Propofol anesthesia improves stroke outcomes over isoflurane anesthesia—a longitudinal multiparametric MRI study in a rodent model of transient middle cerebral artery occlusion

General anesthesia is routinely used in endovascular thrombectomy procedures, for which volatile gas and/or intravenous propofol are recommended. Emerging evidence suggests propofol may have superior effects on disability and/or mortality rates, but a mode-of-action underlying these class-specific effects remains unknown. Here, a moderate isoflurane or propofol dosage on experimental stroke outcomes was retrospectively compared using serial multiparametric MRI and behavioral testing. Adult male rats (N = 26) were subjected to 90-min filament-induced transient middle cerebral artery occlusion. Diffusion-, T2- and perfusion-weighted MRI was performed during occlusion, 0.5 h after recanalization, and four days into the subacute phase. Sequels of ischemic damage—blood–brain barrier integrity, cerebrovascular reactivity and sensorimotor functioning—were assessed after four days. While size and severity of ischemia was comparable between groups during occlusion, isoflurane anesthesia was associated with larger lesion sizes and worsened sensorimotor functioning at follow-up. MRI markers indicated that cytotoxic edema persisted locally in the isoflurane group early after recanalization, coinciding with burgeoning vasogenic edema. At follow-up, sequels of ischemia were further aggravated in the post-ischemic lesion, manifesting as increased blood–brain barrier leakage, cerebrovascular paralysis and cerebral hyperperfusion. These findings shed new light on how isoflurane, and possibly similar volatile agents, associate with persisting injurious processes after recanalization that contribute to suboptimal treatment outcome.</p

Propofol anesthesia improves stroke outcomes over isoflurane anesthesia—a longitudinal multiparametric MRI study in a rodent model of transient middle cerebral artery occlusion

General anesthesia is routinely used in endovascular thrombectomy procedures, for which volatile gas and/or intravenous propofol are recommended. Emerging evidence suggests propofol may have superior effects on disability and/or mortality rates, but a mode-of-action underlying these class-specific effects remains unknown. Here, a moderate isoflurane or propofol dosage on experimental stroke outcomes was retrospectively compared using serial multiparametric MRI and behavioral testing. Adult male rats (N = 26) were subjected to 90-min filament-induced transient middle cerebral artery occlusion. Diffusion-, T2- and perfusion-weighted MRI was performed during occlusion, 0.5 h after recanalization, and four days into the subacute phase. Sequels of ischemic damage—blood–brain barrier integrity, cerebrovascular reactivity and sensorimotor functioning—were assessed after four days. While size and severity of ischemia was comparable between groups during occlusion, isoflurane anesthesia was associated with larger lesion sizes and worsened sensorimotor functioning at follow-up. MRI markers indicated that cytotoxic edema persisted locally in the isoflurane group early after recanalization, coinciding with burgeoning vasogenic edema. At follow-up, sequels of ischemia were further aggravated in the post-ischemic lesion, manifesting as increased blood–brain barrier leakage, cerebrovascular paralysis and cerebral hyperperfusion. These findings shed new light on how isoflurane, and possibly similar volatile agents, associate with persisting injurious processes after recanalization that contribute to suboptimal treatment outcome.</p

Hyperperfusion profiles after recanalization differentially associate with outcomes in a rat ischemic stroke model

Futile recanalization hampers prognoses of ischemic stroke after successful mechanical thrombectomy, hypothetically through post-recanalization perfusion deficits, onset-to-groin delays and sex effects. Clinically, acute multiparametric imaging studies remain challenging. We assessed possible relationships between these factors and disease outcome after experimental cerebral ischemia-reperfusion, using translational MRI, behavioral testing and multi-model inference analyses. Male and female rats (N = 60) were subjected to 45-/90-min filament-induced transient middle cerebral artery occlusion. Diffusion, T2- and perfusion-weighted MRI at occlusion, 0.5 h and four days after recanalization, enabled tracking of tissue fate, and relative regional cerebral blood flow (rrCBF) and -volume (rrCBV). Lesion areas were parcellated into core, salvageable tissue and delayed injury, verified by histology. Recanalization resulted in acute-to-subacute lesion volume reductions, most apparently in females (n = 19). Hyperacute normo-to-hyperperfusion in the post-ischemic lesion augmented towards day four, particularly in males (n = 23). Tissue suffering delayed injury contained higher ratios of hypoperfused voxels early after recanalization. Regressed against acute-to-subacute lesion volume change, increased rrCBF associated with lesion growth, but increased rrCBV with lesion reduction. Similar relationships were detected for behavioral outcome. Post-ischemic hyperperfusion may develop differentially in males and females, and can be beneficial or detrimental to disease outcome, depending on which perfusion parameter is used as explanatory variable.</p

Propofol anesthesia improves stroke outcomes over isoflurane anesthesia: a longitudinal multiparametric MRI study in a rodent model of transient middle cerebral artery occlusion

General anesthesia is routinely used in endovascular thrombectomy procedures, for which volatile gas and/or intravenous propofol are recommended. Emerging evidence suggests propofol may have superior effects on disability and/or mortality rates, but a mode-of-action underlying these class-specific effects remains unknown. Here, a moderate isoflurane or propofol dosage on experimental stroke outcomes was retrospectively compared using serial multiparametric MRI and behavioral testing. Adult male rats (N = 26) were subjected to 90-min filament-induced transient middle cerebral artery occlusion. Diffusion-, T2- and perfusion-weighted MRI was performed during occlusion, 0.5 h after recanalization, and four days into the subacute phase. Sequels of ischemic damage—blood–brain barrier integrity, cerebrovascular reactivity and sensorimotor functioning—were assessed after four days. While size and severity of ischemia was comparable between groups during occlusion, isoflurane anesthesia was associated with larger lesion sizes and worsened sensorimotor functioning at follow-up. MRI markers indicated that cytotoxic edema persisted locally in the isoflurane group early after recanalization, coinciding with burgeoning vasogenic edema. At follow-up, sequels of ischemia were further aggravated in the post-ischemic lesion, manifesting as increased blood–brain barrier leakage, cerebrovascular paralysis and cerebral hyperperfusion. These findings shed new light on how isoflurane, and possibly similar volatile agents, associate with persisting injurious processes after recanalization that contribute to suboptimal treatment outcome

Hyperperfusion profiles after recanalization differentially associate with outcomes in a rat ischemic stroke model

Futile recanalization hampers prognoses of ischemic stroke after successful mechanical thrombectomy, hypothetically through post-recanalization perfusion deficits, onset-to-groin delays and sex effects. Clinically, acute multiparametric imaging studies remain challenging. We assessed possible relationships between these factors and disease outcome after experimental cerebral ischemia-reperfusion, using translational MRI, behavioral testing and multi-model inference analyses. Male and female rats (N = 60) were subjected to 45-/90-min filament-induced transient middle cerebral artery occlusion. Diffusion, T2- and perfusion-weighted MRI at occlusion, 0.5 h and four days after recanalization, enabled tracking of tissue fate, and relative regional cerebral blood flow (rrCBF) and -volume (rrCBV). Lesion areas were parcellated into core, salvageable tissue and delayed injury, verified by histology. Recanalization resulted in acute-to-subacute lesion volume reductions, most apparently in females (n = 19). Hyperacute normo-to-hyperperfusion in the post-ischemic lesion augmented towards day four, particularly in males (n = 23). Tissue suffering delayed injury contained higher ratios of hypoperfused voxels early after recanalization. Regressed against acute-to-subacute lesion volume change, increased rrCBF associated with lesion growth, but increased rrCBV with lesion reduction. Similar relationships were detected for behavioral outcome. Post-ischemic hyperperfusion may develop differentially in males and females, and can be beneficial or detrimental to disease outcome, depending on which perfusion parameter is used as explanatory variable

Sulfated sugars in the extracellular matrix orchestrate ovarian cancer development: 'When sweet turns sour'

Considering the high mortality of ovarian cancer, novel approaches for diagnostics and therapy are urgently needed. Cancer initiation, progression, and invasion occur in a complex and dynamic microenvironment which depends on the interplay between host cell responses and tumor activity. Chondroitin sulfate (CS), a special highly sulfated sugar, forms an important intermediate player in this respect. Depending on the (micro)structural diversity of chondroitin sulfate chains, various ligands interact with this special group of glycosaminoglycans, making it a key molecule for many physiological and pathological processes, including cancer development. This review focuses on the various functions of chondroitin sulfate in tumor growth, angiogenesis, dissemination and immunosilencing of ovarian cancer. We also shed light on possible future diagnostic and therapeutic modalities for ovarian cancer based on the large variety in chondroitin sulfate microstructure and function. It is concluded that the class of chondroitin sulfate represents an attractive target to interfere with the process of ovarian tumorigenesis

Histopathologic assessment of the entire endometrium in asymptomatic women

Contains fulltext : 143499.pdf (publisher's version ) (Closed access)Knowledge on the nature of the endometrium in women without symptoms of endometrial disease is poor. Therefore, the aim of this prospective study was to describe the endometrium of a cohort of asymptomatic women. The entire endometrium of premenopausal and postmenopausal women was embedded for histologic examination. All included patients underwent a hysterectomy on indication of uterovaginal prolapse, from July 2011 to October 2012, in 3 hospitals in the South of the Netherlands. Exclusion criteria were symptoms of postmenopausal vaginal blood loss or premenopausal disordered vaginal bleeding. As a result, 68 women were included in the study, 48 women were postmenopausal and 20 were premenopausal. In the endometrium of 10 women, simple hyperplasia was found (15%); 1, complex hyperplasia (2%); 2, simple atypical hyperplasia (3%); 2, complex atypical hyperplasia (3%); and 2, a small focus of intramucosal endometrioid endometrial carcinoma (3%). In general, the endometrium was heterogeneous, and most lesions were not present in the entire endometrium. In conclusion, after examining the entire endometrium, a remarkable high prevalence of endometrial pathology was found in asymptomatic women. The clinical meaning of these lesions is not yet clear, but endometrial pathology may frequently exist without symptoms

The genomic profile of human malignant glioma is altered early in primary cell culture and preserved in spheroids

Screening of therapeutics relies on representative cancer models. The representation of human glioblastoma by in vitro cell culture models is questionable. We obtained genomic profiles by array comparative genomic hybridization of both short-and long-term primary cell and spheroid cultures, derived from seven glioblastomas and one anaplastic oligodendroglioma. Chromosomal copy numbers were compared between cell cultures and spheroids and related to the parental gliomas using unsupervised hierarchical clustering and correlation coefficient. In seven out of eight short-term cell cultures, the genomic profiles clustered further apart from their parental tumors than spheroid cultures. In four out of eight samples, the genetic changes in cell culture were substantial. T he average correlation coefficient between parental tumors and spheroid profiles was 0.89 (range: 0.79-0.97), whereas that between parental tumors and cell cultures was 0.62 (range: 0.10-0.96). In two out of three long-term cell cultures progressive genetic changes had developed, whereas the spheroid cultures were genetically stable. It is concluded that genomic profiles of primary cell cultures from glioblastoma are frequently deviant from parental tumor profiles, whereas spheroids are genetically more representative of the glioblastoma. This implies that glioma cell culture data have to be handled with the highest cautio

Immunohistochemical and genetic profiles of endometrioid endometrial carcinoma arising from atrophic endometrium

Contains fulltext : 153069.pdf (publisher's version ) (Closed access)OBJECTIVE: Endometrial carcinomas are divided into type I endometrioid endometrial carcinomas (EECs), thought to arise from hyperplastic endometrium, and type II nonendometrioid endometrial carcinomas, thought to arise from atrophic endometrium. However, a minority (20%) of EECs have atrophic background endometrium, which was shown to be a marker of a worse prognosis. This study compares the immunohistochemical and genetic profiles of this possible third type to that of the known two types. METHODS: 43 patients with grade 1 EEC and hyperplastic background endometrium (type I), 43 patients with grade 1 EEC and atrophic background endometrium (type III) and 21 patients with serous carcinoma (type II) were included (n=107). Tissue microarrays of tumor samples were immunohistochemically stained for PTEN, L1CAM, ER, PR, p53, MLH1, PMS2, beta-catenin, E-cadherin and MIB1. The BRAF, KRAS, and PIK3CA genes were analyzed for mutations. RESULTS: A significantly higher expression of ER and PR, and a lower expression of L1CAM, p53 and MLH1 were found in type I and III compared to type II carcinomas. Expression of E-cadherin was significantly reduced in type III compared to type I carcinomas. Mutation analysis showed significantly less mutations of KRAS in type III compared to type I and II carcinomas (p<0.01). CONCLUSION: There appear to be slight immunohistochemical and genetic differences between EECs with hyperplastic and atrophic background endometrium. Carcinogenesis of EEC in atrophic endometrium seems to be characterized by loss of E-cadherin and a lack of KRAS mutations. As expected, endometrioid and serous carcinomas were immunohistochemically different