Frank Hamers - Academia.edu (original) (raw)
Papers by Frank Hamers
Neurosurgery, 1997
OBJECTIVE Melanocortins, peptides related to melanocyte-stimulating hormone (MSH) and corticotrop... more OBJECTIVE Melanocortins, peptides related to melanocyte-stimulating hormone (MSH) and corticotropin (ACTH), exhibit neurotrophic and neuroprotective activity in several established models of peripheral and central nervous system damage. The beneficial effects of melanocortins on functional recovery after experimental brain damage and central demyelinating diseases have prompted us to investigate alpha MSH treatment in a weight drop model of traumatic spinal cord injury in rats. METHODS In two independent randomized blinded experiments, treatment with either alpha MSH (75 micrograms/kg of body weight administered subcutaneously every 48 h for 3 weeks after trauma) or single high-dose (30 mg/kg, 30 min after injury) methylprednisolone was compared with saline treatment in rats subjected to a moderately severe 20-gcm weight drop injury. Spinal cord function was monitored using behavioral, electrophysiological, and histological parameters. RESULTS In both experiments, alpha MSH significantly improved recovery, as illustrated by Tarlov scores, thoracolumbar height, and amplitude of rubrospinal motor evoked potentials. The magnitude of the alpha MSH effect on motor performance was comparable with the one observed after treatment with methylprednisolone. CONCLUSION The reproducible neurological and electrophysiological improvement in spinal cord function of animals treated with alpha MSH suggests a new lead in the treatment of traumatic spinal cord injury.
Experimental Neurology, Nov 1, 2006
We previously demonstrated that the tetraspanin protein CD81 is up-regulated by astrocytes and mi... more We previously demonstrated that the tetraspanin protein CD81 is up-regulated by astrocytes and microglia after traumatic spinal cord injury in rats and that CD81 is involved in adhesion and proliferation of cultured astrocytes and microglia. Since these reactive glial cells contribute to secondary damage and glial scar formation, we studied the effect of local administration of an anti-CD81 antibody in experimental spinal cord injury. Adult rats were subjected to a moderate spinal cord contusion injury and treated for 2 weeks with different doses of the anti-CD81 antibody AMP1 (0.5-5 μg/h) or non-immune IgG (5.0 μg/h). A technique was developed to infuse the antibodies directly into the lesion site via an intraspinal cannula connected to a pump. Functional recovery was monitored during 8 postoperative weeks by means of the Basso, Beattie and Bresnahan (BBB) locomotor rating scale, the BBB subscore and Grid-walk test. At the end of the study, quantitative histology was performed to assess tissue sparing. Our data showed that by itself cannulation of the lesion site resulted in minimal functional and histological impairments. Application of 0.5 μg/h AMP1 resulted in a marked functional recovery (BBB 2 points; Grid-walk 30% less errors compared to control). This recovery was accompanied by an 18% increase in tissue sparing at the lesion epicentre. No gross histological changes in glial scarring were apparent. Our data demonstrate beneficial effects of an anti-CD81 antibody on functional recovery in spinal cord injured rats and suggest that this effect is mediated through a reduction in secondary tissue loss.
Journal of Neuroscience Research, Apr 15, 2000
In many patients treated with cisplatin a peripheral sensory neuropathy develops. This side-effec... more In many patients treated with cisplatin a peripheral sensory neuropathy develops. This side-effect is considered dose-limiting, and therefore restricts the total dose of cisplatin that can be administered. Recent in vitro and in vivo studies suggest that recombinant human Glial Growth Factor 2 (rhGGF2) has neuroprotective effects. This prompted us to investigate in a rat model whether rhGGF2 ameliorates cisplatin neuropathy. A total of 48 rats were randomly divided into four groups of 12 rats each. Three groups received cisplatin and were treated with either 0.1 mg/kg rhGGF2, 0.3 mg/kg rhGGF2 or placebo. The fourth group (saline/placebo) served as age-matched controls. In the cisplatin/placebo treated rats a neuropathy developed, as determined by measurements of the nerve conduction velocity (NCV). Treatment with rhGGF2 dose-dependently protected against the neuropathy. Histological examination and morphometric analysis revealed that rhGGF2 also protects against cisplatin-induced changes in the morphology and size of DRG satellite cell nuclei. In a control study rhGGF2 did not affect normal NCV development. We conclude that rhGGF2 treatment is of benefit in the treatment of cisplatin neuropathy in the rat.
Journal of Neurotrauma, 2006
The purpose of this study was to compare spontaneous functional recovery after different spinal m... more The purpose of this study was to compare spontaneous functional recovery after different spinal motor tract lesions in the rat spinal cord using three methods of analysis, the BBB, the rope test, and the CatWalk. We transected the dorsal corticospinal tract (CSTx) or the rubrospinal tract (RSTx) or the complete dorsal half of the spinal cord (Hx) at thoracic level T8. Functional recovery was monitored for 31 weeks. We found no recovery of consistent inter limb coordination in any experimental group over time using the BBB locomotor rating scale. Quantitative CatWalk analysis revealed significant differences between experimental groups for inter limb coordination (RI). RSTx and Hx animals showed a significant decrease in the RI, and only in the RSTx group did the RI improve from 6 weeks post-lesion onward. Significant differences between experimental groups in step sequence patterns and base of support were also observed. In the rope test all experimental groups had significantly higher error percentages compared to control animals. Tracing of the CST revealed enhanced collateral formation rostral to the lesion in the CSTx group, not in other groups. The results presented here show that locomotor function in all, but CSTx groups gradually improved over time. This is important for studies that employ pharmacological, cell-, and/or gene therapy-based interventions to improve axonal regeneration and functional recovery after spinal cord injury.
Journal of Neurotrauma, Oct 1, 2003
We have recently shown that enriched environment (EE) housing significantly enhances locomotor re... more We have recently shown that enriched environment (EE) housing significantly enhances locomotor recovery following spinal cord contusion injury (SCI) in rats. As the type and intensity of locomotor training with EE housing are rather poorly characterized, we decided to compare the effectiveness of EE housing with that of voluntary wheel running, the latter of which is both well characterized and easily quantified. Female Wistar rats were made familiar with three types of housing conditions, social housing (nine together) in an EE (EHC), individual housing in a running wheel cage (RUN, n = 8), and standard housing two together (CON, n = 10). Subsequently, a 12.5 gcm SCI at Th8 was produced and animals were randomly divided over the three housing conditions. Locomotor function was measured regularly, once a week by means of the BBB score, BBB sub score, TLH test, Gridwalk test, and CatWalk test. In the RUN group, daily distance covered was also measured. Locomotor recovery in the EHC and the RUN groups was equal and significantly better than in the CON group. The extent of recovery at 8 weeks post injury in the RUN group did not correlate with distance covered. We conclude that locomotor training needs to exceed a given threshold in order to be effective in enhancing locomotor recovery in this experimental model, but that once this threshold is exceeded no further improvement occurs, and that the specificity of locomotor training plays little role.
Pain, Mar 1, 2003
A characteristic symptom of neuropathic pain is mechanical allodynia. In animal models of neuropa... more A characteristic symptom of neuropathic pain is mechanical allodynia. In animal models of neuropathic pain, mechanical allodynia is often assessed using von Frey filaments. Although the forces applied with these filaments are highly reproducible, there are various disadvantages of using this method. Testing paradigms and definitions of withdrawal threshold are not standardised. Moreover, measurements may be influenced by various conditions, such as ambient temperature, humidity, weight bearing of the limb and stress. We have therefore investigated another technique to assess mechanical allodynia, the 'CatWalk' automated quantitative gait analysis. With this computer-assisted method of locomotor analysis, it is possible to objectively and rapidly quantify several gait parameters, including duration of different phases of the step cycle and pressure applied during locomotion. We tested rats with a chronic constriction injury of the sciatic nerve, a model of neuropathic pain, both with von Frey filaments and the CatWalk method. We demonstrate that these rats minimise contact with the affected paw during locomotion, as demonstrated by a reduction in stance phase and pressure applied during stance. Moreover, these parameters show a high degree of correlation with mechanical withdrawal thresholds as determined by von Frey filaments. We therefore suggest that the CatWalk method might serve as an additional tool in the investigation of mechanical allodynia.
Brain Research, Mar 1, 2000
Ž. To date, relatively little progress has been made in the treatment of spinal cord injury SCI-r... more Ž. To date, relatively little progress has been made in the treatment of spinal cord injury SCI-related neurological impairments. Until Ž. now, methylprednisolone MP is the only agent with clinically proven beneficial effect on functional outcome after SCI. Although the mechanism of action is not completely clear, experimental data point to protection against membrane peroxidation and edema reduction. The melanocortin melanotropin is known to improve axonal regeneration following sciatic nerve injury, and to stimulate corticospinal outgrowth after partial spinal cord transection. Recently, we showed that intrathecally administered a MSH had beneficial effects on Ž. functional recovery after experimental SCI. Since both drugs have shown their value in intervention studies after experimental spinal Ž. cord injury ESCI , we decided to study the effects of combined treatment. Our results again showed that a MSH enhances functional recovery after ESCI in the rat and that MP, although not affecting functional recovery adversely by itself, abolished the effects observed with a MSH when combined. Our data, thus, suggest that the mechanism of action of MP interferes with that of a MSH.
The Journal of Steroid Biochemistry and Molecular Biology, Sep 1, 1992
Cancer Chemotherapy and Pharmacology, 1993
Physiology & Behavior, Dec 1, 2007
A variety of animal models for neurological disease and injury exist and locomotor performance is... more A variety of animal models for neurological disease and injury exist and locomotor performance is an important outcome parameter in studies employing these models. The CatWalk, an automated quantitative gait analysis method is a method to study over-ground locomotor performance in large groups of animals. In the present study, we used the CatWalk which allowed us to investigate strain differences in over-ground locomotion in three commonly used strains of laboratory rat (i.e. Lewis, Wistar and Sprague-Dawley rats) based on objective data-analysis in a large number of animals. The present results revealed marked strain differences on the static paw parameters; base-of-support, and the relative paw position. Furthermore, strain differences were noted on the static parameter stride length and the dynamic parameters stance-, swing- and stepcycle duration, which are due logically to morphological differences between strains. The parameters related to coordination did not reveal any differences between the strains. Furthermore, the swing duration and the cruciate and alternate patterns i.e. regular step patterns Ca ("cruciate" pattern type a) and Ab ("alternate" pattern type b) were shown to be differentially affected by the locomotor speed. We conclude that differences in gait traits exist between the three laboratory rat strains investigated and several of the examined gait parameters showed strain dependent interdependency with locomotor speed.
Journal of Neuroscience Research, 2004
The use of collagen as a vehicle to transplant neonatal astroglial cells into the lesioned spinal... more The use of collagen as a vehicle to transplant neonatal astroglial cells into the lesioned spinal cord of the adult rat allows a precise application of these cells into the lesion gap and minimizes the migration of the transplanted cells. This approach might lead to anatomical and functional recovery. In the present study, 20 adult female Wistar rats were subjected to a dorsal hemisection at thoracic spinal cord levels. Cultured cortical neonatal rat astrocytes were transplanted into the lesion with collagen as a vehicle (N = 10). Prior to transplantation, the cultured astroglial cells were labelled with fast blue. Control rats received collagen implants only (N = 10). During 1 month of survival time, functional recovery of all rats was continuously monitored. Histological data showed that the prelabelled astroglial cells survived transplantation and were localized predominantly in the collagen implant. Virtually no fast blue‐labelled GFAP‐positive astroglial cells migrated out of the implant into the adjacent host spinal cord. The presence of transplanted neonatal astroglial cells resulted in a significant increase in the number of ingrowing neurofilament‐positive fibers (including anterogradely labeled corticospinal axons) into the implant. Ingrowing fibers were closely associated with the transplanted astroglial cells. The implantation of neonatal astroglial cells did result in modest temporary improvements of locomotor recovery as observed during open‐field locomotion analysis (BBB subscore) or during crossing of a walkway (catwalk). © 2004 Wiley‐Liss, Inc.
Journal of Neurotrauma, Apr 1, 2006
Journal of Neuroscience Research, Jun 1, 1993
Journal of Neuroscience Research, Apr 15, 1996
Journal of the Neurological Sciences, Nov 1, 1994
Journal of Neurotrauma, Dec 1, 1996
To evaluate new pharmacologic agents with potentially beneficial effects on posttraumatic spinal ... more To evaluate new pharmacologic agents with potentially beneficial effects on posttraumatic spinal cord function, we used a modified weight drop (WD) technique to induce spinal cord injuries. These contusive spinal cord injuries in the rat closely mimic the human clinicopathologic situation. Especially for drug screening purposes, the moderate and mild injuries are of interest, as both the beneficial and potentially harmful effects of experimental treatment can be detected. In this study, we describe two new functional tests that were particularly designed to detect small differences in spinal cord function after moderate and mild injuries. First, for examination of locomotion, a computer analysis of the thoracolumbar height (TLH) was designed. Second, for investigation of the conduction properties of the injured rat spinal cord, we measured rubrospinal motor evoked potentials (MEP). The efficacy of the new assessment techniques to monitor spinal cord function was compared to Tarlov scores and to morphometric analysis of preserved white matter at the injury site. The results of this study indicated that for behavioral analysis, TLH measurements as compared with Tarlov rating appeared to be more sensitive for exact and objective discrimination between small differences in motor function. Amplitudes of the rubrospinal MEP, but not latencies or the number of peaks, proved to be most sensitive to determine subtle differences in posttraumatic spinal cord function. A significant linear correlation was found between TLH and amplitude of the rubrospinal MEP. We conclude that for objective assessment of the spinal cord after moderate and mild contusive injury, TLH and rubrospinal MEP amplitudes are very valuable measures to demonstrate small functional differences.
Journal of Neurotrauma, Apr 1, 1999
Melanocortins, peptides related to alpha-melanocortin-stimulating hormone (alpha MSH) and adrenoc... more Melanocortins, peptides related to alpha-melanocortin-stimulating hormone (alpha MSH) and adrenocorticotropic hormone (ACTH), are known to improve axonal regeneration following peripheral nerve injury and stimulate neurite outgrowth from central nervous system (CNS) neurons both in vitro and in vivo. The neurite outgrowth promoting capacity of alpha MSH has prompted us to investigate the effects of intrathecal application of alpha MSH on functional and electrophysiological recovery in a well-characterized model of spinal cord contusion injury. Different doses of alpha MSH were applied via osmotic minipumps into the cisterna magna for 10 days, thereby delivering the peptide directly into the CNS. Functional recovery was monitored during 8 postoperative weeks by means of the Basso, Beattie, and Bresnahan locomotor rating scale, and the thoracolumbar height test. At the end of the study, electrophysiological analysis of rubrospinal motor evoked potentials as performed. Our data showed that application of 3.75 micrograms/kg/h alpha MSH resulted in a marked functional recovery, accompanied by a decrease in the latency of the rMEP. This study demonstrates that intrathecal application of alpha MSH results in functional recovery after spinal cord contusion injury. These findings may initiate new treatment strategies and/or the use of melanocortins in human spinal cord injury.
European Journal of Pharmacology, Mar 1, 1993
European Journal of Cancer and Clinical Oncology, 1991
Neurosurgery, 1997
OBJECTIVE Melanocortins, peptides related to melanocyte-stimulating hormone (MSH) and corticotrop... more OBJECTIVE Melanocortins, peptides related to melanocyte-stimulating hormone (MSH) and corticotropin (ACTH), exhibit neurotrophic and neuroprotective activity in several established models of peripheral and central nervous system damage. The beneficial effects of melanocortins on functional recovery after experimental brain damage and central demyelinating diseases have prompted us to investigate alpha MSH treatment in a weight drop model of traumatic spinal cord injury in rats. METHODS In two independent randomized blinded experiments, treatment with either alpha MSH (75 micrograms/kg of body weight administered subcutaneously every 48 h for 3 weeks after trauma) or single high-dose (30 mg/kg, 30 min after injury) methylprednisolone was compared with saline treatment in rats subjected to a moderately severe 20-gcm weight drop injury. Spinal cord function was monitored using behavioral, electrophysiological, and histological parameters. RESULTS In both experiments, alpha MSH significantly improved recovery, as illustrated by Tarlov scores, thoracolumbar height, and amplitude of rubrospinal motor evoked potentials. The magnitude of the alpha MSH effect on motor performance was comparable with the one observed after treatment with methylprednisolone. CONCLUSION The reproducible neurological and electrophysiological improvement in spinal cord function of animals treated with alpha MSH suggests a new lead in the treatment of traumatic spinal cord injury.
Experimental Neurology, Nov 1, 2006
We previously demonstrated that the tetraspanin protein CD81 is up-regulated by astrocytes and mi... more We previously demonstrated that the tetraspanin protein CD81 is up-regulated by astrocytes and microglia after traumatic spinal cord injury in rats and that CD81 is involved in adhesion and proliferation of cultured astrocytes and microglia. Since these reactive glial cells contribute to secondary damage and glial scar formation, we studied the effect of local administration of an anti-CD81 antibody in experimental spinal cord injury. Adult rats were subjected to a moderate spinal cord contusion injury and treated for 2 weeks with different doses of the anti-CD81 antibody AMP1 (0.5-5 μg/h) or non-immune IgG (5.0 μg/h). A technique was developed to infuse the antibodies directly into the lesion site via an intraspinal cannula connected to a pump. Functional recovery was monitored during 8 postoperative weeks by means of the Basso, Beattie and Bresnahan (BBB) locomotor rating scale, the BBB subscore and Grid-walk test. At the end of the study, quantitative histology was performed to assess tissue sparing. Our data showed that by itself cannulation of the lesion site resulted in minimal functional and histological impairments. Application of 0.5 μg/h AMP1 resulted in a marked functional recovery (BBB 2 points; Grid-walk 30% less errors compared to control). This recovery was accompanied by an 18% increase in tissue sparing at the lesion epicentre. No gross histological changes in glial scarring were apparent. Our data demonstrate beneficial effects of an anti-CD81 antibody on functional recovery in spinal cord injured rats and suggest that this effect is mediated through a reduction in secondary tissue loss.
Journal of Neuroscience Research, Apr 15, 2000
In many patients treated with cisplatin a peripheral sensory neuropathy develops. This side-effec... more In many patients treated with cisplatin a peripheral sensory neuropathy develops. This side-effect is considered dose-limiting, and therefore restricts the total dose of cisplatin that can be administered. Recent in vitro and in vivo studies suggest that recombinant human Glial Growth Factor 2 (rhGGF2) has neuroprotective effects. This prompted us to investigate in a rat model whether rhGGF2 ameliorates cisplatin neuropathy. A total of 48 rats were randomly divided into four groups of 12 rats each. Three groups received cisplatin and were treated with either 0.1 mg/kg rhGGF2, 0.3 mg/kg rhGGF2 or placebo. The fourth group (saline/placebo) served as age-matched controls. In the cisplatin/placebo treated rats a neuropathy developed, as determined by measurements of the nerve conduction velocity (NCV). Treatment with rhGGF2 dose-dependently protected against the neuropathy. Histological examination and morphometric analysis revealed that rhGGF2 also protects against cisplatin-induced changes in the morphology and size of DRG satellite cell nuclei. In a control study rhGGF2 did not affect normal NCV development. We conclude that rhGGF2 treatment is of benefit in the treatment of cisplatin neuropathy in the rat.
Journal of Neurotrauma, 2006
The purpose of this study was to compare spontaneous functional recovery after different spinal m... more The purpose of this study was to compare spontaneous functional recovery after different spinal motor tract lesions in the rat spinal cord using three methods of analysis, the BBB, the rope test, and the CatWalk. We transected the dorsal corticospinal tract (CSTx) or the rubrospinal tract (RSTx) or the complete dorsal half of the spinal cord (Hx) at thoracic level T8. Functional recovery was monitored for 31 weeks. We found no recovery of consistent inter limb coordination in any experimental group over time using the BBB locomotor rating scale. Quantitative CatWalk analysis revealed significant differences between experimental groups for inter limb coordination (RI). RSTx and Hx animals showed a significant decrease in the RI, and only in the RSTx group did the RI improve from 6 weeks post-lesion onward. Significant differences between experimental groups in step sequence patterns and base of support were also observed. In the rope test all experimental groups had significantly higher error percentages compared to control animals. Tracing of the CST revealed enhanced collateral formation rostral to the lesion in the CSTx group, not in other groups. The results presented here show that locomotor function in all, but CSTx groups gradually improved over time. This is important for studies that employ pharmacological, cell-, and/or gene therapy-based interventions to improve axonal regeneration and functional recovery after spinal cord injury.
Journal of Neurotrauma, Oct 1, 2003
We have recently shown that enriched environment (EE) housing significantly enhances locomotor re... more We have recently shown that enriched environment (EE) housing significantly enhances locomotor recovery following spinal cord contusion injury (SCI) in rats. As the type and intensity of locomotor training with EE housing are rather poorly characterized, we decided to compare the effectiveness of EE housing with that of voluntary wheel running, the latter of which is both well characterized and easily quantified. Female Wistar rats were made familiar with three types of housing conditions, social housing (nine together) in an EE (EHC), individual housing in a running wheel cage (RUN, n = 8), and standard housing two together (CON, n = 10). Subsequently, a 12.5 gcm SCI at Th8 was produced and animals were randomly divided over the three housing conditions. Locomotor function was measured regularly, once a week by means of the BBB score, BBB sub score, TLH test, Gridwalk test, and CatWalk test. In the RUN group, daily distance covered was also measured. Locomotor recovery in the EHC and the RUN groups was equal and significantly better than in the CON group. The extent of recovery at 8 weeks post injury in the RUN group did not correlate with distance covered. We conclude that locomotor training needs to exceed a given threshold in order to be effective in enhancing locomotor recovery in this experimental model, but that once this threshold is exceeded no further improvement occurs, and that the specificity of locomotor training plays little role.
Pain, Mar 1, 2003
A characteristic symptom of neuropathic pain is mechanical allodynia. In animal models of neuropa... more A characteristic symptom of neuropathic pain is mechanical allodynia. In animal models of neuropathic pain, mechanical allodynia is often assessed using von Frey filaments. Although the forces applied with these filaments are highly reproducible, there are various disadvantages of using this method. Testing paradigms and definitions of withdrawal threshold are not standardised. Moreover, measurements may be influenced by various conditions, such as ambient temperature, humidity, weight bearing of the limb and stress. We have therefore investigated another technique to assess mechanical allodynia, the 'CatWalk' automated quantitative gait analysis. With this computer-assisted method of locomotor analysis, it is possible to objectively and rapidly quantify several gait parameters, including duration of different phases of the step cycle and pressure applied during locomotion. We tested rats with a chronic constriction injury of the sciatic nerve, a model of neuropathic pain, both with von Frey filaments and the CatWalk method. We demonstrate that these rats minimise contact with the affected paw during locomotion, as demonstrated by a reduction in stance phase and pressure applied during stance. Moreover, these parameters show a high degree of correlation with mechanical withdrawal thresholds as determined by von Frey filaments. We therefore suggest that the CatWalk method might serve as an additional tool in the investigation of mechanical allodynia.
Brain Research, Mar 1, 2000
Ž. To date, relatively little progress has been made in the treatment of spinal cord injury SCI-r... more Ž. To date, relatively little progress has been made in the treatment of spinal cord injury SCI-related neurological impairments. Until Ž. now, methylprednisolone MP is the only agent with clinically proven beneficial effect on functional outcome after SCI. Although the mechanism of action is not completely clear, experimental data point to protection against membrane peroxidation and edema reduction. The melanocortin melanotropin is known to improve axonal regeneration following sciatic nerve injury, and to stimulate corticospinal outgrowth after partial spinal cord transection. Recently, we showed that intrathecally administered a MSH had beneficial effects on Ž. functional recovery after experimental SCI. Since both drugs have shown their value in intervention studies after experimental spinal Ž. cord injury ESCI , we decided to study the effects of combined treatment. Our results again showed that a MSH enhances functional recovery after ESCI in the rat and that MP, although not affecting functional recovery adversely by itself, abolished the effects observed with a MSH when combined. Our data, thus, suggest that the mechanism of action of MP interferes with that of a MSH.
The Journal of Steroid Biochemistry and Molecular Biology, Sep 1, 1992
Cancer Chemotherapy and Pharmacology, 1993
Physiology & Behavior, Dec 1, 2007
A variety of animal models for neurological disease and injury exist and locomotor performance is... more A variety of animal models for neurological disease and injury exist and locomotor performance is an important outcome parameter in studies employing these models. The CatWalk, an automated quantitative gait analysis method is a method to study over-ground locomotor performance in large groups of animals. In the present study, we used the CatWalk which allowed us to investigate strain differences in over-ground locomotion in three commonly used strains of laboratory rat (i.e. Lewis, Wistar and Sprague-Dawley rats) based on objective data-analysis in a large number of animals. The present results revealed marked strain differences on the static paw parameters; base-of-support, and the relative paw position. Furthermore, strain differences were noted on the static parameter stride length and the dynamic parameters stance-, swing- and stepcycle duration, which are due logically to morphological differences between strains. The parameters related to coordination did not reveal any differences between the strains. Furthermore, the swing duration and the cruciate and alternate patterns i.e. regular step patterns Ca ("cruciate" pattern type a) and Ab ("alternate" pattern type b) were shown to be differentially affected by the locomotor speed. We conclude that differences in gait traits exist between the three laboratory rat strains investigated and several of the examined gait parameters showed strain dependent interdependency with locomotor speed.
Journal of Neuroscience Research, 2004
The use of collagen as a vehicle to transplant neonatal astroglial cells into the lesioned spinal... more The use of collagen as a vehicle to transplant neonatal astroglial cells into the lesioned spinal cord of the adult rat allows a precise application of these cells into the lesion gap and minimizes the migration of the transplanted cells. This approach might lead to anatomical and functional recovery. In the present study, 20 adult female Wistar rats were subjected to a dorsal hemisection at thoracic spinal cord levels. Cultured cortical neonatal rat astrocytes were transplanted into the lesion with collagen as a vehicle (N = 10). Prior to transplantation, the cultured astroglial cells were labelled with fast blue. Control rats received collagen implants only (N = 10). During 1 month of survival time, functional recovery of all rats was continuously monitored. Histological data showed that the prelabelled astroglial cells survived transplantation and were localized predominantly in the collagen implant. Virtually no fast blue‐labelled GFAP‐positive astroglial cells migrated out of the implant into the adjacent host spinal cord. The presence of transplanted neonatal astroglial cells resulted in a significant increase in the number of ingrowing neurofilament‐positive fibers (including anterogradely labeled corticospinal axons) into the implant. Ingrowing fibers were closely associated with the transplanted astroglial cells. The implantation of neonatal astroglial cells did result in modest temporary improvements of locomotor recovery as observed during open‐field locomotion analysis (BBB subscore) or during crossing of a walkway (catwalk). © 2004 Wiley‐Liss, Inc.
Journal of Neurotrauma, Apr 1, 2006
Journal of Neuroscience Research, Jun 1, 1993
Journal of Neuroscience Research, Apr 15, 1996
Journal of the Neurological Sciences, Nov 1, 1994
Journal of Neurotrauma, Dec 1, 1996
To evaluate new pharmacologic agents with potentially beneficial effects on posttraumatic spinal ... more To evaluate new pharmacologic agents with potentially beneficial effects on posttraumatic spinal cord function, we used a modified weight drop (WD) technique to induce spinal cord injuries. These contusive spinal cord injuries in the rat closely mimic the human clinicopathologic situation. Especially for drug screening purposes, the moderate and mild injuries are of interest, as both the beneficial and potentially harmful effects of experimental treatment can be detected. In this study, we describe two new functional tests that were particularly designed to detect small differences in spinal cord function after moderate and mild injuries. First, for examination of locomotion, a computer analysis of the thoracolumbar height (TLH) was designed. Second, for investigation of the conduction properties of the injured rat spinal cord, we measured rubrospinal motor evoked potentials (MEP). The efficacy of the new assessment techniques to monitor spinal cord function was compared to Tarlov scores and to morphometric analysis of preserved white matter at the injury site. The results of this study indicated that for behavioral analysis, TLH measurements as compared with Tarlov rating appeared to be more sensitive for exact and objective discrimination between small differences in motor function. Amplitudes of the rubrospinal MEP, but not latencies or the number of peaks, proved to be most sensitive to determine subtle differences in posttraumatic spinal cord function. A significant linear correlation was found between TLH and amplitude of the rubrospinal MEP. We conclude that for objective assessment of the spinal cord after moderate and mild contusive injury, TLH and rubrospinal MEP amplitudes are very valuable measures to demonstrate small functional differences.
Journal of Neurotrauma, Apr 1, 1999
Melanocortins, peptides related to alpha-melanocortin-stimulating hormone (alpha MSH) and adrenoc... more Melanocortins, peptides related to alpha-melanocortin-stimulating hormone (alpha MSH) and adrenocorticotropic hormone (ACTH), are known to improve axonal regeneration following peripheral nerve injury and stimulate neurite outgrowth from central nervous system (CNS) neurons both in vitro and in vivo. The neurite outgrowth promoting capacity of alpha MSH has prompted us to investigate the effects of intrathecal application of alpha MSH on functional and electrophysiological recovery in a well-characterized model of spinal cord contusion injury. Different doses of alpha MSH were applied via osmotic minipumps into the cisterna magna for 10 days, thereby delivering the peptide directly into the CNS. Functional recovery was monitored during 8 postoperative weeks by means of the Basso, Beattie, and Bresnahan locomotor rating scale, and the thoracolumbar height test. At the end of the study, electrophysiological analysis of rubrospinal motor evoked potentials as performed. Our data showed that application of 3.75 micrograms/kg/h alpha MSH resulted in a marked functional recovery, accompanied by a decrease in the latency of the rMEP. This study demonstrates that intrathecal application of alpha MSH results in functional recovery after spinal cord contusion injury. These findings may initiate new treatment strategies and/or the use of melanocortins in human spinal cord injury.
European Journal of Pharmacology, Mar 1, 1993
European Journal of Cancer and Clinical Oncology, 1991