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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

Histological and immunohistological analysis of brains.In Klüver-Barrera stained sections animals of the lesion group (a) and the transplantation group (b) showed clear cystic infarction within the left hemispheres, accompanied by an enlargement of the lateral ventricle and partial destruction of the hippocampus. Immunohistochemical detection of CD68 (green) and cleaved-caspase-3 expression (red) point to the occurrence of inflammation and apoptotic cell death in left hemispheres of animals of the lesion group (c) and transplantation group (d). In contrast, left hemispheres of control animals and right hemispheres of all animals were devoid of CD68 and cleaved-caspase-3 immunosignals (not shown). Immunohistochemical detection of HLA-DR demonstrated the presence of hUCB cells in the vicinity of the lesion in the transplantation group only (f), which are absent in the lesioned brain (e). No HLA-DR positive cells could be detected contralateral to the lesion in both the groups of lesioned (g) and transplanted rats (h). Scale bar left: 5 mm, scale bar right: 50 µm.
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pone-0020194-g002: Histological and immunohistological analysis of brains.In Klüver-Barrera stained sections animals of the lesion group (a) and the transplantation group (b) showed clear cystic infarction within the left hemispheres, accompanied by an enlargement of the lateral ventricle and partial destruction of the hippocampus. Immunohistochemical detection of CD68 (green) and cleaved-caspase-3 expression (red) point to the occurrence of inflammation and apoptotic cell death in left hemispheres of animals of the lesion group (c) and transplantation group (d). In contrast, left hemispheres of control animals and right hemispheres of all animals were devoid of CD68 and cleaved-caspase-3 immunosignals (not shown). Immunohistochemical detection of HLA-DR demonstrated the presence of hUCB cells in the vicinity of the lesion in the transplantation group only (f), which are absent in the lesioned brain (e). No HLA-DR positive cells could be detected contralateral to the lesion in both the groups of lesioned (g) and transplanted rats (h). Scale bar left: 5 mm, scale bar right: 50 µm.

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)

Histological and immunohistological analysis of brains.In Klüver-Barrera stained sections animals of the lesion group (a) and the transplantation group (b) showed clear cystic infarction within the left hemispheres, accompanied by an enlargement of the lateral ventricle and partial destruction of the hippocampus. Immunohistochemical detection of CD68 (green) and cleaved-caspase-3 expression (red) point to the occurrence of inflammation and apoptotic cell death in left hemispheres of animals of the lesion group (c) and transplantation group (d). In contrast, left hemispheres of control animals and right hemispheres of all animals were devoid of CD68 and cleaved-caspase-3 immunosignals (not shown). Immunohistochemical detection of HLA-DR demonstrated the presence of hUCB cells in the vicinity of the lesion in the transplantation group only (f), which are absent in the lesioned brain (e). No HLA-DR positive cells could be detected contralateral to the lesion in both the groups of lesioned (g) and transplanted rats (h). Scale bar left: 5 mm, scale bar right: 50 µm.
© Copyright Policy
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC3105979&req=5

pone-0020194-g002: Histological and immunohistological analysis of brains.In Klüver-Barrera stained sections animals of the lesion group (a) and the transplantation group (b) showed clear cystic infarction within the left hemispheres, accompanied by an enlargement of the lateral ventricle and partial destruction of the hippocampus. Immunohistochemical detection of CD68 (green) and cleaved-caspase-3 expression (red) point to the occurrence of inflammation and apoptotic cell death in left hemispheres of animals of the lesion group (c) and transplantation group (d). In contrast, left hemispheres of control animals and right hemispheres of all animals were devoid of CD68 and cleaved-caspase-3 immunosignals (not shown). Immunohistochemical detection of HLA-DR demonstrated the presence of hUCB cells in the vicinity of the lesion in the transplantation group only (f), which are absent in the lesioned brain (e). No HLA-DR positive cells could be detected contralateral to the lesion in both the groups of lesioned (g) and transplanted rats (h). Scale bar left: 5 mm, scale bar right: 50 µm.
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