Unveiling the Hidden Impact: Hematoma Volumes Unravel Circuit Disruptions in Intracerebral Hemorrhage.

Intracerebral hemorrhage (ICH) imposes a significant burden on patients, and the volume of hematoma plays a crucial role in determining the severity and prognosis of ICH. Although significant recent progress has been made in understanding the cellular and molecular mechanisms of surrounding brain tissue in ICH, our current knowledge regarding the precise impact of hematoma volumes on neural circuit damage remains limited. Here, using a viral tracing technique in a mouse model of striatum ICH, two distinct patterns of injury response were observed in upstream connectivity, characterized by both linear and nonlinear trends in specific brain areas. Notably, even low-volume hematomas had a substantial impact on downstream connectivity. Neurons in the striatum-ICH region exhibited heightened excitability, evidenced by electrophysiological measurements and changes in metabolic markers. Furthermore, a strong linear relationship (R2 = 0.91) was observed between hematoma volumes and NFL damage, suggesting a novel biochemical index for evaluating changes in neural injury. RNA sequencing analysis revealed the activation of the MAPK signaling pathway following hematoma, and the addition of MAPK inhibitor revealed a decrease in neuronal circuit damage, leading to alleviation of motor dysfunction in mice. Taken together, our study highlights the crucial role of hematoma size as a determinant of circuit injury in ICH. These findings have important implications for clinical evaluations and treatment strategies, offering opportunities for precise therapeutic approaches to mitigate the detrimental effects of ICH and improve patient outcomes.

Role of mass effect on neuronal iron deposition after intracerebral hemorrhage.

Mass effect after intracerebral hemorrhage (ICH) not only mechanically induces the brain damage, but also influences the progress of secondary brain damage. However, the influence of mass effect on the iron overload after ICH is still unclear. Here, a fixed volume of ferrous chloride solution and different volumes of poly(N-isopropylacrylamide) (PNIPAM) hydrogel were co-injected into the right basal ganglia of rats to establish the ICH model with certain degree of iron deposition but different degrees of mass effect. We found that mass effect significantly increased the iron deposition on neuronal cells at 6 h after ICH in a volume-dependent manner. Furthermore, the upregulation of Piezo-2, divalent metal transporter 1 (DMT1), transferrin receptor (TfR), and ferroptosis expressions were noted as the increase of mass effect. In addition, the pERK1/2 inhibitor PD98059 treated ICH rats reversed the upregulation of iron uptake protein and ferroptosis. Our findings revealed the relationship between mass effect and the iron uptake and ferroptosis, which are benefit to understand the brain damage process after ICH.

Analysis of physiological responses and expression profiling of boron transporter-like genes in response to excess boron in Populus russkii.

Poplars (Populus species) are tolerant to boron (B) toxicity and have phytoremediation potential in B-contaminated soils. However, the detoxification strategy is largely unknown. To screen the key B transporter-like (BOR-like) genes for B compartmentation, Populus russkii plants were exposed to different levels of excess B and the plant growth, physiological responses, B distribution, and the expression patterns of BOR-like genes were characterized. P. russkii showed moderate tolerance to excess B although the plant growth was inhibited. The enhanced proline level and well-regulated antioxidant defense system were associated with B tolerance in leaves. The B absorbed by plants was predominantly allocated to leaves. Ten BOR-like genes were identified and seven of them showed tissue-specific expression patterns. PrBOR7 was identified as an important BOR-like gene possibly involved in the export of B from leaf cytoplasm because it was expressed specifically in leaves and induced by excess B. Yeast experiment assays verified that PrBOR7 functions as an efflux-type transporter and strongly improved cell tolerance to excess B. The expression patterns of BOR-like genes highlight the diversity of the family members in P. russkii, and PrBOR7 has potential as a candidate gene for B detoxification.