.Z.).
Qianwei
Q
Chen
From the Department of Neurosurgery, Southwest Hospital, Third Military Medical University, Chongqing, China (Q.C., J.T., L.T., J.G., Y.T., L.L., Y.C., X.L., Z.C., H.F.); and Department of Anesthesia, Neurosurgery and Physiology, Loma Linda University, CA (J.H.Z.).
Jun
J
Tang
From the Department of Neurosurgery, Southwest Hospital, Third Military Medical University, Chongqing, China (Q.C., J.T., L.T., J.G., Y.T., L.L., Y.C., X.L., Z.C., H.F.); and Department of Anesthesia, Neurosurgery and Physiology, Loma Linda University, CA (J.H.Z.).
Liang
L
Tan
From the Department of Neurosurgery, Southwest Hospital, Third Military Medical University, Chongqing, China (Q.C., J.T., L.T., J.G., Y.T., L.L., Y.C., X.L., Z.C., H.F.); and Department of Anesthesia, Neurosurgery and Physiology, Loma Linda University, CA (J.H.Z.).
Jing
J
Guo
From the Department of Neurosurgery, Southwest Hospital, Third Military Medical University, Chongqing, China (Q.C., J.T., L.T., J.G., Y.T., L.L., Y.C., X.L., Z.C., H.F.); and Department of Anesthesia, Neurosurgery and Physiology, Loma Linda University, CA (J.H.Z.).
Yihao
Y
Tao
From the Department of Neurosurgery, Southwest Hospital, Third Military Medical University, Chongqing, China (Q.C., J.T., L.T., J.G., Y.T., L.L., Y.C., X.L., Z.C., H.F.); and Department of Anesthesia, Neurosurgery and Physiology, Loma Linda University, CA (J.H.Z.).
Lin
L
Li
From the Department of Neurosurgery, Southwest Hospital, Third Military Medical University, Chongqing, China (Q.C., J.T., L.T., J.G., Y.T., L.L., Y.C., X.L., Z.C., H.F.); and Department of Anesthesia, Neurosurgery and Physiology, Loma Linda University, CA (J.H.Z.).
Yujie
Y
Chen
From the Department of Neurosurgery, Southwest Hospital, Third Military Medical University, Chongqing, China (Q.C., J.T., L.T., J.G., Y.T., L.L., Y.C., X.L., Z.C., H.F.); and Department of Anesthesia, Neurosurgery and Physiology, Loma Linda University, CA (J.H.Z.).
Xin
X
Liu
From the Department of Neurosurgery, Southwest Hospital, Third Military Medical University, Chongqing, China (Q.C., J.T., L.T., J.G., Y.T., L.L., Y.C., X.L., Z.C., H.F.); and Department of Anesthesia, Neurosurgery and Physiology, Loma Linda University, CA (J.H.Z.).
John H
JH
Zhang
From the Department of Neurosurgery, Southwest Hospital, Third Military Medical University, Chongqing, China (Q.C., J.T., L.T., J.G., Y.T., L.L., Y.C., X.L., Z.C., H.F.); and Department of Anesthesia, Neurosurgery and Physiology, Loma Linda University, CA (J.H.Z.). zhichen@tmmu.edu.cn fenghua8888@vip.163.com.
Zhi
Z
Chen
From the Department of Neurosurgery, Southwest Hospital, Third Military Medical University, Chongqing, China (Q.C., J.T., L.T., J.G., Y.T., L.L., Y.C., X.L., Z.C., H.F.); and Department of Anesthesia, Neurosurgery and Physiology, Loma Linda University, CA (J.H.Z.). zhichen@tmmu.edu.cn fenghua8888@vip.163.com.
Hua
H
Feng
D000818:Animals; D001522:Behavior, Animal; D015153:Blotting, Western; D002543:Cerebral Hemorrhage / Q000150:complications / Q000378:metabolism* / Q000473:pathology; D002552:Cerebral Ventricles; D002923:Cilia / Q000648:ultrastructure; D004195:Disease Models, Animal; D004805:Ependyma / Q000473:pathology / Q000648:ultrastructure; D005293:Ferritins / Q000378:metabolism*; D006406:Hematoma / Q000150:complications / Q000378:metabolism* / Q000473:pathology; D006624:Hippocampus / Q000473:pathology; D006849:Hydrocephalus / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D007150:Immunohistochemistry; D007501:Iron / Q000134:cerebrospinal fluid / Q000378:metabolism*; D008279:Magnetic Resonance Imaging; D008297:Male; D008854:Microscopy, Electron; D009483:Neuropsychological Tests; D009929:Organ Size; D051381:Rats; D017207:Rats, Sprague-Dawley
D005293:Ferritins; D007501:Iron
brain injuries; cerebral hemorrhage; cerebrospinal fluid; hydrocephalus; iron