Showing papers by "Anders Björklund published in 1984"
TL;DR: Qualitative observation and correlation analyses indicated that the aged group was heterogeneous in the degree of impairments manifested by the individual animals, and suggested that the development of impairment may progress with aging at different rates in the various tasks and possibly in different underlying neuroanatomical systems.
505 citations
TL;DR: This review focuses on one particular aspect of this technique: the use of intracerebral neural implants for the reestablishment of severed connections, the substitution of lost pathways, and the replacement of tissue defects in the adult mammalian CNS.
Abstract: Neural grafting has emerged over the last decade as a viable approach to studying the development and regeneration of neuronal connections in the CNS ofmamrnals In this review we focus on one particular aspect of this technique: the use of intracerebral neural implants for the reestablishment of severed connections, the substitution of lost pathways, and the replacement of tissue defects in the adult mammalian CNS A survey of the literature shows that grafting of neuronal tissue to the mammalian CNS has been frequently attempt ed since the end of the last century, but that the results of these earlier studies were generally very poor Thompson (1890) and Saltykow ( 1905) were possi bly the fIrst to report results from grafts of adult CNS tissue, and Del Conte (1907) the fIrst to try grafts of embryonic tissues to the brains of mammals Their results were generally unsuccessful and no clear-cut evidence of good long-term survival was obtained Del Conte, in particular, concluded that the brain was an unfavorable transplantation site Similar negative results were subsequently published, eg by Altobelli (1914), Willis (1935), Glees (1955), Wenzel & Barlehner (1969), and Frotscher et al (1970) Some of the early investigators were, however, more successful Ranson (1914) and Tidd (1932) obtained partial survival of grafted sensory ganglia in the cerebral cortex of developing rats, and Dunn (1917) reported survival of four out of 44 grafts of neonatal cerebral cortex, implanted into the cortex of nine to ten day-old
414 citations
TL;DR: The action of cholinergic neurons in the graft onto elements in the host hippocampal circuitry may be a necessary, but perhaps not sufficient, prerequisite for the observed functional recovery in aged rats with severe impairments in spatial learning abilities.
Abstract: Grafts of fetal septal tissue rich in cholinergic neurons were implanted as a dissociated cell suspension into the depth of the hippocampal formation in aged rats with severe impairments in spatial learning abilities. After 2 1/2 to 3 months, the rats with grafts, but not the controls, had improved their performance in a spatial learning test. Their improvement was due, at least in part, to an increased ability to use spatial cues in the task. In all animals the grafts had produced an extensive acetylcholinesterase-positive terminal network in the surrounding host hippocampal formation. Thus, the action of cholinergic neurons in the graft onto elements in the host hippocampal circuitry may be a necessary, but perhaps not sufficient, prerequisite for the observed functional recovery.
365 citations
TL;DR: It is reported here that grafted fetal striatal neurones implanted into the IA-lesioned striatum can significantly ameliorate the lesion-induced locomotor hyperactivity and at least partly normalize the metabolic hyperactivity in the extrapyramidal neuronal system.
Abstract: In rats, striatal neuronal destruction by so-called excitotoxic amino acids, kainic acid or ibotenic acid (IA) produce neuropathological and neurochemical changes in the basal ganglia which resemble those seen in patients with Huntington's chorea. Such lesioned animals show a behavioural syndrome which is reminiscent of the cardinal symptoms of the disease, accompanied by a substantial increase in local cerebral metabolic activity in several striatal target structures within the extrapyramidal motor system. The study was designed to explore the potential of grafted fetal striatal neurones implanted into the IA-lesioned striatum to compensate for the structural, neurochemical, metabolic and behavioural defects of IA-lesioned rats. Extending previous studies, we report here that such striatal implants can significantly ameliorate the lesion-induced locomotor hyperactivity and at least partly normalize the metabolic hyperactivity in the extrapyramidal neuronal system.
302 citations
TL;DR: The results show that the individual rats within an aged rat population develop cognitive impairments to a variable degree and that the aged rats with the most pronounced learning impairments are the ones exhibiting the most severe functional decrements, in terms of glucose utilization, in the septohippocampal system and the prefrontal cortex.
Abstract: Aged rats (22 to 24 months) and young control rats (3 months) were tested in a battery of behavioral tests which included tests of learning, place navigation, sensorimotor integration, motor coordination, activity, and exploration. Following testing all animals were analyzed in an unanesthetized state for their local glucose utilization. Significant differences in glucose utilization were found between the aged and young groups on some behaviors and in some brain regions. There was considerable variability in the aged group in both their behavioral performance and their glucose utilization scores; thus, attempts were made to determine whether the variability in the degree of impairment within any particular behavioral test was correlated to the regional glucose utilization scores in any of the 45 brain regions analyzed. In two of the behavioral tests employed (i.e., one for learning and one for place navigation), the decline in performance correlated significantly with the decrement in regional glucose utilization. Moreover, the performance in these two tests showed significant correlation with glucose use in only five regions (dentate gyrus, medial septum-diagonal band area, hippocampal CA1, hippocampal CA3, and prefrontal cortex). These results show that the learning impairments in the aged rats are related to the extent of decrease in glucose utilization in restricted areas of the limbic system. In addition, the results show that the individual rats within an aged rat population develop cognitive impairments to a variable degree and that the aged rats with the most pronounced learning impairments are the ones exhibiting the most severe functional decrements, in terms of glucose utilization, in the septohippocampal system and the prefrontal cortex. This suggests that aging rats may be interesting not only for the study of the normal aging process, but also as a model of dementia.
249 citations
TL;DR: It is suggested that the DA innervations of the hypothalamic neurosecretory nuclei originate in cell bodies of the diencephalic A11-A14 cell groups and that such intradiencesphalic DA projections participate in the regulation of oxytocin and vasopressin release from the pituitary.
158 citations
TL;DR: The intracerebral grafting technique is used to monitor the availability of survival factors in an adult CNS target area and shows that neonatal rat superior cervical cells, which have an absolute requirement for such factors for their survival, will survive in the hippocampal formation of adult rats only in the presence of a denervating lesion.
Abstract: Target-derived macromolecules in the peripheral nervous system apparently play an important part in the regulation of neuronal survival and maturation during critical stages of development1–7. Similar trophic factors could also be required in the central nervous system (CNS) for the maintenance of intracerebral connections, and neuronal cell death may result from a decrease or failure of a target-derived trophic support8,9. Recent experiments have demonstrated the presence of factors in brain extracts or astrocytic glial cells which can support the survival of embryonic sympathetic, parasympathetic or sensory ganglionic neurones in vitro10–14. The importance of these putative factors for neuronal survival in vivo has, however, so far not been demonstrated. In the study reported here we have used the intracerebral grafting technique to monitor the availability of survival factors in an adult CNS target area and show here that neonatal rat superior cervical cells, which have an absolute requirement for such factors for their survival1,2,3,15, will survive in the hippocampal formation of adult rats only in the presence of a denervating lesion.
148 citations
TL;DR: In adult rats whose nigrostriatal dopamine pathway had been chemically damaged, a fetal mesencephalic graft over the superior colliculus was implanted and joined it to the denervated striatum by means of an approximately 2 cm long segment of heterologous sciatic nerve.
112 citations
TL;DR: A role for the mesohabenular DA system in modulating telencephalic feedback onto the mesencesphalic DA-neurons and also in regulating the output from the dorsal raphe nucleus is suggested.
96 citations
TL;DR: It was demonstrated, by destroying these cells unilaterally, that they were responsible to a large extent for the cholinergic compensatory collateral sprouting in the hippocampus that has previously been shown to develop following complete fimbria-fornix transection.
89 citations
TL;DR: The results are interpreted as suggesting that dopaminergic projections to prefrontal cortex and nucleus accumbens are similarly rather than antagonistically involved in the regulation of drug-induced locomotor activation.
TL;DR: It is concluded that neural tissue transplantation provides a powerful new tool in the study of the functional organization of the hippocampus and its various neurotransmitter‐specific afferent systems.
Abstract: A brief review is provided of the capacity of neural tissue transplants to reinnervate the deafferented hippocampus and repair functional deficits induced by the lesion. The techniques for transplantation of solid pieces of embryonic septum, locus coeruleus or raphe nuclei, or tissue suspensions of embryonic septum, to the adult rat hippocampus are described. Such grafts manifest good long-term survival. provide a good reinnervation of the hippocampus that is histochemically and biochemically appropriate and specific, can establish ultrastructural synaptic contacts with the host, and are electrophysiologically active. Rats with septal grafts manifest recovery of the capacity to learn certain aspects of radial 8-arm maze, T-maze alternation and Morris water-maze tasks. Rats with locus coeruleus grafts manifest an amelioration of lesion-induced hyperactivity. It is concluded that neural tissue transplantation provides a powerful new tool in the study of the functional organization of the hippocampus and its various neurotransmitter-specific afferent systems.
01 Jan 1984
TL;DR: The development and use of the dissociated neuronal cell suspension method are described as a new method for neural transplantation and results of cell survival and axonal elongation are reviewed.
Abstract: General principles of intracerebral grafting are presented in overview The development and use of the dissociated neuronal cell suspension method are described as a new method for neural transplantation Experiments are described involving fetal dopamine cells transplanted to adult striatum and fetal cholinergic cells transplanted to the hippocampal formation, as primary examples The main focus of this review is related to results of cell survival and axonal elongation
01 Jan 1984
TL;DR: This review provides an overview of the attempts to promote regeneration of spinal cord connections by using various transplantation paradigms and demonstrates that neurons of the spinal cord possess the ability to regenerate axons several millimeters into both intrinsic and extrinsic transplants.
Abstract: Transplantation models in the brain have proven successful under conditions in which transplants serve as a “bridge” for the regeneration of axons across a site of injury, or as “release” or “driving” units to replace missing inputs to a particular target area.1–8 Similar models have been applied to the mammalian spinal cord including: (1) intraspinal transplants to form a bridge for the regeneration of spinal cord axons, (2) extraspinal transplants with only the end or ends of the transplants inserted into the cord to bypass the region of injury, and (3) intraspinal neural implants to replace missing supraspinal inputs. These models demonstrate that neurons of the spinal cord possess the ability to regenerate axons several millimeters into both intrinsic and extrinsic transplants; however, the growth of these axons into the tissue of the host spinal cord has been limited. By contrast, embryonic CNS neurons transplanted into the adult spinal cord, possess the ability to grow axons that penetrate several millimeters into spinal cord tissue. This review provides an overview of the attempts to promote regeneration of spinal cord connections by using various transplantation paradigms.
01 Jan 1984
TL;DR: Tello, Tello, 7 and Ramon y Cajal8 were the first to attempt to promote regeneration of lesioned central axons by using implants of peripheral nerve.
Abstract: Following lesions that cause substantial tissue damage, such as spinal cord transection or large hemorrhagic necroses in the brain, mammals exhibit very little evidence of regeneration of the severed axons across the necrosis (see Refs. 1–4 for reviews). This holds true also for those nonmyelinated or finely myelinated systems, such as the monoaminergic and cholinergic neurons, that have been shown to possess a very pronounced regenerative capacity (see Ref. 5 for review). Early this century, Tello6, 7 and Ramon y Cajal8 described this regenerative failure as due to a lack of neurotropic mechanisms and growth pathways in the adult mammalian CNS. Based on this notion, these authors were the first to attempt to promote regeneration of lesioned central axons by using implants of peripheral nerve.