The p21-activated kinases in neural cytoskeletal remodeling and related neurological disorders

The serine/threonine p21-activated kinases (PAKs), as main effectors of the Rho GTPases Cdc42 and Rac, represent a group of important molecular switches linking the complex cytoskeletal networks to broad neural activity. PAKs show wide expression in the brain, but they differ in specific cell types, brain regions, and developmental stages. PAKs play an essential and differential role in controlling neural cytoskeletal remodeling and are related to the development and fate of neurons as well as the structural and functional plasticity of dendritic spines. PAK-mediated actin signaling and interacting functional networks represent a common pathway frequently affected in multiple neurodevelopmental and neurodegenerative disorders. Considering specific small-molecule agonists and inhibitors for PAKs have been developed in cancer treatment, comprehensive knowledge about the role of PAKs in neural cytoskeletal remodeling will promote our understanding of the complex mechanisms underlying neurological diseases, which may also represent potential therapeutic targets of these diseases.

Progress on the molecular pathways of radiation-induced cognitive impairment / 基础医学与临床

Radiation-induced cognitive impairment is hypothesized to occur because of dynamic interactions be -tween multiple cell types, including astrocytes, endothelial cells, microglia, neurons, and oligodendrocytes.Cur-rent researche indicates that radiation-induced changes include the decrease in hippocampus neurogenesis , altera-tions of neuronal functions , particularly synaptic plasticity , as well as the elevation of neuroinflammatory cytokines .

The relationship between the expression of Toll-like receptor 4 and neurological function after fluid percussion brain injury in rats / 中华行为医学与脑科学杂志

Objective To investigate the expression of Toll-like receptor 4 (TLR4),and explore its relationship with neurological function after fluid percussion brain injury in rats.Methods 56 adult rats were randomly divided into traumatic brain injury group(TBI group,n=48) and sham operation group(SO group,n=8).The experimental models were established.The water content of edematous brain and the expression of TLR4 were measured with dry-wet measure,immunohistochemistry and Western Blot at 1 h,6 h,12 h,24 h,3 d,7 d after shock respectively.Results Compared with SO group,neuronal function score decreased in TBI group from 6 h(3.86±0.42),reached to the lowest level at 24 h(2.65±0.32),and gradually rose at 3rd day (3.25±0.17).TLR4 immunoreactive expression increased from 6 h,reached its maxmum at 24 h,lasted to 3rd day,and then began to drop at 7th day.The linear regression analysis indicated that expression of TLR4 had negative correlation with change of neuronal function score (r 1 =-0.824,r w =-0.867,P＜0.05).Conclusion TLR4 expression is upregulated following fluid percussion injury in rats and involved in neurological function impairment by inducing secondary inflammatory brain injury.

The relationship between the expression of inflammatory cytokines and neuronal function score of fluid percussion brain injury in rats / 中华行为医学与脑科学杂志

Objective To investigate the expression of inflanmatory cytokines such as interlukin-1β (IL-1 β),interlukin-6 (IL-6),tumor necrosis factor-α (TNF-α) and intercelluar adhesion molecule-1 (ICAM-1),and explore their relationships with neuronal function score after fluid percussion brain injury in rats.Methods The experimental models were established in 48 adult rats.The water content of edematous brain and the expression of IL-Iβ,IL-6,TNF-α and ICAM-1 were measured with dry-wet measure,immunohistochemistry at 6 h,12 h,24 h,3 d,7 d after operation respectively.Results Compared with animals of shame operation (SO) group,neuronal function score decreased in TBI group from 6h (3.78±0.84),reached to the lowest level at 24h (2.65±0.32),and gradually increased at 3d (4.75±0.71).IL-6,IL-1β,TNF-α and ICAM-limmunoreactive expression increased from 6h,reached its maxmum at 24h,lasted to 3th day,and began to decrease at 7d.The linear regression analysis indicated that expression of IL-1β,IL-6,TNF-α and ICAM-1 had negative correlations with change of neuronal function score(r=-0.912,r=-0.892,r=-0.794,r=-0.887 respectively,P＜0.05).Conclusion IL-6,IL-1β,TNF-α and ICAM-1 expression is upregulated following fluid percussion injury in rats,and shows negative correlations with neuronal function score.The possible mechanisms is that inflammatory cytokines are involved in nerve function impairment by inducing secondary brain injury.

Effects of Cluster Scalp Acupuncture on Behavior and Apoptosis-related Gene bcl-2 in Rats after Acute Cerebral Infarction / 中国康复理论与实践

@#Objective To explore the effects of cluster scalp acupuncture on the behavior and expression of bcl-2 in rats after acute cerebral infarction. Methods 72 male Wistar rats were randomly divided into sham operation group (A), model group (B) and cluster scalp acupuncture group (C), 24 rats in each group. According to time after cerebral infarction, each group was reassigned to 6 h, 24 h and 3 d subgroups, 8 rats in each subgroup. The acute cerebral infarction model was established with the middle cerebral artery occlusion. The effects of cluster scalp acupuncture on the behavior and expression of apoptosis-related gene bcl-2 in the rat brain tissues with acute cerebral infarction were tested at different time. Results 3 d after cerebral infarction, the score of neuronal function in group C was significantly lower than that of group B (P<0.01). The expression of bcl-2 in brain ischemic penumbra increased in group C at different time and reached its peak at 24 h. Compared with group B, there was a statistical difference (P<0.01). Conclusion Cluster scalp acupuncture can significantly reduce the neuronal function score of rats after acute cerebral infarction and then promote the recovery of movement function. The therapy can inhibit the apoptosis by increasing the expression of bcl-2 in penumbra zone of cerebral infarction.