No abstract

Umbilical cord blood can be a rich source of stem/progenitor cells, not only for hematopoetic but also for other tissue-specific lineages. Recently, we have developed a novel, self-renewed neural-like stem cell line named HUCB-NSC from human cord blood. To test if HUCB-NSCs can supply brain in need of regeneration, we injected these cells into immunosuppressed intact rat forebrain and to animals suffering from a photothrombotic cortical lesion at 48 h after injury. The survival, migration, and differentiation of the transplanted HUCB-NSCs were measured at 7 and 30 days post-transplantation by immunohistochemical methods. Results show survival and extensive migration of transplanted neural-like progenitors into damaged brain cortex during the first week of post-stroke recovery. The donor cells accumulated mainly in peri-infarct area and then differentiated showing a strong co-expression of neuronal (NF-200) but only moderate of astrocytic (GFAP) cell markers. However, the paucity of HUCB-NSCs detected within post-ischemic rat brain at the end of a 1 month period, as well as acute rejection of grafted cells by intact, yet cyclosporin A (CsA) immunosuppressed, rat brain tissue, suggests development of a severe adverse host reaction to the presence of alien donor cells and an urgent need for further study of the immunological response evoked by xenotransplantations of human cord blood-derived cells in animal experimental models.

Spontaneous restorative plasticity is reported frequently after stroke. To test whether conditions in perinfarct cortex facilitate plastic changes, we examined experience-dependent plasticity of cortical functional representation of vibrissae in rat brain after focal photothrombotic stroke. Cortical activation was visualized with [C]2-deoxyglucose. To induce plasticity, four rows of whiskers were trimmed on one side of the snout for a month, whereas one row was spared. This deprivation was started immediately after the stroke. In control rats, cortical representation of the spared row whiskers was significantly enlarged compared with undeprived controls. In rats with infarct posterior to the barrel cortex, no plastic change of the spared row representation was observed. We conclude that early after stroke, use-dependent plasticity is impaired in the perinfarct cortex.

Despite indications that brain plasticity may be enhanced after stroke, we have described impairment of experience-dependent plasticity in rat cerebral cortex neighboring the stroke-induced lesion. Photothrombotic stroke was centered behind the barrel cortex in one cerebral hemisphere of rats. Plasticity of cortical representation of one row of vibrissae was induced by sensory deprivation of all surrounding whiskers for 1 month, and visualized with [(14)C]-2-deoxyglucose autoradiography. In control rats deprivation resulted in an enlargement of functional cortical representation of the spared row of vibrissae. After a focal stroke neighbouring the barrel cortex, no plasticity of the spared row representation was found. Investigation of plastic changes with deprivation initiated 1 week and 1 month after stroke have shown that later poststroke onset of deprivation resulted in a partial recovery of cortical plasticity in the barrel field. Western blot analysis of proinflammatory enzyme cyclooxygenase-2 (COX-2) expression revealed its strong upregulation in the barrel cortex 24 h after stroke. When chronic treatment with the anti-inflammatory drug ibuprofen (10 mg/kg or 20 mg/kg) accompanied deprivation, plasticity was restored. Ibuprofen applied before the ischemia also prevented the poststroke upregulation of COX-2. The results strongly suggest that poststroke impairment of experience-dependent cortical plasticity is caused by stroke-induced inflammatory reactions that subside with poststroke delay and can be at least partially ameliorated by pharmacological treatment.