Quantitative anatomic comparison of the extended pterional transtemporal transtentorial approach and the subtemporal transtentorial approach to the petroclival region.

AIM: The anatomic characters and applicability of the extended pterional transtemporal transtentorial (EPTT) approach versus the subtemporal transtentorial (ST) approach for surgical treatment of petroclival tumors were evaluated. MATERIAL AND METHODS: Ten sides from five adult Chinese injected cadavers were manipulated using both two approaches. Four deep bony anatomic landmarks were specified in the skull base to create two adjoining triangles that were respectively located in the anterior and posterior petroclival region. The real, projected area and the percentage of the projected area were determined and calculated to compare the deep exposure from the two approaches. RESULTS: There was no difference regarding the percentage of the projected area was calculated in the anterior triangles (EPTT, 21.5±12.5%; ST, 28.8±14.9%; p=0.1948), but a significant difference was present in the posterior triangles (EPTT, 74.0±4.5%; ST, 51.5±4.3%; p < 0.01). Compared with the ST approach, the EPTT approach provides an equivalent percentage of projected area in the middle cranial fossa and a wider exposed area in the posterior cranial fossa. CONCLUSION: Through anatomic comparative analysis the EPTT approach provides better exposure and is more appropriate than the ST approach for large and giant petroclival tumors predominantly in the posterior cranial fossa with extensive invasion to parasellar structures and the cavernous sinus.

Elevated cerebral cortical CD24 levels in patients and mice with traumatic brain injury: a potential negative role in nuclear factor κb/inflammatory factor pathway.

Increasing evidence indicates that sterile inflammatory response contributes to secondary brain injury following traumatic brain injury (TBI). However, the specific mechanisms remain largely unknown, as is whether CD24, known as an important regulator in the non-infectious inflammatory response, plays a role in secondary brain injury after TBI. Here, the expression of CD24 was detected in samples from patients with TBI by quantitative real-time polymerase chain reaction (PCR), western blotting, immunohistochemistry and immunofluorescence. RNA interference was used to investigate the effects of CD24 on inflammatory response in a mouse model of TBI. Nuclear factor kappa B (NF-κB) DNA-binding activity was measured by electrophoretic mobility shift assay, and the levels of downstream pro-inflammatory cytokines tumor necrosis factor-α (TNF-α) and Interleukin 1ß (IL-1ß) were detected by real-time PCR. The results indicated that both the mRNA and protein levels of CD24 were markedly elevated after TBI in humans and mice, showing a time-dependent expression. The expression of CD24 could be observed in neurons, astrocytes and microglia in both humans and mice. Meanwhile, downregulation of CD24 significantly induced an increase of NF-κB DNA-binding activity and mRNA levels of TNF-α and IL-1ß. These findings indicated that CD24 expression could negatively regulate the NF-κB/inflammatory factor pathway after experimental TBI in mice, thus providing a novel target for therapeutic intervention of TBI.

Knockdown of NF-E2-related factor 2 inhibits the proliferation and growth of U251MG human glioma cells in a mouse xenograft model.

NF-E2-related factor 2 (Nrf2) is a pivotal transcription factor of cellular responses to oxidative stress and recent evidence suggests that Nrf2 plays an important role in cancer pathobiology. However, the underlying mechanism has yet to be elucidated, particularly in glioma. In the present study, we investigated the role of Nrf2 in the clinical prognosis, cell proliferation and tumor growth of human glioblastoma multiforme (GBM). We detected overexpression of Nrf2 protein levels in GBM compared to normal brain tissues. Notably, higher protein levels of Nrf2 were significantly associated with poorer overall survival and 1-year survival for GBM patients. Furthermore, we constructed the plasmid Si-Nrf2 and transduced it into U251MG cells to downregulate the expression of Nrf2 and established stable Nrf2 knockdown cells. The downregulation of Nrf2 suppressed cell proliferation in vitro and tumor growth in mouse xenograft models. We performed immunohistochemistry staining to detect the protein levels of Nrf2, Ki-67, caspase-3 and CD31 in the xenograft tumors and found that the expression levels of Nrf2 and Ki-67 were much lower in the Si-Nrf2 group compared to the Si-control group. In addition, the number of caspase-3-positive cells was significantly increased in the Si-Nrf2 group. By analysis of microvessel density (MVD) assessed by CD31, the MVD value in the Si-Nrf2 group decreased significantly compared to the Si-control group. These findings indicate that the knockdown of Nrf2 may suppress tumor growth by inhibiting cell proliferation, increasing cell apoptosis and inhibiting angiogenesis. These results highlight the potential of Nrf2 as a candidate molecular target to control GBM cell proliferation and tumor growth.

Activation of nuclear factor-κB in the brain after experimental subarachnoid hemorrhage and its potential role in delayed brain injury.

It has been reported that inflammation is involved in brain injury after subarachnoid hemorrhage (SAH). Nuclear factor-κB (NF-κB) is a key transcriptional regulator of inflammatory genes. Here, we used pyrrolidine dithiocarbamate(PDTC), an inhibitor of NF-κB, through intracisternal injection to study the role of NF-κB in delayed brain injury after SAH. A total of 55 rabbits were randomly divided into five groups: the control group; the SAH groups including Day-3, 5, and 7 SAH groups (the rabbits in these groups were sacrificed at 3, 5, 7 days after SAH, respectively); and the PDTC group (n = 11 for each group). Electrophoretic mobility shift assay (EMSA) was performed to detect NF-κB DNA-binding activity. The mRNA levels of tumor necrosis factor (TNF)-α, interleukin (IL)-1ß, and intercellular adhesion molecule (ICAM)-1 were evaluated by RT-PCR analysis. Deoxyribonucleic acid fragmentation was detected by TUNEL and p65 immunoactivity was assessed by immunohistochemistry. Our results showed the activation of NF-κB after SAH, especially at day 3 and 5. The activated p65 was detected in neurons. NF-κB DNA-binding activity was suppressed by intracisternal administration of PDTC. Increased levels of the TNF-α, IL-1ß, and ICAM-1 mRNA were found in the brain at day 5 after SAH, and which were suppressed in the PDTC group. The number of TUNEL-positive cells also decreased significantly in the PDTC group compared with that in the Day-5 SAH group. These results demonstrated that the activated NF-κB in neurons after SAH plays an important role in regulating the expressions of inflammatory genes in the brain, and ultimately contributes to delayed brain injury.

Recombinant high-mobility group box 1 protein (HMGB-1) promotes myeloid differentiation primary response protein 88 (Myd88) upregulation in mouse primary cortical neurons.

Myeloid differentiation primary response protein 88 (Myd88) is a vital factor for inflammation and immunity, and high-mobility group box 1 protein (HMGB-1) can be released from neurons after injury and may contribute to the initial stages of inflammatory response. Therefore, the current study was intended to investigate the expression of Myd88 in cultured neurons following recombinant HMGB-1 (rHMGB-1) addition and to clarify the potential role of Myd88 after neuron injury in vitro. The cultured neurons were randomly divided into six groups: control group and rHMGB-1 groups at hours 1, 6, 12, 24, and 48. The cultured neurons in rHMGB-1 groups were subjected to rHMGB-1 addition. The expression of Myd88 was assessed by quantitative real-time polymerase chain reaction (PCR), Western blotting and immunofluorescence, and nuclear factor kappa B (NF-κB) DNA-binding activity was detected by electrophoretic mobility shift assay, and the levels of tumor necrosis factor-α (TNF-α) and interleukin 1ß (IL-1ß) were measured by quantitative real-time PCR. The elevated mRNA and protein levels of Myd88, peaking at 24 h, were detected after rHMGB-1 addition. NF-κB, TNF-α, and IL-1ß also ascended significantly after rHMGB-1 addition. Interestingly, Myd88 increasingly expressed in a parallel time course to the upregulation of NF-κB, TNF-α, and IL-1ß. These findings indicated a possible role of Myd88 in the inflammatory response after neuron injury, and might provide an attractive therapeutic approach of targeting the Myd88 cascade to achieve better outcomes for patients with central nervous system injury.

Enhanced cortical expression of myeloid differentiation primary response protein 88 (Myd88) in patients with traumatic brain injury.

BACKGROUND: Inflammatory response has been proven to play a crucial role in the pathophysilogical process after traumatic brain injury (TBI). Myeloid differentiation primary response protein 88 (Myd88) is considered as a vital factor for inflammation and immunity. Therefore, it is essential to know the detailed expression of Myd88 after TBI. However, the expression patterns of Myd88 in patients with TBI remain obscure. Hence, the aim of present study was to investigate the cortical expression of Myd88 in human contused brain. METHODS: Nineteen contused brain tissue biopsies were obtained from 19 patients undergoing surgery for brain contusions 3 h-17 d after trauma, and samples of control group were from three patients in the pathway during surgical removal of deep benign tumors. The expression of Myd88 was assessed by quantitative real-time polymerase chain reaction, Western blotting, immunohistochemistry and double immunofluorescent staining, and the messenger RNA (mRNA) levels of tumor necrosis factor-alpha (TNF-α) and interleukin 1beta (IL-1ß) were measured by quantitative real-time polymerase chain reaction. RESULTS: The progressively elevated mRNA and protein levels of Myd88 were detected after trauma, with the maximum after 72 h post-injury, and the distribution of Myd88 was found in neurons, astrocytes, and microglia. TNF-α and IL-1ß mRNA levels ascended significantly within 12 h, and then descended gradually until after 72 h post-injury. Interestingly, there was a positive relationship between the expression of Myd88 and the proinflammatory cytokine TNF-α. CONCLUSIONS: These findings indicated that Myd88 might play an important role in the inflammatory response after human TBI.