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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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Assessment of the sensorimotor skills.The beneficial effects of hUCB treatment were confirmed by the evaluation of the sensorimotor status a) Using the forelimb use asymmetry test we found that lesioned rats were significantly impaired in the right forepaw use compared to controls (p = 0.025) and compared to the left paw (p = 0.015). In contrast, rats treated with hUCB cells showed no differences compared to controls (p = 0.981) and no differences in use between left and right paw (p = 0.184). Bars represent s.e.m. b) Recording footprints of the hindpaws revealed a reduced toespread indicative of spastic paresis in lesioned rats compared to controls (p =  0.038), but normal toespread not different from controls in hUCB-treated rats (p =  0.592). Bars represent s.e.m. Number of rats used: control group n =  10, lesion group n =  19, hUCB group n =  6.
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pone-0020194-g006: Assessment of the sensorimotor skills.The beneficial effects of hUCB treatment were confirmed by the evaluation of the sensorimotor status a) Using the forelimb use asymmetry test we found that lesioned rats were significantly impaired in the right forepaw use compared to controls (p = 0.025) and compared to the left paw (p = 0.015). In contrast, rats treated with hUCB cells showed no differences compared to controls (p = 0.981) and no differences in use between left and right paw (p = 0.184). Bars represent s.e.m. b) Recording footprints of the hindpaws revealed a reduced toespread indicative of spastic paresis in lesioned rats compared to controls (p =  0.038), but normal toespread not different from controls in hUCB-treated rats (p =  0.592). Bars represent s.e.m. Number of rats used: control group n =  10, lesion group n =  19, hUCB group n =  6.

Mentions: The beneficial effects of the hUCB treatment, which resulted in a normalization of cortical processing, were further substantiated by the evaluation of the sensorimotor status of each individual rat (Fig. 6). Using the forelimb use asymmetry test [37] we quantified the percentage of impaired vs. non-impaired forelimb use during spontaneous vertical explorative behaviour. We found that the use of right forepaws in lesioned rats was significantly impaired as compared to controls (lesion: 7%±1%, control 14%±3%; p =  0.025). In contrast, rats treated with hUCB cells (transplantation group) showed no differences compared to controls (treated: 14%±4%, control 14%±3%; p =  0.981). In addition, footprints were recorded to assess sensorimotor skills of the hindpaws. Toe distance 1–5 was significantly reduced in lesioned rats (1.75±0.01 cm) compared to controls (1.87±0.02 cm), indicative of development of spastic paresis due to the lesion. In hUCB-treated rats, we observed normal toe distances (1.82±0.02 cm), which did not differ significantly from controls (p =  0.592).


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)

Assessment of the sensorimotor skills.The beneficial effects of hUCB treatment were confirmed by the evaluation of the sensorimotor status a) Using the forelimb use asymmetry test we found that lesioned rats were significantly impaired in the right forepaw use compared to controls (p = 0.025) and compared to the left paw (p = 0.015). In contrast, rats treated with hUCB cells showed no differences compared to controls (p = 0.981) and no differences in use between left and right paw (p = 0.184). Bars represent s.e.m. b) Recording footprints of the hindpaws revealed a reduced toespread indicative of spastic paresis in lesioned rats compared to controls (p =  0.038), but normal toespread not different from controls in hUCB-treated rats (p =  0.592). Bars represent s.e.m. Number of rats used: control group n =  10, lesion group n =  19, hUCB group n =  6.
© Copyright Policy
Related In: Results  -  Collection

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

pone-0020194-g006: Assessment of the sensorimotor skills.The beneficial effects of hUCB treatment were confirmed by the evaluation of the sensorimotor status a) Using the forelimb use asymmetry test we found that lesioned rats were significantly impaired in the right forepaw use compared to controls (p = 0.025) and compared to the left paw (p = 0.015). In contrast, rats treated with hUCB cells showed no differences compared to controls (p = 0.981) and no differences in use between left and right paw (p = 0.184). Bars represent s.e.m. b) Recording footprints of the hindpaws revealed a reduced toespread indicative of spastic paresis in lesioned rats compared to controls (p =  0.038), but normal toespread not different from controls in hUCB-treated rats (p =  0.592). Bars represent s.e.m. Number of rats used: control group n =  10, lesion group n =  19, hUCB group n =  6.
Mentions: The beneficial effects of the hUCB treatment, which resulted in a normalization of cortical processing, were further substantiated by the evaluation of the sensorimotor status of each individual rat (Fig. 6). Using the forelimb use asymmetry test [37] we quantified the percentage of impaired vs. non-impaired forelimb use during spontaneous vertical explorative behaviour. We found that the use of right forepaws in lesioned rats was significantly impaired as compared to controls (lesion: 7%±1%, control 14%±3%; p =  0.025). In contrast, rats treated with hUCB cells (transplantation group) showed no differences compared to controls (treated: 14%±4%, control 14%±3%; p =  0.981). In addition, footprints were recorded to assess sensorimotor skills of the hindpaws. Toe distance 1–5 was significantly reduced in lesioned rats (1.75±0.01 cm) compared to controls (1.87±0.02 cm), indicative of development of spastic paresis due to the lesion. In hUCB-treated rats, we observed normal toe distances (1.82±0.02 cm), which did not differ significantly from controls (p =  0.592).

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