Axonal regeneration in the lesioned mammalian central nervous system is abortive, and this causes permanent disabilities in individuals with spinal cord injuries. In adult rats, olfactory ensheathing glia (OEG) transplants successfully led to functional and structural recovery after complete spinal cord transection. From 3 to 7 months post surgery, all OEG-transplanted animals recovered locomotor functions and sensorimotor reflexes. They presented voluntary hindlimb movements, they supported their body weight, and their hindlimbs responded to light skin contact and proprioceptive stimuli. In addition, relevant motor axons (corticospinal, raphespinal, and coeruleospinal) regenerated for long distances within caudal cord stumps. Therefore, OEG transplantation provides a useful repair strategy in adult mammals with traumatic spinal cord injuries. Our results with these cells could lead to new therapies for the treatment of spinal cord lesions in humans.
A therapy to treat injuries to the central nervous system (CNS) is, to date, a major clinical challenge. The devastating functional consequences they cause in human patients have encouraged many scientists to search, in animal models, for a repair strategy that could, in the future, be applied to humans. However, although several experimental approaches have obtained some degree of success, very few have been translated into clinical trials. Traumatic and demyelinating lesions of the spinal cord have attracted several groups with the same aim: to find a way to promote axonal regeneration, remyelination, and functional recovery, by using a simple, safe, effective, and viable procedure. During the past decade, olfactory ensheathing glia (OEG) transplantation has emerged as a very promising experimental therapy to promote repair of spinal cords, after different types of injuries. Transplants of these cells promoted axonal regeneration and functional recovery after partial and complete spinal cord lesions. Moreover, olfactory ensheathing glia were able to form myelin sheaths around demyelinated axons. In this article, we review these recent advances and discuss to what extent olfactory ensheathing glia transplantation might have a future as a therapy for different spinal cord affections in humans.
The present work demonstrated that systemic treatment with an NO donor before reperfusion improved renal function and diminished inflammatory responses in a kidney subjected to an I-R process.
Repair of spinal cord injuries (SCIs) is still a major clinical challenge. Several attempts have been made to find a cure for this condition in experimental animals that could be extrapolated to humans. A key for success seems the availability of optimum animal models for testing different therapies. Complete spinal cord lesion in mammals is considered the most accurate injury model. In addition, long-term survival of animals seems more appropriate, as this increases the efficacy of the repair strategies. However, paraplegic animals require special care and treatment for proper longterm maintenance, and to date, there are no published protocols. This lack of available information has discouraged scientists from working with this injury model. Over the past 7 years, we have tested the repair efficacy of olfactory ensheathing glia in paraplegic rats for survival periods of more than 8 months. To keep these animals healthy for this long time, we adapted and administered treatments used in people with paraplegia. These same protocols (developed for rodents in our group) are being applied to paraplegic monkeys. In this review, we provide an overview of the proper handling and care of paraplegic adult laboratory mammals for long periods. This information might help other groups to optimize the outcome obtained and to better evaluate the prospect of a given experimental repair strategy. In addition, the use of human treatments in paraplegic animals provides a more realistic model for a later transfer to the clinical arena.
Insulin‐like growth factor I (IGF‐I) is a trophic factor for both neurons and glia. Its presence in the developing and adult cerebellum suggests a role for this growth factor in this area of the brain. Recently, we have described the existence of an IGF‐I‐containing pathway in afferents of Purkinje neurons arising from the inferior olive. In addition, IGF‐I receptors are present in the molecular layer of the cerebellar cortex. These observations prompted us to investigate whether the Purkinje cell is a target for IGF‐I. Addition of IGF‐I to rat cerebellar cultures produced a 7‐fold increase in the number of Purkinje cells (calbindin‐positive) together with an increase in the calbindin content of the cultures. IGF‐I also doubled the number of surviving neurons and produced a moderate, non‐significant increase in [3H]thymidine incorporation by the cultures. On the other hand, basic fibroblast growth factor (bFGF), which is also present in the cerebellum, produced a dramatic increase in both the proportion of astrocytes and in the mitotic activity of the cultures, without affecting neuron survival. We conclude that IGF‐I is a specific promoter of Purkinje cell survival and that its effects differ from those produced by bFGF in fetal cerebellar cultures. These findings reinforce our hypothesis that the Purkinje cell is a target neuron for IGF‐I action in the developing cerebellum.
Olfactory bulb ensheathing glia (OB-OEG) promote repair of spinal cord injury (SCI) in rats after transplantation at acute or subacute (up to 45 days) stages. The most relevant clinical scenario in humans, however, is chronic SCI, in which no more major cellular or molecular changes occur at the injury site; this occurs after the third month in rodents. Whether adult OB-OEG grafts promote repair of severe chronic SCI has not been previously addressed. Rats with complete SCI that were transplanted with OB-OEG 4 months after injury exhibited progressive improvement in motor function and axonal regeneration from different brainstem nuclei across and beyond the SCI site. A positive correlation between motor outcome and axonal regeneration suggested a role for brainstem neurons in the recovery. Functional and histological outcomes did not differ at subacute or chronic stages. Thus, autologous transplantation is a feasible approach as there is time for patient stabilization and OEG preparation in human chronic SCI; the healing effects of OB-OEG on established injuries may offer new therapeutic opportunities for chronic SCI patients.
SummaryA synthetic tetrasaccharide structurally related to blood groups and sdectin ligands inhibited division of astrocytes, gliomas, and neuroblastomas at rnicromolar concentrationi The compound was cytostatic for primary astrocytes in culture, but cytotoxic for fast proliferating cell lines.
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