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Human umbilical cord blood cells restore brain damage induced changes in rat somatosensory cortex.

Geissler M, Dinse HR, Neuhoff S, Kreikemeier K, Meier C - PLoS ONE (2011)

Bottom Line: We found that the dimensions of cortical maps and receptive fields, which are significantly altered after injury, were largely restored.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.

View Article: PubMed Central - PubMed

Affiliation: Institut fur Neuroinformatik, Neural Plasticity Lab, Ruhr-University, Bochum, Germany.

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.

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Related in: MedlinePlus

Time line of the experiments.Time line of the experiments, indicating the time points of the surgery, the treatment and the electrophysiological and behavioural experiments.
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pone-0020194-g001: Time line of the experiments.Time line of the experiments, indicating the time points of the surgery, the treatment and the electrophysiological and behavioural experiments.

Mentions: Intraperitoneally transplanted hUCB cells migrated to the lesion and were detected in the vicinity of the insult in all animals of the transplantation group (for a time line of the experiments see Fig. 1). This was confirmed by immunohistochemical staining with antibodies recognizing the human leukocyte antigen (HLA)-DR (Fig. 2e,f). In the contralateral hemisphere, no migrated cells could be detected (Fig. 2g,h). Furthermore, histological analysis of lesioned and control brains was performed to assess the extent and location of the insult. In Klüver-Barrera stained sections of the lesion and transplantation group, the lesion was clearly detectable, of identical volume (lesion group: 114.14±11.7 mm3; transplantation group: 110.68±11.87 mm3) and comprised cortex, hippocampus, and basal ganglia of left hemispheres (Fig.2). All control animals had morphologically intact brains. The insult was further assessed immunohistochemically, demonstrating the presence of activated microglia using anti-CD68 antibodies, and the occurrence of apoptotic cells death, assessed by detection of cleaved-caspase-3.


Human umbilical cord blood cells restore brain damage induced changes in rat somatosensory cortex.

Geissler M, Dinse HR, Neuhoff S, Kreikemeier K, Meier C - PLoS ONE (2011)

Time line of the experiments.Time line of the experiments, indicating the time points of the surgery, the treatment and the electrophysiological and behavioural experiments.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3105979&req=5

pone-0020194-g001: Time line of the experiments.Time line of the experiments, indicating the time points of the surgery, the treatment and the electrophysiological and behavioural experiments.
Mentions: Intraperitoneally transplanted hUCB cells migrated to the lesion and were detected in the vicinity of the insult in all animals of the transplantation group (for a time line of the experiments see Fig. 1). This was confirmed by immunohistochemical staining with antibodies recognizing the human leukocyte antigen (HLA)-DR (Fig. 2e,f). In the contralateral hemisphere, no migrated cells could be detected (Fig. 2g,h). Furthermore, histological analysis of lesioned and control brains was performed to assess the extent and location of the insult. In Klüver-Barrera stained sections of the lesion and transplantation group, the lesion was clearly detectable, of identical volume (lesion group: 114.14±11.7 mm3; transplantation group: 110.68±11.87 mm3) and comprised cortex, hippocampus, and basal ganglia of left hemispheres (Fig.2). All control animals had morphologically intact brains. The insult was further assessed immunohistochemically, demonstrating the presence of activated microglia using anti-CD68 antibodies, and the occurrence of apoptotic cells death, assessed by detection of cleaved-caspase-3.

Bottom Line: We found that the dimensions of cortical maps and receptive fields, which are significantly altered after injury, were largely restored.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.

View Article: PubMed Central - PubMed

Affiliation: Institut fur Neuroinformatik, Neural Plasticity Lab, Ruhr-University, Bochum, Germany.

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.

Show MeSH
Related in: MedlinePlus