Lactate accumulation has been observed in the brain with intracerebral hemorrhage (ICH). However, the outcome of lactate accumulation has not been well characterized. Here, we report that lactate accumulation contributes to angiogenesis and neurogenesis in ICH. In the first set of the experiment, a rat model of ICH was induced by injecting collagenase into the brain. The effects of lactate accumulation on the neurological function, apoptosis, and numbers of newborn endothelial cells and neurons, as well as the proliferation-associated signaling pathway, were evaluated in the rat brain. In the second set, exogenous l-lactate was infused into intact rat brains so that its effects could be further assessed. Following ICH, lactate accumulated around the hematoma; the numbers of PCNA⁺/vWF⁺ nuclei and PCNA⁺/DCX⁺ cells were significantly increased compared with the numbers in the Sham group. Moreover, ICH induced translocation of nuclear factor-kappa B (NF-κB) p65 into the nucleus, resulting in a notable upregulation of VEGF and bFGF mRNAs and proteins compared with the levels in the Sham controls. Administration of a lactate dehydrogenase inhibitor dramatically inhibited these effects, decreased the vascular density, and aggravated neurological severity scores and apoptosis after ICH. After exogenous l-lactate infusion, the numbers of PCNA⁺/vWF⁺ nuclei and PCNA⁺/DCX⁺ cells were strikingly increased compared with the numbers in the Sham controls. In addition, lactate facilitated NF-κB translocation to induce increased transcription of VEGF and bFGF. Co-infusion with an NF-κB inhibitor significantly inhibited these effects. These data suggest that lactate potentiates angiogenesis and neurogenesis by activating the NF-κB signaling pathway following ICH.

Glioblastoma (GBM) is a malignant brain tumour with poor prognosis. The potential pathogenesis and therapeutic target are still need to be explored. Herein, TCGA expression profile data and clinical information were downloaded, and the WGCNA was conducted. Hub genes which closely related to poor prognosis of GBM were obtained. Further, the relationship between the genes of interest and prognosis of GBM, and immune microenvironment were analysed. Patients from TCGA were divided into high‐ and low‐risk group. WGCNA was applied to the high‐ and low‐risk group and the black module with the lowest preservation was identified which could distinguish the prognosis level of these two groups. The top 10 hub genes which were closely related to poor prognosis of patients were obtained. GO analysis showed the biological process of these genes mainly enriched in: Cell cycle, Progesterone‐mediated oocyte maturation and Oocyte meiosis. CDCA5 and CDCA8 were screened out as the genes of interest. We found that their expression levels were closely related to overall survival. The difference analysis resulted from the TCGA database proved both CDCA5 and CDCA8 were highly expressed in GBM. After transfection of U87‐MG cells with small interfering RNA, it revealed that knockdown of the CDCA5 and CDCA8 could influence the biological behaviours of proliferation, clonogenicity and apoptosis of GBM cells. Then, single‐gene analysis was performed. CDCA5 and CDCA8 both had good correlations with genes that regulate cell cycle in the p53 signalling pathway. Moreover, it revealed that high amplification of CDCA5 was correlated with CD8⁺ T cells while CDCA8 with CD4⁺ T cells in GBM. These results might provide new molecular targets and intervention strategy for GBM.

Xuefu zhuyu decoction improves cognitive impairment in experimental traumatic brain injury via synaptic regulation Xuefu zhuyu decoction improves cognitive impairment in experimental traumatic brain injury via synaptic regulation

Intracerebral hemorrhage (ICH) is one of the most devastating forms of stroke. Dexmedetomidine (DEX) has shown certain neuroprotective roles in ICH. Nevertheless, the details concerning the underlying molecular mechanism of DEX’s protective effects still need further elucidation. Herein, a model of ICH was established. The rats were randomly divided into the sham group, the ICH group, and the ICH + DEX group. Neurological outcomes, neuronal injury, and apoptosis were evaluated. Brain water content, Evans blue extravasation, and the expression of tight junction-associated proteins were also detected to assess the blood-brain barrier (BBB) integrity. Subsequently, the microglia/macrophage polarization state and inflammatory cytokine levels were observed. To further explore the underlying mechanism, NF-κB signaling pathway-associated proteins were detected. The results showed that DEX exerted neuroprotective effects against ICH-induced neurological deficits. DEX significantly increased the numbers of the surviving neurons and ameliorated neuronal cell loss and apoptosis in ICH. The rats that received the DEX displayed a lower level of brain water content and EB extravasation, moreover, ZO-1, occludin, and claudin-5 were markedly increased by DEX. Additionally, DEX facilitated M2 microglia/macrophage polarization, the M1-associated markers were reduced by DEX, while the M2-associated identification significantly increased. We found that DEX dramatically diminished pro-inflammatory cytokines expression, simultaneously promoting anti-inflammatory cytokines expression. DEX inhibited nuclear translocation of NF-κB in ICH rats. Our data suggest that DEX post-conditioning protects BBB integrity by modulating microglia/macrophage polarization via inhibiting the NF-κB signaling pathway in ICH.