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Background: Perioperative cerebrospinal fluid (CSF) leakage is a major complication of pituitary adenomas transsphenoidal surgery. Lumbar drainage (LD) is a common method of treating CSF leakage. But whether intraoperative LD can prevent CSF leakage during the perioperative period of pituitary adenomas transsphenoidal surgery remains controversial. Clarity on the appropriate use of LD is needed. Methods: A systematic literature review was conducted in the PubMed, EMBASE, and Web of science databases. Articles were included when they compared intraoperative LD with intraoperative no-LD CSF leakage rates during pituitary adenomas transsphenoidal surgery. Results: Overall, 5 studies containing 678 cases met the inclusion criteria. When data were provided on intraoperative CSF leakage rates, the meta-analysis showed a significant difference in favor of intraoperative LD. When data were provided on postoperative CSF leakage rates, the meta-analysis also demonstrated a significant difference in favor of intraoperative LD. Conclusions: Although the results of this meta-analysis suggest intraoperative LD can reduce the risk of CSF leakage during the perioperative period of pituitary adenomas transsphenoidal surgery, the available evidence is indefinite. To some extent the results suggest intraoperative LD's potential positive role. Further studies that include well-designed prospective, randomized controlled clinical trials are necessary for further verification.

IntroductionSepsis-associated encephalopathy (SAE) is a diffuse cerebral dysfunction resulting from a systemic inflammatory response to infection; however, its pathophysiology remains unclear. Sepsis-induced neuroinflammation and blood–brain barrier (BBB) disruption are crucial factors in brain function disturbance in SAE. Mast cells (MCs) activation plays an important role in several neuroinflammation models; however, its role in SAE has not been comprehensively investigated.MethodsWe first established a SAE model by cecal ligation puncture (CLP) surgery and checked the activation of MCs. MCs activation was checked using immumohistochemical staining and Toluidine Blue staining. We administrated cromolyn (10mg/ml), a MC stabilizer, to rescue the septic mice. Brain cytokines levels were measured using biochemical assays. BBB disruption was assessed by measuring levels of key tight-junction (TJ) proteins. Cognitive function of mice was analyzed by Y maze and open field test. Transwell cultures of brain microvascular endothelial cells (BMVECs) co-cultured with MCs were used to assess the interaction of BMVECs and MCs.ResultsResults showed that MCs were overactivated in the hippocampus of CLP-induced SAE mice. Cromolyn intracerebroventricular (i.c.v) injection substantially inhibited the MCs activation and neuroinflammation responses, ameliorated BBB impairment, improved the survival rate and alleviated cognitive dysfunction in septic mice. In vitro experiments, we revealed that MCs activation increased the sensitivity of BMVECs against to lipopolysaccharide (LPS) challenge. Furthermore, we found that the histamine/histamine 1 receptor (H1R) mediated the interaction between MCs and BMVECs, and amplifies the LPS-induced inflammatory responses in BMVECs by modulating the TLR2/4-MAPK signaling pathway.ConclusionsMCs activation could mediate BBB impairment and cognitive dysfunction in septic mice in a histamine-dependent pathway.

Background: Sepsis-associated encephalopathy (SAE) is a diffuse cerebral dysfunction resulting from a systemic inflammatory response to infection, but the pathophysiological mechanism remains unclear. Sepsis-induced neuroinflammation and blood-brain barrier (BBB)disruption have been demonstrated as the crucial factors in the brain functional disturbance in SAE. Mast cells (MCs) activation has been reported to play an important role in several neuroinflammation models. However, the role of MCs in SAE has not been comprehensively investigated. Methods: We first established a SAE model by cecal ligation puncture (CLP) surgery and checked the activation of MCs. We further analyzed the effects of MCs on neuroinflammation response, BBB permeability, cognitive function, and the underlying molecular mechanism in both tissue samples and cellular co-culture system. MCs activation was measured using immumohistochemical staining and 1% Toluidine Blue (TB) staining. We administrated a MC stabilizer, Cromolyn (10mg/ml), to rescue the septic mice. Brain cytokines levels were measured using biochemical assays. BBB disruption was assessed by measuring levels of key tight-junction (TJ) proteins. Cognitive function of mice was analyzed by Y maze and open field test. Transwell cultures of brain microvascular endothelial cells (BMVECs) co-cultured with MCs were used to assess the effect of LPS (1mg/ml) on expression of TJ proteins. The expression of TJ and TLR2/4-MAPK signaling pathway proteins were measured by immunoblotting and/or immunofluorescence. Results: The results showed that MCs were seriously overactivated in the hippocampus of CLP-induced SAE mice. The inhibition of MCs by Cromolyn i.c.v injection significantly inhibited the inflammation responses, ameliorated the impairment of the BBB, improved the survival rate, and alleviated cognitive dysfunction. In vitro experiments, we revealed that MCs activation increased the sensitivity of brain microvascular endothelial cells (BMVECs) against to lipopolysaccharide (LPS) challenge. Furthermore, we found that histamine-H1R mediates the interaction between MCs and BMVECs, and amplifies the LPS induced inflammation response in BMVECs by modulating the TLR2/4-MAPKsignaling pathway. Conclusions: The activation of MCs mediates BBB impairment and cognitive dysfunction of septic mice in a histamine dependent pathway.