Restorative Neurology and Neuroscience - Volume 19, issue 3-4

Authors: Ramirez, Julio J.

Article Type: Other

Citation: Restorative Neurology and Neuroscience, vol. 19, no. 3-4, pp. 157-158, 2001

Authors: Deller, Thomas | Haas, Carola A. | Frotscher, Michael

Article Type: Research Article

Abstract: Entorhinal cortex lesion partially denervates the rat fascia dentata. This is said to induce sprouting of intact fibers from neighboring layers that invade the zone of the degenerating axons. However, recent in vivo and in vitro studies failed to demonstrate sprouting across laminar boundaries. Sprouting does occur, but it mainly involves unlesioned fiber systems terminating within the layer of fiber degeneration. These findings point to laminar cues that promote sprouting of fibers within the denervated zone …while repelling other, adjacent fiber systems that try to grow into the denervated zone. A group of molecules that are likely to guide the sprouting process and the formation of borders are extracellular matrix molecules synthesized by reactive astrocytes. These molecules provide boundaries for growing axons during development. Some extracellular matrix molecules (tenascin-C, DSD- 1 -proteoglycan, neurocan, and brevican) were upregulated within the denervated outer molecular layer after lesion of the entorhinal cortex, suggesting a similar role after lesion. These extracellular matrix components forin a sharp molecular border towards the adjacent nondenervated inner molecular layer, and their pattern of distribution correlates precisely with the laminar termination pattern of the sprouting fiber populations. Thus, extracellular matrix molecules could delineate boundaries of axonal growth after entorhinal cortex lesion and could thus contribute to the molecular processes underlying the postlesional re-patterning of the fascia dentata. Show more

Keywords: entorhinal cortex lesion, perforant pathway, extracellular matrix, proteoglycan, plasticity, hippocampus, lesion, layer-specificity

Citation: Restorative Neurology and Neuroscience, vol. 19, no. 3-4, pp. 159-167, 2001

Authors: Collazos-Castro, Jorge E. | Nieto-Sampedro, Manuel

Article Type: Research Article

Abstract: The lamination of dentate gyrus afferents established during development is maintained following lesion-induced reactive growth in the adult. After partial deafferentation sprouts from undamaged afferents restore most synapses, while respecting the laminae relative boundaries. No evidence of trans-laminar sprouting has been found. Here, we review the information gathered during the last decade on the cellular and molecular bases of dentate synaptogenesis, with special attention to the role of glia during development and …that of reactive glia after deafferentation. The interactions of neurons with astroglia and astroglial macromolecules, particularly proteoglycans, influence synapse segregation in the dentate gyrus, providing us with a reasonable explanation for afferent lamination. Show more

Keywords: reactive astrocytes, dentate gyrus, reactive synaptogenesis, afferent lamination, proteoglycans

Citation: Restorative Neurology and Neuroscience, vol. 19, no. 3-4, pp. 169-187, 2001

Authors: Bechmann, Ingo | Nitsch, Robert

Article Type: Research Article

Abstract: In contrast to other organs where the tissue is capable of replacing lost cells and thus regaining tissue function, immune cell recruitment and activation is suppressed in the CNS in order to minimize secondary damage after lesion. This state of immune privilege has its cost because the injured tissue cannot fully benefit from growth-promoting effects accompanying inflammatory responses. These responses include phagocytosis of growth-inhibiting myelin debris by cells of the innate immune system and the recently …described protection of surviving fibers by myelin-specifie T cells of the adaptive immune system. While the signals suppressing macrophage functions in the CNS are yet to be defined, it seems that help from T cells is diminished by apoptosis-induction via death-inducing ligands. Indeed, the death ligand CD95L (FasL, APO 1 L) is constitutively found on neurons, microglia and astrocytes. Its upregulation on astrocytes during axonal degeneration in the hippocampus after entorhinal lesion is accompanied by the appearance of apoptotic leukocytes. T cells also express CD95L and TNF-related apoptosis- inducing ligand (TRAIL), and the presence of CD95 (Fas, APOI) and TRAIL-receptors renders brain cells putative targets of T cell-induced apoptosis. Thus, blockade of death ligands could be helpful by simultaneously enhancing T cell survival and blocking T cell-mediated brain cell death. This is only one example of how boosting helpful immune cell functions and abrogating their destructive effects might help to overcome the brain's failure to regenerate after axonal lesions. Show more

Keywords: multiple sclerosis, autoimmunity, apoptosis, immune privilege

Citation: Restorative Neurology and Neuroscience, vol. 19, no. 3-4, pp. 189-198, 2001

Authors: Colbert, Costa M.

Article Type: Research Article

Abstract: A hallmark of synaptic plasticity is the associative, or Hebbian, nature of its induction. By associative, we mean that the timing relationships between activity of the pre- and postsynaptic elements of a synapse determine whether synaptic strengths are modified. lt is well-established that associativity results, in large part, from the dual requirements for activation of the N-methyl-D-aspartate receptor-ionophore, namely presynaptic neurotransmitter release and postsynaptic depolarization. However, the specific dendritic events that provide …the postsynaptic depolarization have been relatively unexplored. Increasing evidence suggests that back-propagating (i.e., antidromic) Na^+ action potentials provide the necessary postsynaptic depolarization to allow induction of associative synaptic plasticities. In hippocampal CAI and neocortical layer V pyramidal neurons, these action potentials provide much greater levels of dendritic depolarization than would be expected from synaptic currents alone. Moreover, they provide a relatively brief and synchronous depolarization throughout the dendritic arbor, allowing timing relationships to more directly reflect pre- and postsynaptic cell firing. Interestingly, certain properties of the back-propagating actions potentials differ from axonal or somatic action potentials in ways that seem to reflect their function. For example, the all-or-none property of action potential amplitude does not hold in the dendrites. In this review we discuss the back-propagating action potential as a dendritic signal that provides information to synapses about the firing state of the postsynaptic neuron. First, we consider the evidence that action potentials propagate back from the axon. Second, we describe the characteristics of the back-propagating action potential in terms of interactions of its underlying ionic currents. Third, we describe how these properties contribute to the timing aspects of the induction of long-term potentiation. Finally, we discuss modulation of the underlying ion channels by neurotransmitter systems and other agents and speculate on their roles in learning and memory. Show more

Keywords: hippocampus, learning and memory, neural computation

Citation: Restorative Neurology and Neuroscience, vol. 19, no. 3-4, pp. 199-211, 2001

Authors: Phillips, Linda L. | Reeves, Thomas M.

Article Type: Research Article

Abstract: Hippocampal afferents terminate in well-defined laminae, with a morphological segregation of input which has facilitated the interpretation of structural and functional synaptic reorganization observed after deafferentiation. Historically, most studies have induced hippocampal plasticity using single deafferentiation paradigms, however recent evidence indicates that sequential lesions or models based on combined injuries alter the pattern of dendritic structural reorganization and axonal sprouting. A better understanding of the interaction between deafferentiation-induced …structural remodeling and other pathological mechanisms, which commonly coexist in central nervous system trauma, will require the use of combined injury paradigms where such plasticity can be systematically manipulated. In the context of traumatic brain injury, we have developed an injury model that combines the excessive neuroexcitation of concussive brain insult with the targeted hippocampal deafferentation of entorhinal cortical lesion. This review discusses the role of such an approach in defining posttraumatic hippocampal vulnerability, out- lining the effects of combined pathology on hippocampal circuitry, and considers the greater clinical relevance inherent in the combined injury approach. Experimental evidence obtained with the combined concussive plus deafferentation model is presented, detailing the interaction of injury components and highlighting structural, behavioral and electrophysiological evidence for maladaptive hippocampal plasticity. Subsequent studies utilizing pharmacological methods to manipulate this maladaptive plasticity are described, first targeting glutamate, acetylcholine and dopamine receptor pathways, and then applying select drugs to explore how various molecular mechanisms underlying combined neuroexcitation and deafferentation pathology might affect regenerative plasticity. Evidence implicating postinjury neurotransmitter modulation of exeitatory/inhibitory homeostasis, metalloproteinase regulation of extracellular matrix, and mitochondrial metabolic vulnerability is presented. Finally, the effect of age on outcome after combined neuroexcitation plus deafferentation insult is considered, as well as how future studies in such combined injury models will better define the full range of postinjury hippocampal plasticity possible after brain trauma. Show more

Keywords: traumatic brain injury, deafferentation, neuroexcitation, hippocampus, plasticity, recovery of function

Citation: Restorative Neurology and Neuroscience, vol. 19, no. 3-4, pp. 213-235, 2001

Authors: Ramirez, Julio J.

Article Type: Research Article

Abstract: Functional reorganization is often invoked to account for recovery of function after central nervous system (CNS) injury. The mechanisms underlying this possible reorganization, however, remain uncertain. In the last 30 years, studies of the hippocampal formation of rats have indicated that the CNS is capable of undergoing significant changes in its pattern of connectivity in response to injury. Here, we explore numerous examples of lesion-induced alterations in hippocampal connectivity known as axonal sprouting. Both …homotypic and heterotypic sprouting occur in the denervated hippocampus after unilateral entorhinal cortex lesions. We assess the behavioral relevance of glutamatergic homotypic sprouting emerging from the surviving contralateral entorhinal area (i.e., the crossed temporodentate projection) as well as the heterotypic sprouting from the remaining surviving afferents (e. g., the cholinergic septodentate pathway) to the hippocampus. Studies examining the role of crossed temporodentate sprouting in recovery from memory deficits after entorhinal cortex injury indicate that homotypic sprouting may indeed contribute to a reorganization of cortical function resulting in recovered mnemonic capacity. Heterotypic sprouting is not as clearly linked to recovery of function after bilateral entorhinal injury. We propose a tripartite model for functional reorganization based on homotypic sprouting, neurotrophic factors, and altered inhibitory functioning to account for how relatively small increases in surviving homotypic pathways might restore neurological function. Show more

Keywords: review, neuroplasticity, Alzheimer's disease, dentate gyrus, hippocampus, entorhinal cortex, recovery of function, learning, memory, stroke

Citation: Restorative Neurology and Neuroscience, vol. 19, no. 3-4, pp. 237-262, 2001

Article Type: Abstract

Citation: Restorative Neurology and Neuroscience, vol. 19, no. 3-4, pp. 263-273, 2001