Abstract
Intraperitoneal transplantation of human umbilical cord blood (hUCB) cells has been shown to reduce sensorimotor deficits after hypoxic ischemic brain injury in neonatal rats. However, the neuronal correlate of the functional recovery and how such a treatment enforces plastic remodelling at the level of neural processing remains elusive. Here we show by in-vivo recordings that hUCB cells have the capability of ameliorating the injury-related impairment of neural processing in primary somatosensory cortex. Intact cortical processing depends on a delicate balance of inhibitory and excitatory transmission, which is disturbed after injury. We found that the dimensions of cortical maps and receptive fields, which are significantly altered after injury, were largely restored. Additionally, the lesion induced hyperexcitability was no longer observed in hUCB treated animals as indicated by a paired-pulse behaviour resembling that observed in control animals. The beneficial effects on cortical processing were reflected in an almost complete recovery of sensorimotor behaviour. Our results demonstrate that hUCB cells reinstall the way central neurons process information by normalizing inhibitory and excitatory processes. We propose that the intermediate level of cortical processing will become relevant as a new stage to investigate efficacy and mechanisms of cell therapy in the treatment of brain injury.
Highlights
Cell therapy has become a promising therapeutic option for many human diseases, injuries and stroke [1,2,3,4,5,6,7]
To study the cortical changes evoked by lesion and following human umbilical cord blood (hUCB)-treatment we performed electrophysiological in vivo recordings in primary somatosensory cortex (SI)
This was confirmed by immunohistochemical staining with antibodies recognizing the human leukocyte antigen (HLA)-DR (Fig. 2e,f)
Summary
Cell therapy has become a promising therapeutic option for many human diseases, injuries and stroke [1,2,3,4,5,6,7]. The intraperitoneal transplantation of the mononuclear fraction of human umbilical cord blood (hUCB) cells has been successfully applied in the treatment of perinatal hypoxic ischemic brain injury [8,9], models of stroke [10,11,12] or other diseases [13,14]. We hypothesized that beneficial effects of hUCB treatment, which become apparent behaviourally, must be observable at an intermediate processing level and should be measurable as a normalization of cortical receptive fields, maps and temporal processing abilities. To analyze spatial and temporal tactile processing we measured in both hemispheres the size of the cortical hind paw representation, the size of receptive fields (RFs), and cortical excitability with a tactile paired-pulse stimulation protocol. Using a combination of immunohistochemical, electrophysiological and behavioural studies in a rat model of hypoxic ischemic brain injury, we here demonstrate that hUCB transplantation largely normalizes spatial and temporal cortical processing
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