ObjectiveTo characterize the dynamic expression of Robo3 in the rat model of temporal lobe epilepsy(TLE), and assess the potential contribution of Robo3 to epileptogenesis. MethodsMale Sprague-Dawley (SD) rats were randomly divided into the control group (n=6) and the experimental groups (n=30, 6 per group). The experimental groups were injected intraperitoneally (i.p.) with an aqueous solution of lithium-pilocarpine, and sacrificed at different time points (1, 7, 14, 30 and 60 days) following the seizure. The control group was i.p. with 0.9% sodium chloride instead of pilocarpine. Quantitative real-time PCR were used to detected the mRNA expression of Robo3 and Western bolt were used to detected the protein expression of Robo3. ResultsQuantitative real-time PCR showed that the expression of Robo3 were significantly lower in the rat temporal lobe tissues of the latent and the chronic period group as compared with the controls(P < 0.05), but no significant differences were identified between the acute period group and the controls(P > 0.05). Western blot showed that the protein expression of Robo3 were significantly lower in the rat temporal lobe tissues of the latent and the chronic period group as compared with the controls(P < 0.05), no significant differences were identified between the acute period group and the controls(P > 0.05). ConclusionsRobo3 may be involved in the pathogenesis of temporal lobe epilepsy.
Spinal cord injury (SCI), especially the complete SCI, usually results in complete paralysis below the level of the injury and seriously affects the patient’s quality of life. SCI repair is still a worldwide medical problem. In the last twenty years, Professor DAI Jianwu and his team pioneered complete SCI model by removing spinal tissue with varied lengths in rodents, canine, and non-human primates to verify therapeutic effect of different repair strategies. Moreover, they also started the first clinical study of functional collagen scaffold on patients with acute complete SCI on January 16th, 2015. This review mainly focusses on the possible mechanisms responsible for complete SCI. In common, recovery of some sensory and motor functions post complete SCI include the following three contributing reasons. ① Regeneration of long ascending and descending axons throughout the lesion site to re-connect the original targets; ② New neural circuits formed in the lesion site by newly generated neurons post injury, which effectively re-connect the transected stumps; ③ The combined effect of ① and ②. The numerous studies have confirmed that neural circuits rebuilt across the injury site by newborn neurons might be the main mechanisms for functional recovery of animals from rodents to dogs. In many SCI model, especially the complete spinal cord transection model, many studies have convincingly demonstrated that the quantity and length of regenerated long descending axons, particularly like CST fibers, are too few to across the lesion site that is millimeters in length to realize motor functional recovery. Hence, it is more feasible in guiding neuronal relays formation by bio-scaffolds implantation than directing long motor axons regeneration in improving motor function of animals with complete spinal cord transection. However, some other issues such as promoting more neuronal relays formation, debugging wrong connections, and maintaining adequate neural circuits for functional recovery are urgent problems to be addressed.
Primary or secondary death of retinal ganglion cells (RGC) is a common outcome in various optic neuropathies, often resulting in severe visual damage. The inherent characteristics of RGC include the continuous upregulation of intracellular growth-inhibitory transcription factors and the downregulation of growth-inducing transcription factors during cell differentiation. Additionally, the external inhibitory microenvironment following RGC damage, including oxidative stress, chronic inflammation, lack of neurotrophic factors, high expression of myelin proteins, and the formation of glial scars, all restrict axonal regeneration. Both intrinsic and extrinsic factors lead to the death of damaged RGC and hinder axonal regeneration. Various neuroprotective agents and methods attempt to promote neuroprotection and axonal regeneration from both intrinsic and extrinsic aspects, and well knowledge of these neuroprotective strategies is of significant importance for promoting the neuroprotective experimental research and facilitating its translation into clinical practice.
Objective To explore the changes of morphology and ventricornual motor neuronsin SD rats’ ventral horn of spinal cord after radiated as the therapy protocol for breast cancer, to discover the rule of radiationinduced injury of brachialplexus, and also if there exits the reversible conversion in neurons. Methods Twenty SD rats were selected. The left side of the rats was used as the radiation side, and the right side as the control side. The RIBPI animal models were established by divideddose of radiation. Using 2 Gy/time and 5 times/week, a total administered dose reached 30 Gy after 3 weeks. The behaviour of the rats was observed after radiation. At 3, 5, 7 and 9 weeks after the last radiation (n=4), the wet weights of biceps brachii muscle, upperlimb circumference and compound action potential were examined; the pathological changes of biceps brachiimuscle, the morphological changes, counts of the motor neurons in ventral horn and axons of bilateral spinal cord were observed by HE staining, argentums staining and toluidine blue staining. Results The rats showed lameness and a “claw hand” 3 weeks after radiation. Compared with control side, thewet weights of biceps brachii muscle and upperlimb circumference were significantly reduced, meanwhile, the compound action potential significantly decreased, and its latent period was also significantly prolonged 3, 5, 7 and 9 weeks (Plt;0.05). The histological observation: Musculocutaneous nerve showed decreased medullated fibers, heterogeneous ditribution and decreased density, thin myelin sheath, damaged nerve structure and collagen hyperplasia; biceps brachii muscle showed degeneration, fiber breakage and inflammatory cell infiltration; The account of motor neurons in ventral horn was significantly decreased in the radiation side with time extending, the sign of cell death, such as, the neurons crimple, and karyolysis were observed(Plt;0.05). Conclusion Large dose of X-ray can inducedbrachial plexus injury, and the lameness, a “claw hand”, biceps brachii muscle atrophy and the compound action potential abnormality. The account of motor neurons in ventral horn was significantly decreased. The motor neurons showed oxonal degeneration and myelinec degeration.
Object ive To summa r i z e the advanc ement of cytoske l e ton and axon outgrowth of neuron. Methods The recent l iterature concerning cytoskeleton and axon outgrowth of neuron was reviewed and summarized. Results The actin filaments and microtubules in neuron were highly polarized and dynamic structures confined to the ti ps of axons and the reci procal interactions between these two major cytoskeletal polymers was also dynamic. Attractive or a repulsive cue whose final common path of action was the growth cone cytoskeleton mediated the growth of axons of neuron by intracellular signaling cascades. Regulating the actin filament and microtubule dynamics as well as their interactions in growth cones played a key role in neurite outgrowth and axon guidance. Rho-GTPases and glycogen synthase kinase 3β (GSK-3β), the two major intracellular signal ing pathways had emerged in recent years as candidates for regulating the dynamics of actin filaments and microtubules. Conclusion The axon outgrowth and guidance depend on well-coordinated cytoskeletal and reciprocal interaction dynamics which also mediate axon regeneration after spinal cord injury. Regulating activity of Rho-GTPases and GSK- 3β simultaneously may acts as key role to regulate the dynamics of cytoskeletal and to determine axon outgrowth.
The purpose of this experiment was to elucidate the influence of the low-energy He-Ne laser on the function of regeneration of peripheral nerve. Forty-four rabbits about 2.5 kg body weight were used in the experiment. The animals were divided into 4, 8, 12, 16 weeks groups according to the observation period. Six animals were used in each irradiated group and in the control group 5 rabbits were used in each observation period. Regeneration of the axon and myelinc sheath, the latent rate of the common peroneal nerve, the conditions of the anterior tibital muscle and the toe expansion test were all observed systematically in both groups. The experimental results was: A few thin regenerated axon was seen at 4 weeks in the irradiated group, while in the control group it might be seen at 8 weeks, the P value was lt; 0.01. A low amplitude latent rate of the common peroneal nerve is determined at the peroneal side of the anterior tibial muscle in a few animal at 4 weeks of the irradiated group, and it is not observed in the control group, from 12 to 16 weeks. THe latent rate of the common peroneal nerve was the irradiated group than in the controlled, the P value was lt; 0.01. The regeneration of the myeline sheath was evident in the irradiated group, and also the slstion of the musdle fibers anterior tibial muscle was clearly visible than the controlled. 16 weeks postoperatively, the toe expansion test was normal in the irradiated group, while in the control group it was the same as seen at 12 weeks after operation in the irradiated group. Now it was certain that the low-energy He-Ne laser could promole the function of the spinal motor nerve cells and accelerate the axonal regeneration.
Objective To investigate the effects of Neuritin on the regeneration of the neural axons after acute spinal cord injury (SCI) in rats. Methods The model of acute SCI at T10 was establ ished in 54 adult healthy Wistar rats (half males and half females) weighing 250-300 g by using the improved Allen’s weight-drop method. The rats were randomly dividedinto 3 groups. 100 μL (6 μg) Neuritin and His protein was injected into group A (n=24) and group B (n=24), respectively,through subarachnoid catheter. Six rats from each group were killed 3, 7, 14, and 28 days after injury to receive Basso, Beattie and Bresnahan (BBB) locomotor rating scal ing, HE staining observation, and immunohistochemistry staining observation for neurofilament 200 (NF-200) and growth associated protein 43 (GAP-43). Group C (n=6) served as sham-operated group receiving laminectomy without spinal injury and with an empty catheter in the subarachnoid space and received the above observations 7 days after injury. Results BBB scale: after operation, the scale of groups A and B was increased over time; group A was significantly higher than group B from 14 days (P lt; 0.05); group C was higher than groups A and B at different time points after operation (P lt; 0.05). HE staining: in group C, the injured spinal tissue was normal after operation; from 7 days after operation, group A presented deeper-stained nissl body, less physal iferous cells, and more nerve synapses when compared with group B. NF-200 and GAP-43 immunohistochemistry observation: in group C, there was just l ittle positive expression; while in groups A and B, positive expression of NF-200 and GAP-43 was evident in the spinal cord from 7 days after operation. Mean density integral absorbency (IA) value of NF-200 and GAP-43: group A was higher than group B at each time point (P lt; 0.05) and group C was lower than groups A and B at each time point (P lt; 0.05). Conclusion Local application of exogenous Neuritin can promote the axonal regeneration after acute SCI in rats and the recovery of the locomotion function of hind-limbs in rats.
The ‘glial scar’ has been widely studied in the regeneration of spinal cord injury (SCI). For decades, mainstream scientific concept considers glial scar as a ‘physical barrier’ to impede axonal regeneration after SCI. Moreover, some extracellular molecules produced by glial scar are also regarded as axonal growth inhibitors. With the development of technology and the progress of research, multiple lines of new evidence challenge the pre-existing traditional notions in SCI repair, including the role of glial scar. This review briefly reviewed the history, advance, and controversy of glial scar research in SCI repair since 1930s, hoping to recognize the roles of glial scar and crack the international problem of SCI regeneration.