Ethyl pyruvate improves white matter remodeling in rats after traumatic brain injury

Abstract

Background Severe traumatic brain injury (TBI) results in long‐term neurological deficits associated with white matter injury (WMI). Ethyl pyruvate (EP) is a simple derivative of the endogenous energy substrate pyruvate with neuroprotective properties, but its role in recovery from WMI has not been explored. Aims This study examines the effect of EP treatment on rats following TBI using behavioral tests and white matter histological analysis up to 28 days post‐injury. Materials and Methods Anaesthetised adult rats were subjected to TBI by controlled cortical impact. After surgery, EP or Ringers solution (RS) was administrated intraperitoneally at 15 min after TBI and again at 12, 24, 36, 48, and 60 h after TBI. Sensorimotor deficits were evaluated up to day 21 after TBI by four independent tests. Immunofluorescence and transmission electron microscopy (TEM) were performed to assess white matter injury. Microglia activation and related inflammatory molecules were examined up to day 14 after TBI by immunohistochemistry or real‐time PCR. Results Here, we demonstrate that EP improves sensorimotor function following TBI as well as improves white matter outcomes up to 28 d after TBI, as shown by reduced myelin loss. Furthermore, EP administration during the acute phase of TBI recovery shifted microglia polarization toward the anti‐inflammatoryM2 phenotype, modulating the release of inflammatory‐related factors. Conclusion EP treatment may protect TBI‐induced WMI via modulating microglia polarization toward M2.

Cordycepin confers long-term neuroprotection via inhibiting neutrophil infiltration and neuroinflammation after traumatic brain injury

“…Besides gray matter, white matter is also the main target of TBI closely linked to neurological impairment [ 21 ]. Firstly, MBP and NF-200 were stained to observe myelin and neurofilament changes in the striatum after TBI (Fig.…”

“…In addition to short-term behaviors, we observed long-term behaviors and neuronal tissue loss, providing long-term neuroprotection evidences for cordycepin. TBI-induced WMI is positively correlated with neurological deficits, reducing WMI helps improve neurological functions [ 21 ]. We observed that cordycepin reserved the morphology of white matter and neurofilament on 35 days after TBI.…”

“…Real-time PCR was performed as described [ 21 ]. Briefly, the PCR was performed with the Hieff® qPCR SYBR® Green Master Mix (No Rox) (Shanghai Yeasen, China) in Mastercycler ep realplex (Eppendorf) using corresponding primers (supplementary materials).…”

Edaravone Dexborneol Treatment Attenuates Neuronal Apoptosis and Improves Neurological Function by Suppressing 4-HNE-Associated Oxidative Stress After Subarachnoid Hemorrhage

“…The rotarod test was performed to evaluate the balance and sensorimotor coordination ( Mao et al, 2020 ). After the animals were placed on the rods, the rods began to accelerate to 40 r/min within 30 s, and this speed was maintained until 300 s. The duration on the rods was recorded.…”

Recent Advances in Fluorescence Imaging of Traumatic Brain Injury in Animal Models

“…Neuroinflammatory responses (e.g., microglia/macrophage activation) could be induce by TBI, which is regarded as a key factor in the secondary injury cascade following TBI. Immunofluorescence staining is a classic method to investigate the mechanism of TBI-induced neuroinflammatory responses (Readnower et al, 2010;Villapol et al, 2017;Takahata et al, 2019;Mao et al, 2021). By double-labeling immunofluorescence, the levels of the lipid peroxidation marker 4-hydroxynonenal (4-HNE) and the protein nitration marker 3-nitrotyrosine (3-NT) in brain sections after exposure to blast have been determined (Readnower et al, 2010).…”