ABSTRACT
Recently p75 neurotrophin receptor (p75NTR) has been found to play a critical role in the pathology of neurodegen¬erative! diseases including Alzheimer's disease (AD) , Parkin¬son' s disease ( PI)), Huntington's disease ( HI)) , amyotrophic lateral sclerosis (ALS) and multiple sclerosis (MS).This arti¬cle reviews the research progress of p75NTR in regulating neuron apoptosis, axon degeneration and cognitive impairment, explo¬ring the application of p75NTR as a potential therapeutic target for the treatment of neurodegenerative diseases.
ABSTRACT
After a traumatic injury to the central nervous system, the distal stumps of axons undergo Wallerian degeneration (WD), an event that comprises cytoskeleton and myelin breakdown, astrocytic gliosis, and overexpression of proteins that inhibit axonal regrowth. By contrast, injured neuronal cell bodies show features characteristic of attempts to initiate the regenerative process of elongating their axons. The main molecular event that leads to WD is an increase in the intracellular calcium concentration, which activates calpains, calcium-dependent proteases that degrade cytoskeleton proteins. The aim of our study was to investigate whether preventing axonal degeneration would impact the survival of retinal ganglion cells (RGCs) after crushing the optic nerve. We observed that male Wistar rats (weighing 200-400 g; n=18) treated with an exogenous calpain inhibitor (20 mM) administered via direct application of the inhibitor embedded within the copolymer resin Evlax immediately following optic nerve crush showed a delay in the onset of WD. This delayed onset was characterized by a decrease in the number of degenerated fibers (P<0.05) and an increase in the number of preserved fibers (P<0.05) 4 days after injury. Additionally, most preserved fibers showed a normal G-ratio. These results indicated that calpain inhibition prevented the degeneration of optic nerve fibers, rescuing axons from the process of axonal degeneration. However, analysis of retinal ganglion cell survival demonstrated no difference between the calpain inhibitor- and vehicle-treated groups, suggesting that although the calpain inhibitor prevented axonal degeneration, it had no effect on RGC survival after optic nerve damage.
Subject(s)
Animals , Male , Polyvinyls/pharmacology , Retinal Ganglion Cells/drug effects , Axons/drug effects , Wallerian Degeneration/drug therapy , Glycoproteins/pharmacology , Optic Nerve Injuries/drug therapy , Axons/pathology , Immunohistochemistry , Cell Survival/drug effects , Treatment Outcome , Cell Death/drug effects , Cell Death/physiology , Rats, Wistar , Optic Nerve Injuries/pathology , Microscopy, Electron, Transmission , Nerve CrushABSTRACT
@#Objective To explore pathological characteristics of different white matter tracts at core of the spinal cord injury (SCI) in adult rats. Methods 21 adult female Wistar rats were divided into normal group (n=3), sham group (n=3) and lesion group (n=15). The rats of the lesion group were severely injured at T7-8 using the NYU impactor of 10 g×50 mm. The pathology of spinal cord injury was detected using Luxol fast blue (LFB) staining and NF200 immunohistochemistry staining 1 day, 3 days, 7 days, 14 days and 28 days after injury, while the hindlimbs behavior of rats was rated with Basso-Beattie-Bresnahan (BBB) scores of open-field. Results The BBB scores recovered 3 days after injury and reached a platform from 14 to 28 days after injury. LFB showed that there were spared white matters on ventral white matter (VWM) and lateral white matter (LWM). The percentage of spared white matters area decreased to the lowest 3 days after injury, and reached a platform from 7 to 28 days after injury. The number of NF200-IR axons reduced significantly in white matter tracts after SCI. Conclusion Ventral spared white matters plays a key role in the recovery of motor function in rat with SCI, and the first 3 days was a time window to protect the white matters from injury.
ABSTRACT
Objective To explore pathological characteristics of different white matter tracts at core of the spinal cord injury (SCI) in adult rats. Methods 21 adult female Wistar rats were divided into normal group (n=3), sham group (n=3) and lesion group (n=15). The rats of the lesion group were severely injured at T7-8 using the NYU impactor of 10 g×50 mm. The pathology of spinal cord injury was detected using Luxol fast blue (LFB) staining and NF200 immunohistochemistry staining 1 day, 3 days, 7 days, 14 days and 28 days after injury, while the hindlimbs behavior of rats was rated with Basso-Beattie-Bresnahan (BBB) scores of open-field. Results The BBB scores recov-ered 3 days after injury and reached a platform from 14 to 28 days after injury. LFB showed that there were spared white matters on ventral white matter (VWM) and lateral white matter (LWM). The percentage of spared white matters area decreased to the lowest 3 days after inju-ry, and reached a platform from 7 to 28 days after injury. The number of NF200-IR axons reduced significantly in white matter tracts after SCI. Conclusion Ventral spared white matters plays a key role in the recovery of motor function in rat with SCI, and the first 3 days was a time window to protect the white matters from injury.