Transplantation of neural stem cells modulates apolipoprotein E expression in a rat model of stroke.

The expression of apolipoprotein E (apoE) after ischemic brain damage has been associated with plasticity involved in promoting functional recovery. We therefore examined the expression and distribution of apoE in rats that received intraparenchymal grafts of the conditionally immortal stem cell line MHP36 either ipsilateral or contralateral to the lesion or intraventricular grafts 4 months after transplantation. ApoE immunoreactivity was highly expressed in the striatum, somatosensory cortex, and thalamus of the lesioned hemisphere in all rats subjected to middle cerebral artery occlusion. Only in rats with intraparenchymal grafts, apoE was significantly upregulated in the contralateral hemisphere, whereas levels and distribution in rats with intraventricular grafts resembled those of ischemic controls. In ischemic rats, apoE was seen in both astrocytes and neurons on the lesioned side, and in grafted rats, apoE was present in host and transplanted neurons and astrocytes. Previously we have shown that intraparenchymal grafts reduced sensorimotor asymmetry, whereas intraventricular grafts improved cognitive dysfunction, with transplanted cells being widely distributed in cortex, striatum, and corpus callosum on both sides of the brain in all grafted groups. Thus, stem cells grafted in the parenchyma are not only capable of limited expression of apoE in the host brain but also trigger a robust increase on the side contralateral to stroke damage where this does not normally occur. Findings that parenchymal, but not ventricular, grafts facilitated sensorimotor recovery suggests that apoE might contribute to plastic changes in relevant pathways, possibly on both sides of the brain. In contrast, no evidence was found for an association between apoE and recovery of cognitive function in rats with intraventricular grafts.