Mingyang Zhang

Increased Expression of Calcium/Calmodulin-Dependent Protein Kinase Type II Subunit Delta after Rat Traumatic Brain Injury

Many cellular responses to Ca2+ signals are mediated by Ca2+/calmodulin-dependent enzymes, among which is the Ca2+/calmodulin-dependent protein kinase II (CaMKII). CaMKII was originally described in rat brain tissue. In rat brain, four different subunits of the kinase have been identified: α, β, γ, and δ. This study aims to investigate changes of CaMKIIδ after traumatic brain injury and its possible role. Rat traumatic brain injury (TBI) model was established by controlled cortical injury system. In the present study, we mainly investigated the expression and cellular localization of CaMKIIδ after traumatic brain injury. Western blot analysis revealed that CaMKIIδ was present in normal rat brain cortex. It gradually increased, reached a peak at the third day after TBI, and then decreased. Importantly, more CaMKIIδ was colocalized with neuron. In addition, Western blot detection showed that the third day postinjury was also the apoptosis peak indicated by the elevated expression of caspase-3.Importantly, immunohistochemistry analysis revealed that injury-induced expression of CaMKIIδ was colabeled by caspase-3 (apoptosis cells marker). Moreover, pretreatment with the CaMKII inhibitor (KN62) reduced the injury-induced activation of caspase-3. Noticeably, the CaMKII inhibitor KN-62 could reduce TBI-induced cell injury assessed with lesion volume and attenuate behavioral outcome evaluated by motor test. These data suggested that CaMKIIδ may be implicated in the apoptosis of neuron and the recovery of neurological outcomes. However, the inherent mechanisms remained unknown. Further studies are needed to confirm the exact role of CaMKIIδ after brain injury.

Dynamic Change of Hydrogen Sulfide After Traumatic Brain Injury and its Effect in Mice

Hydrogen sulfide (H2S) is a lipid-soluble, endogenously produced gaseous messenger molecule collectively known as gasotransmitter. Over the last several decades, gasotransmitters have emerged as potent cytoprotective mediators in various models of tissue and cellular injury. In this study, we performed a weight-drop traumatic brain injury (TBI) model in adult mice and investigated changes of H2S and its possible role in the pathogenesis after TBI. Expression of Cystathionine-β-synthase (CBS) mRNA as H2S-producing enzymes in mouse brain was determined by reverse transcriptase-polymerase chain reaction (RT-PCR). From the results of RT-PCR, it was found that the expression of CBS was down-regulated in mouse brain cortex and hippocampus after brain injury. Western blot analysis revealed that CBS was present in normal mouse brain cortex and the hippocampus. It gradually decreased, reached its lowest level and then increased. Hydrogen sulfide in the cortex and hippocampus exhibited dynamic changes after brain injury, in parallel with CBS mRNA and protein expression. Moreover, pretreatment with the H2S donor (NaHS) could protect the neuron against the injury induced by TBI. Noticeably, the H2S donor NaHS could reduce TBI-induced injury assessed with lesion volume. These data suggested that H2S may have a therapeutic potential against neuron damage.

The Expression Changes of Cystathionine-β-synthase in Brain Cortex After Traumatic Brain Injury

Cystathionine-β-synthase (CBS) catalyzes the condensation of serine with homocysteine to form cystathionine and occupies a crucial regulatory position between the methionine cycle and the biosynthesis of cysteine by transsulfuration. It was reported that CBS was a novel marker of both differentiation and proliferation for certain cell types, suggesting that CBS represents a survival-promoting protein. However, its expression and function in the central nervous system lesion are not well understood. To investigate changes of CBS after traumatic brain injury (TBI) and its possible role, mice TBI model was established by controlled cortical impact system, and the expression and cellular localization of CBS after TBI was investigated in the present study. Western blot analysis revealed that CBS was present in normal mice brain cortex. It gradually decreased, reached a valley at the third day after TBI, and then restored to basal level. Importantly, more CBS was colocalized with neuron. In addition, Western blot detection showed that the third day postinjury was also the apoptosis peak indicated by the elevated expression of caspase-3. Importantly, immunohistochemistry analysis revealed that injury-induced expression of CBS was colabeled by Bcl-2 and had no co-localization with caspase-3. These data suggested that CBS may be implicated in the apoptosis of neuron and involved in the pathophysiology of brain after TBI.

The automatic processing of visual information at different visual acuity levels: An ERP study

This study investigated the subjective visual acuity by recording ERPs elicited by task-irrelevant visual changes. Optotypes stimuli were presented in the center of the visual field at three threshold levels (supra-threshold, threshold and sub-threshold) while participants were listening to stories. The results showed that neither vMMN nor P3a component was elicited by optotypes stimuli on the sub-threshold condition, whereas, vMMN was elicited under supra-threshold and threshold conditions, with no significant differences between those vMMN amplitudes of two conditions. The P3a amplitude was larger for supra-threshold condition than that for threshold condition. These data demonstrated that the emergence of vMMN could only reflect the automatic detection of orientation-changes in the supra-threshold and threshold conditions compared to the sub-threshold condition, whereas the P3a amplitude could reflect the difference in processing of supra-threshold and threshold stimuli.

IL-33/ST2L Signaling Provides Neuroprotection Through Inhibiting Autophagy, Endoplasmic Reticulum Stress, and Apoptosis in a Mouse Model of Traumatic Brain Injury

Interleukin-33 (IL-33) is a member of the interleukin-1 (IL-1) cytokine family and an extracellular ligand for the orphan IL-1 receptor ST2. Accumulated evidence shows that the IL-33/ST2 axis plays a crucial role in the pathogenesis of central nervous system (CNS) diseases and injury, including traumatic brain injury (TBI). However, the roles and molecular mechanisms of the IL-33/ST2 axis after TBI remain poorly understood. In this study, we investigated the role of IL-33/ST2 signaling in mouse TBI-induced brain edema and neurobehavioral deficits, and further exploited underlying mechanisms, using salubrinal (SAL), the endoplasmic reticulum (ER) stress inhibitor and anti-ST2L. The increase in IL-33 level and the decrease in ST2L level at injured cortex were first observed at 24 h post-TBI. By immunofluorescent double-labeled staining, IL-33 co-localized in GFAP-positive astrocytes, and Olig-2-positive oligodendrocytes, and predominantly presented in their nucleus. Additionally, TBI-induced brain water content, motor function outcome, and spatial learning and memory deficits were alleviated by IL-33 treatment. Moreover, IL-33 and SAL alone, or their combination prevented TBI-induced the increase of IL-1β and TNF-α levels, suppressed the up-regulation of ER stress, apoptosis and autophagy after TBI. However, anti-ST2L treatment could significantly invert the above effects of IL-33. Together, these data demonstrate that IL-33/ST2 signaling mitigates TBI-induced brain edema, motor function outcome, spatial learning and memory deficits, at least in part, by a mechanism involving suppressing autophagy, ER stress, apoptosis and neuroinflammation.

The magnitude of the central visual field could be detected by active middle-late processing of ERPs.

This study investigated the changes in event-related potential (ERP) waveforms under different central visual field conditions using a three-stimulus oddball paradigm. Circular checkerboards were presented in the center of a computer screen with a visual angle of 5°, 10°, 20°, or 30°, which were regarded as target stimuli. The ERP waveforms were analyzed separately for different stimulus conditions. Participants responded more slowly and had lower accuracy for the 30° visual field level than the other three visual field levels. The ERP results revealed that the amplitudes of target P2 gradually increased from the 5° to 20° visual field conditions, while they decreased abruptly in the 30° visual field condition. Regional effects showed that the amplitudes of target P2 were larger from the occipital electrodes than that from the temporal sites. Besides the negative-going deflection of target N2 and visual mismatch negativity (vMMN) components having an increasing tendency with expansion of the visual field, there was also a trend that the amplitudes of target P3 were decreased and the peak latencies were prolonged with increasing visual field ranges. In addition, the latencies of the difference P3 had a similar trend to the latencies of the target P3, and all the differences were more obvious at the 30° visual field level. The study demonstrated that middle-late components of ERPs can reflect changes in the visual field to some extent.