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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

Effects of hypoxic ischemic brain injury and hUCB treatment on receptive field (RF) and cortical map size.a) In lesioned rats the size of the left cortical hindpaw (HP) representation was significantly reduced after hypoxic ischemic brain injury (HI) (p = 0.005 vs. controls, p = 0.004 vs. contralateral hemisphere). Treatment with hUCB cells prevented map changes in the left cortical HP representation. b)–d) images of the cortical surface of the left hemisphere of a control (b), lesioned (c) and hUCB treated rat (d). Numbers indicate penetration sites, x indicate non-cutaneous responses, hl hindlimb. Borders of the maps are outlined. Scale bar 1 mm. e) In lesioned rats RF size of the right HP was increased (p = 0.007 vs. controls, p = 0.03 vs. HP ipsilateral to the lesion). hUCB treatment lead to moderate RF increase, not significantly different from controls (p = 0.558). Bars represent s.e.m. f–h) examples of RFs on the right and left HP for a control (f), lesioned (g) and hUCB treated rat (h). Number of rats used: control group n =  10, lesion group n =  17, hUCB group n =  6. A total of 975 RFs were recorded (left hemisphere: control 127: lesioned 97, treated 85; right hemisphere: control 192, lesioned 327, treated 147).
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pone-0020194-g003: Effects of hypoxic ischemic brain injury and hUCB treatment on receptive field (RF) and cortical map size.a) In lesioned rats the size of the left cortical hindpaw (HP) representation was significantly reduced after hypoxic ischemic brain injury (HI) (p = 0.005 vs. controls, p = 0.004 vs. contralateral hemisphere). Treatment with hUCB cells prevented map changes in the left cortical HP representation. b)–d) images of the cortical surface of the left hemisphere of a control (b), lesioned (c) and hUCB treated rat (d). Numbers indicate penetration sites, x indicate non-cutaneous responses, hl hindlimb. Borders of the maps are outlined. Scale bar 1 mm. e) In lesioned rats RF size of the right HP was increased (p = 0.007 vs. controls, p = 0.03 vs. HP ipsilateral to the lesion). hUCB treatment lead to moderate RF increase, not significantly different from controls (p = 0.558). Bars represent s.e.m. f–h) examples of RFs on the right and left HP for a control (f), lesioned (g) and hUCB treated rat (h). Number of rats used: control group n =  10, lesion group n =  17, hUCB group n =  6. A total of 975 RFs were recorded (left hemisphere: control 127: lesioned 97, treated 85; right hemisphere: control 192, lesioned 327, treated 147).

Mentions: In lesioned animals, hypoxic ischemic brain damage to the left hemisphere resulted in a significant reorganization of the lesioned side of the brain, indicated by a decrease of the size of the cortical hindpaw representation (Fig. 3a and b). Electrophysiological mapping revealed that size of the left cortical hind paw representation (0.56±0.14 mm2) was significantly smaller as compared to control rats (1.73±0.17 mm2) (p =  0.005), while right hemispheres were not affected by the lesion (control animals: 1.23±0.16 mm2; lesion animals: 1.5±0.11 mm2, Fig. 3). In contrast, in left hemispheres of hUCB treated animals, despite the apparent brain damage the average map size of 1.0±0.26 mm2 did not differ significantly from that observed in control animals (1.73±0.17 mm2). Accordingly, there were no side-to-side differences in hUCB treated animals (right hemisphere: 1.2±0.22 mm2, left hemisphere: 1.0±0.26 mm2, p =  0.366), indicating that the lesion-induced shrinkage of the map could be prevented or substantially ameliorated by the treatment.


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)

Effects of hypoxic ischemic brain injury and hUCB treatment on receptive field (RF) and cortical map size.a) In lesioned rats the size of the left cortical hindpaw (HP) representation was significantly reduced after hypoxic ischemic brain injury (HI) (p = 0.005 vs. controls, p = 0.004 vs. contralateral hemisphere). Treatment with hUCB cells prevented map changes in the left cortical HP representation. b)–d) images of the cortical surface of the left hemisphere of a control (b), lesioned (c) and hUCB treated rat (d). Numbers indicate penetration sites, x indicate non-cutaneous responses, hl hindlimb. Borders of the maps are outlined. Scale bar 1 mm. e) In lesioned rats RF size of the right HP was increased (p = 0.007 vs. controls, p = 0.03 vs. HP ipsilateral to the lesion). hUCB treatment lead to moderate RF increase, not significantly different from controls (p = 0.558). Bars represent s.e.m. f–h) examples of RFs on the right and left HP for a control (f), lesioned (g) and hUCB treated rat (h). Number of rats used: control group n =  10, lesion group n =  17, hUCB group n =  6. A total of 975 RFs were recorded (left hemisphere: control 127: lesioned 97, treated 85; right hemisphere: control 192, lesioned 327, treated 147).
© Copyright Policy
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC3105979&req=5

pone-0020194-g003: Effects of hypoxic ischemic brain injury and hUCB treatment on receptive field (RF) and cortical map size.a) In lesioned rats the size of the left cortical hindpaw (HP) representation was significantly reduced after hypoxic ischemic brain injury (HI) (p = 0.005 vs. controls, p = 0.004 vs. contralateral hemisphere). Treatment with hUCB cells prevented map changes in the left cortical HP representation. b)–d) images of the cortical surface of the left hemisphere of a control (b), lesioned (c) and hUCB treated rat (d). Numbers indicate penetration sites, x indicate non-cutaneous responses, hl hindlimb. Borders of the maps are outlined. Scale bar 1 mm. e) In lesioned rats RF size of the right HP was increased (p = 0.007 vs. controls, p = 0.03 vs. HP ipsilateral to the lesion). hUCB treatment lead to moderate RF increase, not significantly different from controls (p = 0.558). Bars represent s.e.m. f–h) examples of RFs on the right and left HP for a control (f), lesioned (g) and hUCB treated rat (h). Number of rats used: control group n =  10, lesion group n =  17, hUCB group n =  6. A total of 975 RFs were recorded (left hemisphere: control 127: lesioned 97, treated 85; right hemisphere: control 192, lesioned 327, treated 147).
Mentions: In lesioned animals, hypoxic ischemic brain damage to the left hemisphere resulted in a significant reorganization of the lesioned side of the brain, indicated by a decrease of the size of the cortical hindpaw representation (Fig. 3a and b). Electrophysiological mapping revealed that size of the left cortical hind paw representation (0.56±0.14 mm2) was significantly smaller as compared to control rats (1.73±0.17 mm2) (p =  0.005), while right hemispheres were not affected by the lesion (control animals: 1.23±0.16 mm2; lesion animals: 1.5±0.11 mm2, Fig. 3). In contrast, in left hemispheres of hUCB treated animals, despite the apparent brain damage the average map size of 1.0±0.26 mm2 did not differ significantly from that observed in control animals (1.73±0.17 mm2). Accordingly, there were no side-to-side differences in hUCB treated animals (right hemisphere: 1.2±0.22 mm2, left hemisphere: 1.0±0.26 mm2, p =  0.366), indicating that the lesion-induced shrinkage of the map could be prevented or substantially ameliorated by the treatment.

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