Implantation of stimulated homologous macrophages results in partial recovery of paraplegic rats

Rapalino, Otto; Lazarov, Orly; Agranov, Eugenia; Velan, G J; Yoles, Eti; Fraidakis, Matthew J.; Solomon, Arieh S.; Gepstein, Reuven; Katz, Amiram; Belkin, Michael; Hadani, Moshe; Schwartz, Michal

doi:10.1038/nm0798-814

Cited by 733 publications

(433 citation statements)

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“…Two studies revealed that microglial transplants placed into lesioned spinal cord promoted neurite growth (138;142). Although functional recovery was not documented in these latter reports, partial recovery was provided by transplanting activated monocytes into the caudal stump of transected rat spinal cord (143). The success of these pre-clinical models prompted a Phase I clinical trial.…”

Section: Immunomodulatory and Cell-specific Therapies For Scimentioning

confidence: 99%

Inflammation and its role in neuroprotection, axonal regeneration and functional recovery after spinal cord injury

Donnelly

Popovich

2008

Experimental Neurology

838

755

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Trauma to the central nervous system (CNS) triggers intraparenchymal inflammation and activation of systemic immunity with the capacity to exacerbate neuropathology and stimulate mechanisms of tissue repair. Despite our incomplete understanding of the mechanisms that control these divergent functions, immune-based therapies are becoming a therapeutic focus. This review will address the complexities and controversies of post-traumatic neuroinflammation, particularly in spinal cord. In addition, current therapies designed to target neuroinflammatory cascades will be discussed.

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Section: Immunomodulatory and Cell-specific Therapies For Scimentioning

confidence: 99%

Inflammation and its role in neuroprotection, axonal regeneration and functional recovery after spinal cord injury

Donnelly

Popovich

2008

Experimental Neurology

838

755

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“…42 Macrophages have also been shown to provide a suitable environment for central axonal regeneration. 43 The first experiments showing this effect involved the retina and many others have since followed. Fetal transplants have also been used in the brain of animals with variable results.…”

Section: The Autonomic Motor Systemmentioning

confidence: 99%

Neuropathology: the foundation for new treatments in spinal cord injury

2004

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The first step essential in the search for a cure of human spinal cord injury (SCI) is to appreciate the complexity of the disorder. In this regard, it is not only the loss of ambulation but the sensory and autonomic changes that are equally important in recovery. In addition, there are the serious social emotional psychological and lifestyle effects of SCI which should also be taken into account. It is also true that no two SCI lesions are alike as each is the result of a SCI unique to that individual. Clinically of utmost importance is the segmental level of injury and whether it is complete, incomplete or discomplete (loss of all neurological functions below the injury but with physiological or anatomical continuity of Central nervous system tracts across the lesion). We are not concerned here with primary and secondary prevention or methods designed to limit the severity of the lesion after the event, important as they are, but with the requirements for a cure. Clearly, the greater the number of nerve fibers that can be preserved in the acute stage, the better will be the end result. Our focus at present is on the end-stage lesion with the aim of showing that a cure for SCI will depend upon establishing functionally useful central axonal regeneration and reestablishing physiological reconnections. Existing experimental methods are based on stimulating axonal regeneration by neutralizing inhibitory factors, adding positive trophisms and creating a permissive environment. Better results are obtained by bridging the gap with grafts of peripheral nerves or transplants of Schwann cells and genetically engineered fibroblasts. Recently, the potential for stem cells to enhance this process has created great interest. This is because of the ability of pluripotential cells to differentiate into neural tissue. A cure based on the physiopathology of SCI requires pyramidal, extrapyramidal, sensory, cerebellar and autonomic pathways to be regenerated with their appropriate neurotransmitters restored and reflexes integrated physiologically and in synchrony. In human SCI, there is a very long distance anatomically for axonal regrowth to occur in order to reach their relevant nuclei. This is because of continuing Wallerian degeneration. It also presumes that the target neurons are intact and that there has been no transneuronal degeneration above or below the lesion. Alternatively, in place of regenerated long axons, a multisynaptic pathway may be constructed from stem cells that have developed into neurons. Whether such a pathway would restore useful neurological functions is unknown. At present, the transplant and grafting research teams are exploring these possibilities in experimental animals. Moderate success in gaining axonal regeneration has been reported; however, it must be appreciated that the human lesion differs considerably from that of the experimental animal. In order to be successful, the neuropathology and neurophysiology of human SCI must be taken into account. The purpose of this review is to place the req...

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“…Clearly, the environment dictates the response of the macrophage. 68 Lymphocyte infiltration T-lymphocytes are scattered in the uninjured spinal cord and progressively increase in number after injury in parallel with the activation of microglia and influx of peripheral macrophages, within the first week and predominantly within the epicentre. 14 Under normal conditions, activated T cells can cross the BBB and enter the CNS parenchyma.…”

Section: Experimental Modelsmentioning

confidence: 99%