Rupture of the Superior Sagittal Sinus in Penetrating Head Injury—Management of a Rare Trauma Mechanism

Civilian penetrating head injury caused by foreign objects is rare in Germany (Europe), but can result in complex neurovascular damage. We report on a patient who in suicidal intent inflicted on himself a penetrating brain injury near the vertex with a captive bolt gun. A laceration at the junction of the middle to the posterior third of the superior sinus occurred by bolt and bone fragments leading to critical stenosis and subsequent thrombosis. Upon surgery, the proximal and distal sinus openings were completely thrombosed. The sinus laceration was closed by suture and the intraparenchymal bone fragments were retrieved. Postoperative angiography disclosed persistent occlusion of the superior sagittal sinus. The patient did not develop any symptoms due to venous congestion (edema, hemorrhage), suggesting sufficient collateral venous outflow. The patient completely recovered despite the complexity of the lesion.

Early neurovascular retinal changes detected by swept-source OCT in type 2 diabetes and association with diabetic kidney disease

Purpose To evaluate retinal thickness and capillary density in patients with type 2 diabetes (T2D) and their association with diabetic kidney disease (DKD) using swept-source optical coherence tomography (SS-OCT). Methods A cross-sectional study was conducted with T2D patients with mild or no diabetic retinopathy (DR) and nondiabetic controls. Inner retinal layer thickness was measured with SS-OCT. Retinal capillary density and the foveal avascular zone (FAZ) were measured with SS-OCT angiography (OCTA). SS-OCT parameters were compared in patients with and without diabetic kidney disease (DKD) and nondiabetic controls. Results 131 DKD eyes showed decreased ganglion cell layer plus (GCL+) (p = 0.005 TI; p = 0.022 I), retinal nerve fiber layer (RNFL) (p = 0.003), and central retinal thickness (CRT) (p = 0.032), as well as foveal avascular zone (FAZ) enlargement (p = 0.003) and lower capillary density in the superficial vascular plexus (p = 0.016, central quadrant), compared to controls. No statistically significant changes were found between diabetic patients without significant DKD and controls. Conclusion Our findings suggest early neurovascular damage in patients with T2D; these changes were more significant in patients with DKD. Larger longitudinal studies are warranted to determine the role of early neurovascular damage in the pathophysiology of severe DR.

Endothelial Thioredoxin-Interacting Protein Depletion Reduces Hemorrhagic Transformation in Hyperglycemic Mice after Embolic Stroke and Thrombolytic Therapy

We hypothesize that endothelial-specific thioredoxin-interacting protein knock-out (EC-TXNIP KO) mice will be more resistant to the neurovascular damage (hemorrhagic-transformation-HT) associated with hyperglycemia (HG) in embolic stroke. Adult-male EC-TXNIP KO and wild-type (WT) littermate mice were injected with-streptozotocin (40 mg/kg, i.p.) for five consecutive days to induce diabetes. Four-weeks after confirming HG, mice were subjected to embolic middle cerebral artery occlusion (eMCAO) followed by tissue plasminogen activator (tPA)-reperfusion (10 mg/kg at 3 h post-eMCAO). After the neurological assessment, animals were sacrificed at 24 h for neurovascular stroke outcomes. There were no differences in cerebrovascular anatomy between the strains. Infarct size, edema, and HT as indicated by hemoglobin (Hb)-the content was significantly higher in HG-WT mice, with or without tPA-reperfusion, compared to normoglycemic WT mice. Hyperglycemic EC-TXNIP KO mice treated with tPA tended to show lower Hb-content, edema, infarct area, and less hemorrhagic score compared to WT hyperglycemic mice. EC-TXNIP KO mice showed decreased expression of inflammatory mediators, apoptosis-associated proteins, and nitrotyrosine levels. Further, vascular endothelial growth factor-A and matrix-metalloproteinases (MMP-9/MMP-3), which degrade junction proteins and increase blood-brain-barrier permeability, were decreased in EC-TXNIP KO mice. Together, these findings suggest that vascular-TXNIP could be a novel therapeutic target for neurovascular damage after stroke.

Astrocyte Activation in Neurovascular Damage and Repair Following Ischaemic Stroke

Transient or permanent loss of tissue perfusion due to ischaemic stroke can lead to damage to the neurovasculature, and disrupt brain homeostasis, causing long-term motor and cognitive deficits. Despite promising pre-clinical studies, clinically approved neuroprotective therapies are lacking. Most studies have focused on neurons while ignoring the important roles of other cells of the neurovascular unit, such as astrocytes and pericytes. Astrocytes are important for the development and maintenance of the blood–brain barrier, brain homeostasis, structural support, control of cerebral blood flow and secretion of neuroprotective factors. Emerging data suggest that astrocyte activation exerts both beneficial and detrimental effects following ischaemic stroke. Activated astrocytes provide neuroprotection and contribute to neurorestoration, but also secrete inflammatory modulators, leading to aggravation of the ischaemic lesion. Astrocytes are more resistant than other cell types to stroke pathology, and exert a regulative effect in response to ischaemia. These roles of astrocytes following ischaemic stroke remain incompletely understood, though they represent an appealing target for neurovascular protection following stroke. In this review, we summarise the astrocytic contributions to neurovascular damage and repair following ischaemic stroke, and explore mechanisms of neuroprotection that promote revascularisation and neurorestoration, which may be targeted for developing novel therapies for ischaemic stroke.

Vascular dysfunction in the brain; implications for heavy metals exposure

: Normal or diseased conditions that alter the brain’s requirement for oxygen and nutrients via alterations to neurovascular coupling act at the level of the neurovascular unit; comprising neuronal, glial and vascular components. The communications between the components of the neurovascular unit are precise and accurate for its functions, hence a minute disturbance can result in neurovascular dysfunction. Heavy metals such as cadmium, mercury, and lead have been identified to increase the vulnerability of the neurovascular unit to damage. This review examines the role of heavy metals in neurovascular dysfunctions and the possible mechanisms by which these metals act. Risk factors ranging from lifestyle, environment, genetics, infections, and physiologic ageing involved in neurological dysfunctions were highlighted, while stroke, was discussed as the prevalent consequence of neurovascular dysfunctions. Furthermore, the role of these heavy metals in the pathogenesis of stroke consequently pinpoints the importance of understanding the mechanisms of neurovascular damage in a bid to curb the occurrence of neurovascular dysfunctions.

Ultrasound-Guided Decompression of the Intermetatarsal Nerve for Morton's Neuroma: A Novel Closed Surgical Technique

Background This study describes the technique for decompression of the intermetatarsal nerve in Morton's neuroma by ultrasound-guided surgical resection of the transverse intermetatarsal ligament. This technique is based on the premise that Morton's neuroma is primarily a nerve entrapment disease. As with other ultrasound-guided procedures, we believe that this technique is less traumatic, allowing earlier return to normal activity, with less patient discomfort than with traditional surgical techniques. Methods We performed a pilot study on 20 cadavers to ensure that the technique was safe and effective. No neurovascular damage was observed in any of the specimens. In the second phase, ultrasound-guided release of the transverse intermetatarsal ligament was performed on 56 patients through one small (1- to 2-mm) portal using local anesthesia and outpatient surgery. Results Of the 56 participants, 54 showed significant improvement and two did not improve, requiring further surgery (neurectomy). The postoperative wound was very small (1–2 mm). There were no cases of anesthesia of the interdigital space, and there were no infections. Conclusions The ultrasound-guided decompression of intermetatarsal nerve technique for Morton's neuroma by releasing the transverse intermetatarsal ligament is a safe, simple method with minimal morbidity, rapid recovery, and potential advantages over other surgical techniques. Surgical complications are minimal, but it is essential to establish a good indication because other biomechanical alterations to the foot can influence the functional outcome.

Pharmacological and fasting-induced activation of SIRT1/LXRα signaling alleviates diabetes-induced retinopathy

SummaryIn diabetes, the retina, a tissue with unique metabolic needs, demonstrates dysregulation of the intricate balance between nutrient availability and utilization. This results in cholesterol accumulation, pro-inflammatory and pro-apoptotic changes, and consequently neurovascular damage. Sirtuin 1 (SIRT1), a nutrient sensing deacetylase, is downregulated in the diabetic retina. In this study, the effect of SIRT1 stimulation by fasting or by pharmacological activation using SRT1720, was evaluated on retinal cholesterol metabolism, inflammation and neurovascular damage. SIRT1 activation, in retinal endothelial cells (REC) and neuronal retinal progenitor cells (R28), led to Liver X Receptor alpha (LXRα) deacetylation and subsequent increased activity, as measured by increased ATP-binding cassette transporter (ABC) A1 and G1 mRNA expression. In turn, increased cholesterol export resulted in decreased REC cholesterol levels. SIRT1 activation also led to decreased inflammation. SIRT1 activation, in vivo, prevented diabetes-induced inflammation and vascular and neural degeneration. Diabetes-induced visual function impairment, as measured by electroretinogram and optokinetic response, was significantly improved as a result of SIRT1 activation. Taken together, activation of SIRT1 signaling is an effective therapeutic strategy that provides a mechanistic link between the advantageous effects associated with fasting regimes and prevention of diabetic retinopathy (DR).

Lisosan G Protects the Retina from Neurovascular Damage in Experimental Diabetic Retinopathy

Lisosan G (LG), a fermented powder obtained from whole grains, is a recognized antioxidant compound that improves the bioactivity and survival of different cell types. The purpose of this study was to investigate whether LG ameliorates both the neural and the vascular damage characterizing early stages of diabetic retinopathy (DR). The effects of LG were studied in cultured explants of mouse retinas challenged with oxidative stress (OS) or in retinas of streptozotocin (STZ)-treated rats. Apoptosis, vascular endothelial growth factor (VEGF) expression, OS markers, blood-retinal barrier (BRB) integrity, and inflammation were assessed, while retinal function was evaluated with electroretinogram (ERG). LG extensively inhibited apoptosis, VEGF expression, and OS both in retinal explants and in STZ rats. In addition, STZ rats treated with LG displayed an almost total BRB integrity, reduced levels of inflammatory markers and a partially restored visual function as evaluated with ERG. In summary, we demonstrated that LG exhibits antioxidant and anti-inflammatory effects that exert powerful protective actions against neural and vascular defects characteristic of DR. Therefore, LG-containing foods or supplements may be considered to implement DR treatments.