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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

Length profiles of RFs.Percent activity evoked at three locations along the distal-proximal axis of the paw normalized to the activity recorded at the RF center. Data for RFs located on the heel are shown in a) and c), data for RFs with centers on the toe are depicted in b) and d). Top: recordings from the right, intact hemisphere, bottom: recordings from the left hemisphere. Stimulation locations on the paw are shown in the figurines in e). The distance from the RF centre at which 50% of neuronal activity (dashed line) was reached is indicated by arrows. Error bars represent s.e.m. For stimulation of the left paw in all groups comparable length profiles were obtained. In contrast, following stimulation of the right paw, significant differences (asterisks indicate significant differences p<0.05) were found for the length profiles obtained for control vs. lesioned animals, and for lesioned vs. treated animals, but not between control and treated rats. PSTHs recorded from neurons in the left hemisphere, whose RFswere located on the toes in control (f), lesioned (g) and transplanted rats (h) following tactile stimulation at the toe, pad, and heel. Whereas the activity evoked by stimulation on the pad and heel is low in controls (f), we found substantially enhanced activity after pad and heel stimulation in lesioned rats (g). In hUCB treated animals the activity pattern was comparable to control animals lacking the activation observed after pad and heel stimulation found in lesioned rats (h). Number of rats used: control group n =  7, lesion group n =  10, hUCB group n =  5. A total of 153 length profiles were recorded (left hemisphere: control 23: lesioned 24, treated 30; right hemisphere: control 24, lesioned 24, treated 28.
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pone-0020194-g004: Length profiles of RFs.Percent activity evoked at three locations along the distal-proximal axis of the paw normalized to the activity recorded at the RF center. Data for RFs located on the heel are shown in a) and c), data for RFs with centers on the toe are depicted in b) and d). Top: recordings from the right, intact hemisphere, bottom: recordings from the left hemisphere. Stimulation locations on the paw are shown in the figurines in e). The distance from the RF centre at which 50% of neuronal activity (dashed line) was reached is indicated by arrows. Error bars represent s.e.m. For stimulation of the left paw in all groups comparable length profiles were obtained. In contrast, following stimulation of the right paw, significant differences (asterisks indicate significant differences p<0.05) were found for the length profiles obtained for control vs. lesioned animals, and for lesioned vs. treated animals, but not between control and treated rats. PSTHs recorded from neurons in the left hemisphere, whose RFswere located on the toes in control (f), lesioned (g) and transplanted rats (h) following tactile stimulation at the toe, pad, and heel. Whereas the activity evoked by stimulation on the pad and heel is low in controls (f), we found substantially enhanced activity after pad and heel stimulation in lesioned rats (g). In hUCB treated animals the activity pattern was comparable to control animals lacking the activation observed after pad and heel stimulation found in lesioned rats (h). Number of rats used: control group n =  7, lesion group n =  10, hUCB group n =  5. A total of 153 length profiles were recorded (left hemisphere: control 23: lesioned 24, treated 30; right hemisphere: control 24, lesioned 24, treated 28.

Mentions: To scrutinize the RF-data obtained from handplotting, we additionally measured RF-length profiles using computer controlled stimulation based on recordings of PSTHs at 3 defined locations (toe, pad, heel, cf. Fig. 4 e) along the proximal-distal axis of the hindpaw. Examples of PSTHs are shown in Fig. 4f–h, which were recordedin the left hemisphere for neurons whose RF centres were located on the toes. In the lesioned animals, we recorded high levels of spiking activity following stimulation at the pad or heel indicative of large RF dimensions. In the hUCB treated animals, this abnormal response behaviour was no longer observed. As a measure of RF length we calculated that distance from the RF-center where neuronal responses in the PSTHs reached 50% of the maximal activity recorded from the RF-center (Fig. 4a–d). Average RF-length profiles obtained for the control and the treated animals were not different (p = 0.141 when RF centres were on the toes, and p = 0.830, when RF centres were on the heel), but significant differences were found between the control and the lesioned animals (p = 0.005 when RF centres were on the toes, and p<0.001when RF centres were on the heel) as well as between the lesioned and the treated animals (p<0.001for RF centres on the heel, and p<0.001for RF centers on the toes). These data confirm the observations obtained from handplotting that RF size in the treated animals do no longer show signs of lesion-induced RF-enlargement.


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)

Length profiles of RFs.Percent activity evoked at three locations along the distal-proximal axis of the paw normalized to the activity recorded at the RF center. Data for RFs located on the heel are shown in a) and c), data for RFs with centers on the toe are depicted in b) and d). Top: recordings from the right, intact hemisphere, bottom: recordings from the left hemisphere. Stimulation locations on the paw are shown in the figurines in e). The distance from the RF centre at which 50% of neuronal activity (dashed line) was reached is indicated by arrows. Error bars represent s.e.m. For stimulation of the left paw in all groups comparable length profiles were obtained. In contrast, following stimulation of the right paw, significant differences (asterisks indicate significant differences p<0.05) were found for the length profiles obtained for control vs. lesioned animals, and for lesioned vs. treated animals, but not between control and treated rats. PSTHs recorded from neurons in the left hemisphere, whose RFswere located on the toes in control (f), lesioned (g) and transplanted rats (h) following tactile stimulation at the toe, pad, and heel. Whereas the activity evoked by stimulation on the pad and heel is low in controls (f), we found substantially enhanced activity after pad and heel stimulation in lesioned rats (g). In hUCB treated animals the activity pattern was comparable to control animals lacking the activation observed after pad and heel stimulation found in lesioned rats (h). Number of rats used: control group n =  7, lesion group n =  10, hUCB group n =  5. A total of 153 length profiles were recorded (left hemisphere: control 23: lesioned 24, treated 30; right hemisphere: control 24, lesioned 24, treated 28.
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Related In: Results  -  Collection

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getmorefigures.php?uid=PMC3105979&req=5

pone-0020194-g004: Length profiles of RFs.Percent activity evoked at three locations along the distal-proximal axis of the paw normalized to the activity recorded at the RF center. Data for RFs located on the heel are shown in a) and c), data for RFs with centers on the toe are depicted in b) and d). Top: recordings from the right, intact hemisphere, bottom: recordings from the left hemisphere. Stimulation locations on the paw are shown in the figurines in e). The distance from the RF centre at which 50% of neuronal activity (dashed line) was reached is indicated by arrows. Error bars represent s.e.m. For stimulation of the left paw in all groups comparable length profiles were obtained. In contrast, following stimulation of the right paw, significant differences (asterisks indicate significant differences p<0.05) were found for the length profiles obtained for control vs. lesioned animals, and for lesioned vs. treated animals, but not between control and treated rats. PSTHs recorded from neurons in the left hemisphere, whose RFswere located on the toes in control (f), lesioned (g) and transplanted rats (h) following tactile stimulation at the toe, pad, and heel. Whereas the activity evoked by stimulation on the pad and heel is low in controls (f), we found substantially enhanced activity after pad and heel stimulation in lesioned rats (g). In hUCB treated animals the activity pattern was comparable to control animals lacking the activation observed after pad and heel stimulation found in lesioned rats (h). Number of rats used: control group n =  7, lesion group n =  10, hUCB group n =  5. A total of 153 length profiles were recorded (left hemisphere: control 23: lesioned 24, treated 30; right hemisphere: control 24, lesioned 24, treated 28.
Mentions: To scrutinize the RF-data obtained from handplotting, we additionally measured RF-length profiles using computer controlled stimulation based on recordings of PSTHs at 3 defined locations (toe, pad, heel, cf. Fig. 4 e) along the proximal-distal axis of the hindpaw. Examples of PSTHs are shown in Fig. 4f–h, which were recordedin the left hemisphere for neurons whose RF centres were located on the toes. In the lesioned animals, we recorded high levels of spiking activity following stimulation at the pad or heel indicative of large RF dimensions. In the hUCB treated animals, this abnormal response behaviour was no longer observed. As a measure of RF length we calculated that distance from the RF-center where neuronal responses in the PSTHs reached 50% of the maximal activity recorded from the RF-center (Fig. 4a–d). Average RF-length profiles obtained for the control and the treated animals were not different (p = 0.141 when RF centres were on the toes, and p = 0.830, when RF centres were on the heel), but significant differences were found between the control and the lesioned animals (p = 0.005 when RF centres were on the toes, and p<0.001when RF centres were on the heel) as well as between the lesioned and the treated animals (p<0.001for RF centres on the heel, and p<0.001for RF centers on the toes). These data confirm the observations obtained from handplotting that RF size in the treated animals do no longer show signs of lesion-induced RF-enlargement.

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