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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 (HI) and hUCB treatment on paired-pulse behaviour.a–c) PSTHs recorded in the left and right hemisphere of control (a), lesioned (b) and hUCB treated rats (c) at an ISI of 30 ms. Paired-pulse suppression is lost after HI, but restored after hUCB treatment. d–f) Averaged paired-pulse suppression (amplitude ratio - 2nd amplitude/1st amplitude) as a function of ISI for control (d), lesioned (e) and hUCB treated rats (f). Straight line: right, dashed line left hemisphere, asterisks indicate significant interhemispheric differences (p<0.05). The hyperexcitability observed at short ISIs in lesioned animals was ameliorated after hUCB treatment. Bars represent s.e.m. Number of rats used: control group n =  10, lesion group n =  17, hUCB group n =  6. A total of 386 paired pulse curves describing paired pulse behaviour at five different ISIs were recorded (left hemisphere: control 53: lesioned 51, treated 41; right hemisphere: control 65, lesioned 129, treated 47).
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pone-0020194-g005: Effects of hypoxic ischemic brain injury (HI) and hUCB treatment on paired-pulse behaviour.a–c) PSTHs recorded in the left and right hemisphere of control (a), lesioned (b) and hUCB treated rats (c) at an ISI of 30 ms. Paired-pulse suppression is lost after HI, but restored after hUCB treatment. d–f) Averaged paired-pulse suppression (amplitude ratio - 2nd amplitude/1st amplitude) as a function of ISI for control (d), lesioned (e) and hUCB treated rats (f). Straight line: right, dashed line left hemisphere, asterisks indicate significant interhemispheric differences (p<0.05). The hyperexcitability observed at short ISIs in lesioned animals was ameliorated after hUCB treatment. Bars represent s.e.m. Number of rats used: control group n =  10, lesion group n =  17, hUCB group n =  6. A total of 386 paired pulse curves describing paired pulse behaviour at five different ISIs were recorded (left hemisphere: control 53: lesioned 51, treated 41; right hemisphere: control 65, lesioned 129, treated 47).

Mentions: The paired pulse behaviour at short ISIs typically found in control animals consisted of a strong suppression of the second response. This behavior was quantified by calculating the ratio between the second and the first response amplitude (average ratio ISI30: 0.24±0.04, Fig. 5). At longer ISIs, suppression became increasingly smaller as indicated by increasingly higher ratios (ratio ISI50 0.37±0.04, ratio ISI80 0.75±0.07, ratio ISI120 0.72±0.04, ratio ISI200 0.73±0.04, Fig. 5).


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 (HI) and hUCB treatment on paired-pulse behaviour.a–c) PSTHs recorded in the left and right hemisphere of control (a), lesioned (b) and hUCB treated rats (c) at an ISI of 30 ms. Paired-pulse suppression is lost after HI, but restored after hUCB treatment. d–f) Averaged paired-pulse suppression (amplitude ratio - 2nd amplitude/1st amplitude) as a function of ISI for control (d), lesioned (e) and hUCB treated rats (f). Straight line: right, dashed line left hemisphere, asterisks indicate significant interhemispheric differences (p<0.05). The hyperexcitability observed at short ISIs in lesioned animals was ameliorated after hUCB treatment. Bars represent s.e.m. Number of rats used: control group n =  10, lesion group n =  17, hUCB group n =  6. A total of 386 paired pulse curves describing paired pulse behaviour at five different ISIs were recorded (left hemisphere: control 53: lesioned 51, treated 41; right hemisphere: control 65, lesioned 129, treated 47).
© Copyright Policy
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC3105979&req=5

pone-0020194-g005: Effects of hypoxic ischemic brain injury (HI) and hUCB treatment on paired-pulse behaviour.a–c) PSTHs recorded in the left and right hemisphere of control (a), lesioned (b) and hUCB treated rats (c) at an ISI of 30 ms. Paired-pulse suppression is lost after HI, but restored after hUCB treatment. d–f) Averaged paired-pulse suppression (amplitude ratio - 2nd amplitude/1st amplitude) as a function of ISI for control (d), lesioned (e) and hUCB treated rats (f). Straight line: right, dashed line left hemisphere, asterisks indicate significant interhemispheric differences (p<0.05). The hyperexcitability observed at short ISIs in lesioned animals was ameliorated after hUCB treatment. Bars represent s.e.m. Number of rats used: control group n =  10, lesion group n =  17, hUCB group n =  6. A total of 386 paired pulse curves describing paired pulse behaviour at five different ISIs were recorded (left hemisphere: control 53: lesioned 51, treated 41; right hemisphere: control 65, lesioned 129, treated 47).
Mentions: The paired pulse behaviour at short ISIs typically found in control animals consisted of a strong suppression of the second response. This behavior was quantified by calculating the ratio between the second and the first response amplitude (average ratio ISI30: 0.24±0.04, Fig. 5). At longer ISIs, suppression became increasingly smaller as indicated by increasingly higher ratios (ratio ISI50 0.37±0.04, ratio ISI80 0.75±0.07, ratio ISI120 0.72±0.04, ratio ISI200 0.73±0.04, Fig. 5).

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