Glucagon-like peptide-1 (GLP-1) is an incretin hormone known to stimulate glucose-dependent insulin secretion. The GLP-1 receptor agonist, exendin-4, has similar properties to GLP-1 and is currently in clinical use for type 2 diabetes mellitus. As GLP-1 and exendin-4 confer cardioprotection after myocardial infarction, this study was designed to assess the neuroprotective effects of exendin-4 against cerebral ischemia–reperfusion injury. Mice received a transvenous injection of exendin-4, after a 60-minute focal cerebral ischemia. Exendin-4-treated vehicle and sham groups were evaluated for infarct volume, neurologic deficit score, various physiologic parameters, and immunohistochemical analyses at several time points after ischemia. Exendin-4 treatment significantly reduced infarct volume and improved functional deficit. It also significantly suppressed oxidative stress, inflammatory response, and cell death after reperfusion. Furthermore, intracellular cyclic AMP (cAMP) levels were slightly higher in the exendin-4 group than in the vehicle group. No serial changes were noted in insulin and glucose levels in both groups. This study suggested that exendin-4 provides neuroprotection against ischemic injury and that this action is probably mediated through increased intracellular cAMP levels. Exendin-4 is potentially useful in the treatment of acute ischemic stroke.
Although challenging, neuroprotective therapies for ischemic stroke remain an interesting strategy for countering ischemic injury and suppressing brain tissue damage. Among potential neuroprotective molecules, heat shock protein 27 (HSP27) is a strong cell death suppressor. To assess the neuroprotective effects of HSP27 in a mouse model of transient middle cerebral artery occlusion, we purified a “physiological” HSP27 (hHSP27) from normal human lymphocytes. hHSP27 differed from recombinant HSP27 in that it formed dimeric, tetrameric, and multimeric complexes, was phosphorylated, and contained small amounts of αβ-crystallin and HSP20. Mice received intravenous injections of hHSP27 following focal cerebral ischemia. Infarct volume, neurological deficit scores, physiological parameters, and immunohistochemical analyses were evaluated 24 h after reperfusion. Intravenous injections of hHSP27 1 h after reperfusion significantly reduced infarct size and improved neurological deficits. Injected hHSP27 was localized in neurons on the ischemic side of the brain. hHSP27 suppressed neuronal cell death resulting from cytochrome c-mediated caspase activation, oxidative stress, and inflammatory responses. Recombinant HSP27 (rHSP27), which was artificially expressed and purified from Escherichia coli, and dephosphorylated hHSP27 did not have brain protective effects, suggesting that the phosphorylation of hHSP27 may be important for neuroprotection after ischemic insults. The present study suggests that hHSP27 with posttranslational modifications provided neuroprotection against ischemia/reperfusion injury and that the protection was mediated through the inhibition of apoptosis, oxidative stress, and inflammation. Intravenously injected human HSP27 should be explored for the treatment of acute ischemic strokes.
A 68-year-old man experienced a right caudate haemorrhage with intraventricular haemorrhage. Although a subarachnoid haemorrhage was not shown clearly, our investigation demonstrated an aneurysm-like vascular pouch located in the anomalous vessel arising from the A2 segment of the right anterior cerebral artery. Rupture of the vascular pouch was considered to be the cause of the caudate haemorrhage. Neck clipping was performed. In intraoperative observation, the anomalous vessel was diagnosed as a right accessory middle cerebral artery. Histopathology of the saccular wall showed only an adventitia and a fibrin layer, indicating a pseudoaneurysm. We routinely perform detailed vascular evaluation for any cerebrovascular disease. A meticulous vascular survey makes it possible to obtain valuable clues in cases such as caudate haemorrhage due to pseudoaneurysm of the accessory middle cerebral artery, leading to prevention of rebleeding.
BackgroundThe anterior communicating artery (ACoA) often limits surgical exposure in the anterior interhemispheric approach. Although division of the ACoA has been proposed occasionally, it is rarely practiced, and criteria for such a surgical maneuver remain unknown. Our purpose was to identify key factors that allow for predicting the necessity of controlled ACoA division in the bifrontal basal interhemispheric approach.MethodTwenty-two consecutive patients who underwent surgery via the bifrontal basal interhemispheric approach for removal of various pathologic brain lesions were examined. First, tumors were dichotomized into central and lateral lesions. Next, three tumor parameters were compared between cases with and without ACoA division in each, the central and lateral lesion groups, respectively: tumor volume, tumor depth (defined as distance between the ACoA and posterior tumor margin) and tumor laterality angle (defined as the geometric angle between the lateral tumor margin and sagittal midline).ResultsTumor volume was not related in a statistically significant manner to ACoA division in both the central (P = 0.06) and lateral (P = 0.13) lesion groups, respectively. However, tumor depth was significantly correlated with ACoA division in the central lesion group (P = 0.01), whereas in the lateral lesion group, the tumor laterality angle showed a significant correlation with ACoA division (P = 0.04).ConclusionsOur results suggest that controlled ACoA division may be required in central lesions with a depth of 38 mm or more and in lateral lesions with an angle of 23 degrees or more as defined in this study. Two key factors were thus identified that may predict the necessity of controlled ACoA division before surgery.
Summary A 67-year-old woman with a past history of type 2 diabetes mellitus presented with worsening glycemic control. She had some acromegaly symptoms and magnetic resonance imaging demonstrated a pituitary tumor. Endocrinological examination found the resting growth hormone (GH) level within the normal range, but elevated insulin-like growth factor 1 level. A 75 g oral glucose tolerance test showed inadequate suppression of nadir GH levels. Acromegaly due to GH-secreting pituitary tumor was diagnosed. The patient underwent endoscopic transsphenoidal surgery resulting in gross total removal of the tumor and recovered well postoperatively. Histological examination of the tumor showed coexistence of relatively large gangliocytoma cells and pituitary adenoma cells, suggesting mixed gangliocytoma-pituitary adenoma. In addition, colocalization of GH and GH-releasing hormone (GHRH) in pituitary adenoma cells was revealed, so the adenomatous components were more likely to produce GHRH in our mixed gangliocytoma-pituitary adenoma case. Mixed gangliocytoma-pituitary adenoma is very rare, and the present unique case demonstrated only the adenomatous components associated with GHRH production. Learning points: Sellar gangliocytoma coexisting with pituitary adenoma is recognized as a mixed gangliocytoma-pituitary adenoma and is very rare. A proposed developmental mechanism of growth hormone (GH)-secreting mixed gangliocytoma-pituitary adenoma involves GH-releasing hormone (GHRH) produced by the gangliocytic components promoting the growth of tumor including GH-secreting adenomatous components. Since our present case indicated that the adenomatous components of mixed gangliocytoma-pituitary adenoma could secrete both GH and GHRH simultaneously, progression of GH-secreting mixed gangliocytoma and pituitary adenoma may involve exposure to spontaneously produced GHRH due to the adenomatous components.
Meningeal hemangiopericytoma (HPC) is an infrequent but distinct entity affecting the craniospinal axis. A previously healthy 48-year-old man sustained a gradually progressing motor weakness in the left lower extremity. CT showed a hyperdense mass in the right frontal lobe. On MRI, it was 29 × 30 × 36 mm in dimension, appeared isointense on T1 and hyperintense on T2, and was intensely enhanced with erosive changes in the inner table adjacent to the tumor. The patient underwent tumor resection. Reflection of the bone flap revealed a punched-out erosion in the inner table with a defect of the dura over the upper part of the tumor. Microscopic findings were consistent with grade III HPC with dural invasion. A punched-out calvarial erosion and dural defect caused by an extra-axial tumor may be a high-grade HPC that requires extensive surgical resection.
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