Journal of neurotrauma
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Journal of neurotrauma · Feb 2023
TNF-α impairs pericyte-mediated cerebral microcirculation via the NF-κB/iNOS axis after experimental traumatic brain injury.
Secondary structural and functional abnormalities of the neurovascular unit are important pathological mechanisms following traumatic brain injury (TBI). The neurovascular unit maintains blood-brain barrier and vascular integrity through interactions among glial cells, pericytes and endothelial cells. Trauma-induced neuroinflammation and oxidative stress may act as initiating factors for pathological damage after TBI, which in turn impairs cerebral microcirculatory function. ⋯ Inhibition of TNF-α using infliximab reduced NF-κB phosphorylation and nuclear translocation and downregulated iNOS expression, which attenuated the inflammation and oxidative damage. Meanwhile, inhibition of TNF-α reversed pericyte marker loss, and improved pericyte function and microcirculation perfusion after TBI. In conclusion, our study suggests that microglia released TNF-α after TBI, which promoted neuroinflammation and oxidative stress by activating downstream NF-κB/iNOS signals, and this led to pericyte-mediated disturbance of the cerebral microcirculation.
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Journal of neurotrauma · Feb 2023
Improving the Function of Meningeal Lymphatic Vessels to Promote Brain Edema Absorption after Traumatic Brain Injury.
Brain edema is the most common and fatal complication after traumatic brain injury (TBI). Meningeal lymphatic vessels (MLVs) are the conduits that transport cerebrospinal fluid (CSF) and macromolecules to deep extracranial cervical lymph nodes (dCLNs). After TBI, the drainage function of MLVs can become impaired. ⋯ In addition, ketoprofen, 9-cisRA, and VEGF-C upregulated the lymphatic-specific proteins VEGF receptor (VEGFR)3, PROX1, forkhead box protein C2 (FOXC2), and lymphatic vessel endothelial hyaluronan receptor 1 (LYVE1). These results indicate that ketoprofen, 9-cisRA, and VEGF-C may maintain the integrity of the meningeal lymphatic wall and promote lymphatic proliferation by upregulating the expression of lymphatic vessel-specific proteins, improve meningeal lymphatic function after TBI, promote CSF drainage and brain edema absorption, reduce the immune response of the nervous system, and reduce ROS formation, thereby improving prognoses. These findings may provide new ideas for the treatment of brain edema after TBI.
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Journal of neurotrauma · Feb 2023
Functional Connectivity in the Mouse Brainstem Represents Signs of Recovery from Concussion.
Mild traumatic brain injury (mTBI) is one of the most frequent neurological disorders. Diagnostic criteria for mTBI are based on cognitive or neurological symptoms without fully understanding the neuropathological basis for explaining behaviors. From the neuropathological perspective of mTBI, recent neuroimaging studies have focused on structural or functional differences in motor-related cortical regions but did not compare topological network properties between the post-concussion days in the brainstem. ⋯ Functional connectivity and local network properties on post-concussion day 2 were also significantly decreased compared with those on post-concussion day 14, but there were no significant group differences in global network properties between days 2 and 14. We also observed that the local efficiency and clustering coefficient of the brainstem network were significantly correlated with anxiety-like behaviors on post-concussion days 7 and 14. This study suggests that functional connectivity in the mouse brainstem provides vital recovery signs from concussion through functional reorganization.