Pathophysiological and behavioral deficits in developing mice following rotational acceleration-deceleration traumatic brain injury

Wang, Guoxiang; Gao, Zhongwen; Shields, Lisa B.E.; Li, Fang; Chu, Tianci; Lv, Huayi; Moriarty, Thomas; Xu, Xiao–Ming; Yang, Xiaoyu; Shields, Christopher B.; Cai, Jun

doi:10.1242/dmm.030387

Cited by 27 publications

(13 citation statements)

References 100 publications

(141 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This test evaluates locomotor function and coordination and was performed on the RotaRod (UgoBasile 7650 accelerating RotaRod, Varese, Italy) as described previously [34, 44]. In brief, a 2-day training/test regimen was followed with acceleration from 4 to 40 rpm in 300 s. The running time on the rod was recorded until the mouse fell off, and the average time of three trials on the test day was calculated as the Rotarod score.…”

Section: Methodsmentioning

confidence: 99%

Dynamic response of microglia/macrophage polarization following demyelination in mice

Chu

Zhong

et al. 2019

J Neuroinflammation

Self Cite

View full text Add to dashboard Cite

Background The glial response in multiple sclerosis (MS), especially for recruitment and differentiation of oligodendrocyte progenitor cells (OPCs), predicts the success of remyelination of MS plaques and return of function. As a central player in neuroinflammation, activation and polarization of microglia/macrophages (M/M) that modulate the inflammatory niche and cytokine components in demyelination lesions may impact the OPC response and progression of demyelination and remyelination. However, the dynamic behaviors of M/M and OPCs during demyelination and spontaneous remyelination are poorly understood, and the complex role of neuroinflammation in the demyelination-remyelination process is not well known. In this study, we utilized two focal demyelination models with different dynamic patterns of M/M to investigate the correlation between M/M polarization and the demyelination-remyelination process. Methods The temporal and spatial features of M/M activation/polarization and OPC response in two focal demyelination models induced by lysolecithin (LPC) and lipopolysaccharide (LPS) were examined in mice. Detailed discrimination of morphology, sensorimotor function, diffusion tensor imaging (DTI), inflammation-relevant cytokines, and glial responses between these two models were analyzed at different phases. Results The results show that LPC and LPS induced distinctive temporal and spatial lesion patterns. LPS produced diffuse demyelination lesions, with a delayed peak of demyelination and functional decline compared to LPC. Oligodendrocytes, astrocytes, and M/M were scattered throughout the LPS-induced demyelination lesions but were distributed in a layer-like pattern throughout the LPC-induced lesion. The specific M/M polarization was tightly correlated to the lesion pattern associated with balance beam function. Conclusions This study elaborated on the spatial and temporal features of neuroinflammation mediators and glial response during the demyelination-remyelination processes in two focal demyelination models. Specific M/M polarization is highly correlated to the demyelination-remyelination process probably via modulations of the inflammatory niche, cytokine components, and OPC response. These findings not only provide a basis for understanding the complex and dynamic glial phenotypes and behaviors but also reveal potential targets to promote/inhibit certain M/M phenotypes at the appropriate time for efficient remyelination.

show abstract

Section: Methodsmentioning

confidence: 99%

Dynamic response of microglia/macrophage polarization following demyelination in mice

Chu

Zhong

et al. 2019

J Neuroinflammation

Self Cite

View full text Add to dashboard Cite

show abstract

“…Protein samples were prepared in CelLytic™ MT Cell Lysis Reagent (Sigma-Aldrich, St. Louis, MO) containing the complete protease inhibitors (Roche, Indianapolis, IN) on ice. Western blots were performed as described previously (Cai et al, 2012;Wang et al, 2018). Equivalent amounts of total protein (30 μg/lane) were separated using 10% SDS-polyacrylamide gels (Bio-Rad, Hercules, CA) and then electrometrically transferred onto nitrocellulose membranes (Protan BA83, Midwest Scientific, Valley Park, MO).…”

Section: Western Blotsmentioning

confidence: 99%

Diverse changes in myelin protein expression in rat brain after perinatal methadone exposure

Oberoi¹,

Chu²,

Mellen³

et al. 2020

Acta Neurobiologiae Experimentalis

Self Cite

View full text Add to dashboard Cite

The national incidence of neonatal abstinence syndrome has dramatically increased over the last decade due to an increase in antenatal opioid exposure. Recent human and animal studies suggest that antenatal opioid exposure impacts the developing brain. The purpose of this study is to evaluate the effects of perinatal methadone exposure on myelination in multiple regions in the developing rat brain. Pregnant Sprague-Dawley rats were randomly assigned into three experimental groups and subsequently exposed to drinking water alone or drinking water containing methadone from 7 days post coitum through day 7 or through day 19 after delivery. Two male neonatal rats were randomly selected from each litter and terminated at day 19. The cerebral cortex, hippocampus, cerebellum, and brainstem were dissected and analyzed for three myelin specific proteins-CNP, PLP, and MBP-by Western blot analysis. All pups with exposure to methadone demonstrated decreased expression of CNP, PLP, and MBP in the cerebral cortex and hippocampus. In the cerebellum, PLP expression was down-regulated without apparent alteration of CNP and MBP expression. PLP and MBP expression, but not CNP expression, were significantly inhibited in the brainstem. Compared to the pups with postnatal methadone exposure via maternal milk through day 7, partial recovery of CNP and PLP expression only occurred in the cerebral cortices of the pups exposed through day 19. The findings show that antenatal opioid exposure in rat pups is associated with regionally-specific alterations in brain myelination that diversely affects myelin proteins.

show abstract

“…Cerebral blood perfusion (CBP) was dynamically and instantly monitored using Pericam Perfusion Speckle Image (PeriCam PSI) system by a fixed investigator who was blind to the groups, which could display the image and blood flow curve at the same time [44, 45]. The rats lied prone on an homeothermic electric blanket (37 ± 0.5 °C) under anesthesia.…”

Section: Methodsmentioning

confidence: 99%

Lipopolysaccharide worsens the prognosis of experimental cerebral ischemia via interferon gamma-induced protein 10 recruit in the acute stage

et al. 2019

View full text Add to dashboard Cite

BackgroundInfection is an important clinical complication facing stroke-patients and triples the risk of death within 30 days post-stroke via mechanisms which are poorly understood.AimsWe tried to explore the mechanisms that inflammation caused by infections aggravated the ischemic brain injury after middle cerebral artery occlusion (MCAO).MethodsWe used lipopolysaccharide (LPS) as systemic inflammatory stimuli to explore the mechanisms of aggravated ischemic brain injury after Sprague-Dawley male rats subjected to MCAO. Brain damage was evaluated by cerebral blood perfusion, Longa-5 scores, infarct volume and edema degree. Systemic cytokine responses and inflammatory changes in the plasma and brain were analyzed by ELISA kit, RT2 Profiler™ PCR array, and quantitative real-time PCR. The differential genes were subjected to Gene Ontology enrichment analysis and protein–protein interaction (PPI) network construction.ResultsLipopolysaccharide profoundly aggravated the brain damage after 24 h post-MCAO. At the acute stage (ischemia/reperfusion 90 min/3 h), the brain homogenate gene expression of interleukin 6 (IL-6), tumor necrosis factor α (TNF-α), interleukin 1β (IL-1β) and Interferon gamma-induced protein 10 (IP-10) was significantly up-regulated and the contents in plasma and brain homogenate were significantly increased in MCAO and MCAO + LPS group. IP-10 was the only gene with significant difference between MCAO and MCAO + LPS group, which was also in an important position with degrees of ≥ 14 in PPI network.ConclusionsIt was possible that trace LPS aggravated the ischemic brain injury by induction of excessive IP-10 secretion in the acute stage, leading to excessive inflammatory response, which consequently increased the infarct volume and edema degree 24 h post-MCAO.

show abstract

Pathophysiological and behavioral deficits in developing mice following rotational acceleration-deceleration traumatic brain injury

Cited by 27 publications

References 100 publications

Dynamic response of microglia/macrophage polarization following demyelination in mice

Dynamic response of microglia/macrophage polarization following demyelination in mice

Diverse changes in myelin protein expression in rat brain after perinatal methadone exposure

Lipopolysaccharide worsens the prognosis of experimental cerebral ischemia via interferon gamma-induced protein 10 recruit in the acute stage

Contact Info

Product

Resources

About