After Intracerebral Hemorrhage, Oligodendrocyte Precursors Proliferate and Differentiate Inside White-Matter Tracts in the Rat Striatum.

Michael J E Joseph,Lyanne C Schlichter,Jayalakshmi Caliaperumal

doi:10.1007/s12975-015-0445-3

Abstract

Damage to myelinated axons contributes to neurological deficits after acute CNS injury, including ischemic and hemorrhagic stroke. Potential treatments to promote re-myelination will require fully differentiated oligodendrocytes, but almost nothing is known about their fate following intracerebral hemorrhage (ICH). Using a rat model of ICH in the striatum, we quantified survival, proliferation, and differentiation of oligodendrocyte precursor cells (OPCs) (at 1, 3, 7, 14, and 28 days) in the peri-hematoma region, surrounding striatum, and contralateral striatum. In the peri-hematoma, the density of Olig2+ cells increased dramatically over the first 7 days, and this coincided with disorganization and fragmentation of myelinated axon bundles. Very little proliferation (Ki67+) of Olig2+ cells was seen in the anterior subventricular zone from 1 to 28 days. However, by 3 days, many were proliferating in the peri-hematoma region, suggesting that local proliferation expands their population. By 14 days, the density of Olig2+ cells declined in the peri-hematoma region, and, by 28 days, it reached the low level seen in the contralateral striatum. At these later times, many surviving axons were aligned into white-matter bundles, which appeared less swollen or fragmented. Oligodendrocyte cell maturation was prevalent over the 28-day period. Densities of immature OPCs (NG2+Olig2+) and mature (CC-1+Olig2+) oligodendrocytes in the peri-hematoma increased dramatically over the first week. Regardless of the maturation state, they increased preferentially inside the white-matter bundles. These results provide evidence that endogenous oligodendrocyte precursors proliferate and differentiate in the peri-hematoma region and have the potential to re-myelinate axon tracts after hemorrhagic stroke.

Highlights

Materials and MethodsIntracerebral hemorrhage (ICH) comprises 10–20 % of all stroke cases [1] and is a result of spontaneous rupture of brain arterioles, which produces a hematoma in the brain parenchyma
At 1 day, collagenase injection produced a large hematoma that was confined to the striatum, and in both coronal (Fig. 1a) and sagittal (Fig. 1b) sections, cell damage was apparent, as shown by reduced cresyl violet staining of Nissl bodies
The lateral ventricles expanded, which is a common outcome after intracerebral hemorrhage (ICH) and is due to impaired drainage of cerebrospinal fluid (CSF) [21] or tissue loss [22]

Summary

Introduction

Materials and MethodsIntracerebral hemorrhage (ICH) comprises 10–20 % of all stroke cases [1] and is a result of spontaneous rupture of brain arterioles, which produces a hematoma in the brain parenchyma. Cellular debris and breakdown of blood components initiate a secondary injury phase, which can last for days to weeks in the peri-hematoma region adjacent to the hematoma [7, 8]. Therapeutic approaches to treating ICH focus on the peri-hematoma region surrounding the lesion, and on preventing damage from spreading. In the peri-hematoma, in addition to neuronal injury, white matter is damaged but potentially rescuable. White-matter damage was reported in 77 % of ICH patients [9]. CNS white matter is comprised of axons, myelin sheaths that enwrap them, and oligodendrocytes, the cells that produce myelin [12]. Functional recovery and efficacy of potential treatments will require both axon survival and re-myelination

Results

Discussion

Conclusion