Assessment of Brain Lesions in Type 2 Diabetes Mellitus and Hypertension using Magnetic Resonance imaging

Background: Type 2 diabetes mellitus (T2DM) and hypertension (HTN) are risk factors for the spectrum of brain lesions. In this paper, we studied the impact of T2DM and HTN on the incidence of several brain lesions diagnosed with magnetic resonance imaging (MRI). Methods and Results: This retrospective, single-center study was conducted at Royal Care International Hospital (Khartoum, Sudan) from January 2016 to December 2016 and included 80 patients (40 male and 40 female, aged between 20 years and 90 years) with suspected brain disorders. MRI brain examinations were conducted on a 1.5 Tesla MRI system (Toshiba Medical Systems, Tokyo, Japan). The following sequences were analyzed: T1-weighted imaging (T1WI), T2-weighted imaging (T2WI), fluid-attenuated inversion recovery (FLAIR), and diffusion-weighted imaging (DWI). Brain lesions were characterized by magnetic imaging spectroscopy and histopathological analysis. Binary logistic regression analysis was used to establish a mathematical model of the relationship between T2DM/HTN and the prevalence of brain lesions. Among 80 patients, HTN, T2D, and the combination of T2D and HTN were identified in 18(22.5%), 9(11.2%), and 11(13.8%) patients, respectively. Brain lesions were found in 48(60%) patients and were most prevalent in the age group of 66-80 years. The brain lesions included ischemic brain infarction (IBI) (22.5%), brain tumors (11.2%), cerebral hemorrhages (6.2%), brain atrophy (BA) (1.2 %), IBI with BA (16.2%), and brain metastases (2.5%). Regression analysis showed that HTN and T2DM were associated with significantly higher ORs for brain lesions ([OR=2.459, 95% CI: 1.673–3.614, P<0.001] and [OR=1.507, 95% CI: 1.067–2.128, P= 0.042], and [OR=1.078, 95% CI:1.033–1.124, P=0.001], respectively). HTN was associated with significantly higher OR for ischemic brain infarction (OR=7.404, 95% CI: 2.600–21.081, P<0.001). Conclusion: The study showed a significant interaction between HTN and T2DM on the prevalence of brain lesions, especially ischemic brain infarction and brain atrophy.

Silencing the lncRNA Maclpil in pro-inflammatory macrophages attenuates acute experimental ischemic stroke via LCP1 in mice

Long noncoding RNAs (lncRNA) expression profiles change in the ischemic brain after stroke, but their roles in specific cell types after stroke have not been studied. We tested the hypothesis that lncRNA modulates brain injury by altering macrophage functions. Using RNA deep sequencing, we identified 73 lncRNAs that were differentially expressed in monocyte-derived macrophages (MoDMs) and microglia-derived macrophages (MiDMs) isolated in the ischemic brain three days after stroke. Among these, the lncRNA, GM15628, is highly expressed in pro-inflammatory MoDMs but not in MiDMs, and are functionally related to its neighbor gene, lymphocyte cytosolic protein 1 (LCP1), which plays a role in maintaining cell shape and cell migration. We termed this lncRNA as Macrophage contained LCP1 related pro-inflammatory lncRNA, Maclpil. Using cultured macrophages polarized by LPS, M(LPS), we found that downregulation of Maclpil in M(LPS) decreased pro-inflammatory gene expression while promoting anti-inflammatory gene expression. Maclpil inhibition also reduced the migration and phagocytosis ability of MoDMs by inhibiting LCP1. Furthermore, adoptive transfer of Maclpil silenced M(LPS), reduced ischemic brain infarction, improved behavioral performance and attenuated penetration of MoDMs in the ischemic hemisphere. We conclude that by blocking macrophage, Maclpil protects against acute ischemic stroke by inhibiting neuroinflammation.

SLAP/SLAP2 prevent excessive platelet (hem)ITAM signaling in thrombosis and ischemic stroke in mice

Key Points SLAP and SLAP2 have redundant functions in the regulation of platelet (hem)ITAM signaling. SLAP and SLAP2 in platelets limit occlusive thrombus formation and ischemic brain infarction.

Presumptive Ischemic Brain Infarction in a Dog with Evans’ Syndrome

A ten-year-old neutered female mixed breed dog was referred for pale mucous membrane and acute onset of right prosencephalic clinical signs. Brain magnetic resonance imaging was suggestive for right middle cerebral artery ischemic stroke. Based on cell blood count, serum biochemistry and serologic tests and flow cytometric detection of anti-platelets and anti-red blood cells antibodies, a diagnosis of immunomediated haemolytic anemia associated with thrombocytopenia of suspected immunomediated origin was done. Immunosuppresive therapy with prednisone was started and the dog clinically recovered. Two months later complete normalization of CBC and serum biochemistry was documented. The dog remained stable for 7 months without therapy; then she relapsed. CBC revealed mild regenerative anemia with spherocytosis and thrombocytopenia. A conclusive Evans’ syndrome diagnosis was done and prednisone and cyclosporine treatment led to normalization of physical and CBC parameters. The dog is still alive at the time the paper submitted. Possible thrombotic etiopathogenetic mechanisms are illustrated in the paper and the authors suggest introducing Evans’ syndrome in the differential diagnosis list for brain ischemic stroke in dogs.

Only severe thrombocytopenia results in bleeding and defective thrombus formation in mice

Key Points Hemostasis, thrombosis, and ischemic brain infarction efficiently occur at unexpectedly low platelet counts in mice. The threshold platelet count required for occlusive thrombus formation differs between thrombosis models.

Diabetic Ketoacidosis-Associated Stroke in Children and Youth

Diabetic ketoacidosis (DKA) is a state of severe insulin deficiency, either absolute or relative, resulting in hyperglycemia and ketonemia. Although possibly underappreciated, up to 10% of cases of intracerebral complications associated with an episode of DKA, and/or its treatment, in children and youth are due to hemorrhage or ischemic brain infarction. Systemic inflammation is present in DKA, with resultant vascular endothelial perturbation that may result in coagulopathy and increased hemorrhagic risk. Thrombotic risk during DKA is elevated by abnormalities in coagulation factors, platelet activation, blood volume and flow, and vascular reactivity. DKA-associated cerebral edema may also predispose to ischemic injury and hemorrhage, though cases of stroke without concomitant cerebral edema have been identified. We review the current literature regarding the pathogenesis of stroke during an episode of DKA in children and youth.