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Biomedical subjects

T Shiojima

Publications and source records attributed to T Shiojima.

At least 19 recordsLinked to original sources
PubMed1998

SR57746A: a survival factor for motor neurons in vivo.

SR57746A(1-[2-(naphth-2-yl)ethy]]-4-(3-trifluoromethyl phenyl)-1,2,5,6-tetrahydropyridine, hydrochloride) is a non-peptide compound which has been shown to exhibit a wide range of neurotrophic effects both in vitro and in vivo. Here we examine the ability of SR57746A on axotomized spinal motor neuron death in the developing rat spinal cord. After postnatal unilateral section of rat sciatic nerve, there was approximately a 50% survival of motor neurons in the fourth lumbar segment (L4). Intraperitoneal injection of SR57746A for consecutive 14 days rescued motor neuron death but did not preserve the motor neuron diameter both on axotomy and non-axotomy side. These results suggest that SR57746A is a survival factor for motor neurons in vivo and may serve as therapeutic agent for damaged motor neurons.

Animals↗
PubMed1997

S100 beta prevents the death of motor neurons in newborn rats after sciatic nerve section.

We have examined whether S100 beta rescues axotomized spinal motor neuron death. Animals that had undergone transection of the sciatic nerve at birth were treated either with S100 beta, or the vehicle. The number of surviving motor neurons and the motor neuron diameter was assessed 14 days later. Treatment with S100 beta rescued motor neuron death and preserved the motor neuron diameter in the lesioned side. These results suggest that S100 beta is a neurotrophic factor for motor neurons in vivo and this agent may have therapeutic potential in damaged motor neuron disorder.

Animals↗
PubMed1997

Effect of transforming growth factor beta 1 on spinal motor neurons after axotomy.

Glial cell line-derived neurotrophic factor (GDNF), a member of the transforming growth factor beta (TGF-beta) family, has potent effects on developing motor neurons. TGF are pluripotent cytokines that exert biological effects on a variety of neurons. TGF beta 1, on the other hand, promotes motor neuron survival in vitro and saves motor neurons from naturally occurring cell death. Here we investigate the neurotrophic effects of TGF beta 1 for axotomized motor neuron death. The sciatic nerve was cut in newborn rats and TGF beta 1 was injected, either by intraperitoneally or by lesion site, for 14 days after transection. Two or six weeks postlesion, the number and the diameter of motor neurons was assessed. TGF beta 1 significantly attenuated axotomy induced motor neuron death by intraperitoneal administration or by lesion site administration at 2 weeks after neonatal axotomy in a similar way. However, no effect was observed at 6 weeks after nerve lesion, despite continuous application of TGF beta 1 daily for 14 days. These results indicate that TGF beta 1 can prevent the death of motor neurons in vivo, but it cannot permanently rescue lesioned motor neurons.

Animals↗
PubMed1997

Bromocriptine prevents neuron damage following inhibition of superoxide dismutase in cultured ventral spinal cord neurons.

Rosen et al. have reported point mutations in the cytosolic Cu/Zn superoxide dismutase (SOD 1) gene in some families with familial amyotrophic lateral sclerosis (ALS). To determine whether decreased SOD activity could contribute to neuronal damage, rat embryo ventral spinal cord neurons were incubated with diethyldithiocarbamate (DDC), an inhibitor of SOD. There was a marked increase in neuronal damage in cultures exposed to DDC and this phenomenon was dose-related. In this paradigm, these deteriorative changes were prevented by bromocriptine. DDC-treated ventral spinal cord neurons provide an in vitro model of free radical neurotoxicity secondary to decreased SOD activity. Simultaneous treatment with bromocriptine and DDC reduced neurotoxicity, indicating that bromocriptine has a neuroprotective effect against free radicals.

Animals↗
PubMed1997

Basic fibroblast growth factor and platelet-derived growth factor prevent the death of spinal motor neurons after sciatic nerve transection in the neonatal rats.

In vivo, motor neurons are destined to die after axotomy. Several neuronal growth factors, such as ciliary neurotrophic factor, brain-derived neurotrophic factor, and leukemia inhibitory factor rescue neuronal death of axotomized motor neurons. Here, we report that systemically administered basic fibroblast growth factor and platelet-derived growth factor prevented spinal motor neuron death in neonatal rats following sciatic nerve resection. These data indicate that basic fibroblast growth factor and platelet derived growth factor play a role for motor neuron survival in vivo.

Animals↗
PubMed1997

TRH-analog, TA-0910 (3-methyl-(s)-5,6-dihydroorotyl-L-histidyl-L-prolinamide) rescues motor neurons from axotomy-induced cell death.

TA-0910 (3-methyl-(s)-5,6-dihydroorotyl-L-histidyl-L-prolinamide) is a potent and long acting TRH analog. We have studied the effect of TA-0910 on axotomy-induced neuronal death. The left sciatic nerve was transected in neonatal rats. TA-0910 or vehicle was administered on consecutive 14 days with intraperitoneal injections. After the treatment, the number of spinal motor neurons and the motor neuron diameter was assessed at the level of L4-6 segments. In comparison with vehicle, TA-0910 significantly prevented the death of motor neurons and preserved the motor neuron diameter on the lesioned side. These results suggest that TA-0910 is a survival factor for developing spinal motor neurons.

Animals↗
PubMed1996

Bromocriptine prevents spinal motor neuron death following sciatic nerve transection in neonatal rats.

Bromocriptine, a potent dopamine D2 receptor agonist, appears to have neuroprotective actions. In order to investigate the effect of bromocriptine on axotomy-induced cell death, we have examined the survival of spinal motor neurons after sciatic nerve transection in the neonatal rats. Newborn rats were anesthetized with hypothermia. Sciatic nerve was transected near the obturator tendon in the left thigh. Animals were then treated daily with bromocriptine for 14 days with intraperitoneal injections. Control animals received PBS in the same fashion. After the treatment, the number of spinal motor neurons in the L4-6 was counted. There is approximately a 50% loss of spinal motor neurons in the PBS treated group. By contrast, bromocriptine prevents spinal motor neuron death after axotomy. The motor neuron diameter on the lesioned side is significantly larger in the bromocriptine-treated group. These results are consistent with the possible role of bromocriptine as a survival factor for developing spinal motor neurons.

Animals↗
PubMed1996

Coadministration of interleukin-6 (IL-6) and soluble IL-6 receptor delays progression of wobbler mouse motor neuron disease.

Interleukin-6 (IL-6), a multipotential cytokine, initiates signal transduction pathways similar to those of ciliary neurotrophic factor (CNTF) and leukemia inhibitory factor (LIF). These molecules share the signal transducing receptor component, gp130. IL-6 triggers homodimerization of gp130, whereas CNTF and LIF induce heterodimerization of gp130 and LIF receptor. Although CNTF or LIF treatment attenuates motor deficits in wobbler mouse motor neuron disease (MND), neuroprotective effects of IL-6 on this animal have not yet been clarified. Here we studied whether simultaneous treatment with IL-6 and soluble IL-6 receptor (sIL-6R) can ameliorate symptomatic and neuropathological changes in wobbler mouse MND. After clinical diagnosis at postnatal age 3-4 weeks, wobbler mice received subcutaneous injection with human recombinant IL-6 (1.0 mg/kg), human sIL-6R (0.5 mg/kg), IL-6 + sIL-6R or vehicle, daily for 4 weeks in a blind fashion. Compared to vehicle, coadministration with IL-6 and sIL-6R potentiated grip strength, attenuated muscle contractures in the forelimbs, reduced denervation muscle atrophy and prevented degeneration of spinal motor neurons. Single administration with IL-6 or sIL-6R did not retard the symptomatic and neuropathological progression, although IL-6-treated mice did not raise anti-IL-6 antibodies. Treatment with IL-6 + sIL-6R, but not with IL-6 or sIL-6R alone delayed progression of wobbler mouse MND. Our results indicate that the neuroprotective mechanism for IL-6/sIL-6R on wobbler mouse MND differs from that of CNTF or LIF alone. We hypothesize that IL-6/sIL-6R complex may function on motor neurons through activation and homodimerization of gp130.

Animals↗
PubMed1996

Neuroprotective effect of various cytokines on developing spinal motoneurons following axotomy.

Ciliary neurotrophic factor (CNTF), a multipoietic factor, on a variety of neurons, prevents axotomy-induced motoneuron loss and can improve the outcome of murine motor neuron disease (MND). We carried out a study to determine whether other cytokines rescue spinal motoneurons from axotomy-induced cell death. Unilateral sciatic nerve was transected in neonatal rats. Two doses of recombinant murine cholinergic differentiation factor/leukemia inhibitory factor (CDF/LIF), recombinant rat CNTF, recombinant human granulocyte-colony stimulating factor (G-CSF), recombinant human interleukin-6 (IL-6), recombinant human tumor necrosis factor beta (TNF beta), or vehicle were administered daily for 2 weeks by intraperitoneal injection. After treatment, the number of spinal motoneurons was determined at the level of L4-5 segments. In comparison with vehicle, the higher doses of CDF/LIF, CNTF, and IL-6, and the lower doses of CDF/LIF and IL-6 significantly retarded the loss of motoneurons. G-CSF and TNF beta failed to inhibit motoneuron death. CDF/LIF and IL-6 rescued motoneurons from the retrograde death following axotomy, in a similar manner to CNTF. These results provide evidence that several cytokines may have therapeutic potential in human axonopathy or MND.

Animals↗
PubMed1996

Deprenyl and pergolide rescue spinal motor neurons from axotomy-induced neuronal death in the neonatal rat.

It has been reported that both the monoamine oxidase inhibitor, deprenyl and the dopamine receptor agonist, pergolide have neuroprotective actions. To investigate the effect of deprenyl and pergolide on axotomized motor neuron death, we examined the survival of spinal motor neurons after sciatic nerve transection in the neonatal rats. Newborn rats were anesthetized with hypothermia. Sciatic nerve was cut near the obturator tendon in the left thigh. Animals were then treated daily with deprenyl (10 mg kg(-1)), pergolide (5 mg kg(-1)), or PBS for 14 days with intraperitoneal injections in a blind fashion. After the treatment, the number of spinal motor neurons in the L 4-6 was counted. There was approximately a 50% loss of spinal motor neurons in PBS-treated group. By contrast, both deprenyl and pergolide prevents spinal motor neuron death after axotomy Co-administration of deprenyl and pergolide is more effective than either agent alone but not significant. These findings are consistent with the idea that deprenyl and pergolide are survival factors for developing spinal motor neurons.

Animals↗
PubMed1995

CNQX prevents spinal motor neuron death following sciatic nerve transection in newborn rats.

A rapid and reproducible spinal motor neuron death occurs after sciatic nerve transection in neonatal rats. This neuronal death could be due to lack of retrogradely transported target derived neurotrophic factors, such as ciliary neurotrophic factor, brain-derived neurotrophic factor, leukemia inhibitory factor and glial cell line-derived neurotrophic factor. Another hypothesis suggests that glutamate and its receptors has been implicated as possible mechanism for motor neuron death. In order to investigate the effect of N-methyl-D-aspartate (NMDA) and non-NMDA receptor antagonists on axotomy-induced cell death in the spinal motor neurons of neonatal rats, we have studied neuroprotective effects of these receptor antagonists. Newborn rats were anesthetized with hypothermia. Sciatic nerve was transected near the obturator tendon in the left thigh. Animals were then treated daily with MK-801, APV, and CNQX for 14 days with intraperitoneal injections. Control animals received PBS in the same fashion. After the treatment, the number of spinal motor neurons in the L4-6 was counted. MK-801 and APV did not show any significant neuroprotective effect. By contrast, the number of surviving motor neurons was greater in animals that were treated with 1.0, 2.0 and 4.0 mg/kg of CNQX. This neuroprotective effect was not dose-related. We demonstrate that neuroprotective effect of CNQX on axotomized motor neurons, raises a possibility that such a agent may have therapeutic potential in motor neuronopathy and amyotrophic lateral sclerosis.

2-Amino-5-phosphonovalerate↗
PubMed1995

Lecithinized superoxide dismutase retards wobbler mouse motoneuron disease.

Gene mutations of Cu/Zn superoxide dismutase (SOD) have been discovered in familial amyotrophic lateral sclerosis (ALS). Oxidative stress also plays a role in the pathogenesis of sporadic ALS. Whether antioxidant therapy is beneficial in this fatal disease is now crucial. We have shown that SOD treatment improves neuromuscular dysfunction and morphological changes in wobbler mouse motoneuron disease. Progressive spinal motor neuronopathy and axonopathy, predominantly in the cervical cord, occur at postnatal age 3-4 weeks, leading to muscle weakness and contracture of the forelimbs in this animal. These motor deficits rapidly increase by postnatal age 6-8 weeks, and then slowly progress. Wobbler mice were given two doses daily of phosphatidyl choline-bound Cu/Zn SOD (PC-SOD, 10(4), 10(5) U/kg) or a vehicle solution by intraperitoneal injection from postnatal 3-4 to postnatal 7-8 weeks of age. PC-SOD treatment attenuated progression of motor dysfunction, prevented denervation muscle atrophy, and delayed degeneration of spinal motoneurons in wobbler mice. This raises the possibility that PC-SOD may have therapeutic potential in human motoneuron disease.

Animals↗
PubMed1995

Acidic and basic fibroblast growth factors enhance neurite outgrowth in cultured rat spinal cord neurons.

We have studied neurotrophic effects of acidic fibroblast growth factor (aFGF) and basic fibroblast growth factor (bFGF) on explanted ventral and dorsal spinal cord cultures from 13- and 14-day-old rat embryos. Cultures treated with aFGF and bFGF significantly enhanced neurite outgrowth with cultures of ventral spinal cord, but not with cultures of dorsal spinal cord. Our data suggest that aFGF and bFGF are potent neurotrophic factors on rat ventral spinal cord neurons in vitro.

Animals↗
PubMed1995

Amyotrophic lateral sclerosis cerebrospinal fluid is not toxic to cultured spinal motor neurons.

We have studied an effect of cerebrospinal fluid (CSF) from patients with amyotrophic lateral sclerosis (ALS) on explanted and dissociated ventral spinal cord cultures from 13-day-old rat embryos. CSF samples were obtained from 10 ALS patients, 10 other neurological patients, and 10 non-neurological patients. CSF was added at dilution of 10, 25, and 50%. Neurite length and neuronal survival ratio were not significantly different among these three groups. ALS CSF does not contain a neurotoxic factor on the cultured spinal motor neurons.

Adult↗
PubMed1995

Neuroprotective effect of basic fibroblast growth factor on wobbler mouse motor neuron disease.

Basic fibroblast growth factor (bFGF) possesses neuroprotective effects on a variety of neurons. Here we report that it delays progression of motor neuron disease (MND) in the wobbler mouse. After initial diagnosis of MND at post-natal age 3-4 weeks, wobbler mice receive either recombinant human bFGF (1 mg kg-1, n = 10) or vehicle (n = 10), daily for weeks by subcutaneous injection in a blind fashion. We performed symptomatic and neuropathological assessments in both groups. The treatment was fulfilled at 7-8 weeks of age. In comparison with vehicle, bFGF treatment potentiated grip strength (p < 0.008), attenuated forelimb contracture (p < 0.003), and increased weight of the biceps muscle (p < 0.008). bFGF-treated mice retarded denervation muscle atrophy (p < 0.001) and degeneration of spinal motoneurons (p < 0.001). Our study shows that bFGF treatment is beneficial in a murine MND model. We provide a rationale that bFGF may have therapeutic potential in peripheral motor neuropathy or MND.

Animals↗