Progress in translational research on intracerebral hemorrhage: is there an end in sight?

Abstract

Intracerebral hemorrhage (ICH) is a common and often fatal stroke subtype for which specific therapies and treatments remain elusive. To address this, many recent experimental and translational studies of ICH have been conducted, and these have led to several ongoing clinical trials. This review focuses on the progress of translational studies of ICH including those of the underlying causes and natural history of ICH, animal models of the condition, and effects of ICH on the immune and cardiac systems, among others. Current and potential clinical trials also are discussed for both ICH alone and with intraventricular extension.

Keywords: Animal models; Brain edema; Intracerebral hemorrhage; Iron.

Figure 1

CT scan showing a patient with an intracerebral hemorrhage.

Figure 2

T2 MRI (A) and Flair MRI (B) showing brain edema around hematoma at the first day in a patient with an intracerebral hemorrhage.

Figure 3. Marked perihematomal necrotic cell death in a rat model of ICH

Alexa Fluro 488-labeled dopamine- and cAMP-regulated phosphoprotein Mr 32 kDa (DARPP-32) (green) and positive staining for propidium iodide (PI; red) in the ipsilateral basal ganglia at day 3 post- intracerebral hemorrhage. DARPP-32 is a cytosolic protein highly enriched in medium-sized spiny neurons of the striatum. Plasmalemma permeability to PI is associated with markers of cell death. Scale bar = 500 μm (upper panel) and 100 μm (lower panel). The DARPP-32 negative area superimposes the PI-positive area (Jin et al 2013).

Figure 4

T2 and T2* MRI, H&E, and Perls’ staining in a rat model of intracerebral hemorrhage at 1, 3 and 14 days post-hemorrhage (Wu et al 2010).

Figure 5

A: Coronal gross H&E sections eight weeks after intracerebral hemorrhage (ICH) and treatment with vehicle or deferoxamine (DFX; 50 mg/kg). B: Caudate size expressed as a percentage of the contralateral side. Values are expressed as the means ± SD. *p<0.05, #p<0.01 vs. ICH + Vehicle group (Okauchi et al 2009).

Figure 6

Therapeutic time window of deferoxamine (DFX) for use in treating brain atrophy and improving functional outcome. A: Forelimb placing test; B: Corner turn test; C: Ventricle volume expressed as a percentage of the contralateral side at eight weeks post-intracerebral hemorrhage (ICH); D: Caudate size expressed as a percentage of the contralateral side at eight weeks post-ICH. Values are expressed as the means ±SD. *p<0.05, #p<0.01 vs. ICH+Vehicle group, respectively (Okauchi et al 2010).

Figure 7

Fluoro-Jade C positive cells in the perihematomal area (A-C) and Luxol fast blue staining (E & F) post- intracerebral hemorrhage (ICH). Fluoro-Jade C staining was used to detect neuronal degeneration. Luxol fast blue-stained was used to measure white matter. Part D shows four sampled fields for Fluoro-Jade C cell counting. Pigs had ICH and were treated with either vehicle or deferoxamine. Values are means ±SD. *p<0.05, #p<0.01 vs. vehicle, respectively. n=4. Scale bar = 50 μm (A & B) (Gu et al 2009).