Restorative Neurology and Neuroscience - Volume 11, issue 4

Authors: Okura, Yoshio | Tanaka, Ryuichi | Ono, Koji | Yoshida, Seiichi | Tanuma, Naoyuki | Matsumoto, Yoh

Article Type: Research Article

Abstract: The central nervous system (CNS) of mammals has long been thought of as an immunologically privileged site. However, this concept is now changing because the rejection of histo-incompatible neural grafts has been frequently observed in the CNS. In neural transplantation used as therapy for some human neurodegenerative diseases, it is important to determine which factors are related to brain graft rejection. In this study, we examined immunological reactions in brains that had received isogeneic (rat to rat) and xenogeneic (mouse to rat) neural transplants. In the immunohistochemical analysis, antibodies against T cell receptor αβ (R73), macrophage and microglia (0X42), MHC …class II antigens (0X6), CD4 (W3/25), CD8 (0X8), NK cell (3.2.3), B cell (RLN-9D3), T cell receptor (TCR) Vβ8.2 (R78), TCR Vβ8.5 (B73) and TCR Vβl0 (G101) were used. At the early stage of both isogeneic and xenogeneic transplantation, a nonspecific inflammatory reaction characterized by macrophage infiltration was observed along the needle track which was produced by the grafting procedure. From the day 7 stage onwards, the non-specific inflammatory reaction was replaced by the specific immune reactions of T cell infiltration, neovascularization and necrosis of xenogeneic grafts. Marked T cell infiltration was detected in the lesions, whereas NK and B cells were not. Quantitative analysis of T cell subsets revealed that both CD4+ and CD8+ T cells were found in the xenogeneic transplants. Microglia became activated and strongly expressed MHC class II antigens at the time of graft rejection. Isogeneic transplants, in contrast, showed no histological characteristics of rejection, and numerous dopaminergic neurons with several neurites were observed in the grafts. Based on these findings, we concluded that T cells are the principal effectors in the rejection of xenogeneic neural grafts, and that activated microglia may have some role in presenting antigens to the infiltrating T cells during the rejection process. Show more

Keywords: Xenogeneic neural transplantation, Rejection response, Immunohistochemical analysis

DOI: 10.3233/RNN-1997-11401

Citation: Restorative Neurology and Neuroscience, vol. 11, no. 4, pp. 177-187, 1997

Authors: Bertelli, Jayme Augusto | Taleb, Madjid | Mira, Jean-Claude | Calixto, Joao Batista | Kassar, Lina

Article Type: Research Article

Abstract: In the experiments reported here, the musculocutaneous nerve was repaired by peripheral nerve grafts directly implanted into the dorsal and ventral side of the contralateral spinal cord. Six months later, the brachial plexus involved was retrograde labelled with True Blue, while the contralateral side was labelled with Diamidino Yellow. Regenerated sensory ganglionic neurons were found between C3 and C8 in both sides of the spinal cord. Motoneurons were found only in the contralateral brachial plexus between C5 and C6, close to the graft implantation. No double-labelled neurons were found. Supernumerary axon regeneration from undamaged neurons was not observed in the …current studies, in spite of axogenic influence of Schwann cells from the peripheral nerve grafts. Show more

Keywords: Nerve repair, Nerve regeneration, Nerve grafts, Nerve transfer, Regeneration, Reinnervation, Skeletal-muscle

DOI: 10.3233/RNN-1997-11402

Citation: Restorative Neurology and Neuroscience, vol. 11, no. 4, pp. 189-194, 1997

Authors: Roy, Adip | Agrawal, Ashok K. | Husain, Raushan | Seth, Prahlad K.

Article Type: Research Article

Abstract: Trimethyltin produces a selective loss of pyramidal neurons in the hippocampus resulting in functional deficits. The present study was aimed to assess the comparative restoration of behavioural and neurochemical deficits in trimethyltin chloride (7.5 mg/Kg body weight, i.p) treated rats following single or multiple site fetal hippocampal transplants. Exposure to trimethyltin caused a decrease in learning ability (51 %), an increase in locomotor activity (92 %) and decrease in acetylcholinesterase activity (36%) and muscarinic receptor binding (31%). Trimethyltin treated rats receiving multiple transplants of fetal hippocampal cell suspension (0.25 μl at 8 stereotaxic coordinates) showed significant restoration of the functional …deficits 4 weeks post transplantation. This restoration by multiple site transplants persisted upto 16 weeks post transplantation. Restoration of the above deficits by single site transplants (2 μl at a single coordinate), 4 weeks post transplantation was less marked in comparison to multiple transplants and was evident only in learning ability and muscarinic receptor binding after 16 weeks of transplantation. The results suggest that multiple site transplants provide better restoration , on long term basis, in chemical induced neurodegeneration. Show more

Keywords: Trimethyltin, Hippocampus, Transplantation, Single, Multiple

DOI: 10.3233/RNN-1997-11403

Citation: Restorative Neurology and Neuroscience, vol. 11, no. 4, pp. 195-201, 1997

Authors: Rich, Keith M. | Tong, Jianxin X.

Article Type: Research Article

Abstract: The diphenylpiperazine, flunarizine, partially prevents apoptosis after trophic factor deprivation in neural crest-derived neurons. Flunarizine protects dorsal root ganglion neurons (DRG) after nerve growth factor (NGF) withdrawal in vitro and after peripheral nerve injury in newborn rats in vivo. We have further studied the mechanisms of neuronal protection by flunarizine. Oligosomal DNA fragmentation, a hallmark of apoptosis, was significantly decreased by treatment of DRG neurons with flunarizine after NGF deprivation. We examined the effect on survival of the timing of administration of flunarizine to DRG neurons both in vitro and in vivo. Flunarizine effectively rescued dissociated DRG neurons if administered …up to six hours after NGF withdrawal. In vivo, flunarizine prevented DRG neuronal death after sciatic axotomy in newborn rats if given soon after injury. Long-term experiments were done to test the ability of flunarizine to protect neurons and enhance regeneration after sciatic nerve injury. Newborn rats were subjected to peripheral nerve injury and administered flunarizine for four weeks; no further treatment was given for an additional 12 weeks. The group treated with flunarizine demonstrated a significantly increased number of DRG and spinal motor neurons that had regenerated axons into the distal sciatic nerve as determined by retrograde labeling with HRR Myelinated axons in the sural nerve in the group treated with flunarizine increased by nearly two-fold compared to control animals. Thus, flunarizine was able to enhance survival and promote long-term regeneration of sensory and motor spinal neurons after peripheral nerve injury. Show more

Keywords: Apoptosis, Dorsal root ganglion neuron, Diphenylpiperazines, Deprenyl, Axotomy, Neuronal protection

DOI: 10.3233/RNN-1997-11404

Citation: Restorative Neurology and Neuroscience, vol. 11, no. 4, pp. 203-209, 1997

Authors: Onifer, Stephen M. | Rodríguez, José F. | Santiago, Deyanira I. | Benitez, Juan C. | Kim, David T. | Brunschwig, Jean-Pierre R. | Pacheco, Jeffrey T. | Perrone, John V. | Llorente, Orlando | Hesse, Donald H. | Martinez-Arizala, Alberto

Article Type: Research Article

Abstract: Traumatic injury to the adult human spinal cord most frequently occurs at the mid-to-low cervical segments and produces tetraplegia. To investigate treatments for improving upper extremity function after cervical spinal cord injury (SCI), three behavioral tests were examined for their potential usefulness in evaluating forelimb function in an adult rat model that mimics human low cervical SCI. Testing was conducted pre- and up to 4 weeks post-operation in adult female rats subjected to either contusion injury at the C7 spinal cord segment or sham-surgery. Modified Forelimb Tarlov scales revealed significant proximal and distal forelimb extension dysfunction in lesion rats at …l-to-4 weeks post-cervical SCI. The Forelimb Grip Strength Test showed a significant decrease in forelimb grip strength of lesion rats throughout the 4 weeks post-cervical SCI. Significant deficits in reach and pellet retrieval by lesion rats were measured at l-to-4 weeks post-cervical SCI with the conditioned pellet retrieval Staircase Test. The results demonstrate that these qualitative and quantitative forelimb behavioral tests can be used to evaluate forelimb function following low cervical SCI and may be useful to investigate treatments for improving forelimb function in these lesions. Show more

Keywords: behavior, retrieval, grasp, grip strength, reach, Staircase Test, Tarlov Scale

DOI: 10.3233/RNN-1997-11405

Citation: Restorative Neurology and Neuroscience, vol. 11, no. 4, pp. 211-223, 1997

Article Type: Research Article

DOI: 10.3233/RNN-1997-11406

Citation: Restorative Neurology and Neuroscience, vol. 11, no. 4, pp. 225-242, 1997

Article Type: Other

DOI: 10.3233/RNN-1997-11407

Citation: Restorative Neurology and Neuroscience, vol. 11, no. 4, pp. 243-245, 1997