Manipulations of spinal cord excitability evoke developmentally-dependent compensatory changes in the lamprey spinal cord

We have examined homeostatic or compensatory plasticity evoked by tonic changes in spinal cord excitability in the lamprey, a model system for investigating spinal cord function. In larval animals, reducing excitability by incubating in tetrodotoxin or the glutamate receptor antagonists CNQX or CNQX/AP5 for 20–48 h resulted in a diverse set of cellular and synaptic changes that together were consistent with an increase in spinal cord excitability. Similar changes occurred to a tonic increase in excitation evoked by incubating in high potassium physiological solution (i.e. responses were unidirectional). We also examined developmental influences on these effects. In animals developing from the larval to adult form effects were reduced or absent, suggesting that at this stage the spinal cord was more tolerant of changes in activity levels. Responses had returned in adult animals, but they were now bi-directional (i.e. opposite effects were evoked by an increase or decrease in excitability). The spinal cord can thus monitor and adapt cellular and synaptic properties to tonic changes in excitability levels. This should be considered in analyses of spinal cord plasticity and injury.     

Regeneration in the spinal cord

Important advances have been made in our understanding of conditions that influence the intrinsic capacity of mature CNS neurons to initiate and maintain a regrowth response. The combination of exogenous neurotrophic support with strategies to alter the terrain at the injury site itself suggests that there are important interactions between them that lead to increased axonal regeneration. The ability of chronically injured neurons to initiate a regeneration response is unexpected. Our view of the role that inhibitors play in restricting axonal growth has also expanded. The findings indicate that the windows of opportunity for enhancing growth after spinal cord injury may be more numerous than previously thought.     

Increased expression of spinal cord Fos protein induced by bladder stimulation after spinal cord injury

These studies examined Fos protein expression in spinal cord neurons synaptically activated by stimulation of bladder afferent pathways after spinal cord injury (SCI). In urethan-anesthetized Wistar rats after SCI for 6 wk, intravesical saline distension significantly (P 相似文献   

Transplantation of adult spinal cord grafts into spinal cord transected rats improves their locomotor function

Grafted embryonic central neural tissue pieces can recover function of hemisected spinal cord in neonatal rats and promote axonal growth in adults. However, spinal cord segments from adults have not been used as donor segments for allogeneic transplantation. Here, we utilized adult spinal cord tissue grafts(aSCGs) as donor constructs for repairing complete spinal cord injury(SCI). Moreover, to provide a favourable microenvironment for SCI treatment, a growth factor cocktail containing three growth factors(brain-derived neurotrophic factor, neurotrophin-3 and vascular endothelial growth factor), was applied to the aSCG transplants. We found that the locomotor function was significantly improved 12 weeks after transplantation of aSCGs into the spinal cord lesion site in adult rats. Transplantation of aSCGs combined with these growth factors enhanced neuron and oligodendrocyte survival and functional restoration. These encouraging results indicate that treatment of complete SCI by transplanting aSCGs, especially in the presence of growth factors, has a positive effect on motor functional recovery, and therefore could be considered as a possible therapeutic strategy for SCI.     

Transplantation of adult spinal cord tissue: Transection spinal cord repair and potential clinical translation

Science China Life Sciences -     

Brain and spinal cord interaction: protective effects of exercise prior to spinal cord injury

We have investigated the effects of a spinal cord injury on the brain and spinal cord, and whether exercise provided before the injury could organize a protective reaction across the neuroaxis. Animals were exposed to 21 days of voluntary exercise, followed by a full spinal transection (T7-T9) and sacrificed two days later. Here we show that the effects of spinal cord injury go beyond the spinal cord itself and influence the molecular substrates of synaptic plasticity and learning in the brain. The injury reduced BDNF levels in the hippocampus in conjunction with the activated forms of p-synapsin I, p-CREB and p-CaMK II, while exercise prior to injury prevented these reductions. Similar effects of the injury were observed in the lumbar enlargement region of the spinal cord, where exercise prevented the reductions in BDNF, and p-CREB. Furthermore, the response of the hippocampus to the spinal lesion appeared to be coordinated to that of the spinal cord, as evidenced by corresponding injury-related changes in BDNF levels in the brain and spinal cord. These results provide an indication for the increased vulnerability of brain centers after spinal cord injury. These findings also imply that the level of chronic activity prior to a spinal cord injury could determine the level of sensory-motor and cognitive recovery following the injury. In particular, exercise prior to the injury onset appears to foster protective mechanisms in the brain and spinal cord.     

Pregnancy following spinal cord injury.

Each year about 2,000 women of childbearing age in the United States have a spinal cord injury. Only a few mostly anecdotal reports describe pregnancy after such an injury. In a retrospective study of 16 women with a spinal cord injury, half of whom have a complete injury and about half quadriplegia, 25 pregnancies occurred, with 21 carried to full term. The women delayed pregnancy an average of 6.5 years after their injury, with an average age at first pregnancy of 26.8 years. Cesarean section was necessary in 4 patients because of inadequate progress of labor. In 5 deliveries an episiotomy and local anesthesia were required, 7 required epidural anesthesia, including all cesarean sections, and 10 did not require anesthesia. Several complications have been identified in the antepartum, intrapartum, and postpartum periods including autonomic hyperreflexia, premature labor, pressure sores, urinary tract infections, abnormal presentation, and failure to progress. Ultrasonography and amniocentesis were used selectively. Women with spinal cord injuries can have healthy children, although there are significant risks and these women have special needs.     

Dorsal spinal cord inhibits oligodendrocyte development

Oligodendrocytes are the myelinating cells of the mammalian central nervous system. In the mouse spinal cord, oligodendrocytes are generated from strictly restricted regions of the ventral ventricular zone. To investigate how they originate from these specific regions, we used an explant culture system of the E12 mouse cervical spinal cord and hindbrain. In this culture system O4(+) cells were first detected along the ventral midline of the explant and were subsequently expanded to the dorsal region similar to in vivo. When we cultured the ventral and dorsal spinal cords separately, a robust increase in the number of O4(+) cells was observed in the ventral fragment. The number of both progenitor cells and mature cells also increased in the ventral fragment. This phenomenon suggests the presence of inhibitory factor for oligodendrocyte development from dorsal spinal cord. BMP4, a strong candidate for this factor that is secreted from the dorsal spinal cord, did not affect oligodendrocyte development. Previous studies demonstrated that signals from the notochord and ventral spinal cord, such as sonic hedgehog and neuregulin, promote the ventral region-specific development of oligodendrocytes. Our present study demonstrates that the dorsal spinal cord negatively regulates oligodendrocyte development.