Restorative Neurology and Neuroscience - Volume 1, issue 5

Authors: Goldstein, Larry B. | Davis, James N.

Article Type: Research Article

Abstract: Treatment with amphetamine increases the rate of recovery of beam-walking in rats when administered after a unilateral suction-ablation lesion of the sensorimotor cortex. It is thought that amphetamine treatment must be combined with postlesion practice on the beam since confinement to prevent locomotion blocks amphetamine-facilitated recovery. However, rats which are confined are also isolated and not handled. In the present experiment, beam-walking recovery was compared among groups of rats which were treated with either amphetamine or saline and then either handled and allowed to walk in a home cage or given practice on the beam. Although amphetamine treatment and postlesion …practice had independent beneficial effects on recovery, the group of rats given both treatments had the greatest improvement in beam-walking scores. Show more

Keywords: Motor recovery, Experience, Amphetamine, Beam-walking, Brain injury, Stroke, Cortical lesion, Rat

DOI: 10.3233/RNN-1990-1501

Citation: Restorative Neurology and Neuroscience, vol. 1, no. 5, pp. 311-314, 1990

Authors: Simonds, Gary W. | Schwarz, Saul | Krauthamer, Eleanor | Freed, William J.

Article Type: Research Article

Abstract: Bilateral lesioning of rat substantia nigra results in a syndrome of aphagia, adipsia, and akinesia. Rats can be protected from the development of this syndrome if they have previously received intraventricular fetal substantia nigra grafts as neonates. In this experiment, we determined whether neonatal adrenal medulla grafts would offer similar protection. One day old Sprague–Dawley rat pups received bilateral intraventricular allografts of either adrenal medulla or sciatic nerve from adult donors. At 3–4 months of age the rats received bilateral lesions of the substantia nigra with 6-hydroxydopamine. After lesioning, food and water consumption were greater in the rats receiving adrenal …medulla grafts, as compared to the sciatic nerve control group. Nevertheless, food and water consumption was markedly decreased in both groups, and activity levels did not differ between the two groups. Histology showed consistently surviving grafts with large numbers of surviving catecholamine-containing cells. Thus adrenal medulla grafts in neonatal hosts offer partial protection against the syndrome of adipsia and aphagia produced by subsequent substantia nigra lesions, but this protection is much less than that produced by substantia nigra grafts. Show more

Keywords: Adrenal medulla, Chromaffin cells, Substantia nigra, Catecholamine, Transplantation, Brain grafts, Development, 6-Hydroxy-dopamine

DOI: 10.3233/RNN-1990-1502

Citation: Restorative Neurology and Neuroscience, vol. 1, no. 5, pp. 315-322, 1990

Authors: Hernandez, Theresa D. | Schallert, Timothy

Article Type: Research Article

Abstract: Diazepam and other GABA-related agents can prevent or delay recovery from an otherwise short-term somatosensory asymmetry caused by unilateral cortical lesions. Postrecovery treatment does not affect behavior. One possible contributive site of action for these agents is remaining cortical tissue. In the present study, following unilateral anteromedial cortex (AMC) lesions or sham operations, the GABA agonist muscimol or saline was infused once a day for 7 days into the adjacent sensorimotor cortex (SMC) or, as a control, into the more remote occipital cortex (OC) of the ipsilateral hemisphere. Each day the animals were given somatosensory and motor coordination tests at …21 h postinfusion. The SMC-muscimol regimen, but not the SMC-saline or OC-muscimol, retarded recovery from somatosensory asymmetry. The disruptive effect on recovery was enduring, greatly outlasting the week of exposure to muscimol. In sham-operated animals, SMC-muscimoI did not yield a chronic effect on behavior, although during the first hour after each infusion, in which the muscimol presumably was still present in the SMC, somatosensory asymmetry could be observed. Although the AMC lesion created a vulnerability to muscimol in the SMC, no detectable difference in the extent of cortical damage in this group could account for the prolongation of behavioral asymmetry. SMC-muscimol (but not SMC-saline) led to atrophy of SMC projection areas in the ipsilateral thalamus. However, in sham-operated animals, SMC-muscimol did not affect thalamic size. These behavioral and anatomical data suggest that systemically delivered GABAergic drugs might interfere with restoration of function after AMC lesions in part by adversely influencing events in the SMC. Show more

Keywords: Brain damage, Anteromedial cortex, Muscimol, γ-Aminobutyric acid, Sensorimotor cortex, Recovery of function, Somatosensory asymmetry, Thalamic degeneration

DOI: 10.3233/RNN-1990-1503

Citation: Restorative Neurology and Neuroscience, vol. 1, no. 5, pp. 323-330, 1990

Authors: Granholm, Ann-Charlotte

Article Type: Research Article

Abstract: The effects of thyroid hormone deficiency on the noradrenergic innervation of hippocampus from locus coeruleus (LC) were examined using intraocular double transplants in albino rats. Fetal brainstem pieces containing the nucleus LC were transplanted to the anterior chamber of the eye of thyroidectomized and normal recipients and the brain grafts were allowed to mature for 8 weeks. Pieces of fetal hippocampal formation were introduced into the anterior eye chamber and placed in contact with the LC grafts or placed in previously operated eyes. As evidenced by high performance liquid chromatography, hippocampal transplants in contact with a brainstem graft gradually became …hyperinnervated by noradrenergic fibers from these grafts. The levels of norepinephrine were lower in single control grafts and in double grafts in thyroidectomized animals than in control double grafts. Extracellular recordings of single neuronal activity were performed in hippocampal transplants in all 3 groups after 10–14 months in oculo. Superfusion with the α2 - adrenergic agonist clonidine and the α-adrenergic antagonist phentolamine elicited significant increases in discharge rate of hippocampal neurons in control double transplants, but not in single hippocampal grafts or in double grafts in thyroidectomized hosts. The β-adrenergic antagonist timolol did not change the neuronal firing rate in any of the 3 groups. Superfusion with penicillin over single hippocampal transplants caused long-lasting increases in slow-wave activity. This increased bioelectric activity remained after the cessation of drug application. A similar increase in slow-wave activity was found in hyperinnervated control double transplants only when penicillin was combined with clonidine or phentolamine. However, the hippocampal portion of double grafts in thyroidectomized recipients readily responded to penicillin with seizures and/or interictal spiking. The data presented here suggest that chronic lack of thyroid hormones leads to significant disturbances of the central noradrenergic transmission in isolated LC-hippocampal circuits. Show more

Keywords: Locus coeruleus, Hippocampal formation, Central noradrenergic transmission, Intraocular transplants, Adrenergic receptors, Thyroid hormone deficiency

DOI: 10.3233/RNN-1990-1504

Citation: Restorative Neurology and Neuroscience, vol. 1, no. 5, pp. 331-338, 1990

Authors: Griffiths, Russell | Horch, Kenneth | Stensaas, Larry

Article Type: Research Article

Abstract: A biodegradable tube consisting of alternating laminae of aldehyde and heat-treated collagen and fibrin was tested as a nerve repair device. Tubes placed around intact nerves for 3 weeks showed a high degree of biocompatibility as evidenced by the absence of reactive or toxic alterations of epineurium contacting the implant and the presence of normal perineurial and endoneurial components. Tubes used to bridge a 5 mm gap in the rat tibial nerve showed good vascularization of the collagen laminae, a well-confined nerve regenerate, and advanced resorption of the fibrin component at 3 months. One year after being used to bridge …5–12 mm gaps in the cat radial and saphenous nerves, the tubes were replaced by well-vascularized connective tissue which surrounded a dense nerve regenerate. However, inadequate stabilization of the implants by the small anchoring sutures apparently caused some of the repairs to fail. In sum, the implants appear to promote regeneration of axons across a nerve gap by providing an oriented, well-vascularized physical substrate for neurite outgrowth. Show more

Keywords: Collagen, Fibrin, Nerve repair, Tubulization, Nerve regeneration

DOI: 10.3233/RNN-1990-1505

Citation: Restorative Neurology and Neuroscience, vol. 1, no. 5, pp. 339-346, 1990

Authors: Pollack, Ian F. | Lund, Raymond D. | Rao, Kanchan

Article Type: Research Article

Abstract: Fetal mouse retinae transplanted to the mesencephalon of neonatal rats generally survive for prolonged periods of time without immune suppression suggesting that such grafts enjoy a degree of immunological privilege. A small, but consistent percentage of these transplants, however, ultimately undergo spontaneous rejection. In addition, rejection can be induced by (1) systemically sensitizing the host to the donor antigens by placing a mouse skin graft or (2) producing a local degenerative process adjacent to the graft by removing the host eye contralateral to the side of the retinal transplant. To elucidate the immunological events that underly spontaneous and induced rejection …in this system, we examined the distribution of lymphocytes, astrocytes, microglia, and cells expressing major histocompatibility complex (MHC) antigens in unrejected grafts, in transplants showing spontaneous rejection, and in grafts undergoing induced rejection. In unrejected grafts, increased astrocytic and microglial staining was seen around the photoreceptor layer of the graft and at the graft–host interface, but no lymphocytes and only occasional cells expressing MHC antigens were detected. In contrast, spontaneously rejecting grafts showed widespread MHC, lymphocytic, astrocytic, and microglial immunoreactivity that extended well beyond the limits of the transplant into the surrounding host brain. Skin graft-induced rejection produced a temporally consistent, comparatively localized enhancement of astrocytic, microglial and MHC immunoreactivity and infiltration of lymphocytes. Four to five days after skin grafting, before neural graft rejection was detectable histologically, MHC immunoreactivity was demonstrated within the transplant coinciding with the presence of small numbers of lymphocytes and an increase in microglial staining. By 8 days, grafts had undergone profound necrosis. Intense astrocytosis, microglial staining, MHC immunoreactivity, and perivascular lymphocytic cuffing were present within the graft and at the graft–host interface. With longer survival times, several of these changes were also detected within the visual pathways, suggesting that the regions to which the graft projected were also involved, though in a delayed fashion. After eye removal, the temporal pattern of rejection was more protracted and considerably less uniform than that seen after skin grafting. At 7 days, prominent microglial, astrocytic, and MHC immunoreactivity was seen in the area of distribution of the host optic axons within the superior colliculus and to a lesser extent around the graft itself, however, no infiltration of lymphocytes was detected. With longer survival times, an increasing percentage of grafts showed signs of overt rejection with perivascular cuffing by lymphocytes; however, even at 21 days, a small number of grafts remained free of lymphocytic infiltration, despite the presence of intense MHC, astrocytic, and microglial staining. We conclude that the different rejection models studied may involve fundamentally different triggers of the host immune system, but that in each case MHC expression may be the precedent step to graft rejection. Show more

Keywords: Immune privilege, Major histocompatibility (MHC) antigens, Neural transplantation, Rejection, Skin graft, Xenograft

DOI: 10.3233/RNN-1990-1506

Citation: Restorative Neurology and Neuroscience, vol. 1, no. 5, pp. 347-360, 1990

Authors: Gulati, Adarsh K. | Swift, Thomas R. | McBride, Russell L. | Feringa, Earl R.

Article Type: Short Communication

Abstract: Spinal cord transection is known to cause progressive changes in motor neurons and hind limb muscles. In the present study, regeneration of the peroneal nerve was examined in rats 25 weeks after a T9 spinal cord transection. Successful regeneration and innervation of the target muscle was observed after crush injury to the nerve in the spinal cord transected animals. It is concluded that the ability of peripheral nerve to regenerate remains preserved after spinal cord injury.

Keywords: Spinal cord, Transection, Motor neuron, Peripheral nerve, Regeneration, Rat

DOI: 10.3233/RNN-1990-1507

Citation: Restorative Neurology and Neuroscience, vol. 1, no. 5, pp. 361-364, 1990

Authors: Will, Bruno E. | Majchrzak, Monique | Cassel, Jean-Christophe

Article Type: Book Review

DOI: 10.3233/RNN-1990-1508

Citation: Restorative Neurology and Neuroscience, vol. 1, no. 5, pp. 365-365, 1990