Journal of Neurodegeneration and RegenerationAbstracts
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Journal of Neurodegeneration and Regeneration
Fall 2008, Volume 1
, Number 1

From the publisher Exploring a new medical frontier . . .
Richard A. DeVito, Jr.
Fall 2008; pages 5-5

Editorial Adult neural stem cells from promise to treatment: The road ahead
Philippe Taupin, PhD
Fall 2008; pages 7-8

Editorial Understanding nervous system degeneration, injury, and repair: New territory that may require new methodological approaches for success
Cathy M. Helgason, MD
Fall 2008; pages 9-10

Changes in NADPH-d/nitric oxide synthase perivascular networks in rat cerebral cortex after autologous blood injection in the subarachnoid spaces
Diego Garbossa, MD; Marco Fontanella, MD; Alessandro Ducati, MD; Alessandro Vercelli, MD
Fall 2008; pages 11-18

Nitric oxide (NO) plays multiple roles in the central nervous system. NO producing neurons make perivascular networks with cerebral cortex microvessels and contribute to cerebral cortex vascular tone regulation. The authors analyzed the distribution of neuronal/inducible NO synthase and nicotinamidedinucleotide phosphate diaphorase (NADPH-d) in the rat cerebral cortex after autologous blood injection in the subarachnoid spaces, to understand the role of NO in the pathogenesis of subarachnoid hemorrhage (SAH)-induced cortical damages. Autologous blood was injected in rats into the cisterna magna. Sham-operated rats received saline injections. Animals were killed at different time intervals (6 hours to 1 week) perfused, and their brains were removed for histochemistry and immunohistochemistry. The transverse diameter of the basilar artery was measured. Six to twelve hours after SAH, there were no differences between sham and SAH rats; iNOS staining was absent. Twenty-four hours after SAH, diffuse NADPH-d and nNOS reactivity increased in treated rats and moderate iNOS staining appeared without basilar diameter variations. Forty-eight hours, 72 hours to 1 week after SAH, NADPH-d/nNOS labeling changed in treated animals when compared with controls; iNOS immunoreactivity was intense. Basilar diameter suggested vasospasm. These results suggest a role of neuronal NO in SAH cortical damages and vasospasm. Key words: nitric oxide, subarachnoid hemorrhage, vasospasm, brain injury, NADPH-d

Presence of glatiramer acetate-specific TH2 cells in the cerebrospinal fluid of patients with multiple sclerosis 12 months after the start of therapy with glatiramer acetate
Tjalf Ziemssen, MD; Heinz Reichmann, MD; Hauke Schneider, MD
Fall 2008; pages 19-22

The proposed mechanism of action of glatiramer acetate (GA) from animal models is that GA-specific T cells enter the CNS to act there. To evaluate GA-specific T cells in patients with multiple sclerosis (MS), we tried to culture GA specific T cell lines from the CSF of the identical patients with MS before and during GA therapy. Before treatment T cell lines could not be obtained, whereas after at least 1 year of GA treatment 12 GA-specific T cell lines secreting TH2 cytokines and BDNF could be generated from the CSF. Key words: multiple sclerosis, glatiramer acetate, mechanism of action

LIF treatment reduces Nogo-A deposits in spinal cord injury modulating Rho GTPase activity and CRMP-2 phosphorylation
Michael F. Azari, BAppSc(Chiro), PhD; Ezgi Ozturk, BSc(Hons); Christos Profyris, BSc(Hons), BA; Shunhe Wang, MD; David H. Small, PhD; Claude C.A. Bernard, DES, DSc; Steven Petratos, PhD
Fall 2008; pages 23-29

We have previously shown that systemically administered leukemia inhibitory factor (LIF), following overhemisection spinal cord injury (SCI) in the mouse, prevents oligodendrocyte death and secondary demyelination. Here, we report that the prevention of oligodendrocyte death by LIF treatment reduces Nogo-A deposits above and below the transection site. This finding is associated with modulation of Nogo-A-dependent signaling whereby active RhoA (GTP-RhoA) is decreased and the levels of its downstream target, the phospho-Thr555- collapsin response mediator protein-2 (p-Thr555-CRMP-2), are reduced in the white matter axons near the lesion. The potential for axonal growth in LIF-treated animals is enhanced through upregulation of the neurite growthrelated molecules GAP-43 and GTP-Rac1. These findings suggest a mechanism by which exogenous LIF can promote axonal growth in the mammalian spinal cord following injury, by providing a permissive tissue environment for endogenous regrowth. Key words: SCI, LIF, Nogo-A, RhoA, CRMP-2

Differential actions of pituitary adenylyl cyclase-activating polypeptide and interferon gamma on Th2- and Th1-associated chemokine expression in cultured murine microglia
Derek A. Wainwright, MS; Junping Xin, MD; Virginia M. Sanders, PhD; Kathryn J. Jones, PhD
Fall 2008; pages 31-34

Microglia are the immune cells that reside in the central nervous system (CNS). Following the facial nerve injury in the mouse, microglia are activated in the facial motor nucleus, coincident with an increase in the proinflammatory cytokine interferon-gamma (IFN-?). The authors have previously shown that maximal facial motoneuron (FMN) survival after injury depends on the CD4+T-cell interaction with microglia. Furthermore, it appears that the anti-inflammatory T helper (Th) 2 CD4+T-cell subset is required in the facial nucleus, although the mechanism of CNS recruitment is not known. Pituitary adenylyl cyclase-activating polypeptide (PACAP) is a neuropeptide that has previously been demonstrated to be expressed by injured FMN. Interestingly, PACAP has been shown to act on peripheral macrophages by inducing chemokine expression capable of recruiting Th2 cells. Whether CNS-resident microglia, a related lineage to peripheral macrophages, respond to PACAP by expressing Th2-associated chemokines is not known. In this study, fluorescence-activated cell sorting was utilized to measure the frequency of microglia positive for different chemokines after exposure to various treatments. The results indicate that PACAP increases the frequency of microglia expressing Th2-associated chemokine, CCL11, and decreases the frequency of microglia expressing Th1- associated chemokine, CXCL11. In contrast, IFN- ? decreases the frequency of microglia expressing Th2-associated chemokine, CCL11, and increases the frequency of microglia expressing Th1-associated chemokine, CXCL11. Treatment with both PACAP and IFN-_ reversed the proinflammatory effect of IFN- ?. Given the recent focus on the therapeutic value of Th2 cells in the CNS during neurodegenerative disease, PACAP may be a future therapeutic target for improving neuroregeneration after injury. Key words: neuroprotection, CCL11, CXCL11, facial nerve axotomy

Role of testosterone in patients with Alzheimer’s disease
Vasileios T. Papaliagkas, MD; Georgios A. Anogianakis, MD, PhD; Magda N. Tsolaki, MD, PhD
Fall 2008; pages 35-41

Alzheimer’s disease (AD) is the most common form of dementia in the elderly. It is growing rapidly and affects millions of people worldwide. Over the last 20 years, scientists have explored the potential beneficial roles of estrogens in the treatment of AD. Recent studies suggest that testosterone might also be involved in the pathogenesis of AD and more specifically that decreased levels of testosterone are linked with AD. This review summarizes the outcomes of research into the role of testosterone on cognitive ability of patients with AD. Keywords: testosterone, Alzheimer, testosterone supplementation

Effects of nerve graft implantation technique on axonal regeneration after spinal cord injury
Liudmila N. Novikova, PhD
Fall 2008; pages 43-49

Surgical management of injured spinal cord could require reconnection across the lesion gap by means of bridging grafts. The present study compares the effects of different grafting strategies on the number of neurons and myelinated axons regenerating into peripheral nerve graft at 8 weeks after cervical spinal cord injury in adult rats. After C4 cervical hemisection, the trauma zone was expanded to the entire length of the C4 spinal segment. An autologous peripheral nerve graft was implanted into C3 spinal segment using “intralesional” or “supralesional” grafting technique (Decherchi P, Gauthier P: Neuroscience. 2000;101:197-210). For intralesional transplantation, the graft was placed into the lesion cavity and (i) attached superficially to the rostral cavity wall or (ii) inserted 1 mm deep into the C3 spinal segment. During supralesional grafting, the nerve was implanted into a 1-mm-deep stab wound in the lateral funiculus 2 mm rostral to the lesion cavity (iii) immediately or (iv) at 1 week after the injury. The number of retrogradely labeled neurons in the brainstem and spinal cord regenerating into the graft was similar between the different grafting models. Regeneration of dorsal root ganglion neurons was significantly increased after delayed supralesional transplantation. The number of myelinated axons in the graft showed a twofold increase after intraspinal insertion compared with superficial graft attachment. The results of this study demonstrate that the technique and timing of graft implantation are parameters that could influence the extent of axonal regeneration and sprouting. Key words: adult rat, axonal regeneration, axonal sprouting, retrograde labeling, transplantation, peripheral nerve graft

Adult neurogenesis and pharmacology in Alzheimer’s disease and depression
Philippe Taupin, PhD
Fall 2008; pages 51-55

The confirmation that neurogenesis occurs in the adult brain and neural stem cells reside in the adult central nervous system has significantly contributed to modify our understanding of the functioning of the nervous system, and it holds the promise to treat a broad range of neurological diseases and injuries. Adult neurogenesis is modulated in neurological diseases and disorders, like in Alzheimer’s disease and depression, and by drugs used to treat them. This suggests that adult neurogenesis is affected by the pathologies of the nervous system, and it mediates the activities of drugs that are used to treat neurological diseases and disorders. Hence, adult neurogenesis is as important for our understanding of the etiology and pathogenesis of neurological diseases and disorders as for their pharmacology. Research on the pharmacology of adult neurogenesis may lead to new treatments and drug design. Key words: Alzhemeir’s disease, depression, neural stem cells, tetraploid